2,538 results on '"Havlir, Diane"'
Search Results
2. Rapid biphasic decay of intact and defective HIV DNA reservoir during acute treated HIV disease.
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Barbehenn, Alton, Shi, Lei, Shao, Junzhe, Hoh, Rebecca, Hartig, Heather, Pae, Vivian, Sarvadhavabhatla, Sannidhi, Donaire, Sophia, Sheikhzadeh, Caroline, Milush, Jeffrey, Laird, Gregory, Mathias, Mignot, Ritter, Kristen, Peluso, Michael, Martin, Jeffrey, Hecht, Frederick, Pilcher, Christopher, Cohen, Stephanie, Buchbinder, Susan, Havlir, Diane, Gandhi, Monica, Henrich, Timothy, Hatano, Hiroyu, Wang, Jingshen, Deeks, Steven, and Lee, Sulggi
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Humans ,HIV Infections ,DNA ,Viral ,Viral Load ,CD4-Positive T-Lymphocytes ,HIV-1 ,Male ,Female ,Virus Latency ,Adult ,CD4 Lymphocyte Count ,Middle Aged ,Anti-HIV Agents ,Longitudinal Studies ,Acute Disease ,Models ,Theoretical - Abstract
Despite antiretroviral therapy (ART), HIV persists in latently-infected cells (the HIV reservoir) which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people living with HIV (PLWH) treated during acute infection, we developed a mathematical model to predict reservoir decay from peripheral CD4 + T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t1/2 ~ 2.83 weeks; week 5-24: t1/2 ~ 15.4 weeks) that extended out to 1 year. These estimates were ~5-fold faster than prior decay estimates among chronic treated PLWH. Defective DNA had a similar biphasic pattern, but data were more variable. Predicted intact and defective decay rates were faster for PLWH with earlier timing of ART initiation, higher initial CD4 + T cell count, and lower pre-ART viral load. In this study, we advanced our limited understanding of HIV reservoir decay at the time of ART initiation, informing future curative strategies targeting this critical time.
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- 2024
3. Client experiences with “Dynamic Choice Prevention,” a model for flexible patient‐centred HIV prevention delivery in rural Eastern Africa
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Camlin, Carol S, Arunga, Titus, Johnson‐Peretz, Jason, Akatukwasa, Cecilia, Atwine, Fredrick, Onyango, Angeline, Owino, Lawrence, Kamya, Moses R, Petersen, Maya L, Chamie, Gabriel, Kakande, Elijah, Kabami, Jane, Balzer, Laura B, Havlir, Diane V, and Ayieko, James
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Biomedical and Clinical Sciences ,Health Services and Systems ,Public Health ,Clinical Sciences ,Health Sciences ,Mental Health ,Infectious Diseases ,Sexually Transmitted Infections ,Clinical Research ,HIV/AIDS ,Prevention ,Women's Health ,Health Disparities ,Behavioral and Social Science ,7.1 Individual care needs ,8.1 Organisation and delivery of services ,Generic health relevance ,Infection ,Good Health and Well Being ,Humans ,HIV Infections ,Female ,Male ,Adult ,Rural Population ,Pre-Exposure Prophylaxis ,Qualitative Research ,Interviews as Topic ,Africa ,Eastern ,Young Adult ,Patient-Centered Care ,Middle Aged ,Anti-HIV Agents ,pre-exposure prophylaxis ,post-exposure prophylaxis ,HIV self-testing ,differentiated care ,HIV stigma ,sub-Saharan Africa ,HIV self‐testing ,post‐exposure prophylaxis ,pre‐exposure prophylaxis ,sub‐Saharan Africa ,Public Health and Health Services ,Other Medical and Health Sciences ,Clinical sciences ,Epidemiology ,Public health - Abstract
IntroductionIdentifying the optimal approaches to offering HIV prevention to meet the needs of those at risk is a high priority, particularly given the expanding toolkit of biomedical HIV prevention options. An ongoing study in rural East African communities evaluated the uptake of choices in product, testing mode and location of care delivery through a structured patient-centred HIV prevention delivery model. In this qualitative study, we sought to understand clients' experiences of this "dynamic choice prevention model" (DCP) and highlight pathways of action to inform HIV prevention delivery models.MethodsIn-depth semi-structured interviews were conducted from November 2021 through March 2022 with a purposively selected sample of n = 56 participants in DCP trials (across outpatient departments, antenatal clinics and community settings), and n = 21 healthcare providers (total n = 77). A seven-person multi-regional team translated and inductively coded transcript data. We used a framework analysis approach to identify emergent themes.ResultsIndividuals taking up HIV pre-exposure prophylaxis (PrEP) reported feelings of relief, liberation from fears of acquiring HIV and satisfaction with being able to take action despite partners' behaviours. Couples used a range of approaches afforded by the study to persuade partners to get tested and opt for PrEP. Post-exposure prophylaxis (PEP) use was less common, although women welcomed it in the event of sexual coercion or assault. Participants discussed switching from PEP to PrEP after familiarizing themselves with usage and ascertaining ongoing risk. Participants felt respected by providers, trusted them and appreciated being able to contact them directly for telephone support. Prevention uptake was hindered by stigma, limited experience with and knowledge of prevention methods, gendered and generational power dynamics within intimate partnerships and families, and negative perceptions of methods due to the products themselves. Participants anticipated long-acting injectable PrEP could solve their challenges regarding pill size, daily pill burden and the likelihood of unwanted disclosure.ConclusionsDiverse preferences and barriers to uptake of prevention require a choice of HIV prevention options, locations and delivery modalities-but in addition, flexible, competent and friendly care provision is crucial to promote uptake. Helping clients feel valued, and addressing their unique needs and challenges, enables their agency to prioritize their health.
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- 2024
4. Causal Inference in Randomized Trials with Partial Clustering
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Nugent, Joshua, Kakande, Elijah, Chamie, Gabriel, Kabami, Jane, Owaraganise, Asiphas, Havlir, Diane V., Kamya, Moses, and Balzer, Laura
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Statistics - Methodology - Abstract
Clustering and dependence are common in trials. For example, in some cluster randomized trials (CRTs), pre-existing clusters are enrolled, randomized, and serve as the basis of intervention delivery. Such CRTs are "fully clustered": participants are dependent within clusters. In contrast, "partially clustered" trials contain a mix of participants that are dependent within clusters and participants that are completely independent. One example of this design is a trial where participants are artificially grouped together for the purposes of randomization only; then, for intervention participants, the groups are the basis for intervention delivery, while control participants are un-grouped. Another example is an individually randomized group treatment trial (IRGTT) where participants are individually randomized and, post-randomization, intervention participants are grouped for intervention delivery, while the control participants remain un-grouped. For the three trial designs, we use causal models to non-parametrically describe the data generating process and formalize the observed data dependence structure. We show that despite the different randomization approach, both designs can be represented with the same dependence structure, enabling the use of the same statistical methods for estimation and inference of causal effects. We propose a novel implementation of targeted minimum loss-based estimation (TMLE) for these trials. TMLE is model-robust, leverages covariate adjustment and machine learning, and estimates many causal effects. In simulations, TMLE achieved comparable higher statistical power than alternatives for partially clustered designs. Finally, application to real data from the SEARCH-IPT trial resulted in 20-57% efficiency gains, demonstrating the consequences of our proposed approach.
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- 2024
5. Illness Narratives Without the Illness: Biomedical HIV Prevention Narratives from East Africa
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Johnson-Peretz, Jason, Atwine, Fredrick, Kamya, Moses R., Ayieko, James, Petersen, Maya L., Havlir, Diane V., and Camlin, Carol S.
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- 2024
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6. When exposure affects subgroup membership: Framing relevant causal questions in perinatal epidemiology and beyond
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Gupta, Shalika, Balzer, Laura B., Kamya, Moses R., Havlir, Diane V., and Petersen, Maya L.
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Statistics - Methodology - Abstract
Perinatal epidemiology often aims to evaluate exposures on infant outcomes. When the exposure affects the composition of people who give birth to live infants (e.g., by affecting fertility, behavior, or birth outcomes), this "live birth process" mediates the exposure effect on infant outcomes. Causal estimands previously proposed for this setting include the total exposure effect on composite birth and infant outcomes, controlled direct effects (e.g., enforcing birth), and principal stratum direct effects. Using perinatal HIV transmission in the SEARCH Study as a motivating example, we present two alternative causal estimands: 1) conditional total effects; and 2) conditional stochastic direct effects, formulated under a hypothetical intervention to draw mediator values from some distribution (possibly conditional on covariates). The proposed conditional total effect includes impacts of an intervention that operate by changing the types of people who have a live birth and the timing of births. The proposed conditional stochastic direct effects isolate the effect of an exposure on infant outcomes excluding any impacts through this live birth process. In SEARCH, this approach quantifies the impact of a universal testing and treatment intervention on infant HIV-free survival absent any effect of the intervention on the live birth process, within a clearly defined target population of women of reproductive age with HIV at study baseline. Our approach has implications for the evaluation of intervention effects in perinatal epidemiology broadly, and whenever causal effects within a subgroup are of interest and exposure affects membership in the subgroup.
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- 2024
7. The effect of an intervention to promote isoniazid preventive therapy on leadership and management abilities.
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Christian, C, Kakande, E, Nahurira, V, Balzer, L, Owaraganise, A, Nugent, J, DiIeso, W, Rast, D, Kabami, J, Peretz, J, Camlin, C, Shade, S, Kamya, M, Havlir, Diane, and Chamie, G
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Change Leadership Questionnaire ,IPT ,Leadership Behavior Description Questionnaire ,health system strengthening ,implementation science ,sub-Saharan Africa ,tuberculosis - Abstract
BACKGROUND: Across sub-Saharan Africa, mid-level healthcare managers oversee implementation of national guidelines. It remains unclear whether leadership and management training can improve population health outcomes. METHODS: We sought to evaluate leadership/management skills among district-level health managers in Uganda participating in the SEARCH-IPT randomised trial to promote isoniazid preventive therapy (IPT) for persons with HIV (PWH). The intervention, which led to higher IPT rates, included annual leadership/management training of managers. We conducted a cross-sectional survey assessing leadership/management skills among managers at trial completion. The survey evaluated self-reported use of leadership/management tools and general leadership/management. We conducted a survey among a sample of providers to understand the interventions impact. Targeted minimum loss-based estimation (TMLE) was used to compare responses between trial arms. RESULTS: Of 163 managers participating in the SEARCH-IPT trial, 119 (73%) completed the survey. Intervention managers reported more frequent use of leadership/management tools taught in the intervention curriculum than control managers (+3.64, 95% CI 1.98-5.30, P < 0.001). There were no significant differences in self-reported leadership skills in the intervention as compared to the control group. Among providers, the average reported quality of guidance and supervision was significantly higher in intervention vs control districts (+1.08, 95% CI 0.63-1.53, P = 0.001). CONCLUSIONS: A leadership and management training intervention increased the use of leadership/management tools among mid-level managers and resulted in higher perceived quality of supervision among providers in intervention vs control districts in Uganda. These findings suggest improved leadership/management among managers contributed to increased IPT use among PWH in the intervention districts of the SEARCH-IPT trial.
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- 2024
8. Randomized Trial of Dynamic Choice HIV Prevention at Antenatal and Postnatal Care Clinics in Rural Uganda and Kenya
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Kabami, Jane, Koss, Catherine A, Sunday, Helen, Biira, Edith, Nyabuti, Marilyn, Balzer, Laura B, Gupta, Shalika, Chamie, Gabriel, Ayieko, James, Kakande, Elijah, Bacon, Melanie C, Havlir, Diane, Kamya, Moses R, Petersen, Maya, and Team, SEARCH Study
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Biomedical and Clinical Sciences ,Public Health ,Health Sciences ,Clinical Sciences ,Prevention ,HIV/AIDS ,Behavioral and Social Science ,Health Services ,Clinical Research ,Sexually Transmitted Infections ,Pediatric ,Women's Health ,Clinical Trials and Supportive Activities ,Infectious Diseases ,3.1 Primary prevention interventions to modify behaviours or promote wellbeing ,Reproductive health and childbirth ,Good Health and Well Being ,Female ,Humans ,Pregnancy ,HIV Infections ,Kenya ,Postnatal Care ,Postpartum Period ,Pre-Exposure Prophylaxis ,Uganda ,Adolescent ,Young Adult ,HIV ,PrEP ,PEP ,antenatal care ,postnatal care ,person-centered ,SEARCH Study Team ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundPregnant and postpartum women in Sub-Saharan Africa are at high risk of HIV acquisition. We evaluated a person-centered dynamic choice intervention for HIV prevention (DCP) among women attending antenatal and postnatal care.SettingRural Kenya and Uganda.MethodsWomen (aged 15 years or older) at risk of HIV acquisition seen at antenatal and postnatal care clinics were individually randomized to DCP vs. standard of care (SEARCH; NCT04810650). The DCP intervention included structured client choice of product (daily oral pre-exposure prophylaxis or postexposure prophylaxis), service location (clinic or out of facility), and HIV testing modality (self-test or provider-administered), with option to switch over time and person-centered care (phone access to clinician, structured barrier assessment and counseling, and provider training). The primary outcome was biomedical prevention coverage-proportion of 48-week follow-up with self-reported pre-exposure prophylaxis or postexposure prophylaxis use, compared between arms using targeted maximum likelihood estimation.ResultsBetween April and July 2021, we enrolled 400 women (203 intervention and 197 control); 38% were pregnant, 52% were aged 15-24 years, and 94% reported no pre-exposure prophylaxis or postexposure prophylaxis use for ≥6 months before baseline. Among 384/400 participants (96%) with outcome ascertained, DCP increased biomedical prevention coverage 40% (95% CI: 34% to 47%; P < 0.001); the coverage was 70% in intervention vs. 29% in control. DCP also increased coverage during months at risk of HIV (81% in intervention, 43% in control; 38% absolute increase; 95% CI: 31% to 45%; P < 0.001).ConclusionA person-centered dynamic choice intervention that provided flexibility in product, testing, and service location more than doubled biomedical HIV prevention coverage in a high-risk population already routinely offered access to biomedical prevention options.
