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Background: The use of molecular HIV cluster analysis to supplement public health contact tracing has shown promise in addressing HIV outbreaks. However, the potential of HIV cluster analysis as an adjunct to daily, person-by-person HIV prevention efforts remains unknown. We documented lessons learned within a unique public health-academic partnership while guiding workaday HIV prevention efforts with near-real-time molecular cluster analysis., Setting: A public health-academic partnership in the State of Rhode Island, the United States., Methods: We recorded perceptions of our team of academicians and public health practitioners that were encountered in an 18-month study evaluating the integration of molecular cluster analysis with HIV contact tracing for public health benefit. The focus was on monthly conferences where molecular clustering of each new statewide diagnosis was discussed to facilitate targeted interventions and on attempted reinterviews of all newly HIV-diagnosed persons statewide whose HIV sequences clustered to increase partner naming., Results: Three main themes emerged: First, multidisciplinary conferences are substantially beneficial for gleaning actionable inferences from integrating molecular cluster analysis and public health data. Second, universal reinterviews were perceived to potentially have negative consequences but may be selectively beneficial. Third, the translation of cluster analysis into public health action is hampered by jurisdictional surveillance boundaries and within-jurisdictional data silos, across which data sharing is problematic., Conclusions: Insights from a statewide public health-academic partnership support integration of molecular HIV cluster analyses with public health efforts, which can guide public health activities to prevent transmission while identifying substantial barriers to integration, informing continued research., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The rich longitudinal individual level data available from electronic health records (EHRs) can be used to examine treatment effect heterogeneity. However, estimating treatment effects using EHR data poses several challenges, including time-varying confounding, repeated and temporally non-aligned measurements of covariates, treatment assignments and outcomes, and loss-to-follow-up due to dropout. Here, we develop the subgroup discovery for longitudinal data algorithm, a tree-based algorithm for discovering subgroups with heterogeneous treatment effects using longitudinal data by combining the generalized interaction tree algorithm, a general data-driven method for subgroup discovery, with longitudinal targeted maximum likelihood estimation. We apply the algorithm to EHR data to discover subgroups of people living with human immunodeficiency virus who are at higher risk of weight gain when receiving dolutegravir (DTG)-containing antiretroviral therapies (ARTs) versus when receiving non-DTG-containing ARTs., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. [br]For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To assess overall and by neighborhood risk environments whether multilevel resilience resources were associated with HIV virologic suppression among African American/Black adults in the Southeastern United States., Setting and Methods: This clinical cohort sub-study included 436 African American/Black participants enrolled in two parent HIV clinical cohorts. Resilience was assessed using the Multilevel Resilience Resource Measure (MRM) for African American/Black adults living with HIV, where endorsement of a MRM statement indicated agreement that a resilience resource helped a participant continue HIV care despite challenges or was present in a participant's neighborhood. Modified Poisson regression models estimated adjusted prevalence ratios (aPRs) for virologic suppression as a function of categorical MRM scores, controlling for demographic, clinical, and behavioral characteristics at or prior to sub-study enrollment. We assessed for effect measure modification (EMM) by neighborhood risk environments., Results: Compared to participants with lesser endorsement of multilevel resilience resources, aPRs for virologic suppression among those with greater or moderate endorsement were 1.03 (95% confidence interval: 0.96-1.11) and 1.03 (0.96-1.11), respectively. Regarding multilevel resilience resource endorsement, there was no strong evidence for EMM by levels of neighborhood risk environments., Conclusions: Modest positive associations between higher multilevel resilience resource endorsement and virologic suppression were at times most compatible with the data. However, null findings were also compatible. There was no strong evidence for EMM concerning multilevel resilience resource endorsement, which could have been due to random error. Prospective studies assessing EMM by levels of the neighborhood risk environment with larger sample sizes are needed., (© 2023. W. Montague Cobb-NMA Health Institute.)

Orphans are at higher risk of HIV infection and several important HIV risk factors than non-orphans; however, this may be due to a combination of related social, psychological, and economic factors, as well as care environment, rather than orphan status alone. Understanding these complex relationships may aid policy makers in supporting evidence-based, cost-effective programming for this vulnerable population. This longitudinal study uses a causal effect model to examine, through decomposition, the relationship between care environment and HIV risk factors in orphaned and separated adolescents and youths (OSAY) in Uasin Gishu County, Kenya; considering resilience, social, peer, or family support, volunteering, or having one's material needs met as potential mediators. We analysed survey responses from 1105 OSAY age 10-26 living in Charitable Children's Institutions (CCI) (orphanages) and family-based care settings (FBS). Follow-up time was 7-36 months. Care in CCIs (vs. FBS) was associated with a decreased likelihood of engaging in forced, exchange, and consensual sex. Excess relative risks (ERR) attributable to the indirect pathway, mediation, or interaction were not significant in any model. Care environment was not statistically associated with differences in substance use. Our findings support the direct, unmediated, association between institutional care and HIV risk factors.

Background: Population-level estimates of linkage to HIV care among children and adolescents (CAs) can facilitate progress toward 95-95-95 goals., Setting: This study was conducted in Bunyala, Chulaimbo, and Teso North subcounties, Western Kenya., Methods: Linkage to care was defined among CAs diagnosed with HIV through Academic Model Providing Access to Healthcare (AMPATH)'s home-based counseling and testing initiative (HBCT) by merging HBCT and AMPATH Medical Record System data. Using follow-up data from Bunyala, we examined factors associated with linkage or death, using weighted multinomial logistic regression to account for selection bias from double-sampled visits. Based on the estimated model, we imputed the trajectory for each person in 3 subcounties until a simulated linkage or death occurred or until the end of 8 years when an individual was simulated to be censored., Results: Of 720 CAs in the analytic sample, 68% were between 0 and 9 years and 59% were female. Probability of linkage among CAs in the combined 3 subcounties was 48%-49% at 2 years and 64%-78% at 8 years while probability of death was 13% at 2 years and 19% at 8 years. Single or double orphanhood predicted linkage (adjusted odds ratio [aOR]: 2.66, 95% confidence interval [CI]: 1.33 to 5.32) and death (aOR: 9.85 [95% CI: 2.21 to 44.01]). Having a mother known to be HIV-positive also predicted linkage (aOR = 1.94, 95% CI: 0.97 to 3.86) and death (aOR: 14.49, 95% CI: 3.32 to 63.19)., Conclusion: HIV testers/counselors should continue to ensure linkage among orphans and CAs with mothers known to be HIV-positive and also to support other CAs to link to HIV care., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Characterizing HIV-related stigma and its impacts are important for interventions toward their elimination. A cross-sectional study was conducted in 2016 to evaluate enacted and internalized stigma among adult people living with HIV (PLWH) across four cities in Myanmar using the India Stigma Index questionnaire. Multivariable regression analyses were performed to determine differences in measured enacted and internalized stigma outcomes. Among 1,006 participants, 89% reported any stigma indicator, 47% enacted stigma, and 87% internalized stigma. In regression analysis, city and duration of illness were associated with higher enacted stigma, and younger age was associated with higher internalized stigma. Those with HIV duration > 7.4 years had mean enacted stigma nearly 2 units higher than the overall mean. Internalized stigma increased with duration of illness and leveled off at 5 years. PLWH from smaller cities experienced lower stigma. In Myanmar, nearly 90% of PLWH experience stigma, results that reflect a unique transition point., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To compare the incidence of HIV, death, and abuse among orphaned children to nonorphaned children living in households caring for orphaned children in Western Kenya., Study Design: A random sample was taken of 300 households caring for at least one orphaned child in Uasin Gishu County, Kenya. All orphaned and nonorphaned children in each selected household were enrolled in a prospective cohort study between 2010 and 2013. A total of 1488 children (487 double orphans, 743 single orphans, and 258 nonorphans) were followed up annually until 2019. Survival analysis was used to estimate hazard ratios and 95% confidence intervals (CIs) of the association between the number of parents the child had lost (none, 1, or 2), and HIV incidence, death, combined HIV incidence or death, and incident abuse., Results: Among 1488 children enrolled, 52% of participants were females, 23 were HIV positive, and the median age was 10.4 years. Over the course of the study, 16 orphaned children died and 11 acquired HIV. No deaths or incident HIV infections were observed among the nonorphaned children. Among children who were HIV negative at enrollment, loss of a parent was strongly associated with incident HIV (adjusted hazard ratio: 2.21 per parent lost, 95% CI: 1.03-4.73) and HIV or death (adjusted hazard ratio: 2.46 per parent lost, 95% CI: 1.37-4.42). There were no significant associations between orphan level and abuse., Conclusions: In similar households, orphaned children experience a higher risk of HIV and death than nonorphaned children. Both orphaned children and the families caring for them need additional support to prevent adverse health outcomes., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Drug resistance remains a global challenge in children and adolescents living with HIV (CALWH). Characterizing resistance evolution, specifically using next generation sequencing (NGS) can potentially inform care, but remains understudied, particularly in antiretroviral therapy (ART)-experienced CALWH in resource-limited settings. We conducted reverse-transcriptase NGS and investigated short-and long-term resistance evolution and its predicted impact in a well-characterized cohort of Kenyan CALWH failing 1st-line ART and followed for up to ~8 years. Drug resistance mutation (DRM) evolution types were determined by NGS frequency changes over time, defined as evolving (up-trending and crossing the 20% NGS threshold), reverting (down-trending and crossing the 20% threshold) or other. Exploratory analyses assessed potential impacts of minority resistance variants on evolution. Evolution was detected in 93% of 42 participants, including 91% of 22 with short-term follow-up, 100% of 7 with long-term follow-up without regimen change, and 95% of 19 with long-term follow-up with regimen change. Evolving DRMs were identified in 60% and minority resistance variants evolved in 17%, with exploratory analysis suggesting greater rate of evolution of minority resistance variants under drug selection pressure and higher predicted drug resistance scores in the presence of minority DRMs. Despite high-level pre-existing resistance, NGS-based longitudinal follow-up of this small but unique cohort of Kenyan CALWH demonstrated continued DRM evolution, at times including low-level DRMs detected only by NGS, with predicted impact on care. NGS can inform better understanding of DRM evolution and dynamics and possibly improve care. The clinical significance of these findings should be further evaluated.

