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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.

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.

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 (

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.

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

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

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.

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.

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.

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.

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

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.

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.

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.

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.

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..

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.

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.

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;

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.

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.

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.

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.

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.

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.

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.

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.

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.

BackgroundSequencing of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities.MethodsSARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during 22 November to 1 December, 2020, and 10-29 January 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants.ResultsA total of 12 124 tests were performed yielding 1099 positives. From these, 928 high-quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the "California" or "West Coast" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, risk ratio [RR] = 1.28; 95% confidence interval [CI]: 1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.3%).ConclusionsThe increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants. Summary: We observed a growing prevalence and modestly elevated attack rate for "West Coast" severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in a community testing setting in San Francisco during January 2021, suggesting its modestly higher transmissibility.

The Sustainable East Africa Research in Community Health (SEARCH) trial was a universal test-and-treat (UTT) trial in rural Uganda and Kenya, aiming to lower regional HIV-1 incidence. Here, we quantify breakthrough HIV-1 transmissions occurring during the trial from population-based, dried blood spot samples. Between 2013 and 2017, we obtained 549 gag and 488 pol HIV-1 consensus sequences from 745 participants: 469 participants infected prior to trial commencement and 276 SEARCH-incident infections. Putative transmission clusters, with a 1.5% pairwise genetic distance threshold, were inferred from maximum likelihood phylogenies; clusters arising after the start of SEARCH were identified with Bayesian time-calibrated phylogenies. Our phylodynamic approach identified nine clusters arising after the SEARCH start date: eight pairs and one triplet, representing mostly opposite-gender linked (6/9), within-community transmissions (7/9). Two clusters contained individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, both linked to intervention communities. The identification of SEARCH-incident, within-community transmissions reveals the role of unsuppressed individuals in sustaining the epidemic in both arms of a UTT trial setting. The presence of transmitted NNRTI resistance, implying treatment failure to the efavirenz-based antiretroviral therapy (ART) used during SEARCH, highlights the need to improve delivery and adherence to up-to-date ART recommendations, to halt HIV-1 transmission.

BackgroundKey components of Ending the HIV Epidemic (EHE) plan include increasing HIV antiretroviral therapy (ART) and HIV pre-exposure prophylaxis (PrEP) coverage. One complication to addressing this service delivery challenge is the wide heterogeneity of HIV burden and health care access across the United States. It is unclear how the effectiveness and efficiency of expanded PrEP will depend on different baseline ART coverage.MethodsWe used a network-based model of HIV transmission for men who have sex with men (MSM) in San Francisco. Model scenarios increased varying levels of PrEP coverage relative under current empirical levels of baseline ART coverage and 2 counterfactual levels. We assessed the effectiveness of PrEP with the cumulative percentage of infections averted (PIA) over the next decade and efficiency with the number of additional person-years needed to treat (NNT) by PrEP required to avert one HIV infection.ResultsIn our projections, only the highest levels of combined PrEP and ART coverage achieved the EHE goals. Increasing PrEP coverage up to 75% showed that PrEP effectiveness was higher at higher baseline ART coverage. Indeed, the PIA was 61% in the lowest baseline ART coverage population and 75% in the highest. The efficiency declined with increasing ART (NNT range from 41 to 113).ConclusionsImproving both PrEP and ART coverage would have a synergistic impact on HIV prevention even in a high baseline coverage city such as San Francisco. Efforts should focus on narrowing the implementation gaps to achieve higher levels of PrEP retention and ART sustained viral suppression.

To assess SARS-CoV-2 outcomes, we matched a municipal COVID-19 registry and clinic rosters from a municipal primary care network containing a large HIV clinic and assessed clinical outcomes by HIV status. The risk of severe COVID-19 was higher among people with HIV (PWH, adjusted relative risk = 1.84, 95% confidence interval = 1.05-3.25), while SARS-CoV-2 incidence was lower despite higher testing rates. SARS-CoV-2 vaccination campaigns should prioritize PWH to prevent severe COVID-19 disease given potentially higher risk.