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- 2024
9. Geographic mobility and HIV care engagement among people living with HIV in rural Kenya and Uganda
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Ayieko, James, Thorp, Marguerite, Getahun, Monica, Gandhi, Monica, Maeri, Irene, Gutin, Sarah A, Okiring, Jaffer, Kamya, Moses R, Bukusi, Elizabeth A, Charlebois, Edwin D, Petersen, Maya, Havlir, Diane V, Camlin, Carol S, and Murnane, Pamela M
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- 2023
10. Clinical Implications of HIV Treatment and Prevention for Polygamous Families in Kenya and Uganda: "My Co-Wife Is the One Who Used to Encourage Me".
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Johnson-Peretz, Jason, Onyango, Anjeline, Gutin, Sarah A, Balzer, Laura, Akatukwasa, Cecilia, Owino, Lawrence, Arunga, Titus MO, Atwine, Fred, Petersen, Maya, Kamya, Moses, Ayieko, James, Ruel, Ted, Havlir, Diane, and Camlin, Carol S
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Health Services and Systems ,Biomedical and Clinical Sciences ,Health Sciences ,Human Society ,Infectious Diseases ,Prevention ,Mental Health ,Behavioral and Social Science ,Sexually Transmitted Infections ,Pediatric ,Pediatric AIDS ,HIV/AIDS ,Clinical Research ,Generic health relevance ,Good Health and Well Being ,Humans ,Uganda ,Kenya ,HIV Infections ,Male ,Female ,Adult ,Marriage ,Spouses ,Qualitative Research ,Young Adult ,Middle Aged ,Rural Population ,Family Characteristics ,Interviews as Topic ,HIV ,polygamy ,PrEP ,differentiated care ,serodifferent couples ,adolescents - Abstract
Polygamy is the practice of marriage to multiple partners. Approximately 6-11% of households in Uganda and 4-11% of households in Kenya are polygamous. The complex families produced by polygamous marriage customs give rise to additional considerations for healthcare providers and public health messaging around HIV care. Using 27 in-depth, semi-structured qualitative interviews with participants in two studies in rural Kenya and Uganda, we analysed challenges and opportunities that polygamous families presented in the diagnosis, treatment and prevention of HIV, and provider roles in improving HIV outcomes in these families. Overall, prevention methods seemed more justifiable to families where co-wives live far apart than when all members live in the same household. In treatment, diagnosis of one member did not always lead to disclosure to other members, creating an adverse home environment; but sometimes diagnosis of one wife led not only to diagnosis of the other, but also to greater household support.
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- 2024
11. Exploring HIV risk perception mechanisms among youth in a test-and-treat trial in Kenya and Uganda
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Owino, Lawrence, Johnson-Peretz, Jason, Lee, Joi, Getahun, Monica, Coppock-Pector, Dana, Maeri, Irene, Onyango, Anjeline, Cohen, Craig R, Bukusi, Elizabeth A, Kabami, Jane, Ayieko, James, Petersen, Maya, Kamya, Moses R, Charlebois, Edwin, Havlir, Diane, and Camlin, Carol S
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Biomedical and Clinical Sciences ,Public Health ,Clinical Sciences ,Health Sciences ,Human Society ,Infectious Diseases ,Women's Health ,Clinical Research ,HIV/AIDS ,Behavioral and Social Science ,Social Determinants of Health ,Prevention ,Pediatric AIDS ,Pediatric ,Sexually Transmitted Infections ,Adolescent Sexual Activity ,Prevention of disease and conditions ,and promotion of well-being ,3.1 Primary prevention interventions to modify behaviours or promote wellbeing ,Infection ,Reproductive health and childbirth ,Good Health and Well Being ,Gender Equality - Abstract
Understanding risk perception and risk-taking among youth can inform targeted prevention efforts. Using a health beliefs model-informed framework, we analysed 8 semi-structured, gender-specific focus group discussions with 93 youth 15-24 years old (48% male, 52% female), drawn from the SEARCH trial in rural Kenya and Uganda in 2017-2018, coinciding with the widespread introduction of PrEP. Highly connected social networks and widespread uptake of antiretrovirals shaped youth HIV risk perception. Amid conflicting information about HIV prevention methods, youth felt exposed to multiple HIV risk factors like the high prevalence of HIV, belief that people with HIV(PWH) purposefully infect others, dislike of condoms, and doubts about PrEP efficacy. Young women also reported minimal sexual autonomy in the context of economic disadvantages, the ubiquity of intergenerational and transactional sex, and peer pressure from other women to have many boyfriends. Young men likewise reported vulnerability to intergenerational sex, but also adopted a sexual conquest mentality. Comprehensive sexuality education and economic empowerment, through credible and trusted sources, may moderate risk-taking. Messaging should leverage youth's social networks to spread fact-based, gender- and age-appropriate information. PrEP should be offered alongside other reproductive health services to address both pregnancy concerns and reduce HIV risk.
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- 2024
12. Randomized Trial of a “Dynamic Choice” Patient-Centered Care Intervention for Mobile Persons With HIV in East Africa
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Ayieko, James, Balzer, Laura B, Inviolata, Colette, Kakande, Elijah, Opel, Fred, Wafula, Erick M, Kabami, Jane, Owaraganise, Asiphas, Mwangwa, Florence, Nakato, Hellen, Bukusi, Elizabeth A, Camlin, Carol S, Charlebois, Edwin D, Bacon, Melanie C, Petersen, Maya L, Kamya, Moses R, Havlir, Diane V, Chamie, Gabriel, and Team, SEARCH Study
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Health Services and Systems ,Biomedical and Clinical Sciences ,Health Sciences ,Clinical Research ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Sexually Transmitted Infections ,HIV/AIDS ,Infection ,Good Health and Well Being ,Female ,Humans ,Adult ,Male ,HIV Infections ,Kenya ,Uganda ,Ambulatory Care Facilities ,Patient-Centered Care ,mobile ,HIV retention ,ART possession ,viral suppression ,SEARCH Study Team ,Clinical Sciences ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
BackgroundPersons with HIV (PWH) with high mobility face obstacles to HIV care engagement and viral suppression. We sought to understand whether a patient-centered intervention for mobile PWH would improve viral suppression and retention in care, and if so, which subgroups would benefit most.MethodsIn a randomized trial, we evaluated the effect of an intervention designed to address barriers to care among mobile (≥2 weeks out of community in previous year) PWH with viral nonsuppression or recent missed visits in Kenya and Uganda (NCT04810650). The intervention included dynamic choice of a "travel pack" (emergency antiretroviral therapy [ART] supply, discrete ART packaging, and travel checklist), multimonth and offsite refills, facilitated transfer to out-of-community clinics, and hotline access to a mobility coordinator. The primary outcome was viral suppression (
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- 2024
13. Geographical, social, and political contexts of tuberculosis control and intervention, as reported by mid-level health managers in Uganda: ‘The activity around town’
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Johnson-Peretz, Jason, Chamie, Gabriel, Kakande, Elijah, Christian, Canice, Kamya, Moses R, Akatukwasa, Cecilia, Atwine, Fred, Havlir, Diane V, and Camlin, Carol S
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Health Services and Systems ,Public Health ,Health Sciences ,Human Society ,Policy and Administration ,Rare Diseases ,Tuberculosis ,Prevention ,Clinical Research ,HIV/AIDS ,Infectious Diseases ,Infection ,Good Health and Well Being ,Humans ,Uganda ,Government Programs ,IPT ,HIV ,DHO ,Management ,Medical and Health Sciences ,Economics ,Studies in Human Society ,Health sciences ,Human society - Abstract
Training district-level health officers and other mid-level health system managers revealed multiple contextual factors across political, administrative, and social axes affecting tuberculosis (TB) and TB control in Uganda. Individual relationships between local health, political, and media leaders affect efforts to inform the public and provide services, yet greater administrative coordination between national-level logistics, implementing partner funding, and local needs is required. Social challenges to TB control include high population mobility, local industries, poverty with high-density living and social venues, and misinformation about TB. Capitalizing on implementation knowledge and sharing data can overcome social geographic challenges to TB-prevention planning through strategic healthcare capacity-building at the district level.
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- 2023
14. A community‐based dynamic choice model for HIV prevention improves PrEP and PEP coverage in rural Uganda and Kenya: a cluster randomized trial
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Kakande, Elijah R, Ayieko, James, Sunday, Helen, Biira, Edith, Nyabuti, Marilyn, Agengo, George, Kabami, Jane, Aoko, Colette, Atuhaire, Hellen N, Sang, Norton, Owaranganise, Asiphas, Litunya, Janice, Mugoma, Erick W, Chamie, Gabriel, Peng, James, Schrom, John, Bacon, Melanie C, Kamya, Moses R, Havlir, Diane V, Petersen, Maya L, Balzer, Laura B, and Team, for the SEARCH Study
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Biomedical and Clinical Sciences ,Health Services and Systems ,Public Health ,Clinical Sciences ,Health Sciences ,Behavioral and Social Science ,Health Disparities ,Sexually Transmitted Infections ,Clinical Research ,Women's Health ,Prevention ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Health Services ,Mental Health ,HIV/AIDS ,3.1 Primary prevention interventions to modify behaviours or promote wellbeing ,Infection ,Good Health and Well Being ,Humans ,Female ,Male ,HIV Infections ,Kenya ,Uganda ,HIV Testing ,Self-Testing ,Pre-Exposure Prophylaxis ,Anti-HIV Agents ,client-centred ,community health worker ,dynamic choice ,pre-exposure prophylaxis ,post-exposure prophylaxis ,village health team ,SEARCH Study Team ,Public Health and Health Services ,Other Medical and Health Sciences ,Clinical sciences ,Epidemiology ,Public health - Abstract
IntroductionOptimizing HIV prevention may require structured approaches for providing client-centred choices as well as community-based entry points and delivery. We evaluated the effect of a dynamic choice model for HIV prevention, delivered by community health workers (CHWs) with clinician support, on the use of biomedical prevention among persons at risk of HIV in rural East Africa.MethodsWe conducted a cluster randomized trial among persons (≥15 years) with current or anticipated HIV risk in 16 villages in Uganda and Kenya (SEARCH; NCT04810650). The intervention was a client-centred HIV prevention model, including (1) structured client choice of product (pre-exposure prophylaxis [PrEP] or post-exposure prophylaxis [PEP]), service location (clinic or out-of-clinic) and HIV testing modality (self-test or rapid test), with the ability to switch over time; (2) a structured assessment of patient barriers and development of a personalized support plan; and (3) phone access to a clinician 24/7. The intervention was delivered by CHWs and supported by clinicians who oversaw PrEP and PEP initiation and monitoring. Participants in control villages were referred to local health facilities for HIV prevention services, delivered by Ministry of Health staff. The primary outcome was biomedical prevention coverage: a proportion of 48-week follow-up with self-reported PrEP or PEP use.ResultsFrom May to July 2021, we enrolled 429 people (212 intervention; 217 control): 57% women and 35% aged 15-24 years. Among intervention participants, 58% chose PrEP and 58% chose PEP at least once over follow-up; self-testing increased from 52% (baseline) to 71% (week 48); ≥98% chose out-of-facility service delivery. Among 413 (96%) participants with the primary outcome ascertained, average biomedical prevention coverage was 28.0% in the intervention versus 0.5% in the control: a difference of 27.5% (95% CI: 23.0-31.9%, p
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- 2023
15. Effect of a brief alcohol counselling intervention on HIV viral suppression and alcohol use among persons with HIV and unhealthy alcohol use in Uganda and Kenya: a randomized controlled trial
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Puryear, Sarah B, Mwangwa, Florence, Opel, Fred, Chamie, Gabriel, Balzer, Laura B, Kabami, Jane, Ayieko, James, Owaraganise, Asiphas, Kakande, Elijah, Agengo, George, Bukusi, Elizabeth, Kabageni, Stella, Omoding, Daniel, Bacon, Melanie, Schrom, John, Woolf‐King, Sarah, Petersen, Maya L, Havlir, Diane V, Kamya, Moses, and Hahn, Judith A
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Biomedical and Clinical Sciences ,Public Health ,Health Sciences ,Alcoholism ,Alcohol Use and Health ,Substance Misuse ,Clinical Research ,Women's Health ,Infectious Diseases ,Clinical Trials and Supportive Activities ,Screening And Brief Intervention For Substance Abuse ,Prevention ,Sexually Transmitted Infections ,HIV/AIDS ,Good Health and Well Being ,Humans ,Male ,Female ,HIV Infections ,Alcoholism ,Uganda ,Kenya ,Counseling ,Ethanol ,HIV ,viral suppression ,alcohol use ,brief counselling intervention ,sub-Saharan Africa ,randomized controlled trial ,Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences ,Clinical sciences ,Epidemiology ,Public health - Abstract
IntroductionUnhealthy alcohol use significantly contributes to viral non-suppression among persons with HIV (PWH). It is unknown whether brief behavioural interventions to reduce alcohol use can improve viral suppression among PWH with unhealthy alcohol use in sub-Saharan Africa (SSA).MethodsAs part of the SEARCH study (NCT04810650), we conducted an individually randomized trial in Kenya and Uganda of a brief, skills-based alcohol intervention among PWH with self-reported unhealthy alcohol use (Alcohol Use Disorders Identification Test-Consumption [AUDIT-C], prior 3 months, ≥3/female; ≥4/male) and at risk of viral non-suppression, defined as either recent HIV viral non-suppression (≥400 copies/ml), missed visits, out of care or new diagnosis. The intervention included baseline and 3-month in-person counselling sessions with interim booster phone calls every 3 weeks. The primary outcome was HIV viral suppression (200 ng/ml (RR 0.97, 95% CI: 0.92-1.02).ConclusionsIn a randomized trial of 401 PWH with unhealthy alcohol use and risk for viral non-suppression, a brief alcohol intervention reduced unhealthy alcohol use but did not affect viral suppression at 24 weeks. Brief alcohol interventions have the potential to improve the health of PWH in SSA by reducing alcohol use, a significant driver of HIV-associated co-morbidities.