Background: The HADITHI study is a cluster-randomized trial of children living with HIV and their caregivers in Kenya that aimed to increase rates of caregiver disclosure of their child's HIV status, encourage earlier status disclosure, and improve pediatric mental health and HIV outcomes. This analysis identified characteristics predicting caregiver non-responsiveness and compared outcomes among children based on disclosure status., Methods: A penalized logistic regression model with lasso regularization identified the most important predictors of disclosure. The two-stage least squares instrumental variable approach was used to assess outcomes accounting for non-compliance to disclosure., Results: Caregiver non-isolation and shorter time on antiretroviral therapy were predictive of HIV status disclosure. There were no statistically significant differences found in CD4 percentage, depression status, or mental and emotional status based on disclosure status up to 24 months-post intervention., Conclusion: These findings have implications for specialists seeking to tailor disclosure interventions to improve caregiver-child dyad responsiveness., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Magill, Nyandiko, Baum, Aluoch, Chory, Ashimoshi, Lidweye, Njoroge, Sang, Nyagaya, Scanlon, Hogan and Vreeman.)

Molecular HIV cluster data can guide public health responses towards ending the HIV epidemic. Currently, real-time data integration, analysis, and interpretation are challenging, leading to a delayed public health response. We present a comprehensive methodology for addressing these challenges through data integration, analysis, and reporting. We integrated heterogeneous data sources across systems and developed an open-source, automatic bioinformatics pipeline that provides molecular HIV cluster data to inform public health responses to new statewide HIV-1 diagnoses, overcoming data management, computational, and analytical challenges. We demonstrate implementation of this pipeline in a statewide HIV epidemic and use it to compare the impact of specific phylogenetic and distance-only methods and datasets on molecular HIV cluster analyses. The pipeline was applied to 18 monthly datasets generated between January 2020 and June 2022 in Rhode Island, USA, that provide statewide molecular HIV data to support routine public health case management by a multi-disciplinary team. The resulting cluster analyses and near-real-time reporting guided public health actions in 37 phylogenetically clustered cases out of 57 new HIV-1 diagnoses. Of the 37, only 21 (57%) clustered by distance-only methods. Through a unique academic-public health partnership, an automated open-source pipeline was developed and applied to prospective, routine analysis of statewide molecular HIV data in near-real-time. This collaboration informed public health actions to optimize disruption of HIV transmission.

Objectives: Molecular epidemiology is a powerful tool to characterize HIV epidemics and prioritize public health interventions. Typically, HIV clusters are assumed to have uniform patterns over time. We hypothesized that assessment of cluster evolution would reveal distinct cluster behavior, possibly improving molecular epidemic characterization, towards disrupting HIV transmission., Design: Retrospective cohort., Methods: Annual phylogenies were inferred by cumulative aggregation of all available HIV-1 pol sequences of individuals with HIV-1 in Rhode Island (RI) between 1990 and 2020, representing a statewide epidemic. Molecular clusters were detected in annual phylogenies by strict and relaxed cluster definition criteria, and the impact of annual newly-diagnosed HIV-1 cases to the structure of individual clusters was examined over time., Results: Of 2153 individuals, 31% (strict criteria) - 47% (relaxed criteria) clustered. Longitudinal tracking of individual clusters identified three cluster types: normal, semi-normal and abnormal. Normal clusters (83-87% of all identified clusters) showed predicted growing/plateauing dynamics, with approximately three-fold higher growth rates in large (15-18%) vs. small (∼5%) clusters. Semi-normal clusters (1-2% of all clusters) temporarily fluctuated in size and composition. Abnormal clusters (11-16% of all clusters) demonstrated collapses and re-arrangements over time. Borderline values of cluster-defining parameters explained dynamics of non-normal clusters., Conclusions: Comprehensive tracing of molecular HIV clusters over time in a statewide epidemic identified distinct cluster types, likely missed in cross-sectional analyses, demonstrating that not all clusters are equal. This knowledge challenges current perceptions of consistent cluster behavior over time and could improve molecular surveillance of local HIV epidemics to better inform public health strategies., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

While expanded HIV testing is needed in South Africa, increasing accurate self-report of HIV status is an essential parallel goal in this highly mobile population. If self-report can ascertain true HIV-positive status, persons with HIV (PWH) could be linked to life-saving care without the existing delays required by producing medical records or undergoing confirmatory testing, which are especially burdensome for the country's high prevalence of circular migrants. We used Wave 1 data from The Migration and Health Follow-Up Study, a representative adult cohort, including circular migrants and permanent residents, randomly sampled from the Agincourt Health and Demographic Surveillance System in a rural area of Mpumalanga Province. Within the analytic sample (n = 1,918), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of self-report were calculated with dried blood spot (DBS) HIV test results as the standard. Among in-person participants (n = 2,468), 88.8% consented to DBS-HIV testing. HIV prevalence was 25.3%. Sensitivity of self-report was 43.9% (95% CI: 39.5-48.5), PPV was 93.4% (95% CI: 89.5-96.0); specificity was 99.0% (95% CI: 98.3-99.4) and NPV was 83.9% (95% CI: 82.8-84.9). Self-report of an HIV-positive status was predictive of true status for both migrants and permanent residents in this high-prevalence setting. Persons who self-reported as living with HIV were almost always truly positive, supporting a change to clinical protocol to immediately connect persons who say they are HIV-positive to ART and counselling. However, 56% of PWH did not report as HIV-positive, highlighting the imperative to address barriers to disclosure., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

We sought to determine the relationship between continuity of care and adherence to clinic appointments among patients receiving HIV care in high vs. low clinician-to-patient (C:P) ratios facilities in western Kenya. This retrospective analysis included 12,751 patients receiving HIV care from the Academic Model Providing Access to Healthcare (AMPATH) program, between February 2016-2019. We used logistic regression analysis with generalized estimating equations to estimate the relationship between continuity of care (two consecutive visits with the same provider) and adherence to clinic appointments (within 7 days of a scheduled appointment) over time. Adjusting for covariates, patients in low C:P ratio facilities who had continuity of care, were more likely to be adherent to their appointments compared to those without continuity (adjusted odds ratio = 1.50; 95% confidence interval, 1.33-1.69). Continuity in HIV care may be a factor in clinical adherence among patients in low C:P ratio facilities and should therefore be promoted., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

HIV-1 drug resistance remains a global challenge, yet access to testing is limited, particularly in resource-limited settings. We examined feasibility and limitations of genotyping using dried filter analytes in treatment-experienced Kenyan youth with HIV. Youth infected with HIV perinatally were enrolled in 2016-2018 at the Academic Model Providing Access to Healthcare in Eldoret, western Kenya. Samples were shipped in real-time at ambient temperature to the US, and those with viral load (VL)>1,000 copies/mL were tested based on convenience. Dried blood spots genotyping was attempted when unsuccessful from Hemaspots. Multiple logistic regression was used to examine predictors of genotyping success. Samples from 49 participants (median age 15 years, 43% female, median CD4 496 cells/μL [18%], median 8 years on therapy, median VL 11,827 copies/mL) were shipped after median 7 days from collection, arrived in 20 shipments after median 5 days, and extracted after median 2 days (1 day for samples processed on arrival; and 42 days for frozen Hemaspots). Overall, 29/49 (59%) samples with VL > 1,000 copies/mL and 25/32 (78%) with VL > 5,000 copies/mL were genotyped by either Hemaspots or DBS. Successful genotyping was associated with higher Hemaspot volume and higher VL. Real-life HIV-1 drug resistance testing from dried filter analytes is feasible, even in settings with constrained resources. Findings, particularly relevant where resistance testing is limited for clinical care, raise awareness to implementation practicability of this guidelines-recommended test in care of more individuals and populations. Further optimization of filter analytes is needed to overcome related challenges. IMPORTANCE In this manuscript we use dried filter analytes shipped from Kenya to the US in real time, to demonstrate the real-life feasibility of conducting HIV drug resistance testing in a vulnerable population of young children and adolescents with HIV in a resource limited setting. Such testing, which is recommended in resource-rich settings, is unavailable in most resource limited settings for individual clinical care. We show that real-life HIV drug resistance testing from dried filter analytes is feasible, even in settings with constrained resources. These findings raise awareness to the importance of HIV drug resistance for individual care, even in such settings, and emphasize the implementation practicability of this guidelines-recommended test.