BackgroundWe tested the hypothesis that patient-centered, streamlined human immunodeficiency virus (HIV) care would achieve lower mortality than the standard treatment model for persons with HIV and CD4 ≤ 350/uL in the setting of population-wide HIV testing.MethodsIn the SEARCH (Sustainable East Africa Research in Community Health) Study (NCT01864603), 32 communities in rural Uganda and Kenya were randomized to country-guided antiretroviral therapy (ART) versus streamlined ART care that included rapid ART start, visit spacing, flexible clinic hours, and welcoming environment. We assessed persons with HIV and CD4 ≤ 350/uL, ART eligible in both arms, and estimated the effect of streamlined care on ART initiation and mortality at 3 years. Comparisons between study arms used a cluster-level analysis with survival estimates from Kaplan-Meier; estimates of ART start among ART-naive persons treated death as a competing risk.ResultsAmong 13 266 adults with HIV, 2973 (22.4%) had CD4 ≤ 350/uL. Of these, 33% were new diagnoses, and 10% were diagnosed but ART-naive. Men with HIV were almost twice as likely as women with HIV to have CD4 ≤ 350/uL and be untreated (15% vs 8%, respectively). Streamlined care reduced mortality by 28% versus control (risk ratio [RR] = 0.72; 95% confidence interval [CI]: .56, .93; P = .02). Despite eligibility in both arms, persons with CD4 ≤ 350/uL started ART faster under streamlined care versus control (76% vs 43% by 12 months, respectively; P

BackgroundThe SEARCH study provided community-based HIV and multidisease testing and antiretroviral therapy (ART) to 32 communities in East Africa and reported no statistically significant difference in 3-year HIV incidence. We used mathematical modeling to estimate the effect of control arm viral suppression and community mixing on SEARCH trial outcomes.SettingUganda and Kenya.MethodsUsing the individual-based HIV modeling software EMOD-HIV, we configured a new model of SEARCH communities. The model was parameterized using demographic, HIV prevalence, male circumcision, and viral suppression data and calibrated to HIV prevalence, ART coverage, and population size. Using assumptions about ART scale-up in the control arm, degree of community mixing, and effect of baseline testing, we estimated comparative HIV incidence under multiple scenarios.ResultsBefore the trial results, we predicted that SEARCH would report a 4%-40% reduction between arms, depending on control arm ART linkage rates and community mixing. With universal baseline testing followed by rapidly expanded ART eligibility and uptake, modeled effect sizes were smaller than the study was powered to detect. Using interim viral suppression data, we estimated 3-year cumulative incidence would have been reduced by up to 27% in the control arm and 43% in the intervention arm compared with a counterfactual without universal baseline testing.ConclusionsOur model suggests that the active control arm substantially reduced expected effect size and power of the SEARCH study. However, compared with a counterfactual "true control" without increased ART linkage because of baseline testing, SEARCH reduced HIV incidence by up to 43%.

BackgroundThere is an urgent need to understand the dynamics and risk factors driving ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission during shelter-in-place mandates.MethodsWe offered SARS-CoV-2 reverse-transcription polymerase chain reaction (PCR) and antibody (Abbott ARCHITECT IgG) testing, regardless of symptoms, to all residents (aged ≥4 years) and workers in a San Francisco census tract (population: 5174) at outdoor, community-mobilized events over 4 days. We estimated SARS-CoV-2 point prevalence (PCR positive) and cumulative incidence (antibody or PCR positive) in the census tract and evaluated risk factors for recent (PCR positive/antibody negative) vs prior infection (antibody positive/PCR negative). SARS-CoV-2 genome recovery and phylogenetics were used to measure viral strain diversity, establish viral lineages present, and estimate number of introductions.ResultsWe tested 3953 persons (40% Latinx; 41% White; 9% Asian/Pacific Islander; and 2% Black). Overall, 2.1% (83/3871) tested PCR positive: 95% were Latinx and 52% were asymptomatic when tested; 1.7% of census tract residents and 6.0% of workers (non-census tract residents) were PCR positive. Among 2598 tract residents, estimated point prevalence of PCR positives was 2.3% (95% confidence interval [CI], 1.2%-3.8%): 3.9% (95% CI, 2.0%-6.4%) among Latinx persons vs 0.2% (95% CI, .0-.4%) among non-Latinx persons. Estimated cumulative incidence among residents was 6.1% (95% CI, 4.0%-8.6%). Prior infections were 67% Latinx, 16% White, and 17% other ethnicities. Among recent infections, 96% were Latinx. Risk factors for recent infection were Latinx ethnicity, inability to shelter in place and maintain income, frontline service work, unemployment, and household income