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- 2023
16. Financial incentives for reduced alcohol use and increased isoniazid adherence during tuberculosis preventive therapy among people with HIV in Uganda: an open-label, factorial randomised controlled trial
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Chamie, Gabriel, Hahn, Judith A, Kekibiina, Allen, Emenyonu, Nneka I, Beesiga, Brian, Marson, Kara, Fatch, Robin, Lodi, Sara, Adong, Julian, Thirumurthy, Harsha, McDonell, Michael G, Gandhi, Monica, Bryant, Kendall, Havlir, Diane V, Kamya, Moses R, and Muyindike, Winnie R
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Epidemiology ,Health Services and Systems ,Public Health ,Health Sciences ,Alcoholism ,Alcohol Use and Health ,Clinical Research ,Behavioral and Social Science ,Clinical Trials and Supportive Activities ,Substance Misuse ,Prevention ,HIV/AIDS ,Infectious Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Mental health ,Infection ,Good Health and Well Being ,Adult ,Humans ,Male ,Female ,Adolescent ,Middle Aged ,Isoniazid ,Motivation ,Uganda ,Alcoholism ,Treatment Outcome ,Tuberculosis ,HIV Infections ,Ethanol ,Biomarkers ,Microbiology ,Public Health and Health Services ,Health services and systems ,Public health - Abstract
BackgroundAlcohol use is common among people with HIV and is a risk factor for tuberculosis disease and non-adherence to isoniazid preventive therapy (IPT). Few interventions exist to reduce alcohol use and increase IPT adherence in sub-Saharan Africa. The aim of this study was to test the hypothesis that financial incentives conditional on point-of-care negative urine alcohol biomarker testing and positive urine isoniazid testing would reduce alcohol use and increase isoniazid adherence, respectively, in people with HIV who have latent tuberculosis infection and hazardous alcohol use.MethodsWe conducted an open-label, 2×2 factorial randomised controlled trial in Uganda. Eligible for the study were non-pregnant HIV-positive adults (aged ≥18 years) prescribed antiretroviral therapy for at least 6 months, with current heavy alcohol use confirmed by urine ethyl glucuronide (biomarker of recent alcohol use) and a positive Alcohol Use Disorders Identification Test-Consumption (AUDIT-C; ≥3 for women, ≥4 for men) for the past 3 months' drinking, no history of active tuberculosis, tuberculosis treatment, or tuberculosis preventive therapy, and a positive tuberculin skin test. We randomly assigned participants (1:1:1:1) initiating 6 months of IPT to: no incentives (group 1); or incentives for recent alcohol abstinence (group 2), isoniazid adherence (group 3), or both (group 4). Escalating incentives were contingent on monthly point-of-care urine tests negative for ethyl glucuronide (groups 2 and 4), or positive on IsoScreen (biomarker of recent isoniazid use; groups 3 and 4). The primary alcohol outcome was non-hazardous use by self-report (AUDIT-C
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- 2023
17. Universal HIV Testing and Treatment With Patient-Centered Care Improves ART Uptake and Viral Suppression Among Adults Reporting Hazardous Alcohol Use in Uganda and Kenya
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Puryear, Sarah B, Ayieko, James, Hahn, Judith A, Mucunguzi, Atukunda, Owaraganise, Asiphas, Schwab, Joshua, Balzer, Laura B, Kwarisiima, Dalsone, Charlebois, Edwin D, Cohen, Craig R, Bukusi, Elizabeth A, Petersen, Maya L, Havlir, Diane V, Kamya, Moses R, and Chamie, Gabriel
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Biomedical and Clinical Sciences ,Public Health ,Health Sciences ,Sexually Transmitted Infections ,Alcoholism ,Alcohol Use and Health ,Clinical Trials and Supportive Activities ,Clinical Research ,Women's Health ,Health Services ,Substance Misuse ,Behavioral and Social Science ,HIV/AIDS ,Prevention ,Infectious Diseases ,Generic health relevance ,Infection ,Good Health and Well Being ,Adult ,Female ,Humans ,Male ,Alcoholism ,HIV Infections ,HIV Testing ,Kenya ,Patient-Centered Care ,Uganda ,Adolescent ,HIV ,alcohol ,AUDIT-C ,viral suppression ,ART uptake ,sub-Saharan Africa ,Clinical Sciences ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
ObjectivesDetermine whether patient-centered, streamlined HIV care achieves higher antiretroviral therapy (ART) uptake and viral suppression than the standard treatment model for people with HIV (PWH) reporting hazardous alcohol use.DesignCommunity cluster-randomized trial.MethodsThe Sustainable East Africa Research in Community Health trial (NCT01864603) compared an intervention of annual population HIV testing, universal ART, and patient-centered care with a control of baseline population testing with ART by country standard in 32 Kenyan and Ugandan communities. Adults (15 years or older) completed a baseline Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) and were classified as no/nonhazardous (AUDIT-C 0-2 women/0-3 men) or hazardous alcohol use (≥3 women/≥4 men). We compared year 3 ART uptake and viral suppression of PWH reporting hazardous use between intervention and control arms. We compared alcohol use as a predictor of year 3 ART uptake and viral suppression among PWH, by arm.ResultsOf 11,070 PWH with AUDIT-C measured, 1723 (16%) reported any alcohol use and 893 (8%) reported hazardous use. Among PWH reporting hazardous use, the intervention arm had higher ART uptake (96%) and suppression (87%) compared with control (74%, adjusted risk ratio [aRR] = 1.28, 95% CI: 1.19 to 1.38; and 72%, aRR = 1.20, 95% CI: 1.10 to 1.31, respectively). Within arm, hazardous alcohol use predicted lower ART uptake in control (aRR = 0.86, 95% CI: 0.78 to 0.96), but not intervention (aRR = 1.02, 95% CI: 1.00 to 1.04); use was not predictive of suppression in either arm.ConclusionsThe Sustainable East Africa Research in Community Health intervention improved ART uptake and viral suppression among PWH reporting hazardous alcohol use and eliminated gaps in ART uptake between PWH with hazardous and no/nonhazardous use. Patient-centered HIV care may decrease barriers to HIV care for PWH with hazardous alcohol use.
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- 2023
18. San Francisco’s Citywide COVID-19 Response: Strategies to Reduce COVID-19 Severity and Health Disparities, March 2020 Through May 2022
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Sachdev, Darpun D, Petersen, Maya, Havlir, Diane V, Schwab, Joshua, Enanoria, Wayne TA, Nguyen, Trang Q, Mercer, Mary P, Scheer, Susan, Bennett, Ayanna, Tenner, Andrea G, Marks, James D, Bobba, Naveena, Philip, Susan, and Colfax, Grant
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Good Health and Well Being ,COVID-19 ,San Francisco ,excess mortality ,public health response ,Nursing ,Public Health and Health Services ,Policy and Administration ,Public Health - Abstract
San Francisco implemented one of the most intensive, comprehensive, multipronged COVID-19 pandemic responses in the United States using 4 core strategies: (1) aggressive mitigation measures to protect populations at risk for severe disease, (2) prioritization of resources in neighborhoods highly affected by COVID-19, (3) timely and adaptive data-driven policy making, and (4) leveraging of partnerships and public trust. We collected data to describe programmatic and population-level outcomes. The excess all-cause mortality rate in 2020 in San Francisco was half that seen in 2019 in California as a whole (8% vs 16%). In almost all age and race and ethnicity groups, excess mortality from COVID-19 was lower in San Francisco than in California overall, with markedly diminished excess mortality among people aged >65 years. The COVID-19 response in San Francisco highlights crucial lessons, particularly the importance of community responsiveness, joint planning, and collective action, to inform future pandemic response and advance health equity.
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- 2023
19. Demonstration Project of Long-Acting Antiretroviral Therapy in a Diverse Population of People With HIV.
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Gandhi, Monica, Hickey, Matthew, Imbert, Elizabeth, Grochowski, Janet, Mayorga-Munoz, Francis, Szumowski, John D, Oskarsson, Jon, Shiels, Mary, Sauceda, John, Salazar, Jorge, Dilworth, Samantha, Nguyen, Janet Q, Glidden, David V, Havlir, Diane V, and Christopoulos, Katerina A
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Biomedical and Clinical Sciences ,Clinical Sciences ,Minority Health ,Sexually Transmitted Infections ,Clinical Trials and Supportive Activities ,Prevention ,Infectious Diseases ,Mental Health ,HIV/AIDS ,Health Disparities ,Behavioral and Social Science ,Clinical Research ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Adult ,Male ,Humans ,Middle Aged ,Anti-HIV Agents ,Viremia ,HIV Infections ,Rilpivirine ,Cohort Studies ,Viral Load ,Public Health and Health Services - Abstract
BackgroundIntramuscular cabotegravir (CAB) and rilpivirine (RPV) is the only long-acting antiretroviral therapy (LA-ART) regimen approved for people with HIV (PWH). Long-acting ART holds promise for improving outcomes among populations with barriers to adherence but is only approved for PWH who have virologic suppression with use of oral ART before initiating injectables.ObjectiveTo examine LA-ART in a population of PWH that includes those with viremia.DesignObservational cohort study.SettingUrban academic safety-net HIV clinic.PatientsPublicly insured adults living with HIV with and without viral suppression, high rates of unstable housing, mental illness, and substance use.InterventionDemonstration project of long-acting injectable CAB-RPV.MeasurementsDescriptive statistics summarizing cohort outcomes to date, based on pharmacy team logs and electronic medical record data.ResultsBetween June 2021 and November 2022, 133 PWH at the Ward 86 HIV Clinic were started on LA-ART, 76 of whom had virologic suppression while using oral ART and 57 of whom had viremia. The median age was 46 years (IQR, 25 to 68 years); 117 (88%) were cisgender men, 83 (62%) had non-White race, 56 (42%) were experiencing unstable housing or homelessness, and 45 (34%) had substance use. Among those with virologic suppression, 100% (95% CI, 94% to 100%) maintained suppression. Among PWH with viremia, at a median of 33 days, 54 of 57 had viral suppression, 1 showed the expected 2-log10 reduction in HIV RNA level, and 2 experienced early virologic failure. Overall, 97.5% (CI, 89.1% to 99.8%) were projected to achieve virologic suppression by a median of 33 weeks. The current virologic failure rate of 1.5% in the cohort is similar to that across registrational clinical trials at 48 weeks.LimitationSingle-site study.ConclusionThis project demonstrates the ability of LA-ART to achieve virologic suppression among PWH, including those with viremia and challenges to adherence. Further data on the ability of LA-ART to achieve viral suppression in people with barriers to adherence are needed.Primary funding sourceNational Institutes of Health, City and County of San Francisco, and Health Resources and Services Administration.
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- 2023
20. Uptake of a patient‐centred dynamic choice model for HIV prevention in rural Kenya and Uganda: SEARCH SAPPHIRE study
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Kabami, Jane, Kakande, Elijah, Chamie, Gabriel, Balzer, Laura B, Petersen, Maya L, Camlin, Carol S, Nyabuti, Marilyn, Koss, Catherine A, Bukusi, Elizabeth A, Kamya, Moses R, Havlir, Diane V, and Ayieko, James
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Biomedical and Clinical Sciences ,Health Services and Systems ,Public Health ,Clinical Sciences ,Health Sciences ,Clinical Trials and Supportive Activities ,Behavioral and Social Science ,Prevention ,HIV/AIDS ,Health Services ,Clinical Research ,Infectious Diseases ,Infection ,Good Health and Well Being ,Adult ,Humans ,Male ,Female ,Pregnancy ,Young Adult ,HIV Infections ,Kenya ,Uganda ,Delivery of Health Care ,Ambulatory Care Facilities ,Pre-Exposure Prophylaxis ,Anti-HIV Agents ,antenatal ,HIV prevention ,outpatient and community ,PEP ,PrEP ,Public Health and Health Services ,Other Medical and Health Sciences ,Clinical sciences ,Epidemiology ,Public health - Abstract
IntroductionPerson-centred HIV prevention delivery models that offer structured choices in product, testing and visit location may increase coverage. However, data are lacking on the actual uptake of choices among persons at risk of HIV in southern Africa. In an ongoing randomized study (SEARCH; NCT04810650) in rural East Africa, we evaluated the uptake of choices made when offered in a person-centred, dynamic choice model for HIV prevention.MethodsUsing the PRECEDE framework, we developed a persont-centred, Dynamic Choice HIV Prevention (DCP) intervention for persons at risk of HIV in three settings in rural Kenya and Uganda: antenatal clinic (ANC), outpatient department (OPD) and in the community. Components include: provider training on product choice (predisposing); flexibility and responsiveness to client desires and choices (pre-exposure prophylaxis [PrEP]/post-exposure prophylaxis [PEP], clinic vs. off-site visits and self- or clinician-based HIV testing) (enabling); and client and staff feedback (reinforcing). All clients received a structured assessment of barriers with personalized plans to address them, mobile phone access to clinicians (24 hours/7 days/week) and integrated reproductive health services. In this interim analysis, we describe the uptake of choices of product, location and testing during the first 24 weeks of follow-up (April 2021-March 2022).ResultsA total of 612 (203 ANC, 197 OPD and 212 community) participants were randomized to the person-centred DCP intervention. We delivered the DCP intervention in all three settings with diverse populations: ANC: 39% pregnant; median age: 24 years; OPD: 39% male, median age 27 years; and community: 42% male, median age: 29 years. Baseline choice of PrEP was highest in ANC (98%) vs. OPD (84%) and community (40%); whereas the proportion of adults selecting PEP was higher in the community (46%) vs. OPD (8%) and ANC (1%). Personal preference for off-site visits increased over time (65% at week 24 vs. 35% at baseline). Interest in alternative HIV testing modalities grew over time (38% baseline self-testing vs. 58% at week 24).ConclusionsA person-centred model incorporating structured choice in biomedical prevention and care delivery options in settings with demographically diverse groups, in rural Kenya and Uganda, was responsive to varying personal preferences over time in HIV prevention programmes.