Introduction: HIV continues to have great impact on millions of lives. Novel methods are needed to disrupt HIV transmission networks. In the USA, public health departments routinely conduct contact tracing and partner services and interview newly HIV-diagnosed index cases to obtain information on social networks and guide prevention interventions. Sequence clustering methods able to infer HIV networks have been used to investigate and halt outbreaks. Incorporation of such methods into routine, not only outbreak-driven, contact tracing and partner services holds promise for further disruption of HIV transmissions., Methods and Analysis: Building on a strong academic-public health collaboration in Rhode Island, we designed and have implemented a state-wide prospective study to evaluate an intervention that incorporates real-time HIV molecular clustering information with routine contact tracing and partner services. We present the rationale and study design of our approach to integrate sequence clustering methods into routine public health interventions as well as related important ethical considerations. This prospective study addresses key questions about the benefit of incorporating a clustering analysis triggered intervention into the routine workflow of public health departments, going beyond outbreak-only circumstances. By developing an intervention triggered by, and incorporating information from, viral sequence clustering analysis, and evaluating it with a novel design that avoids randomisation while allowing for methods comparison, we are confident that this study will inform how viral sequence clustering analysis can be routinely integrated into public health to support the ending of the HIV pandemic in the USA and beyond., Ethics and Dissemination: The study was approved by both the Lifespan and Rhode Island Department of Health Human Subjects Research Institutional Review Boards and study results will be published in peer-reviewed journals., Competing Interests: Competing interests: MH reports fees from Competition Economics and The Miriam Hospital for consulting, outside the submitted work. RK reports receiving a research grant from Gilead Sciences for work that is not related to HIV or this paper., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Long-term impact of drug resistance in perinatally infected children and adolescents living with HIV (CALWH) is poorly understood. We determined drug resistance and examined its long-term impact on failure and mortality in Kenyan CALWH failing first-line non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy (ART)., Setting: Academic Model Providing Access to Healthcare, western Kenya., Methods: Participants were enrolled in 2010-2013 (timepoint 1) and a subsample re-enrolled after 4-7 years (timepoint 2). Viral load (VL) was performed on timepoint 1 samples, with genotyping of those with detectable VL. Primary endpoints were treatment failure (VL >1000 copies/mL) at and death before timepoint 2. Multinomial regression analysis was used to characterize resistance effect on death, failure, and loss-to-follow-up, adjusting for key variables., Results: The initial cohort (n = 480) was 52% (n = 251) female, median age 8 years, median CD4% 31%, 79% (n = 379) on zidovudine/abacavir + lamivudine + efavirenz/nevirapine for median 2 years. Of these, 31% (n = 149) failed at timepoint 1. Genotypes at timepoint 1, available on n = 128, demonstrated 93% (n = 119) extensive resistance, affecting second line. Of 128, 22 failed at timepoint 2, 17 died, and 32 were lost to follow-up before timepoint 2. Having >5 resistance mutations at timepoint 1 was associated with higher mortality [relative risk ratio (RRR) = 8.7, confidence interval (CI) 2.1 to 36.3] and loss to follow-up (RRR = 3.2, CI 1.1 to 9.2). Switching to second line was associated with lower mortality (RRR <0.05, CI <0.05 to 0.1) and loss to follow-up (RRR = 0.1, CI <0.05 to 0.3)., Conclusion: Extensive resistance and limited switch to second line in perinatally infected Kenyan CALWH failing first-line ART were associated with long-term failure and mortality. Findings emphasize urgency for interventions to sustain effective, life-long ART in this vulnerable population., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

There is growing evidence for the key role of social determinants of health (SDOH) in understanding morbidity and mortality outcomes globally. Factors such as stigma, racism, poverty or access to health and social services represent complex constructs that affect population health via intricate relationships to individual characteristics, behaviors and disease prevention and treatment outcomes. Modeling the role of SDOH is both critically important and inherently complex. Here we describe different modeling approaches and their use in assessing the impact of SDOH on HIV/AIDS. The discussion is thematically divided into mechanistic models and statistical models, while recognizing the overlap between them. To illustrate mechanistic approaches, we use examples of compartmental models and agent-based models; to illustrate statistical approaches, we use regression and statistical causal models. We describe model structure, data sources required, and the scope of possible inferences, highlighting similarities and differences in formulation, implementation, and interpretation of different modeling approaches. We also indicate further needed research on representing and quantifying the effect of SDOH in the context of models for HIV and other health outcomes in recognition of the critical role of SDOH in achieving the goal of ending the HIV epidemic and improving overall population health., (© 2021. The Author(s).)

Objective: To measure associations between participation in community-based microfinance groups, retention in HIV care, and death among people with HIV (PWH) in low-resource settings., Design and Methods: We prospectively analyzed data from 3609 patients enrolled in an HIV care program in western Kenya. HIV patients who were eligible and chose to participate in a Group Integrated Savings for Health Empowerment (GISHE) microfinance group were matched 1 : 2 on age, sex, year of enrollment in HIV care, and location of initial HIV clinic visit to patients not participating in GISHE. Follow-up data were abstracted from medical records from January 2018 through February 2020. Logistic regression analysis examined associations between GISHE participation and two outcomes: retention in HIV care (i.e. >1 HIV care visit attended within 6 months prior to the end of follow-up) and death. Socioeconomic factors associated with HIV outcomes were included in adjusted models., Results: The study population was majority women (78.3%) with a median age of 37.4 years. Microfinance group participants were more likely to be retained in care relative to HIV patients not participating in a microfinance group [adjusted odds ratio (aOR) = 1.31, 95% confidence interval (CI) 1.01-1.71; P = 0.046]. Participation in group microfinance was associated with a reduced odds of death during the follow-up period (aOR = 0.57, 95% CI 0.28-1.09; P = 0.105)., Conclusion: Participation in group-based microfinance appears to be associated with better HIV treatment outcomes. A randomized trial is needed to assess whether microfinance groups can improve clinical and socioeconomic outcomes among PWH in similar settings., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Importance: In 2015, there were nearly 140 million orphaned children globally, particularly in low- and middle-income regions, and millions more for whom the street is central to their everyday lives. A total of 16.6 million children were orphaned because of deaths associated with HIV/AIDS, of whom 90% live in sub-Saharan Africa. Although most orphaned and separated children and adolescents in this region are cared for by extended family, the large number of children requiring care has produced a proliferation of institutional care. Few studies have investigated the association between care environment and physical health among orphaned and separated youths in sub-Saharan Africa., Objective: To examine the association of care environment with incident HIV and death among orphaned and separated children and adolescents who were living in charitable children's institutions, family-based settings, and street settings in western Kenya over almost 10 years., Design, Setting, and Participants: The Orphaned and Separated Children's Assessments Related to Their Health and Well-Being (OSCAR) project was an observational prospective cohort study conducted in Uasin Gishu County, Kenya. The cohort comprised 2551 orphaned, separated, and street-connected children from communities within 8 administrative locations, which included 300 randomly selected households (family-based settings) caring for children who were orphaned from all causes, 19 charitable children's institutions (institutional settings), and a convenience sample of 100 children who were practicing self-care on the streets (street settings). Participants were enrolled from May 31, 2010, to April 24, 2013, and were followed up until November 30, 2019., Exposures: Care environment (family-based, institutional, or street setting)., Main Outcomes and Measures: Survival regression models were used to investigate the association between care environment and incident HIV, death, and time to incident HIV or death., Results: Among 2551 participants, 1230 youths were living in family-based settings, 1230 were living in institutional settings, and 91 were living in street settings. Overall, 1321 participants (51.8%) were male, with a mean (SD) age at baseline of 10.4 (4.8) years. Most participants who were living in institutional (1047 of 1230 youths [85.1%]) or street (71 of 91 youths [78.0%]) settings were double orphaned (ie, both parents had died). A total of 59 participants acquired HIV infection or died during the study period. After adjusting for sex, age, and baseline HIV status, living in a charitable children's institution was not associated with death (adjusted hazard ratio [AHR], 0.26; 95% CI, 0.07-1.02) or incident HIV (AHR, 1.49; 95% CI, 0.46-4.83). Compared with living in a family-based setting, living in a street setting was associated with death (AHR, 5.46; 95% CI, 2.30-12.94), incident HIV (AHR, 17.31; 95% CI, 5.85-51.25), and time to incident HIV or death (AHR, 7.82; 95% CI, 3.48-17.55)., Conclusions and Relevance: In this study, after adjusting for potential confounders, no association was found between care environment and HIV incidence or death among youths living in institutional vs family-based settings. However, living in a street setting vs a family-based setting was associated with both HIV incidence and death. This study's findings suggest that strengthening of child protection systems and greater investment in evidence-based family support systems that improve child and adolescent health and prevent youth migration to the street are needed for safe and beneficial deinstitutionalization to be implemented at scale.