ObjectiveHomelessness is the greatest risk factor for HIV viremia in San Francisco. Innovative care models for people with HIV (PWH) with homelessness or unstable housing (HUH) are needed to address this inequity. We developed a novel low-barrier clinic-based program for PWH-HUH in an urban safety-net clinic ('POP-UP') and report outcomes on care engagement and viral suppression.DesignA prospective cohort study.SettingSan Francisco General Hospital HIV Clinic (Ward 86).ParticipantsWe enrolled PWH who are HUH, viraemic and for whom usual care is not working (at least one missed primary care appointment and at least two drop-in visits at Ward 86 in the last year).InterventionPOP-UP provides drop-in comprehensive primary care, housing assistance and case management, financial incentives and patient navigation with frequent contact.Main outcome measuresWe describe uptake of eligible patients into POP-UP, and cumulative incidence of antiretroviral therapy (ART) initiation, return to care and virologic suppression 6 months post-enrolment, estimated via Kaplan--Meier.ResultsOut of 192 referred patients, 152 were eligible, and 75 enrolled. All 75 were off ART and viraemic; 100% had a substance use disorder; and 77% had a mental health diagnosis. Over three-quarters restarted ART within 7 days of enrolment, and 91% returned for follow-up within 90 days. The cumulative incidence of viral suppression at 6 months was 55% (95% confidence interval 43-68).ConclusionA novel care model for PWH-HUH demonstrates early success in engaging viraemic patients in care and improving viral suppression. Low-barrier, high-contact primary care programmes offering comprehensive services and incentives may improve outcomes for this vulnerable population.

BackgroundSocial isolation among HIV-positive persons might be an important barrier to care. Using data from the SEARCH Study in rural Kenya and Uganda, we constructed 32 community-wide, sociocentric networks and evaluated whether less socially connected HIV-positive persons were less likely to know their status, have initiated treatment, and be virally suppressed.MethodsBetween 2013 and 2014, 168,720 adult residents in the SEARCH Study were census-enumerated, offered HIV testing, and asked to name social contacts. Social networks were constructed by matching named contacts to other residents. We characterized the resulting networks and estimated risk ratios (aRR) associated with poor HIV care outcomes, adjusting for sociodemographic factors and clustering by community with generalized estimating equations.ResultsThe sociocentric networks contained 170,028 residents (nodes) and 362,965 social connections (edges). Among 11,239 HIV-positive persons who named ≥1 contact, 30.9% were previously undiagnosed, 43.7% had not initiated treatment, and 49.4% had viral nonsuppression. Lower social connectedness, measured by the number of persons naming an HIV-positive individual as a contact (in-degree), was associated with poorer outcomes in Uganda, but not Kenya. Specifically, HIV-positive persons in the lowest connectedness tercile were less likely to be previously diagnosed (Uganda-West aRR: 0.89 [95% confidence interval (CI): 0.83, 0.96]; Uganda-East aRR: 0.85 [95% CI: 0.76, 0.96]); on treatment (Uganda-West aRR: 0.88 [95% CI: 0.80, 0.98]; Uganda-East aRR: 0.81 [0.72, 0.92]), and suppressed (Uganda-West aRR: 0.84 [95% CI: 0.73, 0.96]; Uganda-East aRR: 0.74 [95% CI: 0.58, 0.94]) than those in the highest connectedness tercile.ConclusionsHIV-positive persons named as a contact by fewer people may be at higher risk for poor HIV care outcomes, suggesting opportunities for targeted interventions.