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- 2023
21. Weight Change Following Switch to Dolutegravir for HIV Treatment in Rural Kenya During Country Roll-Out
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Hickey, Matthew D, Wafula, Erick, Ogachi, Sabina M, Ojwando, Hellen, Orori, Gordon, Adede, Richard O, Garraza, Lucas Godoy, Petersen, Maya L, Havlir, Diane V, Balzer, Laura B, and Ayieko, James
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Biomedical and Clinical Sciences ,Clinical Sciences ,Health Sciences ,Infectious Diseases ,Sexually Transmitted Infections ,Health Disparities ,Nutrition ,Clinical Research ,HIV/AIDS ,Women's Health ,Obesity ,Prevention ,Rural Health ,Infection ,Zero Hunger ,Adult ,Male ,Humans ,Female ,Anti-HIV Agents ,Retrospective Studies ,HIV Infections ,Prospective Studies ,Kenya ,Oxazines ,Tenofovir ,Heterocyclic Compounds ,3-Ring ,Pyridones ,Weight Gain ,weight gain ,dolutegravir ,switch ,Public Health and Health Services ,Virology ,Clinical sciences ,Epidemiology ,Public health - Abstract
IntroductionSwitch to dolutegravir (DTG) in treatment-experienced people living with HIV (PLH) is associated with excess weight gain in some settings; data are limited from rural low-income settings with low obesity prevalence.MethodsIn rural Kenya, we conducted a retrospective cohort study at 8 HIV clinics and a single-site prospective cohort study including adults switching to DTG during countrywide transition to DTG/tenofovir DF(TDF)/emtricitabine as first-line HIV treatment. In the retrospective analysis, we used preswitch data to model postswitch weight trajectory had each participant not switched to DTG and contrasted observed vs. predicted postswitch weight. In the prospective analysis, we measured weight post-DTG switch and evaluated predictors of 6-month weight change.ResultsOur retrospective cohort included 4445 PLH who switched to DTG between 2018 and 2020. Mean 12-month weight change was 0.6 kg preswitch and 0.8 kg postswitch. Among those on TDF throughout (n = 3374; 83% on efavirenz preswitch), 12-month postswitch weight was 0.7 kg more than predicted for women (95% CI: 0.4, 1.0) and similar among men (0.04 kg; 95% CI -0.3, 0.4). In our prospective cohort (n = 135, 100% female), mean 6-month weight change was +0.4 kg (IQR -1.1, 2.0 kg). Predicted gain varied by baseline food insecurity: +1.1 kg (95% CI: 0.34, 1.87) among food secure, -0.09 kg (95% CI -0.71, 0.54) among moderate insecure, and +0.27 kg (95% CI -0.82, 1.36) among severe insecurity.ConclusionIn contrast to some reports of large weight gain following switch to DTG, we observed small weight increases in women and no weight change in men following DTG switch when on TDF throughout. Weight gain may be attenuated by food insecurity, though was modest even among food secure.
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- 2023
22. Two-Stage TMLE to reduce bias and improve efficiency in cluster randomized trials
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Balzer, Laura B, van der Laan, Mark, Ayieko, James, Kamya, Moses, Chamie, Gabriel, Schwab, Joshua, Havlir, Diane V, and Petersen, Maya L
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Mathematical Sciences ,Statistics ,Clinical Trials and Supportive Activities ,Clinical Research ,8.4 Research design and methodologies (health services) ,Health and social care services research ,Good Health and Well Being ,Humans ,Randomized Controlled Trials as Topic ,Probability ,Bias ,Outcome Assessment ,Health Care ,Research Design ,Cluster Analysis ,Computer Simulation ,Clustered data ,Cluster randomized trials ,Covariate adjustment ,Data-adaptive ,Double robust ,Group randomized trials ,Missing data ,Multi-level models ,Super Learner ,TMLE ,Genetics ,Statistics & Probability - Abstract
Cluster randomized trials (CRTs) randomly assign an intervention to groups of individuals (e.g., clinics or communities) and measure outcomes on individuals in those groups. While offering many advantages, this experimental design introduces challenges that are only partially addressed by existing analytic approaches. First, outcomes are often missing for some individuals within clusters. Failing to appropriately adjust for differential outcome measurement can result in biased estimates and inference. Second, CRTs often randomize limited numbers of clusters, resulting in chance imbalances on baseline outcome predictors between arms. Failing to adaptively adjust for these imbalances and other predictive covariates can result in efficiency losses. To address these methodological gaps, we propose and evaluate a novel two-stage targeted minimum loss-based estimator to adjust for baseline covariates in a manner that optimizes precision, after controlling for baseline and postbaseline causes of missing outcomes. Finite sample simulations illustrate that our approach can nearly eliminate bias due to differential outcome measurement, while existing CRT estimators yield misleading results and inferences. Application to real data from the SEARCH community randomized trial demonstrates the gains in efficiency afforded through adaptive adjustment for baseline covariates, after controlling for missingness on individual-level outcomes.
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- 2023
23. Postexposure Doxycycline to Prevent Bacterial Sexually Transmitted Infections.
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Luetkemeyer, Anne, Donnell, Deborah, Dombrowski, Julia, Cohen, Stephanie, Grabow, Cole, Brown, Clare, Malinski, Cheryl, Perkins, Rodney, Nasser, Melody, Lopez, Carolina, Vittinghoff, Eric, Buchbinder, Susan, Scott, Hyman, Soge, Olusegun, Celum, Connie, Charlebois, Edwin, and Havlir, Diane
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Female ,Humans ,Male ,Chlamydia Infections ,Doxycycline ,Gonorrhea ,HIV Infections ,Homosexuality ,Male ,Pre-Exposure Prophylaxis ,Sexual and Gender Minorities ,Sexually Transmitted Diseases ,Syphilis ,Primary Prevention ,Anti-Infective Agents ,Anti-Bacterial Agents ,Transgender Persons - Abstract
BACKGROUND: Interventions to reduce sexually transmitted infections (STIs) among men who have sex with men (MSM) are needed. METHODS: We conducted an open-label, randomized study involving MSM and transgender women who were taking preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV) infection (PrEP cohort) or living with HIV infection (persons living with HIV infection [PLWH] cohort) and who had had Neisseria gonorrhoeae (gonorrhea), Chlamydia trachomatis (chlamydia), or syphilis in the past year. Participants were randomly assigned in a 2:1 ratio to take 200 mg of doxycycline within 72 hours after condomless sex (doxycycline postexposure prophylaxis) or receive standard care without doxycycline. STI testing was performed quarterly. The primary end point was the incidence of at least one STI per follow-up quarter. RESULTS: Of 501 participants (327 in the PrEP cohort and 174 in the PLWH cohort), 67% were White, 7% Black, 11% Asian or Pacific Islander, and 30% Hispanic or Latino. In the PrEP cohort, an STI was diagnosed in 61 of 570 quarterly visits (10.7%) in the doxycycline group and 82 of 257 quarterly visits (31.9%) in the standard-care group, for an absolute difference of -21.2 percentage points and a relative risk of 0.34 (95% confidence interval [CI], 0.24 to 0.46; P
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- 2023
24. Pragmatic randomized trial of a pre-visit intervention to improve the quality of telemedicine visits for vulnerable patients living with HIV
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Hickey, Matthew D, Sergi, Francesco, Zhang, Kevin, Spinelli, Matthew A, Black, Douglas, Sola, Cyril, Blaz, Vanessa, Nguyen, Janet Q, Oskarsson, Jon, Gandhi, Monica, and Havlir, Diane V
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Public Health ,Health Sciences ,Sexually Transmitted Infections ,Clinical Research ,Clinical Trials and Supportive Activities ,Social Determinants of Health ,Health Services ,Infectious Diseases ,Prevention ,HIV/AIDS ,Telehealth ,Health Disparities ,Infection ,Good Health and Well Being ,Humans ,Pandemics ,COVID-19 ,Telephone ,Telemedicine ,HIV Infections ,HIV ,digital health ,randomised controlled trial ,Information Systems ,Biomedical Engineering ,Public Health and Health Services ,Medical Informatics ,Health services and systems ,Public health - Abstract
IntroductionThe COVID-19 pandemic has required a shift of many routine primary care visits to telemedicine, potentially widening disparities in care access among vulnerable populations. In a publicly-funded HIV clinic, we aimed to evaluate a pre-visit phone-based planning intervention to address anticipated barriers to telemedicine.MethodsWe conducted a pragmatic randomized controlled trial of patients scheduled for a phone-based HIV primary care visit at the Ward 86 HIV clinic in San Francisco from 15 April to 15 May 2020. Once reached by phone, patients were randomized to either have a structured pre-visit planning intervention to address barriers to an upcoming telemedicine visit versus a standard reminder call. The primary outcome was telemedicine visit attendance.ResultsOf 476 scheduled telemedicine visits, 280 patients were reached by a pre-visit call to offer enrollment. Patients were less likely to be reached if virally unsuppressed (odds ratio (OR) 0.11, 95% confidence intervals (CI) 0.03-0.48), CD4
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- 2023
25. Statistical Analysis Plan for Primary and Selected Secondary Health Endpoints of the SEARCH-Youth Study
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Balzer, Laura B., Ruel, Theodore, Havlir, Diane V., and Team, the SEARCH-Youth Study
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Statistics - Applications - Abstract
This document provides the statistical analytic plan (SAP) for evaluating health outcomes in the SEARCH-Youth study, a cluster randomized trial designed to evaluate the effect of a combination intervention on HIV viral suppression among adolescents and young adults with HIV in rural Uganda and Kenya (Clinicaltrials.gov: NCT03848728). The SAP was locked prior to unblinding and effect estimation. This SAP was embargoed until November 04, 2022 when it was submitted to arXiv., Comment: 14 pages, 1 figure
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- 2022
26. HIV post-treatment controllers have distinct immunological and virological features
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Etemad, Behzad, Sun, Xiaoming, Li, Yijia, Melberg, Meghan, Moisi, Daniela, Gottlieb, Rachel, Ahmed, Hayat, Aga, Evgenia, Bosch, Ronald J, Acosta, Edward P, Yuki, Yuko, Martin, Maureen P, Carrington, Mary, Gandhi, Rajesh T, Jacobson, Jeffrey M, Volberding, Paul, Connick, Elizabeth, Mitsuyasu, Ronald, Frank, Ian, Saag, Michael, Eron, Joseph J, Skiest, Daniel, Margolis, David M, Havlir, Diane, Schooley, Robert T, Lederman, Michael M, Yu, Xu G, and Li, Jonathan Z
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Clinical Research ,Sexually Transmitted Infections ,Infectious Diseases ,Genetics ,HIV/AIDS ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Humans ,CD8-Positive T-Lymphocytes ,Killer Cells ,Natural ,Lymphocyte Activation ,RNA ,HIV Infections ,Viremia ,HIV ,analytical treatment interruption ,post-treatment controller ,reservoir ,T cell - Abstract
HIV post-treatment controllers (PTCs) are rare individuals who maintain low levels of viremia after stopping antiretroviral therapy (ART). Understanding the mechanisms of HIV post-treatment control will inform development of strategies aiming at achieving HIV functional cure. In this study, we evaluated 22 PTCs from 8 AIDS Clinical Trials Group (ACTG) analytical treatment interruption (ATI) studies who maintained viral loads ≤400 copies/mL for ≥24 wk. There were no significant differences in demographics or frequency of protective and susceptible human leukocyte antigen (HLA) alleles between PTCs and post-treatment noncontrollers (NCs, n = 37). Unlike NCs, PTCs demonstrated a stable HIV reservoir measured by cell-associated RNA (CA-RNA) and intact proviral DNA assay (IPDA) during analytical treatment interruption (ATI). Immunologically, PTCs demonstrated significantly lower CD4+ and CD8+ T cell activation, lower CD4+ T cell exhaustion, and more robust Gag-specific CD4+ T cell responses and natural killer (NK) cell responses. Sparse partial least squares discriminant analysis (sPLS-DA) identified a set of features enriched in PTCs, including a higher CD4+ T cell% and CD4+/CD8+ ratio, more functional NK cells, and a lower CD4+ T cell exhaustion level. These results provide insights into the key viral reservoir features and immunological profiles for HIV PTCs and have implications for future studies evaluating interventions to achieve an HIV functional cure.