Background: HIV molecular epidemiology is increasingly integrated into public health prevention. We conducted cluster typing to enhance characterization of a densely sampled statewide epidemic towards informing public health., Methods: We identified HIV clusters, categorized them into types, and evaluated their dynamics between 2004 and 2019 in Rhode Island. We grouped sequences by diagnosis year, assessed cluster changes between paired phylogenies, t0 and t1, representing adjacent years and categorized clusters as stable (cluster in t0 phylogeny = cluster in t1 phylogeny) or unstable (cluster in t0 ≠ cluster in t1). Unstable clusters were further categorized as emerging (t1 phylogeny only) or growing (larger in t1 phylogeny). We determined proportions of each cluster type, of individuals in each cluster type, and of newly diagnosed individuals in each cluster type, and assessed trends over time., Results: A total of 1727 individuals with available HIV-1 subtype B pol sequences were diagnosed in Rhode Island by 2019. Over time, stable clusters and individuals in them dominated the epidemic, increasing over time, with reciprocally decreasing unstable clusters and individuals in them. Conversely, proportions of newly diagnosed individuals in unstable clusters significantly increased. Within unstable clusters, proportions of emerging clusters and of individuals in them declined; whereas proportions of newly diagnosed individuals in growing clusters significantly increased over time., Conclusion: Distinct molecular cluster types were identified in the Rhode Island epidemic. Cluster dynamics demonstrated increasing stable and decreasing unstable clusters driven by growing, rather than emerging clusters, suggesting consistent in-state transmission networks. Cluster typing could inform public health beyond conventional approaches and direct interventions., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: In Kenya, distance to health facilities, inefficient vertical care delivery and limited financial means are barriers to retention in HIV care. Furthermore, the increasing burden of non-communicable diseases (NCDs) among people living with HIV complicates chronic disease treatment and strains traditional care delivery models. Potential strategies for improving HIV/NCD treatment outcomes are differentiated care, community-based care and microfinance (MF)., Methods and Analysis: We will use a cluster randomised trial to evaluate integrated community-based (ICB) care incorporated into MF groups in medium and high HIV prevalence areas in western Kenya. We will conduct baseline assessments with n=900 HIV positive members of 40 existing MF groups. Group clusters will be randomised to receive either (1) ICB or (2) standard of care (SOC). The ICB intervention will include: (1) clinical care visits during MF group meetings inclusive of medical consultations, NCD management, distribution of antiretroviral therapy (ART) and NCD medications, and point-of-care laboratory testing; (2) peer support for ART adherence and (3) facility referrals as needed. MF groups randomised to SOC will receive regularly scheduled care at a health facility. Findings from the two trial arms will be compared with follow-up data from n=300 matched controls. The primary outcome will be VS at 18 months. Secondary outcomes will be retention in care, absolute mean change in systolic blood pressure and absolute mean change in HbA1c level at 18 months. We will use mediation analysis to evaluate mechanisms through which MF and ICB care impact outcomes and analyse incremental cost-effectiveness of the intervention in terms of cost per HIV suppressed person-time, cost per patient retained in care and cost per disability-adjusted life-year saved., Ethics and Dissemination: The Moi University Institutional Research and Ethics Committee approved this study (IREC#0003054). We will share data via the Brown University Digital Repository and disseminate findings via publication., Trial Registration Number: NCT04417127., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the baseline types of HPV infection among HIV-positive and HIV-negative women in western Kenya undergoing cryotherapy or loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia., Methods: A prospective observational study was conducted of baseline HPV characteristics of women undergoing visual inspection with acetic acid (VIA) and cryotherapy or LEEP. After a positive VIA in HIV-positive and HIV-negative women, data on demographics, CD4 count, and use of antiretroviral therapy and a cervical swab were collected. HPV typing was performed using the Roche Linear Array., Results: Of 175 participants, 86 (49.1%) were HIV-positive and had a higher prevalence of low-risk HPV types (odds ratio [OR] 5.28, P=0.005) compared with HIV-negative women. The most common high-risk (HR)-HPV types in HIV-positive women were HPV 16 (13.9%) and HPV 18 (11.1%). HIV-positive women requiring LEEP were more likely to have HR-HPV types (OR 6.67, P=0.012) and to be infected with multiple HR-HPV types (OR 7.79, P=0.024) compared to those undergoing cryotherapy., Conclusion: HIV-positive women requiring LEEP versus cryotherapy had a higher prevalence of any HR-HPV type and multiple HR-HPV types. There were no such differences in HPV types identified among HIV-negative women., (© 2020 International Federation of Gynecology and Obstetrics.)

Public health interventions guided by clustering of HIV-1 molecular sequences may be impacted by choices of analytical approaches. We identified commonly-used clustering analytical approaches, applied them to 1886 HIV-1 Rhode Island sequences from 2004-2018, and compared concordance in identifying molecular HIV-1 clusters within and between approaches. We used strict (topological support ≥ 0.95; distance 0.015 substitutions/site) and relaxed (topological support 0.80-0.95; distance 0.030-0.045 substitutions/site) thresholds to reflect different epidemiological scenarios. We found that clustering differed by method and threshold and depended more on distance than topological support thresholds. Clustering concordance analyses demonstrated some differences across analytical approaches, with RAxML having the highest (91%) mean summary percent concordance when strict thresholds were applied, and three (RAxML-, FastTree regular bootstrap- and IQ-Tree regular bootstrap-based) analytical approaches having the highest (86%) mean summary percent concordance when relaxed thresholds were applied. We conclude that different analytical approaches can yield diverse HIV-1 clustering outcomes and may need to be differentially used in diverse public health scenarios. Recognizing the variability and limitations of commonly-used methods in cluster identification is important for guiding clustering-triggered interventions to disrupt new transmissions and end the HIV epidemic.

Background : The global push to achieve the 90-90-90 targets designed to end the HIV epidemic has called for the removing of policy barriers to prevention and treatment, and ensuring financial sustainability of HIV programs. Universal health insurance is one tool that can be used to this end. In sub-Saharan Africa, where HIV prevalence and incidence remain high, the use of health insurance to provide comprehensive HIV care is limited. This study looked at the factors that best predict social health insurance enrollment among HIV positive pregnant women using data from the Academic Model Providing Access to Healthcare (AMPATH) in western Kenya. Methods : Cross-sectional clinical encounter data were extracted from the electronic medical records (EMR) at AMPATH. We used univariate and multivariate logistic regressions to estimate the predictors of health insurance enrollment among HIV positive pregnant women. The analysis was further stratified by HIV disease severity (based on CD4 cell count <350 and 350>) to test the possibility of differential enrollment given HIV disease state. Results : Approximately 7% of HIV infected women delivering at a healthcare facility had health insurance. HIV positive pregnant women who deliver at a health facility had twice the odds of enrolling in insurance [2.46 Adjusted Odds Ratio (AOR), Confidence Interval (CI) 1.24-4.87]. They were 10 times more likely to have insurance if they were lost to follow-up to HIV care during pregnancy [9.90 AOR; CI 3.42-28.67], and three times more likely to enroll if they sought care at an urban clinic [2.50 AOR; 95% CI 1.53-4.12]. Being on HIV treatment was negatively associated with health insurance enrollment [0.22 AOR; CI 0.10-0.49]. Stratifying the analysis by HIV disease severity while statistically significant did not change these results. Conclusions : The findings indicated that health insurance enrollment among HIV positive pregnant women was low mirroring national levels. Additionally, structural factors, such as access to institutional delivery and location of healthcare facilities, increased the likelihood of health insurance enrollment within this population. However, behavioral aspects, such as being lost to follow-up to HIV care during pregnancy and being on HIV treatment, had an ambiguous effect on insurance enrollment. This may potentially be because of adverse selection and information asymmetries. Further understanding of the relationship between insurance and HIV is needed if health insurance is to be utilized for HIV treatment and prevention in limited resource settings.