BackgroundEarly virologic suppression (VS) after human immunodeficiency virus (HIV) infection improves individual health outcomes and decreases onward transmission. In San Francisco, immediate antiretroviral therapy (ART) at HIV diagnosis was piloted in 2013-2014 and expanded citywide in 2015 in a rapid start initiative to link all new diagnoses to care within 5 days and start ART at the first care visit.MethodsHIV providers and linkage navigators were trained on a rapid start protocol with sites caring for vulnerable populations prioritized. Dates of HIV diagnosis, first care visit, ART initiation, and VS were abstracted from the San Francisco Department of Public Health HIV surveillance registry.ResultsDuring 2013-2017, among 1354 new HIV diagnoses in San Francisco, median days from diagnosis to first VS decreased from 145 to 76 (48%; P

BackgroundRoutine viral testing strategies for SARS-CoV-2 infection might facilitate safe airline travel during the COVID-19 pandemic and mitigate global spread of the virus. However, the effectiveness of these test-and-travel strategies to reduce passenger risk of SARS-CoV-2 infection and population-level transmission remains unknown.MethodsIn this simulation study, we developed a microsimulation of SARS-CoV-2 transmission in a cohort of 100 000 US domestic airline travellers using publicly available data on COVID-19 clinical cases and published natural history parameters to assign individuals one of five health states of susceptible to infection, latent period, early infection, late infection, or recovered. We estimated a per-day risk of infection with SARS-CoV-2 corresponding to a daily incidence of 150 infections per 100 000 people. We assessed five testing strategies: (1) anterior nasal PCR test within 3 days of departure, (2) PCR within 3 days of departure and 5 days after arrival, (3) rapid antigen test on the day of travel (assuming 90% of the sensitivity of PCR during active infection), (4) rapid antigen test on the day of travel and PCR test 5 days after arrival, and (5) PCR test 5 days after arrival. Strategies 2 and 4 included a 5-day quarantine after arrival. The travel period was defined as 3 days before travel to 2 weeks after travel. Under each scenario, individuals who tested positive before travel were not permitted to travel. The primary study outcome was cumulative number of infectious days in the cohort over the travel period without isolation or quarantine (population-level transmission risk), and the key secondary outcome was the number of infectious people detected on the day of travel (passenger risk of infection).FindingsWe estimated that in a cohort of 100 000 airline travellers, in a scenario with no testing or screening, there would be 8357 (95% uncertainty interval 6144-12831) infectious days with 649 (505-950) actively infectious passengers on the day of travel. The pre-travel PCR test reduced the number of infectious days from 8357 to 5401 (3917-8677), a reduction of 36% (29-41) compared with the base case, and identified 569 (88% [76-92]) of 649 actively infectious travellers on the day of flight; the addition of post-travel quarantine and PCR reduced the number of infectious days to 2520 days (1849-4158), a reduction of 70% (64-75) compared with the base case. The rapid antigen test on the day of travel reduced the number of infectious days to 5674 (4126-9081), a reduction of 32% (26-38) compared with the base case, and identified 560 (86% [83-89]) actively infectious travellers; the addition of post-travel quarantine and PCR reduced the number of infectious days to 3124 (2356-495), a reduction of 63% (58-66) compared with the base case. The post-travel PCR alone reduced the number of infectious days to 4851 (3714-7679), a reduction of 42% (35-49) compared with the base case.InterpretationRoutine asymptomatic testing for SARS-CoV-2 before travel can be an effective strategy to reduce passenger risk of infection during travel, although abbreviated quarantine with post-travel testing is probably needed to reduce population-level transmission due to importation of infection when travelling from a high to low incidence setting.FundingUniversity of California, San Francisco.