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- 2023
27. Effect of Malaria and Malaria Chemoprevention Regimens in Pregnancy and Childhood on Neurodevelopmental and Behavioral Outcomes in Children at 12, 24, and 36 Months: A Randomized Clinical Trial
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Bangirana, Paul, Conroy, Andrea L, Opoka, Robert O, Semrud-Clikeman, Margaret, Jang, Jeong H, Apayi, Claire, Kakuru, Abel, Muhindo, Mary K, Georgieff, Michael K, Dorsey, Grant M, Kamya, Moses R, Havlir, Diane, and John, Chandy C
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Medical Microbiology ,Biomedical and Clinical Sciences ,Clinical Sciences ,Pediatric ,Behavioral and Social Science ,Neurosciences ,Mental Health ,Prevention ,Vector-Borne Diseases ,Clinical Trials and Supportive Activities ,Infectious Diseases ,Malaria ,Rare Diseases ,Clinical Research ,3.3 Nutrition and chemoprevention ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Prevention of disease and conditions ,and promotion of well-being ,Reproductive health and childbirth ,Good Health and Well Being ,Child ,Female ,Pregnancy ,Humans ,Antimalarials ,Pyrimethamine ,Sulfadoxine ,Artemisinins ,Drug Combinations ,Quinolines ,Chemoprevention ,malaria ,chemoprevention ,pregnancy ,development ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundMalaria in pregnancy has been associated with worse cognitive outcomes in children, but its association with behavioral outcomes and the effectiveness of malaria chemoprevention on child neurodevelopment are not well characterized.MethodsTo determine if more effective malaria chemoprevention in mothers and their children results in better neurodevelopment, 305 pregnant women were randomly assigned to 3 doses of sulfadoxine-pyrimethamine, 3 doses of dihydroartemisinin-piperaquine (DP), or monthly DP during pregnancy, and their 293 children were assigned to DP every 3 months or monthly DP from 2 to 24 months of age. Cognition, language, and motor function were assessed at 12, 24. and 36 months of age, and attention, memory, behavior, and executive function were assessed at 24 and 36 months of age.ResultsChildren of mothers with versus without malaria in pregnancy had worse scores on cognitive, behavioral, and executive function outcomes at 24 months. Clinical malaria in children within the first 12 months was similarly associated with poorer scores in behavior and executive function at 24 months, language at 24 and 36 months, and motor function scores at 36 months. However, more effective malaria chemoprevention in the mothers and children was not associated with better outcomes.ConclusionsMalaria in pregnancy was associated with worse cognitive, behavioral, and executive function scores in affected children, but more effective malaria chemoprevention measures did not result in better outcomes. Malaria chemoprevention prior to and early in gestation and with even higher efficacy in mothers and children may be required to prevent neurodevelopmental impairment in children. Clinical Trials Registration. NCT02557425.
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- 2023
28. The Association Between Social Network Characteristics and Tuberculosis Infection Among Adults in 9 Rural Ugandan Communities
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Marquez, Carina, Chen, Yiqun, Atukunda, Mucunguzi, Chamie, Gabriel, Balzer, Laura B, Kironde, Joel, Ssemmondo, Emmanuel, Mwangwa, Florence, Kabami, Jane, Owaraganise, Asiphas, Kakande, Elijah, Abbott, Rachel, Ssekyanzi, Bob, Koss, Catherine, Kamya, Moses R, Charlebois, Edwin D, Havlir, Diane V, and Petersen, Maya L
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,HIV/AIDS ,Prevention ,Tuberculosis ,Infectious Diseases ,Rare Diseases ,Behavioral and Social Science ,Aetiology ,2.2 Factors relating to the physical environment ,Infection ,Good Health and Well Being ,Adult ,Male ,Humans ,Female ,Uganda ,Mycobacterium tuberculosis ,Rural Population ,Tuberculin Test ,Latent Tuberculosis ,HIV Infections ,tuberculosis infection ,social network analysis ,tuberculosis case finding ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundSocial network analysis can elucidate tuberculosis transmission dynamics outside the home and may inform novel network-based case-finding strategies.MethodsWe assessed the association between social network characteristics and prevalent tuberculosis infection among residents (aged ≥15 years) of 9 rural communities in Eastern Uganda. Social contacts named during a census were used to create community-specific nonhousehold social networks. We evaluated whether social network structure and characteristics of first-degree contacts (sex, human immunodeficiency virus [HIV] status, tuberculosis infection) were associated with revalent tuberculosis infection (positive tuberculin skin test [TST] result) after adjusting for individual-level risk factors (age, sex, HIV status, tuberculosis contact, wealth, occupation, and Bacillus Calmette-Guérin [BCG] vaccination) with targeted maximum likelihood estimation.ResultsAmong 3 335 residents sampled for TST, 32% had a positive TST results and 4% reported a tuberculosis contact. The social network contained 15 328 first-degree contacts. Persons with the most network centrality (top 10%) (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.1]) and the most (top 10%) male contacts (1.5 [1.3-1.9]) had a higher risk of prevalent tuberculosis, than those in the remaining 90%. People with ≥1 contact with HIV (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.6]) and ≥2 contacts with tuberculosis infection were more likely to have tuberculosis themselves (2.6 [ 95% confidence interval: 2.2-2.9]).ConclusionsSocial networks with higher centrality, more men, contacts with HIV, and tuberculosis infection were positively associated with tuberculosis infection. Tuberculosis transmission within measurable social networks may explain prevalent tuberculosis not associated with a household contact. Further study on network-informed tuberculosis case finding interventions is warranted.
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- 2023
29. First Demonstration Project of Long-Acting Injectable Antiretroviral Therapy for Persons With and Without Detectable Human Immunodeficiency Virus (HIV) Viremia in an Urban HIV Clinic
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Christopoulos, Katerina A, Grochowski, Janet, Mayorga-Munoz, Francis, Hickey, Matthew D, Imbert, Elizabeth, Szumowski, John D, Dilworth, Samantha, Oskarsson, Jon, Shiels, Mary, Havlir, Diane, and Gandhi, Monica
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Medical Microbiology ,Biomedical and Clinical Sciences ,Immunology ,Infectious Diseases ,HIV/AIDS ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being ,Male ,Humans ,Middle Aged ,HIV ,Anti-HIV Agents ,Viremia ,HIV Infections ,Treatment Outcome ,CD4 Lymphocyte Count ,Viral Load ,AIDS ,long-acting antiretroviral therapy ,injectable cabotegravir and rilpivirine ,viral suppression ,engagement in care ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundLong-acting injectable antiretroviral therapy (LAI-ART) is approved for treatment-naive or experienced people with human immunodeficiency virus (HIV; PWH) based on trials that only included participants with viral suppression. We performed the first LAI-ART demonstration project to include PWH unable to achieve or maintain viral suppression due to challenges adhering to oral ART.MethodsWard 86 is a large HIV clinic in San Francisco that serves publicly insured and underinsured patients. We started patients on LAI-ART via a structured process of provider referral, multidisciplinary review (MD, RN, pharmacist), and monitoring for on-time injections. Inclusion criteria were willingness to receive monthly injections and a reliable contact method.ResultsBetween June 2021 and April 2022, 51 patients initiated LAI-ART, with 39 receiving at least 2 follow-up injections by database closure (median age, 46 years; 90% cisgender men, 61% non-White, 41% marginally housed, 54% currently using stimulants). Of 24 patients who initiated injections with viral suppression (median CD4 cell count, 706 cells/mm3), 100% (95% confidence interval [CI], 86%-100%) maintained viral suppression. Of 15 patients who initiated injections with detectable viremia (median CD4 cell count, 99 cells/mm3; mean log10 viral load, 4.67; standard deviation, 1.16), 12 (80%; 95% CI, 55%-93%) achieved viral suppression, and the other 3 had a 2-log viral load decline by a median of 22 days.ConclusionsThis small demonstration project of LAI-ART in a diverse group of patients with high levels of substance use and marginal housing demonstrated promising early treatment outcomes, including in those with detectable viremia due to adherence challenges. More data on LAI-ART in hard-to-reach populations are needed.
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- 2023
30. A 2-Gene Host Signature for Improved Accuracy of COVID-19 Diagnosis Agnostic to Viral Variants.
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Albright, Jack, Mick, Eran, Sanchez-Guerrero, Estella, Kamm, Jack, Mitchell, Anthea, Detweiler, Angela M, Neff, Norma, Tsitsiklis, Alexandra, Hayakawa Serpa, Paula, Ratnasiri, Kalani, Havlir, Diane, Kistler, Amy, DeRisi, Joseph L, Pisco, Angela Oliveira, and Langelier, Charles R
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Humans ,Sensitivity and Specificity ,Pandemics ,COVID-19 ,SARS-CoV-2 ,COVID-19 Testing ,classifier ,diagnostics ,gene expression ,metagenomics ,transcriptomics ,Genetics ,Infectious Diseases ,Vaccine Related ,Prevention ,Biodefense ,Emerging Infectious Diseases ,Biotechnology ,Lung ,Detection ,screening and diagnosis ,4.2 Evaluation of markers and technologies ,Infection ,Good Health and Well Being - Abstract
The continued emergence of SARS-CoV-2 variants is one of several factors that may cause false-negative viral PCR test results. Such tests are also susceptible to false-positive results due to trace contamination from high viral titer samples. Host immune response markers provide an orthogonal indication of infection that can mitigate these concerns when combined with direct viral detection. Here, we leverage nasopharyngeal swab RNA-seq data from patients with COVID-19, other viral acute respiratory illnesses, and nonviral conditions (n = 318) to develop support vector machine classifiers that rely on a parsimonious 2-gene host signature to diagnose COVID-19. We find that optimal classifiers include an interferon-stimulated gene that is strongly induced in COVID-19 compared with nonviral conditions, such as IFI6, and a second immune-response gene that is more strongly induced in other viral infections, such as GBP5. The IFI6+GBP5 classifier achieves an area under the receiver operating characteristic curve (AUC) greater than 0.9 when evaluated on an independent RNA-seq cohort (n = 553). We further provide proof-of-concept demonstration that the classifier can be implemented in a clinically relevant RT-qPCR assay. Finally, we show that its performance is robust across common SARS-CoV-2 variants and is unaffected by cross-contamination, demonstrating its utility for improved accuracy of COVID-19 diagnostics. IMPORTANCE In this work, we study upper respiratory tract gene expression to develop and validate a 2-gene host-based COVID-19 diagnostic classifier and then demonstrate its implementation in a clinically practical qPCR assay. We find that the host classifier has utility for mitigating false-negative results, for example due to SARS-CoV-2 variants harboring mutations at primer target sites, and for mitigating false-positive viral PCR results due to laboratory cross-contamination. Both types of error carry serious consequences of either unrecognized viral transmission or unnecessary isolation and contact tracing. This work is directly relevant to the ongoing COVID-19 pandemic given the continued emergence of viral variants and the continued challenges of false-positive PCR assays. It also suggests the feasibility of pan-respiratory virus host-based diagnostics that would have value in congregate settings, such as hospitals and nursing homes, where unrecognized respiratory viral transmission is of particular concern.
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- 2023
31. Two or more significant life-events in 6-months are associated with lower rates of HIV treatment and virologic suppression among youth with HIV in Uganda and Kenya
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Mwangwa, Florence, Charlebois, Edwin D, Ayieko, James, Olio, Winter, Black, Douglas, Peng, James, Kwarisiima, Dalsone, Kabami, Jane, Balzer, Laura B, Petersen, Maya L, Kapogiannis, Bill, Kamya, Moses R, Havlir, Diane V, and Ruel, Theodore D
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Public Health ,Health Sciences ,Human Society ,Infectious Diseases ,Clinical Research ,Alcoholism ,Alcohol Use and Health ,Pediatric ,Mental Health ,Substance Misuse ,HIV/AIDS ,Behavioral and Social Science ,Management of diseases and conditions ,7.1 Individual care needs ,Infection ,Good Health and Well Being ,Adolescent ,Female ,Humans ,Pregnancy ,Anti-HIV Agents ,Anti-Retroviral Agents ,Cross-Sectional Studies ,HIV Infections ,Kenya ,Uganda ,Viral Load ,Youth ,HIV ,treatment ,Africa ,Public Health and Health Services ,Psychology ,Public health ,Sociology ,Clinical and health psychology - Abstract
Youth living with HIV in sub-Saharan Africa have poor HIV care outcomes. We determined the association of recent significant life-events with HIV antiretroviral treatment (ART) initiation and HIV viral suppression in youth aged 15-24 years living with HIV in rural Kenya and Uganda. This was a cross-sectional analysis of 995 youth enrolled in the SEARCH Youth study. At baseline, providers assessed recent (within 6 months) life-events, defined as changes in schooling/employment, residence, partnerships, sickness, incarceration status, family strife or death, and birth/pregnancy, self-reported alcohol use, being a parent, and HIV-status disclosure. We examined the frequencies of events and their association with ART status and HIV viral suppression (2 significant life-events (aOR = 0.61, 95% CI:0.45-0.85) and consuming alcohol (aOR = 0.61, 95% CI:0.43-0.87) were associated with a lower odds of HIV viral suppression, while disclosure of HIV-status to partner (aOR = 2.39, 95% CI:1.6-3.5) or to family (aOR = 1.86, 95% CI:1.3-2.7), being a parent (aOR = 1.8, 95% CI:1.2-2.5), and being single (aOR = 1.6, 95% CI:1.3-2.1) had a higher odds. This suggest that two or more recent life-events and alcohol use are key barriers to ART initiation and achievement of viral suppression among youth living with HIV in rural East Africa.Trial registration: ClinicalTrials.gov identifier: NCT03848728..