Background: Reducing maternal morbidity and mortality remains a top global health agenda especially in high HIV/AIDS endemic locations where there is increased likelihood of mother to child transmission (MTCT) of HIV. Social health insurance (SHI) has emerged as a viable option to improve population access to health services, while improving outcomes for disenfranchised populations, particularly HIV+ women. However, the effect of SHI on healthcare access for HIV+ persons in limited resource settings is yet to undergo rigorous empirical evaluation. This study analyzes the effect of health insurance on obstetric healthcare access including institutional delivery and skilled birth attendants for HIV+ pregnant women in Kenya., Methods: We analyzed cross-sectional data from HIV+ pregnant women (ages 15-49 years) who had a delivery (full term, preterm, miscarriage) between 2008 and 2013 with their insurance enrollment status available in the electronic medical records database of a HIV healthcare system in Kenya. We estimated linear and logistic regression models and implemented matching and inverse probability weighting (IPW) to improve balance on observable individual characteristics. Additionally, we estimated heterogeneous effects stratified by HIV disease severity (CD4 < 350 as "Severe HIV disease", and CD4 > 350 otherwise)., Findings: Health Insurance enrollment is associated with improved obstetric health services utilization among HIV+ pregnant women in Kenya. Specifically, HIV+ pregnant women covered by NHIF have greater access to institutional delivery (12.5-percentage points difference) and skilled birth attendants (19-percentage points difference) compared to uninsured. Notably, the effect of NHIF on obstetric health service use is much greater for those who are sicker (CD4 < 350) - 20 percentage points difference., Conclusion: This study confirms conceptual and practical considerations around health insurance and healthcare access for HIV+ persons. Further, it helps to inform relevant policy development for health insurance and HIV financing and delivery in Kenya and in similar countries in sub-Saharan Africa in the universal health coverage (UHC) era.

Background: As the noncommunicable disease (NCD) burden is rising in regions with high HIV prevalence, patients with comorbid HIV and chronic NCDs may benefit from integrated chronic disease care. There are few evaluations of the effectiveness of such strategies, especially those that directly leverage and extend the existing HIV care system to provide co-located care for NCDs., Setting: Academic Model of Providing Access to Healthcare, Kenya, provides care to over 160,000 actively enrolled patients in catchment area of 4 million people., Methods: Using a difference-in-differences design, we analyzed retrospective clinical records of 3603 patients with comorbid HIV and hypertension during 2009-2016 to evaluate the addition of chronic disease management (CDM) to an existing HIV care program. Outcomes were blood pressure (BP), hypertension control, and adherence to HIV care., Results: Compared with the HIV standard of care, the addition of CDM produced statistically significant, although clinically small improvements in hypertension control, decreasing systolic BP by 0.76 mm Hg (P < 0.001), diastolic BP by 1.28 mm Hg (P < 0.001), and increasing the probability of BP <140/90 mm Hg by 1.51 percentage points (P < 0.001). However, sustained control of hypertension for >1 year improved by 7 percentage points (P < 0.001), adherence to HIV care improved by 6.8 percentage points (P < 0.001) and retention in HIV care with no gaps >6 months increased by 10.5 percentage points (P < 0.001)., Conclusion: A CDM program that co-locates NCD and HIV care shows potential to improve BP and retention in care. Further evaluation of program implementation across settings can inform how to maximize hypertension control among patients with comorbid HIV, and better understand the effect on adherence.

Introduction: Data on engagement in HIV care from population-based samples in sub-Saharan Africa are limited. The objective of this study was to use double-sampling methods to estimate linkage to HIV care, ART initiation, and mortality among all adults diagnosed with HIV by a comprehensive home-based counseling and testing (HBCT) program in western Kenya., Methods: HBCT was conducted door-to-door from December 2009 to April 2011 in three sub-counties of western Kenya by AMPATH (Academic Model Providing Access to Healthcare). For those identified as HIV-positive, data were merged with electronic medical records to determine engagement with HIV care. A randomly-drawn follow-up sample of 120 adults identified via HBCT who had not linked to care as of June 2015 in Bunyala sub-county were visited by trained fieldworkers to ascertain HIV care engagement and vital status. Double-sampled data were used to generate, via multinomial regression, predicted probabilities of engagement in care and mortality among those whose status could not be ascertained by matching with the electronic medical records in the three catchments., Results: Incorporating information from the double-sampling yielded estimates of prospective linkage to HIV care that ranged from 40-45%. Mortality estimates of those who did not engage in care following HBCT ranged from 12-16%. Among those who linked to care following HBCT, between 72-81% initiated ART., Discussion: In settings without universal national identifiers, rates of linkage to care from community-based programs may be subject to substantial underestimation. Follow-up samples of those with missing information can be used to partially correct this bias, as has been demonstrated previously for mortality among those who were lost-to-care programs. There is a need for harmonized data systems across health systems and programs., Competing Interests: The authors have declared that no competing interests exist.

Objective: We evaluated the impact of a patient-centred, culturally and age-appropriate disclosure counselling intervention on HIV disclosure rates among Kenyan children living with HIV., Design: A prospective, clinic-cluster randomized trial., Methods: We followed 285 child-caregiver dyads (children ages 10-14 years) attending eight HIV clinics (randomized to intervention or control) in Kenya. Participants at intervention clinics received intensive counselling with trained disclosure counsellors and culturally tailored materials, compared with control clinics with standard care. Disclosure was treated as a time-to-event outcome, measured on a discrete time scale, with assessments at 0, 6, 12, 18 and 24 months. Mental health and behavioural outcomes were assessed using standardized questionnaires., Results: Mean age was 12.3 years [standard deviation (SD) 1.5], 52% were girls, with average time-on-treatment of 4.5 years (SD 2.4). Between 0 and 6 months, disclosure prevalence increased from 47 to 58% in the control group and from 50 to 70% in the intervention group. Differences in disclosure were not sustained over the following 18 months. The prevalence of depression symptoms was significantly higher in the intervention than in the control group at 6 months (odds ratio 2.07, 95% confidence interval 1.01-4.25); however, there was no evidence that these differences were sustained after 6 months., Conclusion: The clinic-based intervention increased disclosure of HIV status to children living with HIV in the short-term, resulting in earlier disclosures, but had less clear impacts longer-term. Although well tailored interventions may support disclosure, children may still experience increased levels of depression symptoms immediately following disclosure.

Evidence supporting the current World Health Organization recommendations of early antiretroviral therapy (ART) initiation for adolescents is inconclusive. We leverage a large observational data and compare, in terms of mortality and CD4 cell count, the dynamic treatment initiation rules for human immunodeficiency virus-infected adolescents. Our approaches extend the marginal structural model for estimating outcome distributions under dynamic treatment regimes, developed in Robins et al. (2008), to allow the causal comparisons of both specific regimes and regimes along a continuum. Furthermore, we propose strategies to address three challenges posed by the complex data set: continuous-time measurement of the treatment initiation process; sparse measurement of longitudinal outcomes of interest, leading to incomplete data; and censoring due to dropout and death. We derive a weighting strategy for continuous-time treatment initiation, use imputation to deal with missingness caused by sparse measurements and dropout, and define a composite outcome that incorporates both death and CD4 count as a basis for comparing treatment regimes. Our analysis suggests that immediate ART initiation leads to lower mortality and higher median values of the composite outcome, relative to other initiation rules., (© 2019 The International Biometric Society.)