IntroductionAntiretroviral-based HIV prevention, including pre-exposure prophylaxis (PrEP), is expanding in generalized epidemic settings, but additional prevention options are needed for individuals with periodic, high-risk sexual exposures. Non-occupational post-exposure prophylaxis (PEP) is recommended in global guidelines. However, in Africa, awareness of and access to PEP for sexual exposures are limited. We assessed feasibility, acceptability, uptake and adherence in a pilot study of a patient-centred PEP programme with options for facility- or community-based service delivery.MethodsAfter population-level HIV testing with universal access to PrEP for persons at elevated HIV risk (SEARCH Trial:NCT01864603), we conducted a pilot PEP study in five rural communities in Kenya and Uganda between December 2018 and May 2019. We assessed barriers to PEP in the population and implemented an intervention to address these barriers, building on existing in-country PEP protocols. We used community leaders for sensitization. Test kits and medications were acquired through the Ministry of Health supply chain and healthcare providers based at the Ministry of Health clinics were trained on PEP delivery. Additional intervention components were (a)PEP availability seven days/week, (b)PEP hotline staffed by providers and (c)option for out-of-facility medication delivery. We assessed implementation using the Proctor framework and measured seroconversions via repeat HIV testing. Successful "PEP completion" was defined as self-reported adherence over four weeks of therapy with post-PEP HIV testing.ResultsCommunity leaders were able to sensitize and mobilize for PEP. The Ministry of Health supplied test kits and PEP medications; after training, healthcare providers delivered the 28-day regimen with high completion rates. Among 124 persons who sought PEP, 66% were female, 24% were ≤25 years and 42% were fisherfolk. Of these, 20% reported exposure with a serodifferent partner, 72% with a new or existing relationship and 7% from transactional sex. 12% of all visits were conducted at out-of-facility community-based sites; 35% of participants had ≥1 out-of-facility visit. No serious adverse events were reported. Overall, 85% met the definition of PEP completion. There were no HIV seroconversions.ConclusionsAmong individuals with elevated-risk exposures in rural East African communities, patient-centred PEP was feasible, acceptable and provides a promising addition to the current prevention toolkit.

ObjectiveSub-Saharan Africa faces twin epidemics of HIV and noncommunicable diseases including hypertension. Integrating hypertension care into chronic HIV care is a global priority, but cost estimates are lacking. In the SEARCH Study, we performed population-level HIV/hypertension testing, and offered integrated streamlined chronic care. Here, we estimate costs for integrated hypertension/HIV care for HIV-positive individuals, and costs for hypertension care for HIV-negative individuals in the same clinics.DesignMicrocosting analysis of healthcare expenditures within Ugandan HIV clinics.MethodsSEARCH (NCT: 01864603) conducted community health campaigns for diagnosis and linkage to care for both HIV and hypertension. HIV-positive patients received hypertension/HIV care jointly including blood pressure monitoring and medications; HIV-negative patients received hypertension care at the same clinics. Within 10 Ugandan study communities during 2015-2016, we estimated incremental annual per-patient hypertension care costs using micro-costing techniques, time-and-motion personnel studies, and administrative/clinical records review.ResultsOverall, 70 HIV-positive and 2355 HIV-negative participants received hypertension care. For HIV-positive participants, average incremental cost of hypertension care was $6.29 per person per year, a 2.1% marginal increase over prior estimates for HIV care alone. For HIV-negative participants, hypertension care cost $11.39 per person per year, a 3.8% marginal increase over HIV care costs. Key costs for HIV-positive patients included hypertension medications ($6.19 per patient per year; 98% of total) and laboratory testing ($0.10 per patient per year; 2%). Key costs for HIV-negative patients included medications ($5.09 per patient per year; 45%) and clinic staff salaries ($3.66 per patient per year; 32%).ConclusionFor only 2-4% estimated additional costs, hypertension care was added to HIV care, and also expanded to all HIV-negative patients in prototypic Ugandan clinics, demonstrating substantial synergy. Our results should encourage accelerated scale-up of hypertension care into existing clinics.

There are limited data characterizing HIV retesting among high-risk adults in sub-Saharan Africa. From October-December 2018, we distributed recruitment cards offering health evaluations with HIV testing at venues frequented by individuals at-risk of HIV infection in Southwest Uganda. Those who attended were asked about their HIV testing history and risk factors: having >1 sexual partner, an HIV+ partner, STIs, and/or transactional sex. We defined "highest risk" as ≥3 risk factors and "frequent testing" as ≥3 tests within the past year. Of 1,777 cards distributed, 1,482 (83%) adults came to clinic: median age was 26(IQR: 22-31), 598 (40%) were men, and 334 (23%) were HIV+. Of 1,148 HIV-negative adults, 338 (29%) were highest risk and 205 (18%) were frequent testers. Frequent testing was similar in women (19%) and men (16%, p = 0.22). Among women, those at highest risk were more likely to report any testing (90% vs. 81%, p = 0.01) and frequent testing (25% vs. 18%, p = 0.06) than those at lower risk. Among men, any testing and frequent testing were similar between risk levels. Among adults recruited from high-risk venues in peri-urban Uganda, HIV risk behaviors were commonly reported, yet frequent retesting remained low. Interventions to promote retesting are needed, particularly among men.