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- 2023
32. Feasibility and preliminary effectiveness of integrating HIV prevention into an adolescent empowerment and livelihood intervention at youth clubs in rural Uganda
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Christian, Canice, Kabami, Jane, Kwarisiima, Dalsone, Beinamatsiko, Blian, Nakato, Hellen, Khakshi, James Ward, Sulaiman, Munshi, Komugisha, Annah, Thirumurthy, Harsha, Havlir, Diane V, Kamya, Moses R, and Chamie, Gabriel
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Health Services and Systems ,Public Health ,Health Sciences ,Human Society ,Infectious Diseases ,Pediatric AIDS ,Mental Health ,Pediatric ,Clinical Research ,Prevention ,Clinical Trials and Supportive Activities ,HIV/AIDS ,Behavioral and Social Science ,Adolescent Sexual Activity ,Prevention of disease and conditions ,and promotion of well-being ,3.1 Primary prevention interventions to modify behaviours or promote wellbeing ,Infection ,Good Health and Well Being ,Adult ,Male ,Humans ,Adolescent ,Female ,HIV Infections ,Anti-HIV Agents ,Uganda ,Feasibility Studies ,Men ,Pre-Exposure Prophylaxis ,Pre-exposure prophylaxis ,post-exposure prophylaxis ,HIV prevention ,youth ,East Africa ,Public Health and Health Services ,Psychology ,Public health ,Sociology ,Clinical and health psychology - Abstract
The uptake of HIV prevention services is lower among youth than adults in sub-Saharan Africa. Existing youth livelihood trainings offer a potential entry point to HIV prevention services. We determined feasibility and preliminary effectiveness of integrating HIV prevention into youth clubs implementing an empowerment and livelihood for adolescents (ELA) intervention in rural Uganda. Staff conducted community mobilization for youth (15-24 years) over one month. Clubs met (3×/week) over six months, with local peer mentors trained to teach life-skills and sexual/reproductive health education. We integrated mentor-led education on HIV prevention, including pre- and post-exposure prophylaxis (PrEP/PEP). Clubs offered on-site HIV testing, a field trip to a local clinic and PrEP referrals after one month and six months. Surveys were conducted at baseline and six months. Forty-two participants (24 adolescent girls/young women (AGYW) and 18 adolescent boys/young men (ABYM)) joined the clubs. At baseline, no participants accepted referral for PrEP, whereas 5/18 (28%) sexually active, HIV-negative AGYW requested PrEP referral at follow-up. One ABYM requested PEP referral. Integration of HIV prevention services into an established ELA curriculum at mentor-led youth clubs in rural Uganda was feasible. PrEP uptake increased among sexually active AGYW. Evaluation of this approach for HIV prevention among youth merits further study.
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- 2023
33. Improving care engagement for mobile people living with HIV in rural western Kenya
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Ayieko, James, Charlebois, Edwin D, Maeri, Irene, Owino, Lawrence, Thorp, Marguerite, Bukusi, Elizabeth A, Petersen, Maya L, Kamya, Moses R, Havlir, Diane V, and Camlin, Carol S
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Health Services and Systems ,Biomedical and Clinical Sciences ,Health Sciences ,Health Services ,Clinical Research ,Infectious Diseases ,HIV/AIDS ,Behavioral and Social Science ,Sexually Transmitted Infections ,8.1 Organisation and delivery of services ,Health and social care services research ,7.1 Individual care needs ,Management of diseases and conditions ,Infection ,Good Health and Well Being ,Humans ,Kenya ,Quality Improvement ,Anti-HIV Agents ,Qualitative Research ,HIV Infections ,General Science & Technology - Abstract
BackgroundAntiretroviral therapy (ART) assures major gains in health outcomes among people living with HIV, however, this benefit may not be realized by all due to care interruptions. Mobile populations comprise a subgroup that is likely to have sub-optimal care engagement, resulting in discontinuation of ART. We sought to evaluate the barriers to care engagement among highly mobile individuals living with HIV and explore options aimed at improving engagement in care for this group.MethodsQualitative in-depth interviews were conducted in 2020 among a purposive sample of twelve persons living with HIV and eight health care providers in western Kenya, within a mixed methods study of mobility in communities participating in the SEARCH trial (NCT01864603). We explored the barriers to care engagement among mobile individuals living with HIV and explored different options aimed at enhancing care engagement. These included options such as a coded card containing treatment details, alternative drug packaging to conceal drug identity, longer refills to cover travel period, wrist bands with data storage capability to enable data transfer and "warm handoff" by providers to new clinics upon transfer. Data were inductively analyzed to understand the barriers and acceptability of potential interventions to address them.ResultsStigma and lack of disclosure, rigid work schedules, and unpredictability of travel were major barriers to care engagement for highly mobile individuals living with HIV. Additionally, lack of flexibility in clinic schedules and poor provider attitude were identified as health-system-associated barriers to care engagement. Options that enhance flexibility, convenience and access to care were viewed as the most effective means of addressing the barriers to care by both patients and providers. The most preferred option was a coded card with treatment details followed by alternative drug packaging to conceal drug identity due to stigma and longer refills to cover travel periods.ConclusionHighly mobile individuals living with HIV desire responsive, flexible, convenient and patient-centered care delivery models to enhance care engagement. They embraced simple health delivery improvements such as coded cards, alternative drug packaging and longer refills to address challenges of mobility.
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- 2023
34. Field assessment of BinaxNOW antigen tests as COVID-19 treatment entry point at a community testing site in San Francisco during evolving omicron surges
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Schrom, John, Marquez, Carina, Wang, Chung-Yu, Saxena, Aditi, Mitchell, Anthea M, Ribeiro, Salu, Pilarowski, Genay, Nakamura, Robert, Rojas, Susana, Black, Douglas, Oseguera, Maria G Contreras, Diaz, Edgar Castellanos, Payan, Joselin, Rojas, Susy, Jones, Diane, Tulier-Laiwa, Valerie, Zavaleta, Aleks, Martinez, Jacqueline, Chamie, Gabriel, Glaser, Carol, Jacobson, Kathy, Petersen, Maya, DeRisi, Joseph, and Havlir, Diane V
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Biomedical and Clinical Sciences ,Clinical Sciences ,Emerging Infectious Diseases ,Infectious Diseases ,Good Health and Well Being ,Humans ,COVID-19 ,SARS-CoV-2 ,San Francisco ,COVID-19 Drug Treatment ,Immunologic Tests ,Sensitivity and Specificity ,General Science & Technology - Abstract
COVID-19 oral treatments require initiation within 5 days of symptom onset. Although antigen tests are less sensitive than RT-PCR, rapid results could facilitate entry to treatment. We collected anterior nasal swabs for BinaxNOW and RT-PCR testing and clinical data at a walk-up, community site in San Francisco, California between January and June 2022. SARS-CoV-2 genomic sequences were generated from positive samples and classified according to subtype and variant. Monte Carlo simulations were conducted to estimate the expected proportion of SARS-CoV-2 infected persons who would have been diagnosed within 5 days of symptom onset using RT-PCR versus BinaxNOW testing. Among 25,309 persons tested with BinaxNOW, 2,799 had concomitant RT-PCR. 1137/2799 (40.6%) were SARS-CoV-2 RT-PCR positive. We identified waves of predominant omicron BA.1, BA.2, BA.2.12, BA.4, and BA.5 among 720 sequenced samples. Among 1,137 RT-PCR positive samples, 788/1137 (69%) were detected by BinaxNOW; 94% (669/711) of those with Ct value
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- 2023
35. HIV Treatment Outcomes in POP-UP: Drop-in HIV Primary Care Model for People Experiencing Homelessness
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Hickey, Matthew D, Imbert, Elizabeth, Appa, Ayesha, Del Rosario, Jan Bing, Lynch, Elizabeth, Friend, John, Avila, Rodrigo, Clemenzi-Allen, Angelo, Riley, Elise D, Gandhi, Monica, and Havlir, Diane V
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Biomedical and Clinical Sciences ,Health Sciences ,Mental Health ,Health Services ,Homelessness ,Substance Misuse ,Women's Health ,Clinical Research ,Behavioral and Social Science ,Social Determinants of Health ,Sexually Transmitted Infections ,HIV/AIDS ,Infectious Diseases ,Infection ,Good Health and Well Being ,Drug Overdose ,HIV Infections ,Ill-Housed Persons ,Humans ,Primary Health Care ,Substance-Related Disorders ,Treatment Outcome ,HIV ,homelessness and unstable housing ,care engagement ,care model ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundPeople with HIV experiencing homelessness have low rates of viral suppression, driven by sociostructural barriers and traditional care system limitations. Informed by the capability-opportunity-motivation-behavior (COM-B) model and patient preference research, we developed POP-UP, an integrated drop-in (nonappointment-based) HIV clinic with wrap-around services for persons with housing instability and viral nonsuppression in San Francisco.MethodsWe report HIV viral suppression (VS;
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- 2022
36. Providers' Attitudes and Experiences with Pre-Exposure Prophylaxis Implementation in a Population-Based Study in Kenya and Uganda
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Camlin, Carol S, Getahun, Monica, Koss, Catherine A, Owino, Lawrence, Akatukwasa, Cecilia, Itiakorit, Harriet, Onyango, Anjeline, Bakanoma, Robert, Atwine, Fredrick, Maeri, Irene, Ayieko, James, Atukunda, Mucunguzi, Owaraganise, Asiphas, Mwangwa, Florence, Sang, Norton, Kabami, Jane, Kaplan, Rachel L, Chamie, Gabriel, Petersen, Maya L, Cohen, Craig R, Bukusi, Elizabeth A, Kamya, Moses R, Havlir, Diane V, and Charlebois, Edwin D
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Health Services and Systems ,Biomedical and Clinical Sciences ,Clinical Sciences ,Health Sciences ,Infectious Diseases ,Prevention ,Clinical Research ,Clinical Trials and Supportive Activities ,Behavioral and Social Science ,Pediatric AIDS ,HIV/AIDS ,Mental Health ,Pediatric ,Infection ,Good Health and Well Being ,Adult ,Adolescent ,Female ,Humans ,Pre-Exposure Prophylaxis ,Anti-HIV Agents ,Kenya ,Uganda ,HIV Infections ,Attitude ,HIV prevention ,pre-exposure prophylaxis ,health personnel ,Africa south of the Sahara ,Public Health and Health Services ,Virology ,Clinical sciences ,Public health - Abstract
Pre-exposure prophylaxis (PrEP) implementation is underway across sub-Saharan Africa. However, little is known about health care providers' experiences with PrEP provision in generalized epidemic settings, particularly outside of selected risk groups. In this study (NCT01864603), universal access to PrEP was offered to adolescents and adults at elevated risk during population-level HIV testing in rural Kenya and Uganda. Providers received training on PrEP prescribing and support from local senior clinicians. We conducted in-depth interviews with providers (n = 19) in four communities in Kenya and Uganda to explore the attitudes and experiences with implementation. Transcripts were coded and analyzed using interpretivist methods. Providers had heterogenous attitudes toward PrEP in its early implementation: some expressed enthusiasm, while others feared being blamed for "failures" (HIV seroconversions) if participants were nonadherent, or that offering PrEP would increase "immorality." Providers supported PrEP usage among HIV-serodifferent couples, whose mutual support for daily pill-taking facilitated harmony and protection from HIV. Providers reported challenges with counseling on "seasons of risk," and safely stopping and restarting PrEP. They felt uptake was hampered for women by difficulties negotiating with partners, and for youth by parental consent requirements. They believed PrEP continuation was hindered by transportation costs, stigma, pill burden, and side effects, and was facilitated by counseling, proactive management of side effects, and home/community-based provision. Providers are critical "implementation actors" in interventions to promote adoption of new technologies such as PrEP. Dedicated training and ongoing support for providers may facilitate successful scale-up.
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- 2022
37. CROI 2022: tuberculosis and infectious complications in persons With HIV.
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Kerkhoff, Andrew D and Havlir, Diane V
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Humans ,Tuberculosis ,Tuberculosis ,Multidrug-Resistant ,HIV Infections ,Antitubercular Agents ,Moxifloxacin ,Comparative Effectiveness Research ,Clinical Research ,Antimicrobial Resistance ,Emerging Infectious Diseases ,Rare Diseases ,Prevention ,HIV/AIDS ,Clinical Trials and Supportive Activities ,Cancer ,Infectious Diseases ,Orphan Drug ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Infection ,Good Health and Well Being - Abstract
Early treatment of anal high-grade squamous intraepithelial lesions compared with active monitoring reduced the risk of anal cancer by 57% in persons with HIV in a landmark randomized trial of 4446 participants. In a multi- country randomized trial, an entirely oral combination regimen consisting of bedaquiline, pretomanid, linezolid, and moxifloxacin for 24 weeks outperformed the World Health Organization-recommended 36- to 96-week standard of care regimen for multidrug-resistant tuberculosis (TB), ushering in a new era of shorter multidrug-resistant TB treatment. These and other studies of TB and coinfections in persons with HIV presented at the 2022 Conference on Retroviruses and Opportunistic Infections pro vided new insights and are summarized herein.