Introduction: Despite the central role of caregivers in managing HIV treatment for children living with HIV, viral suppression within caregiver-child dyads in which both members are living with HIV is not well described., Methods: We conducted a retrospective analysis of children living with HIV <15 years of age and their caregivers living with HIV attending HIV clinics affiliated with the Academic Model Providing Access to Healthcare (AMPATH) in Kenya between 2015 and 2017. To be included in the analysis, children and caregivers must have had ≥1 viral load (VL) during the study period while receiving antiretroviral therapy (ART) for ≥6 months, and the date of the caregiver's VL must have occurred ±90 days from the date of the child's VL. The characteristics of children, caregivers and dyads were descriptively summarized. Multivariable logistic regression was used to estimate the odds of viral non-suppression (≥ 1000 copies/mL) in children, adjusting for caregiver and child characteristics., Results: Of 7667 children who received care at AMPATH during the study period, 1698 were linked to a caregiver living with HIV and included as caregiver-child dyads. For caregivers, 94% were mothers, median age at ART initiation 32.8 years, median CD4 count at ART initiation 164 cells/mm 3 and 23% were not virally suppressed. For children, 52% were female, median age at ART initiation 4.2 years, median CD4 values at ART initiation were 15% (age < 5 years) and 396 cells/mm 3 (age ≥ 5 years), and 38% were not virally suppressed. In the multivariable model, children were found more likely to not be virally suppressed if their caregivers were not suppressed compared to children with suppressed caregivers (aOR = 2.40, 95% CI: 1.86 to 3.10). Other characteristics associated with child viral non-suppression included caregiver ART regimen change prior to the VL, caregiver receipt of a non-NNRTI-based regimen at the time of the VL, younger child age at ART initiation and child tuberculosis treatment at the time of the VL., Conclusions: Children were at higher risk of viral non-suppression if their caregivers were not virally suppressed compared to children with suppressed caregivers. A child's viral suppression status should be closely monitored if his or her caregiver is not suppressed., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Objective: Characterize failure and resistance above and below guidelines-recommended 1000 copies/ml virologic threshold, upon second-line failure., Design: Cross-sectional study., Methods: Kenyan adults on lopinavir/ritonavir-based second-line were enrolled at AMPATH (Academic Model Providing Access to Healthcare). Charts were reviewed for demographic/clinical characteristics and CD4/viral load were obtained. Participants with detectable viral load had a second visit and pol genotyping was attempted in both visits. Accumulated resistance was defined as mutations in the second, not the first visit. Low-level viremia (LLV) was detectable viral load less than 1000 copies/ml. Failure and resistance associations were evaluated using logistic and Poisson regression, Fisher Exact and t-tests., Results: Of 394 participants (median age 42, 60% women, median 1.9 years on second-line) 48% had detectable viral load; 21% had viral load more than 1000 copies/ml, associated with younger age, tuberculosis treatment, shorter time on second-line, lower CD4count/percentage, longer first-line treatment interruption and pregnancy. In 105 sequences from the first visit (35 with LLV), 79% had resistance (57% dual-class, 7% triple-class; 46% with intermediate-to-high-level resistance to ≥1 future drug option). LLV was associated with more overall and NRTI-associated mutations and with predicted resistance to more next-regimen drugs. In 48 second-visit sequences (after median 55 days; IQR 28-33), 40% accumulated resistance and LLV was associated with more mutation accumulation., Conclusion: High resistance upon second-line failure exists at levels above and below guideline-recommended virologic-failure threshold, impacting future treatment options. Optimization of care should include increased viral load monitoring, resistance testing and third-line ART access, and consideration of lowering the virologic failure threshold, though this demands further investigation.

Objectives: Studies examining engagement in HIV care often capture cross-sectional patient status to estimate retention and identify predictors of attrition, which ignore longitudinal patient care-seeking behaviors. We describe the cyclical nature of (dis)engagement and re-entry into HIV care using the state transition framework., Design: We represent the dynamic patterns of patient care-retention using five states: engaged in care, missed one, two, three, or more expected visits, and deceased. Then we describe various care-seeking behaviors in terms of transitioning from one state to another (e.g. from disengaged to engaged). This analysis includes 31 009 patients enrolled in the Center for AIDS Research Network of Integrated Systems (CNICS) in the United States from 1996 to 2014., Method: Multistate models for longitudinal data were used to identify barriers to retention and subgroups at higher risk of falling out of care., Results: The initial 2 years following primary engagement in care were a crucial time for improving retention. Patients who had not initiated antiretroviral therapy, with lower CD4 cell counts, higher viral load, or not having an AIDS-defining illness were less likely to be retained in care., Conclusion: Beyond the individual patient characteristics typically used to characterize retention in HIV care, we identified specific periods of time and points in the care continuum associated with elevated risk of transitioning out of care. Our findings can contribute to evidence-based recommendations to enhance long-term retention in CNICS. This approach can also be applied to other cohort data to identify retention strategies tailored to each population.

We use a socioecological model of health to define resilience, review the definition and study of resilience among persons living with human immunodeficiency virus (PLWH) in the existing peer-reviewed literature, and discuss the strengths and limitations of how resilience is defined and studied in HIV research. We conducted a review of resilience research for HIV-related behaviors/outcomes of antiretroviral therapy (ART) adherence, clinic attendance, CD4 cell count, viral load, viral suppression, and/or immune functioning among PLWH. We performed searches using PubMed, PsycINFO and Google Scholar databases. The initial search generated 14,296 articles across the three databases, but based on our screening of these articles and inclusion criteria, n = 54 articles were included for review. The majority of HIV resilience research defines resilience only at the individual (i.e., psychological) level or studies individual and limited interpersonal resilience (e.g., social support). Furthermore, the preponderance of HIV resilience research uses general measures of resilience; these measures have not been developed with or tailored to the needs of PLWH. Our review suggests that a socioecological model of health approach can more fully represent the construct of resilience. Furthermore, measures specific to PLWH that capture individual, interpersonal, and neighborhood resilience are needed.

Background: Home-based counseling and testing (HBCT) achieves earlier HIV diagnosis than other testing modalities; however, retention in care for these healthier patients is unknown. The objective of this study was to determine the association between point of HIV testing and retention in care and mortality., Setting: Academic Model Providing Access to Healthcare (AMPATH) has provided HIV care in western Kenya since 2001., Methods: AMPATH initiated HBCT in 2007. This retrospective analysis included individuals 13 years and older, enrolled in care between January 2008 and September 2016, with data on point of testing. Discrete-time multistate models were used to estimate the probability of transition between the following states: engaged, disengaged, transfer, and death, and the association between point of diagnosis and transition probabilities., Results: Among 77,358 patients, 67% women, median age: 35 years and median baseline CD4: 248 cells/mm. Adjusted results demonstrated that patients from HBCT were less likely to disengage [relative risk ratio (RRR) = 0.87, 95% CI: 0.83 to 0.91] and die (RRR = 0.65, 95% CI: 0.55 to 0.75), whereas those diagnosed through provider-initiated counseling and testing were more likely to disengage (RRR = 1.09, 95% CI: 1.07 to 1.12) and die (RRR = 1.13, 95% CI: 1.06 to 1.20), compared with patients from voluntary counseling and testing. Once disengaged, patients from HBCT were less likely to remain disengaged, compared with patients from voluntary counseling and testing., Conclusions: Patients entering care from different HIV-testing programs demonstrate differences in retention in HIV care over time beyond disease severity. Additional research is needed to understand the patient and system level factors that may explain the associations between testing program, retention, and mortality.

Introduction: Weaknesses in care programmes providing anti-retroviral therapy (ART) persist and are often instigated by late HIV diagnosis and poor linkage to care. We investigated the potential for a home-based counselling and testing (HBCT) campaign to be improved through the optimal timing and enhancement of testing rounds to generate greater health outcomes at minimum cost., Methods: Using a mathematical model of HIV care calibrated to longitudinal data from The Academic Model Providing Access To Healthcare (AMPATH) in Kenya, we simulated HBCT campaigns between 2016 and 2036, assessing the impact and total cost of care for each, for a further 20 years., Results: We find that simulating five equally spaced rounds averts 1.53 million disability-adjusted life-years (DALYs) at a cost of $1617 million. By altering the timing of HBCT rounds, a four-round campaign can produce greater impact for lower cost. With "front-loaded" rounds, the cost per DALY averted is reduced by 12% as fewer rounds are required ($937 vs. $1060). Furthermore, improvements to HBCT coverage and linkage to care avert over two million DALYs at a cost per DALY averted of $621 (41% less than the reference scenario)., Conclusions: Countries implementing HBCT can reduce costs by optimally timing rounds and generate greater health outcomes through improving linkage, coverage, and retention. Tailoring HBCT campaigns to individual settings can enhance patient outcomes for minimal cost., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.)

Reducing racial/ethnic disparities in human immunodeficiency virus (HIV) disease is a high priority. Reductions in HIV racial/ethnic disparities can potentially be achieved by intervening on important intermediate factors. The potential population impact of intervening on intermediates can be evaluated using observational data when certain conditions are met. However, using standard stratification-based approaches commonly employed in the observational HIV literature to estimate the potential population impact in this setting may yield results that do not accurately estimate quantities of interest. Here we describe a useful conceptual and methodological framework for using observational data to appropriately evaluate the impact on HIV racial/ethnic disparities of interventions. This framework reframes relevant scientific questions in terms of a controlled direct effect and estimates a corresponding proportion eliminated. We review methods and conditions sufficient for accurate estimation within the proposed framework. We use the framework to analyze data on 2,329 participants in the CFAR [Centers for AIDS Research] Network of Integrated Clinical Systems (2008-2014) to evaluate the potential impact of universal prescription of and ≥95% adherence to antiretroviral therapy on racial disparities in HIV virological suppression. We encourage the use of the described framework to appropriately evaluate the potential impact of targeted interventions in addressing HIV racial/ethnic disparities using observational data., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The human immunodeficiency virus (HIV) care cascade is a conceptual model used to outline the benchmarks that reflects effectiveness of HIV care in the whole HIV care continuum. The models can be used to identify barriers contributing to poor outcomes along each benchmark in the cascade such as disengagement from care or death. Recently, the HIV care cascade has been widely applied to monitor progress towards HIV prevention and care goals in an attempt to develop strategies to improve health outcomes along the care continuum. Yet, there are challenges in quantifying successes and gaps in HIV care using the cascade models that are partly due to the lack of analytic approaches. The availability of large cohort data presents an opportunity to develop a coherent statistical framework for analysis of the HIV care cascade. Motivated by data from the Academic Model Providing Access to Healthcare, which has provided HIV care to nearly 200,000 individuals in Western Kenya since 2001, we developed a state transition framework that can characterize patient-level movements through the multiple stages of the HIV care cascade. We describe how to transform large observational data into an analyzable format. We then illustrate the state transition framework via multistate modeling to quantify dynamics in retention aspects of care. The proposed modeling approach identifies the transition probabilities of moving through each stage in the care cascade. In addition, this approach allows regression-based estimation to characterize effects of (time-varying) predictors of within and between state transitions such as retention, disengagement, re-entry into care, transfer-out, and mortality. Copyright © 2017 John Wiley & Sons, Ltd., (Copyright © 2017 John Wiley & Sons, Ltd.)