BackgroundFrequent retesting for HIV among persons at increased risk of HIV infection is critical to early HIV diagnosis of persons and delivery of combination HIV prevention services. There are few evidence-based interventions for promoting frequent retesting for HIV. We sought to determine the effectiveness of financial incentives and deposit contracts in promoting quarterly HIV retesting among adults at increased risk of HIV.Methods and findingsIn peri-urban Ugandan communities from October to December 2018, we randomized HIV-negative adults with self-reported risk to 1 of 3 strategies to promote HIV retesting: (1) no incentive; (2) cash incentives (US$7) for retesting at 3 and 6 months (total US$14); or (3) deposit contracts: participants could voluntarily deposit US$6 at baseline and at 3 months that would be returned with interest (total US$7) upon retesting at 3 and 6 months (total US$14) or lost if participants failed to retest. The primary outcome was retesting for HIV at both 3 and 6 months. Of 1,482 persons screened for study eligibility following community-based recruitment, 524 participants were randomized to either no incentive (N = 180), incentives (N = 172), or deposit contracts (N = 172): median age was 25 years (IQR: 22 to 30), 44% were women, and median weekly income was US$13.60 (IQR: US$8.16 to US$21.76). Among participants randomized to deposit contracts, 24/172 (14%) made a baseline deposit, and 2/172 (1%) made a 3-month deposit. In intent-to-treat analyses, HIV retesting at both 3 and 6 months was significantly higher in the incentive arm (89/172 [52%]) than either the control arm (33/180 [18%], odds ratio (OR) 4.8, 95% CI: 3.0 to 7.7, p < 0.001) or the deposit contract arm (28/172 [16%], OR 5.5, 95% CI: 3.3 to 9.1, p < 0.001). Among those in the deposit contract arm who made a baseline deposit, 20/24 (83%) retested at 3 months; 11/24 (46%) retested at both 3 and 6 months. Among 282 participants who retested for HIV during the trial, three (1%; 95%CI: 0.2 to 3%) seroconverted: one in the incentive group and two in the control group. Study limitations include measurement of retesting at the clinic where baseline enrollment occurred, only offering clinic-based (rather than community-based) HIV retesting and lack of measurement of retesting after completion of the trial to evaluate sustained retesting behavior.ConclusionsOffering financial incentives to high-risk adults in Uganda resulted in significantly higher HIV retesting. Deposit contracts had low uptake and overall did not increase retesting. As part of efforts to increase early diagnosis of HIV among high-risk populations, strategic use of incentives to promote retesting should receive greater consideration by HIV programs.Trial registrationclinicaltrials.gov: NCT02890459.

We evaluated the performance of the Abbott BinaxNOW rapid antigen test for coronavirus disease 2019 (Binax-CoV2) to detect virus among persons, regardless of symptoms, at a public plaza site of ongoing community transmission. Titration with cultured severe acute respiratory syndrome coronavirus 2 yielded a human observable threshold between 1.6 × 104-4.3 × 104 viral RNA copies (cycle threshold [Ct], 30.3-28.8). Among 878 subjects tested, 3% (26 of 878) were positive by reverse-transcription polymerase chain reaction, of whom 15 of 26 had a Ct

Tuberculosis (TB) remains a main driver of morbidity and mortality among people with HIV along with other opportunistic infections. This review summarizes key highlights related to TB, and other opportunistic infections in HIV as well as studies from the virtual 2021 Conference on Retroviruses and Oppoprtunitstic Infections evaluating outcomes among HIV-COVID-19 coinfected patients.

BackgroundSequencing of the SARS-CoV-2 viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities.MethodsSARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during November 22-December 1, 2020 and January 10-29, 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants.ResultsA total of 12,124 tests were performed yielding 1,099 positives. From these, 928 high quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the "California" or "West Coast" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, RR=1.28; 95% CI:1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.3%).ConclusionsThe increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants.