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- 2022
38. Dynamic choice HIV prevention with cabotegravir long-acting injectable in rural Uganda and Kenya: a randomised trial extension
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Kamya, Moses R, Balzer, Laura B, Ayieko, James, Kabami, Jane, Kakande, Elijah, Chamie, Gabriel, Sutter, Nicole, Sunday, Helen, Litunya, Janice, Schwab, Joshua, Schrom, John, Bacon, Melanie, Koss, Catherine A, Rinehart, Alex R, Petersen, Maya, and Havlir, Diane V
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- 2024
- Full Text
- View/download PDF
39. Same‐day test and treat for infants with HIV infection: finally within reach
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Vojnov, Lara, Havlir, Diane, Myer, Landon, Abrams, Elaine, and Jani, Ilesh
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Biomedical and Clinical Sciences ,Epidemiology ,Public Health ,Clinical Sciences ,Health Sciences ,HIV Infections ,HIV-1 ,Humans ,Infant ,Infectious Disease Transmission ,Vertical ,Public Health and Health Services ,Other Medical and Health Sciences ,Clinical sciences ,Public health - Published
- 2022
40. A mid-level health manager intervention to promote uptake of isoniazid preventive therapy among people with HIV in Uganda: a cluster randomised trial
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Kakande, Elijah, Christian, Canice, Balzer, Laura B, Owaraganise, Asiphas, Nugent, Joshua R, DiIeso, William, Rast, Derek, Kabami, Jane, Peretz, Jason Johnson, Camlin, Carol S, Shade, Starley B, Geng, Elvin H, Kwarisiima, Dalsone, Kamya, Moses R, Havlir, Diane V, and Chamie, Gabriel
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Biomedical and Clinical Sciences ,Health Services and Systems ,Public Health ,Health Sciences ,Clinical Sciences ,Behavioral and Social Science ,Clinical Research ,HIV/AIDS ,Clinical Trials and Supportive Activities ,Prevention ,Emerging Infectious Diseases ,Infectious Diseases ,Sexually Transmitted Infections ,Women's Health ,3.1 Primary prevention interventions to modify behaviours or promote wellbeing ,Infection ,Good Health and Well Being ,Adult ,Antitubercular Agents ,COVID-19 ,HIV Infections ,Humans ,Isoniazid ,Pandemics ,Uganda ,Medical and Health Sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
BackgroundDespite longstanding guidelines endorsing isoniazid preventive therapy (IPT) for people with HIV, uptake is low across sub-Saharan Africa. Mid-level health managers oversee IPT programmes nationally; interventions aimed at this group have not been tested. We aimed to establish whether providing structured leadership and management training and facilitating subregional collaboration and routine data feedback to mid-level managers could increase IPT initiation among people with HIV compared with standard practice.MethodsWe conducted a cluster randomised trial in Uganda among district-level health managers. We randomly assigned clusters of between four and seven managers in a 1:1 ratio to intervention or control groups. Our intervention convened managers into mini-collaboratives facilitated by Ugandan experts in tuberculosis and HIV, and provided business leadership and management training, SMS platform access, and data feedback. The control was standard practice. Participants were not masked to trial group, but study statisticians were masked until trial completion. The primary outcome was IPT initiation rates among adults with HIV in facilities overseen by participants over a period of 2 years (2019-21). We conducted prespecified analyses that excluded the third quarter of 2019 (Q3-2019) to understand intervention effects independent of a national 100-day IPT push tied to a financial contingency during Q3-2019. This trial is registered with ClinicalTrials.gov (NCT03315962), and is ongoing.FindingsBetween Nov 15, 2017, and March 14, 2018, managers from 82 of 82 eligible districts (61% of Uganda's 135 districts) were enrolled and randomised: 43 districts to intervention, 39 to control. Intervention delivery took place between Dec 6, 2017, and Feb 2, 2022. Over 2 years, IPT initiation rates were 0·74 versus 0·65 starts per person-year in intervention versus control groups (incidence rate ratio [IRR] 1·14, 95% CI 0·88-1·46; p=0·16). Excluding Q3-2019, IPT initiation was higher in the intervention group versus the control group: 0·32 versus 0·25 starts per person-year (IRR 1·27, 95% CI 1·00-1·61; p=0·026).InterpretationFollowing an intervention targeting managers in more than 60% of Uganda's districts, IPT initiation rates were not significantly higher in intervention than control groups. After accounting for large increases in IPT from a 100-day push in both groups, the intervention led to significantly increased IPT rates, sustained after the push and during the COVID-19 pandemic. Our findings suggest that interventions centred on mid-level health managers can improve IPT implementation on a large, subnational scale, and merit further exploration to address key public health challenges for which strong evidence exists but implementation remains suboptimal.FundingNational Institute of Allergy and Infectious Diseases.
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- 2022
41. Impact of Multicomponent Support Strategies on Human Immunodeficiency Virus Virologic Suppression Rates During Coronavirus Disease 2019: An Interrupted Time Series Analysis
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Spinelli, Matthew A, Le Tourneau, Noelle, Glidden, David V, Hsu, Ling, Hickey, Matthew D, Imbert, Elizabeth, Arreguin, Mireya, Jain, Jennifer P, Oskarsson, Jon J, Buchbinder, Susan P, Johnson, Mallory O, Havlir, Diane, Christopoulos, Katerina A, and Gandhi, Monica
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Biomedical and Clinical Sciences ,Clinical Sciences ,Health Disparities ,Coronaviruses ,Infectious Diseases ,Social Determinants of Health ,Sexually Transmitted Infections ,HIV/AIDS ,Emerging Infectious Diseases ,Good Health and Well Being ,COVID-19 ,Female ,HIV ,HIV Infections ,Ill-Housed Persons ,Humans ,Interrupted Time Series Analysis ,Male ,Middle Aged ,Pandemics ,HIV virologic suppression ,housing support ,telemedicine ,homelessness ,Virologic Suppression ,Interrupted time series ,housing intervention ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
BackgroundAfter coronavirus disease 2019 (COVID-19) shelter-in-place (SIP) orders, viral suppression (VS) rates initially decreased within a safety-net human immunodeficiency virus (HIV) clinic in San Francisco, particularly among people living with HIV (PLWH) who are experiencing homelessness. We sought to determine if proactive outreach to provide social services, scaling up of in-person visits, and expansion of housing programs could reverse this decline.MethodsWe assessed VS 24 months before and 13 months after SIP using mixed-effects logistic regression followed by interrupted time series (ITS) analysis to examine changes in the rate of VS per month. Loss to follow-up (LTFU) was assessed via active clinic tracing.ResultsData from 1816 patients were included; the median age was 51 years, 12% were female, and 14% were experiencing unstable housing/homelessness. The adjusted odds of VS increased 1.34 fold following institution of the multicomponent strategies (95% confidence interval [CI], 1.21-1.46). In the ITS analysis, the odds of VS continuously increased 1.05 fold per month over the post-intervention period (95% CI, 1.01-1.08). Among PLWH who previously experienced homelessness and successfully received housing support, the odds of VS were 1.94-fold higher (95% CI, 1.05-3.59). The 1-year LTFU rate was 2.8 per 100 person-years (95% CI, 2.2-3.5).ConclusionsThe VS rate increased following institution of the multicomponent strategies, with a lower LFTU rate compared with prior years. Maintaining in-person care for underserved patients, with flexible telemedicine options, along with provision of social services and permanent expansion of housing programs, will be needed to support VS among underserved populations during the COVID-19 pandemic.
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- 2022
42. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission Dynamics and Immune Responses in a Household of Vaccinated Persons
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Liu, Jamin, Laurie, Matthew T, Rubio, Luis, Vazquez, Sara E, Sunshine, Sara, Mitchell, Anthea M, Hapte-Selassie, Matthias, Mann, Sabrina A, Pilarowski, Genay, Black, Douglas, Marquez, Carina, Rojas, Susana, Lionakis, Michail S, Petersen, Maya, Whitman, Jeffrey D, Jain, Vivek, Anderson, Mark, Havlir, Diane, and DeRisi, Joseph
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Medical Microbiology ,Biomedical and Clinical Sciences ,Biodefense ,Vaccine Related ,Emerging Infectious Diseases ,Coronaviruses ,Infectious Diseases ,Immunization ,Prevention ,Infection ,Good Health and Well Being ,Antibodies ,Viral ,COVID-19 ,COVID-19 Vaccines ,Humans ,Immunity ,SARS-CoV-2 ,antibody neutralization ,breakthrough infection ,anti ,interferon autoantibody ,autoimmunity ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Clinical sciences - Abstract
While SARS-CoV-2 vaccines prevent severe disease effectively, postvaccination "breakthrough" COVID-19 infections and transmission among vaccinated individuals remain ongoing concerns. We present an in-depth characterization of transmission and immunity among vaccinated individuals in a household, revealing complex dynamics and unappreciated comorbidities, including autoimmunity to type 1 interferon in the presumptive index case.
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- 2022
43. “I was still very young”: agency, stigma and HIV care strategies at school, baseline results of a qualitative study among youth in rural Kenya and Uganda
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Johnson‐Peretz, Jason, Lebu, Sarah, Akatukwasa, Cecilia, Getahun, Monica, Ruel, Theodore, Lee, Joi, Ayieko, James, Mwangwa, Florence, Owino, Lawrence, Onyango, Anjeline, Maeri, Irene, Atwine, Frederick, Charlebois, Edwin D, Bukusi, Elizabeth A, Kamya, Moses R, Havlir, Diane V, and Camlin, Carol S
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Health Services and Systems ,Biomedical and Clinical Sciences ,Health Sciences ,Pediatric ,Clinical Research ,HIV/AIDS ,Social Determinants of Health ,Pediatric AIDS ,Prevention ,Mental Health ,Sexually Transmitted Infections ,Behavioral and Social Science ,Infectious Diseases ,Management of diseases and conditions ,7.1 Individual care needs ,Good Health and Well Being ,Adolescent ,Adult ,Anti-Retroviral Agents ,HIV Infections ,Humans ,Kenya ,Medication Adherence ,Qualitative Research ,Social Stigma ,Uganda ,Young Adult ,adolescent ,eastern Africa ,highly active antiretroviral therapy ,HIV ,medication adherence ,social stigma ,Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences ,Clinical sciences ,Epidemiology ,Public health - Abstract
IntroductionAdolescents and young adults living with HIV (AYAH) have the lowest rates of retention in HIV care and antiretroviral therapy (ART) adherence, partly due to the demands of school associated with this life stage, to HIV-related stigma and to fears of serostatus disclosure. We explore the implications of school-based stigma and disclosure on the development of agency during a critical life stage in rural Kenya and Uganda.MethodsWe conducted a qualitative study in the baseline year of the SEARCH Youth study, a combination intervention using a life-stage approach among youth (15-24 years old) living with HIV in western Kenya and southwestern Uganda to improve viral load suppression and health outcomes. We conducted in-depth, semi-structured interviews in 2019 with three cohorts of purposively selected study participants (youth [n = 83], balanced for sex, life stage and HIV care status; recommended family members of youth [n = 33]; and providers [n = 20]). Inductive analysis exploring contextual factors affecting HIV care engagement revealed the high salience of schooling environments.ResultsStigma within school settings, elicited by non-consensual serostatus disclosure, medication schedules and clinic appointments, exerts a constraining factor around which AYAH must navigate to identify and pursue opportunities available to them as young people. HIV status can affect cross-generational support and cohort formation, as AYAH differ from non-AYAH peers because of care-related demands affecting schooling, exams and graduation. However, adolescents demonstrate a capacity to overcome anticipated stigma and protect themselves by selectively disclosing HIV status to trusted peers and caregivers, as they develop a sense of agency concomitant with this life stage. Older adolescents showed greater ability to seek out supportive relationships than younger ones who relied on adult caregivers to facilitate this support.ConclusionsSchool is a potential site of HIV stigma and also a setting for learning how to resist such stigma. School-going adolescents should be supported to identify helpful peers and selectively disclose serostatus as they master decision making about when and where to take medications, and who should know. Stigma is avoided by fewer visits to the clinic; providers should consider longer refills, discreet packaging and long-acting, injectable ART for students.