We evaluated treatment failure misclassification in human immunodeficiency virus-infected Kenyan children whose targeted viral loads were determined after suspected immunologic/clinical failure according to 2006 and 2010/2013 World Health Organization guidelines. The misclassification rate was 21% for the 2006 guidelines and 46% for the 2010/2013 guidelines, which supports current recommendations for routine viral load monitoring but not necessarily the proposed CD4 thresholds., (© The Author 2016. Published by Oxford University Press on behalf of the Pediatric Infectious Diseases Society. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: Improve pooled viral load (VL) testing to increase HIV treatment monitoring capacity, particularly relevant for resource-limited settings., Design: We developed marker-assisted mini-pooling with algorithm (mMPA), a new VL pooling deconvolution strategy that uses information from low-cost, routinely collected clinical markers to determine an efficient order of sequential individual VL testing and dictates when the sequential testing can be stopped., Methods: We simulated the use of pooled testing to ascertain virological failure status on 918 participants from 3 studies conducted at the Academic Model Providing Access to Healthcare in Eldoret, Kenya, and estimated the number of assays needed when using mMPA and other pooling methods. We also evaluated the impact of practical factors, such as specific markers used, prevalence of virological failure, pool size, VL measurement error, and assay detection cutoffs on mMPA, other pooling methods, and single testing., Results: Using CD4 count as a marker to assist deconvolution, mMPA significantly reduces the number of VL assays by 52% [confidence interval (CI): 48% to 57%], 40% (CI: 38% to 42%), and 19% (CI: 15% to 22%) compared with individual testing, simple mini-pooling, and mini-pooling with algorithm, respectively. mMPA has higher sensitivity and negative/positive predictive values than mini-pooling with algorithm, and comparable high specificity. Further improvement is achieved with additional clinical markers, such as age and time on therapy, with or without CD4 values. mMPA performance depends on prevalence of virological failure and pool size but is insensitive to VL measurement error and VL assay detection cutoffs., Conclusions: mMPA can substantially increase the capacity of VL monitoring.

Background: With expanded access to antiretroviral therapy (ART) in sub-Saharan Africa, HIV mortality has decreased, yet life-years are still lost to AIDS. Strengthening of treatment programmes is a priority. We examined the state of an HIV care programme in Kenya and assessed interventions to improve the impact of ART programmes on population health., Methods: We created an individual-based mathematical model to describe the HIV epidemic and the experiences of care among adults infected with HIV in Kenya. We calibrated the model to a longitudinal dataset from the Academic Model Providing Access To Healthcare (known as AMPATH) programme describing the routes into care, losses from care, and clinical outcomes. We simulated the cost and effect of interventions at different stages of HIV care, including improvements to diagnosis, linkage to care, retention and adherence of ART, immediate ART eligibility, and a universal test-and-treat strategy., Findings: We estimate that, of people dying from AIDS between 2010 and 2030, most will have initiated treatment (61%), but many will never have been diagnosed (25%) or will have been diagnosed but never started ART (14%). Many interventions targeting a single stage of the health-care cascade were likely to be cost-effective, but any individual intervention averted only a small percentage of deaths because the effect is attenuated by other weaknesses in care. However, a combination of five interventions (including improved linkage, point-of-care CD4 testing, voluntary counselling and testing with point-of-care CD4, and outreach to improve retention in pre-ART care and on-ART) would have a much larger impact, averting 1·10 million disability-adjusted life-years (DALYs) and 25% of expected new infections and would probably be cost-effective (US$571 per DALY averted). This strategy would improve health more efficiently than a universal test-and-treat intervention if there were no accompanying improvements to care ($1760 per DALY averted)., Interpretation: When resources are limited, combinations of interventions to improve care should be prioritised over high-cost strategies such as universal test-and-treat strategy, especially if this is not accompanied by improvements to the care cascade. International guidance on ART should reflect alternative routes to programme strengthening and encourage country programmes to evaluate the costs and population-health impact in addition to the clinical benefits of immediate initiation., Funding: Bill & Melinda Gates Foundation, United States Agency for International Development, National Institutes of Health., (Copyright © 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Tenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment programme in western Kenya., Methods: We determined viral load (VL), drug resistance and their correlates in patients on ≥six months of tenofovir-based first-line ART. Based on enrolled patients' characteristics, we described these measures in those with (prior ART group) and without (tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher's exact tests., Results: Among 333 participants (55% female; median age 41 years; median CD4 336 cells/µL), detectable (>40 copies/mL) VL was found in 18%, and VL>1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with VL>40 copies/mL; 15% vs. 1% with VL>1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4 values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL>40 copies/mL (69% subtype A), any resistance was found in 89% and dual-class resistance in 83%. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations., Conclusions: In this Kenyan cohort, tenofovir-based first-line ART resulted in good (90%) virologic suppression including high suppression (99%) after switch from non-tenofovir-based ART. Lower virologic suppression (85%) and high observed resistance levels (89%) in the tenofovir-only group impact future treatment options, support recommendations for widespread VL monitoring in such resource limited settings to identify early treatment failure and suggest consideration of individualized resistance testing to design effective subsequent regimens.

Background: Molecular epidemiological evaluation of HIV-1 transmission networks can elucidate behavioral components of transmission that can be targets for intervention., Methods: We combined phylogenetic and statistical approaches using pol sequences from patients diagnosed between 2004 and 2011 at a large HIV center in Rhode Island, following 75% of the state's HIV population. Phylogenetic trees were constructed using maximum likelihood, and putative transmission clusters were evaluated using latent class analyses to determine association of cluster size with underlying demographic/behavioral characteristics. A logistic growth model was used to assess intracluster dynamics over time and predict "active" clusters that were more likely to harbor undiagnosed infections., Results: Of the 1166 HIV-1 subtype B sequences, 31% were distributed among 114 statistically supported, monophyletic clusters (range: 2-15 sequences/cluster). Sequences from men who have sex with men (MSM) formed 52% of clusters. Latent class analyses demonstrated that sequences from recently diagnosed (2008-2011) MSM with primary HIV infection (PHI) and other sexually transmitted infections (STIs) were more likely to form larger clusters (odds ratio: 1.62-11.25, P < 0.01). MSM in clusters were more likely to have anonymous partners and meet partners at sex clubs and pornographic stores. Four large clusters with 38 sequences (100% male, 89% MSM) had a high probability of harboring undiagnosed infections and included younger MSM with PHI and STIs., Conclusions: In this first large-scale molecular epidemiological investigation of HIV-1 transmission in New England, sexual networks among recently diagnosed MSM with PHI and concomitant STIs contributed to the ongoing transmission. Characterization of transmission dynamics revealed actively growing clusters, which may be targets for intervention.