Coronavirus disease-2019 (COVID-19) threatens to further worsen HIV outcomes among people experiencing homelessness. We conducted an interrupted time-series analysis of care engagement and viral suppression among unhoused individuals in the 'POP-UP' low-barrier, high-intensity HIV primary care program during COVID-19. Among 85 patients, care engagement and viral suppression did not decrease in the 5 months following implementation of San Francisco's 'shelter-in-place' ordinance. Low-barrier, in-person HIV care for homeless individuals may be important for maintaining HIV outcomes during COVID-19.

BackgroundOral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, but data are limited on HIV incidence among PrEP users in generalized epidemic settings, particularly outside of selected risk groups. We performed a population-based PrEP study in rural Kenya and Uganda and sought to evaluate both changes in HIV incidence and clinical and virologic outcomes following seroconversion on PrEP.Methods and findingsDuring population-level HIV testing of individuals ≥15 years in 16 communities in the Sustainable East Africa Research in Community Health (SEARCH) study (NCT01864603), we offered universal access to PrEP with enhanced counseling for persons at elevated HIV risk (based on serodifferent partnership, machine learning-based risk score, or self-identified HIV risk). We offered rapid or same-day PrEP initiation and flexible service delivery with follow-up visits at facilities or community-based sites at 4, 12, and every 12 weeks up to week 144. Among participants with incident HIV infection after PrEP initiation, we offered same-day antiretroviral therapy (ART) initiation and analyzed HIV RNA, tenofovir hair concentrations, drug resistance, and viral suppression (

BackgroundRapid coronavirus disease 2019 (COVID-19) diagnosis and isolation of infectious persons are critical to stopping forward transmission, and the care cascade framework can identify gaps in the COVID-19 response.MethodsWe described a COVID-19 symptom to isolation cascade and barriers among symptomatic persons who tested polymerase chain reaction positive for severe acute respiratory disease coronavirus 2 (SARS-CoV-2) at a low-barrier testing site serving a low-income Latinx community in San Francisco. Steps in the cascade are defined as days from symptom onset to test, test to result, and result to counseling on self-isolation. We examined SARS-CoV-2 cycle threshold (Ct) values to assess the likelihood of infectiousness on the day of testing and during missed isolation days.ResultsAmong 145 persons, 97% were Latinx and 81% had an income of

BackgroundDelays in the diagnosis of tuberculosis (TB) contribute to a substantial proportion of TB-related mortality, especially among people living with HIV (PLHIV). We sought to characterize the diagnostic journey for HIV-positive and HIV-negative patients with a new TB diagnosis in Zambia, to understand drivers of delay, and characterize their preferences for service characteristics to inform improvements in TB services.MethodsWe assessed consecutive adults with newly microbiologically-confirmed TB at two public health treatment facilities in Lusaka, Zambia. We administered a survey to document critical intervals in the TB care pathway (time to initial care-seeking, diagnosis and treatment initiation), identify bottlenecks and their reasons. We quantified patient preferences for a range of characteristics of health services using a discrete choice experiment (DCE) that assessed 7 attributes (distance, wait times, hours of operation, confidentiality, sex of provider, testing incentive, TB test speed and notification method).ResultsAmong 401 patients enrolled (median age of 34 years, 68.7% male, 46.6% HIV-positive), 60.9% and 39.1% were from a first-level and tertiary hospital, respectively. The median time from symptom onset to receipt of TB treatment was 5.0 weeks (IQR: 3.6-8.0) and was longer among HIV-positive patients seeking care at a tertiary hospital than HIV-negative patients (6.4 vs. 4.9 weeks, p = 0.002). The time from symptom onset to initial presentation for evaluation accounted for the majority of time until treatment initiation (median 3.0 weeks, IQR: 1.0-5.0)-an important minority of 11.0% of patients delayed care-seeking ≥8 weeks. The DCE found that patients strongly preferred same-day TB test results (relative importance, 37.2%), facilities close to home (18.0%), and facilities with short wait times (16.9%). Patients were willing to travel to a facility up to 7.6 kilometers further away in order to access same-day TB test results. Preferences for improving current TB services did not differ according to HIV status.ConclusionsProlonged intervals from TB symptom onset to treatment initiation were common, especially among PLHIV, and were driven by delayed health-seeking. Addressing known barriers to timely diagnosis and incorporating patients' preferences into TB services, including same-day TB test results, may facilitate earlier TB care engagement in high burden settings.