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- 2022
44. Statistical Analysis Plan for Health Outcomes in Phase 1 of the SEARCH-IPT Study
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Balzer, Laura B., Nugent, Joshua, Havlir, Diane V., and Chamie, Gabriel
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Statistics - Applications - Abstract
This document provides the statistical analytic plan (SAP) for evaluating health outcomes in Phase 1 of the SEARCH-IPT Study, a cluster randomized trial to evaluate whether a multicomponent intervention increases uptake of isoniazid (INH) preventive therapy (IPT) and reduces the incidence of tuberculosis (TB) in Uganda (Clinicaltrials.gov: NCT03315962). The SAP was locked prior to unblinding and effect estimation. This SAP was embargoed until November 19, 2021 when it was submitted to arXiv., Comment: 13 pages and 1 figure
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- 2021
45. Brief Report: Heterogeneous Preferences for Care Engagement Among People With HIV Experiencing Homelessness or Unstable Housing During the COVID-19 Pandemic
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Imbert, Elizabeth, Hickey, Matthew D, Del Rosario, Jan Bing, Conte, Madellena, Kerkhoff, Andrew D, Clemenzi-Allen, Angelo, Riley, Elise D, Havlir, Diane V, and Gandhi, Monica
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Biomedical and Clinical Sciences ,Epidemiology ,Public Health ,Clinical Sciences ,Health Sciences ,Sexually Transmitted Infections ,Coronaviruses ,Infectious Diseases ,Clinical Research ,HIV/AIDS ,Emerging Infectious Diseases ,Health Services ,Social Determinants of Health ,Infection ,Good Health and Well Being ,COVID-19 ,HIV Infections ,Ill-Housed Persons ,Housing ,Humans ,Pandemics ,HIV ,homeless persons ,care engagement ,discrete choice experiment ,patient preference ,Public Health and Health Services ,Virology ,Clinical sciences ,Public health - Abstract
Background/settingIn San Francisco, HIV viral suppression is 71% among housed individuals but only 20% among unhoused individuals. We conducted a discrete choice experiment at a San Francisco public HIV clinic to evaluate care preferences among people living with HIV (PLH) experiencing homelessness/unstable housing during the COVID-19 pandemic.MethodsFrom July to November 2020, we conducted a discrete choice experiment among PLH experiencing homelessness/unstable housing who accessed care through (1) an incentivized, drop-in program (POP-UP) or (2) traditional primary care. We investigated 5 program features: single provider vs team of providers; visit incentives ($0, $10, and $20); location (current site vs current + additional site); drop-in vs scheduled visits; in-person only vs optional telehealth visits; and navigator assistance. We estimated relative preferences using mixed-effects logistic regression and conducted latent class analysis to evaluate preference heterogeneity.ResultsWe enrolled 115 PLH experiencing homelessness/unstable housing, 40% of whom lived outdoors. The strongest preferences were for the same provider (β = 0.94, 95% CI: 0.48 to 1.41), visit incentives (β = 0.56 per $5; 95% CI: 0.47 to 0.66), and drop-in visits (β = 0.47, 95% CI: 0.12 to 0.82). Telehealth was not preferred. Latent class analysis revealed 2 distinct groups: 78 (68%) preferred a flexible care model, whereas 37 (32%) preferred a single provider.ConclusionsWe identified heterogeneous care preferences among PLH experiencing homelessness/unstable housing during the COVID-19 pandemic, with two-thirds preferring greater flexibility and one-third preferring provider continuity. Telehealth was not preferred, even with navigator facilitation. Including patient choice in service delivery design can improve care engagement, particularly for marginalized populations, and is an essential tool for ending the HIV epidemic.
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- 2022
46. SARS-CoV-2 Variant Exposures Elicit Antibody Responses With Differential Cross-Neutralization of Established and Emerging Strains Including Delta and Omicron
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Laurie, Matthew T, Liu, Jamin, Sunshine, Sara, Peng, James, Black, Douglas, Mitchell, Anthea M, Mann, Sabrina A, Pilarowski, Genay, Zorn, Kelsey C, Rubio, Luis, Bravo, Sara, Marquez, Carina, Sabatino, Joseph J, Mittl, Kristen, Petersen, Maya, Havlir, Diane, and DeRisi, Joseph
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Medical Microbiology ,Biomedical and Clinical Sciences ,Vaccine Related ,Coronaviruses Vaccines ,Coronaviruses ,Infectious Diseases ,Prevention ,Emerging Infectious Diseases ,Immunization ,2.1 Biological and endogenous factors ,Infection ,Good Health and Well Being ,Antibodies ,Neutralizing ,Antibodies ,Viral ,Antibody Formation ,COVID-19 ,Humans ,SARS-CoV-2 ,Spike Glycoprotein ,Coronavirus ,neutralization ,variant ,B ,1 ,617 ,2 ,529 ,vaccination ,natural infection ,antibody escape ,immune exposure ,B.1.1.529 ,B.1.617.2 ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
The wide spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of immune responses to different spike protein versions. Here, we compare neutralization of variants of concern, including B.1.617.2 (delta) and B.1.1.529 (omicron), in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing certain spike mutations with the immunizing exposure, and exposure to multiple spike variants increases breadth of variant cross-neutralization. These findings contribute to understanding relationships between exposures and antibody responses and may inform booster vaccination strategies.
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- 2022
47. PEP for HIV prevention: are we missing opportunities to reduce new infections?
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Ayieko, James, Petersen, Maya L, Kamya, Moses R, and Havlir, Diane V
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Humans ,HIV Infections ,Anti-HIV Agents ,Homosexuality ,Male ,Male ,Clinical Sciences ,Public Health and Health Services ,Other Medical and Health Sciences - Published
- 2022
48. Cost-effectiveness of easy-access, risk-informed oral pre-exposure prophylaxis in HIV epidemics in sub-Saharan Africa: a modelling study
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Phillips, Andrew N, Bershteyn, Anna, Revill, Paul, Bansi-Matharu, Loveleen, Kripke, Katharine, Boily, Marie-Claude, Martin-Hughes, Rowan, Johnson, Leigh F, Mukandavire, Zindoga, Jamieson, Lise, Meyer-Rath, Gesine, Hallett, Timothy B, Brink, Debra ten, Kelly, Sherrie L, Nichols, Brooke E, Bendavid, Eran, Mudimu, Edinah, Taramusi, Isaac, Smith, Jennifer, Dalal, Shona, Baggaley, Rachel, Crowley, Siobhan, Terris-Prestholt, Fern, Godfrey-Faussett, Peter, Mukui, Irene, Jahn, Andreas, Case, Kelsey K, Havlir, Diane, Petersen, Maya, Kamya, Moses, Koss, Catherine A, Balzer, Laura B, Apollo, Tsitsi, Chidarikire, Thato, Mellors, John W, Parikh, Urvi M, Godfrey, Catherine, Cambiano, Valentina, and Consortium, HIV Modelling
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Cost Effectiveness Research ,Mental Health ,Clinical Research ,Prevention ,HIV/AIDS ,Infectious Diseases ,Infection ,Good Health and Well Being ,Adult ,Anti-HIV Agents ,Cost-Benefit Analysis ,Epidemics ,Female ,HIV Infections ,Humans ,Male ,Pre-Exposure Prophylaxis ,HIV Modelling Consortium ,Medical and Health Sciences - Abstract
BackgroundApproaches that allow easy access to pre-exposure prophylaxis (PrEP), such as over-the-counter provision at pharmacies, could facilitate risk-informed PrEP use and lead to lower HIV incidence, but their cost-effectiveness is unknown. We aimed to evaluate conditions under which risk-informed PrEP use is cost-effective.MethodsWe applied a mathematical model of HIV transmission to simulate 3000 setting-scenarios reflecting a range of epidemiological characteristics of communities in sub-Saharan Africa. The prevalence of HIV viral load greater than 1000 copies per mL among all adults (HIV positive and negative) varied from 1·1% to 7·4% (90% range). We hypothesised that if PrEP was made easily available without restriction and with education regarding its use, women and men would use PrEP, with sufficient daily adherence, during so-called seasons of risk (ie, periods in which individuals are at risk of acquiring infection). We refer to this as risk-informed PrEP. For each setting-scenario, we considered the situation in mid-2021 and performed a pairwise comparison of the outcomes of two policies: immediate PrEP scale-up and then continuation for 50 years, and no PrEP. We estimated the relationship between epidemic and programme characteristics and cost-effectiveness of PrEP availability to all during seasons of risk. For our base-case analysis, we assumed a 3-monthly PrEP cost of US$29 (drug $11, HIV test $4, and $14 for additional costs necessary to facilitate education and access), a cost-effectiveness threshold of $500 per disability-adjusted life-year (DALY) averted, an annual discount rate of 3%, and a time horizon of 50 years. In sensitivity analyses, we considered a cost-effectiveness threshold of $100 per DALY averted, a discount rate of 7% per annum, the use of PrEP outside of seasons of risk, and reduced uptake of risk-informed PrEP.FindingsIn the context of PrEP scale-up such that 66% (90% range across setting-scenarios 46-81) of HIV-negative people with at least one non-primary condomless sex partner take PrEP in any given period, resulting in 2·6% (0·9-6·0) of all HIV negative adults taking PrEP at any given time, risk-informed PrEP was predicted to reduce HIV incidence by 49% (23-78) over 50 years compared with no PrEP. PrEP was cost-effective in 71% of all setting-scenarios, and cost-effective in 76% of setting-scenarios with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%. In sensitivity analyses with a $100 per DALY averted cost-effectiveness threshold, a 7% per year discount rate, or with PrEP use that was less well risk-informed than in our base case, PrEP was less likely to be cost-effective, but generally remained cost-effective if the prevalence of HIV viral load greater than 1000 copies per mL among all adults was higher than 3%. In sensitivity analyses based on additional setting-scenarios in which risk-informed PrEP was less extensively used, the HIV incidence reduction was smaller, but the cost-effectiveness of risk-informed PrEP was undiminished.InterpretationUnder the assumption that making PrEP easily accessible for all adults in sub-Saharan Africa in the context of community education leads to risk-informed use, PrEP is likely to be cost-effective in settings with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%, suggesting the need for implementation of such approaches, with ongoing evaluation.FundingUS Agency for International Development, US President's Emergency Plan for AIDS Relief, and Bill & Melinda Gates Foundation.
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- 2022
49. Viral Load Among Vaccinated and Unvaccinated, Asymptomatic and Symptomatic Persons Infected With the SARS-CoV-2 Delta Variant.
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Acharya, Charlotte B, Schrom, John, Mitchell, Anthea M, Coil, David A, Marquez, Carina, Rojas, Susana, Wang, Chung Yu, Liu, Jamin, Pilarowski, Genay, Solis, Leslie, Georgian, Elizabeth, Belafsky, Sheri, Petersen, Maya, DeRisi, Joseph, Michelmore, Richard, and Havlir, Diane
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19 ,COVID ,Ct value ,Delta variant ,SARS-CoV-2 ,asymptomatic testing ,Emerging Infectious Diseases ,Clinical Research ,Vaccine Related ,Infectious Diseases ,Biodefense ,Prevention ,Lung ,Immunization ,Infection ,Good Health and Well Being - Abstract
We found no significant difference in cycle threshold values between vaccinated and unvaccinated persons infected with severe acute respiratory syndrome coronavirus 2 Delta, overall or stratified by symptoms. Given the substantial proportion of asymptomatic vaccine breakthrough cases with high viral levels, interventions, including masking and testing, should be considered in settings with elevated coronavirus disease 2019 transmission.
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- 2022
50. Comparison of SARS-CoV-2 Reverse Transcriptase Polymerase Chain Reaction and BinaxNOW Rapid Antigen Tests at a Community Site During an Omicron Surge
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Schrom, John, Marquez, Carina, Pilarowski, Genay, Wang, Chung-Yu, Mitchell, Anthea, Puccinelli, Robert, Black, Doug, Rojas, Susana, Ribeiro, Salustiano, Tulier-Laiwa, Valerie, Martinez, Jacqueline, Payan, Joselin, Rojas, Susy, Jones, Diane, Martinez, Daniel, Nakamura, Robert, Chamie, Gabriel, Jain, Vivek, Petersen, Maya, DeRisi, Joe, and Havlir, Diane
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Biomedical and Clinical Sciences ,Clinical Sciences ,Emerging Infectious Diseases ,Infectious Diseases ,Vaccine Related ,Clinical Research ,Prevention ,HIV/AIDS ,Biotechnology ,Infection ,Good Health and Well Being ,Antigens ,Viral ,COVID-19 ,COVID-19 Testing ,Cross-Sectional Studies ,Humans ,Reverse Transcriptase Polymerase Chain Reaction ,SARS-CoV-2 ,Sensitivity and Specificity ,Medical and Health Sciences ,General & Internal Medicine ,Clinical sciences - Abstract
BackgroundSARS-CoV-2 rapid antigen tests are an important public health tool.ObjectiveTo evaluate field performance of the BinaxNOW rapid antigen test (Abbott) compared with reverse transcriptase polymerase chain reaction (RT-PCR) for detecting infection with the Omicron variant of SARS-CoV-2.DesignCross-sectional surveillance study.SettingFree, walk-up, outdoor, urban community testing and vaccine site led by Unidos en Salud, serving a predominantly Latinx community highly impacted by COVID-19.ParticipantsPersons seeking COVID-19 testing in January 2022.MeasurementsSimultaneous BinaxNOW and RT-PCR from nasal, cheek, and throat swabs, including cycle threshold (Ct) measures; a lower Ct value is a surrogate for higher amounts of virus.ResultsAmong 731 persons tested with nasal swabs, there were 296 (40.5%) positive results on RT-PCR; 98.9% were the Omicron variant. BinaxNOW detected 95.2% (95% CI, 91% to 98%) of persons who tested positive on RT-PCR with a Ct value below 30, 82.1% (CI, 77% to 87%) of those who tested positive on RT-PCR with a Ct value below 35, and 65.2% (CI, 60% to 71%) of all who were positive on RT-PCR. Among 75 persons with simultaneous nasal and cheek swabs, BinaxNOW using a cheek swab failed to detect 91% (20 of 22) of specimens that were positive on BinaxNOW with a nasal swab. Among persons with simultaneous nasal and throat swabs who were positive on RT-PCR with a Ct value below 30, 42 of 49 (85.7%) were detected by nasal BinaxNOW, 23 of 49 (46.9%) by throat BinaxNOW, and 44 of 49 (89.8%) by either.LimitationParticipants were a cross-sectional sample from a community-based sentinel surveillance site, precluding study of viral or symptom dynamics.ConclusionBinaxNOW detected persons with high SARS-CoV-2 levels during the Omicron surge, enabling rapid responses to positive test results. Cheek or throat swabs should not replace nasal swabs. As currently recommended, high-risk persons with an initial negative BinaxNOW result should have repeated testing.Primary funding sourceUniversity of California, San Francisco.
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- 2022
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