Introduction: Antiretroviral resistance leads to treatment failure and resistance transmission. Resistance data in western Kenya are limited. Collection of non-plasma analytes may provide additional resistance information., Methods: We assessed HIV diversity using the REGA tool, transmitted resistance by the WHO mutation list and acquired resistance upon first-line failure by the IAS-USA mutation list, at the Academic Model Providing Access to Healthcare (AMPATH), a major treatment programme in western Kenya. Plasma and four non-plasma analytes, dried blood-spots (DBS), dried plasma-spots (DPS), ViveST(TM)-plasma (STP) and ViveST-blood (STB), were compared to identify diversity and evaluate sequence concordance., Results: Among 122 patients, 62 were treatment-naïve and 60 treatment-experienced; 61% were female, median age 35 years, median CD4 182 cells/µL, median viral-load 4.6 log10 copies/mL. One hundred and ninety-six sequences were available for 107/122 (88%) patients, 58/62 (94%) treatment-naïve and 49/60 (82%) treated; 100/122 (82%) plasma, 37/78 (47%) attempted DBS, 16/45 (36%) attempted DPS, 14/44 (32%) attempted STP from fresh plasma and 23/34 (68%) from frozen plasma, and 5/42 (12%) attempted STB. Plasma and DBS genotyping success increased at higher VL and shorter shipment-to-genotyping time. Main subtypes were A (62%), D (15%) and C (6%). Transmitted resistance was found in 1.8% of plasma sequences, and 7% combining analytes. Plasma resistance mutations were identified in 91% of treated patients, 76% NRTI, 91% NNRTI; 76% dual-class; 60% with intermediate-high predicted resistance to future treatment options; with novel mutation co-occurrence patterns. Nearly 88% of plasma mutations were identified in DBS, 89% in DPS and 94% in STP. Of 23 discordant mutations, 92% in plasma and 60% in non-plasma analytes were mixtures. Mean whole-sequence discordance from frozen plasma reference was 1.1% for plasma-DBS, 1.2% plasma-DPS, 2.0% plasma-STP and 2.3% plasma-STB. Of 23 plasma-STP discordances, one mutation was identified in plasma and 22 in STP (p<0.05). Discordance was inversely significantly related to VL for DBS., Conclusions: In a large treatment programme in western Kenya, we report high HIV-1 subtype diversity; low plasma transmitted resistance, increasing when multiple analytes were combined; and high-acquired resistance with unique mutation patterns. Resistance surveillance may be augmented by using non-plasma analytes for lower-cost genotyping in resource-limited settings.

Access to antiretroviral therapy is increasing globally and drug resistance evolution is anticipated. Currently, protease (PR) and reverse transcriptase (RT) sequence generation is increasing, including the use of in-house sequencing assays, and quality assessment prior to sequence analysis is essential. We created a computational HIV PR/RT Sequence Quality Analysis Tool (SQUAT) that runs in the R statistical environment. Sequence quality thresholds are calculated from a large dataset (46,802 PR and 44,432 RT sequences) from the published literature ( http://hivdb.Stanford.edu ). Nucleic acid sequences are read into SQUAT, identified, aligned, and translated. Nucleic acid sequences are flagged if with >five 1-2-base insertions; >one 3-base insertion; >one deletion; >six PR or >18 RT ambiguous bases; >three consecutive PR or >four RT nucleic acid mutations; >zero stop codons; >three PR or >six RT ambiguous amino acids; >three consecutive PR or >four RT amino acid mutations; >zero unique amino acids; or <0.5% or >15% genetic distance from another submitted sequence. Thresholds are user modifiable. SQUAT output includes a summary report with detailed comments for troubleshooting of flagged sequences, histograms of pairwise genetic distances, neighbor joining phylogenetic trees, and aligned nucleic and amino acid sequences. SQUAT is a stand-alone, free, web-independent tool to ensure use of high-quality HIV PR/RT sequences in interpretation and reporting of drug resistance, while increasing awareness and expertise and facilitating troubleshooting of potentially problematic sequences.

Background: In resource-poor settings, mortality is at its highest during the first 3 months after combination antiretroviral treatment (cART) initiation. A clear predictor of mortality during this period is having a low CD4 count at the time of treatment initiation. The objective of this study was to evaluate the effect on survival and clinic retention of a nurse-based rapid assessment clinic for high-risk individuals initiating cART in a resource-constrained setting., Methods: The USAID-AMPATH Partnership has enrolled more than 140,000 patients at 25 clinics throughout western Kenya. High Risk Express Care (HREC) provides weekly or bi-weekly rapid contacts with nurses for individuals initiating cART with CD4 counts of ≤100 cells/mm3. All HIV-infected individuals aged 14 years or older initiating cART with CD4 counts of ≤100 cells/mm3 were eligible for enrolment into HREC and for analysis. Adjusted hazard ratios (AHRs) control for potential confounding using propensity score methods., Results: Between March 2007 and March 2009, 4,958 patients initiated cART with CD4 counts of ≤100 cells/mm3. After adjusting for age, sex, CD4 count, use of cotrimoxazole, treatment for tuberculosis, travel time to clinic and type of clinic, individuals in HREC had reduced mortality (AHR: 0.59; 95% confidence interval: 0.45-0.77), and reduced loss to follow up (AHR: 0.62; 95% CI: 0.55-0.70) compared with individuals in routine care. Overall, patients in HREC were much more likely to be alive and in care after a median of nearly 11 months of follow up (AHR: 0.62; 95% CI: 0.57-0.67)., Conclusions: Frequent monitoring by dedicated nurses in the early months of cART can significantly reduce mortality and loss to follow up among high-risk patients initiating treatment in resource-constrained settings.

Aims: Dual epidemics of human immunodeficiency virus (HIV) and alcohol use disorders, and a dearth of professional resources for behavioral treatment in sub-Saharan Africa, suggest the need for development of culturally relevant and feasible interventions. The purpose of this study was to test the preliminary efficacy of a culturally adapted six-session gender-stratified group cognitive-behavioral therapy (CBT) intervention delivered by paraprofessionals to reduce alcohol use among HIV-infected out-patients in Eldoret, Kenya., Design: Randomized clinical trial comparing CBT against a usual care assessment-only control., Setting: A large HIV out-patient clinic in Eldoret, Kenya, part of the Academic Model for Providing Access to Healthcare collaboration., Participants: Seventy-five HIV-infected out-patients who were antiretroviral (ARV)-initiated or ARV-eligible and who reported hazardous or binge drinking., Measurements: Percentage of drinking days (PDD) and mean drinks per drinking days (DDD) measured continuously using the Time line Follow back method., Findings: There were 299 ineligible and 102 eligible out-patients with 12 refusals. Effect sizes of the change in alcohol use since baseline between the two conditions at the 30-day follow-up were large [d=0.95, P=0.0002, mean difference=24.93, 95% confidence interval (CI): 12.43, 37.43 PDD; d=0.76, P=0.002, mean difference=2.88, 95% CI: 1.05, 4.70 DDD]. Randomized participants attended 93% of the six CBT sessions offered. Reported alcohol abstinence at the 90-day follow-up was 69% (CBT) and 38% (usual care). Paraprofessional counselors achieved independent ratings of adherence and competence equivalent to college-educated therapists in the United States. Treatment effect sizes were comparable to alcohol intervention studies conducted in the United States., Conclusions: Cognitive-behavioral therapy can be adapted successfully to group paraprofessional delivery in Kenya and may be effective in reducing alcohol use among HIV-infected Kenyan out-patients., (© 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.)

This study examined the association between recent trends in CD4 and viral loads and cognitive test performance with the expectation that recent history could predict cognitive performance. Eighty-three human immunodeficiency virus (HIV)-infected patients with a mean CD4 count of 428 copies/ml were examined in this study (62% with undetectable plasma viral load [PVL]). We investigated the relationships between nadir CD4 cell count, 1-year trends in immunologic function/PVLs, and cognitive performance across several domains using linear regression models. Nadir CD4 cell count was predictive of current executive function (p = .004). One year clinical history for CD4 cell counts and/or PVLs were predictive of executive function, attention/working memory, and learning/memory measures (p < .05). Models that combined recent clinical history trends and nadir CD4 cell counts suggested that recent clinical trends were more important in predicting current cognitive performance for all domains except executive function. This research suggests that recent CD4 and viral load history is an important predictor of current cognitive function across several cognitive domains. If validated, clinical variables and cognitive dysfunction models may improve our understanding of the dynamic relationships between disease evolution and progression and CNS involvement.

Recent reports suggest that a growing number of human immunodeficiency virus (HIV)-infected persons show signs of persistent cognitive impairment even in the context of combination antiretroviral therapies (cART). The basis for this finding remains poorly understood as there are only a limited number of studies examining the relationship between CNS injury, measures of disease severity, and cognitive function in the setting of stable disease. This study examined the effects of HIV infection on cerebral white matter using quantitative morphometry of the midsagittal corpus callosum (CC) in 216 chronically infected participants from the multisite HIV Neuroimaging Consortium study currently receiving cART and 139 controls. All participants underwent MRI assessment, and HIV-infected subjects also underwent measures of cognitive function and disease severity. The midsagittal slice of the CC was quantified using two semi-automated procedures. Group comparisons were accomplished using ANOVA, and the relationship between CC morphometry and clinical covariates (current CD4, nadir CD4, plasma and CSF HIV RNA, duration of HIV infection, age, and ADC stage) was assessed using linear regression models. HIV-infected patients showed significant reductions in both the area and linear widths for several regions of the CC. Significant relationships were found with ADC stage and nadir CD4 cell count, but no other clinical variables. Despite effective treatment, significant and possibly irreversible structural loss of the white matter persists in the setting of chronic HIV disease. A history of advanced immune suppression is a strong predictor of this complication and suggests that antiretroviral intervention at earlier stages of infection may be warranted.