Impact of Variable Sampling on Estimates of HIV-1 Reservoir Formation Dates.

Timing of human immunodeficiency virus-1 (HIV-1) reservoir formation is important for informing HIV cure efforts. It is unclear how much of the variability seen in dating reservoir formation is due to sampling and gene-specific differences. We used a Bayesian extension of root to tip regression (bayroot) to reestimate formation date distributions in participants from Swedish and South African cohorts, and assessed the impact of variable timing, frequency, and depth of sampling on these estimates. Significant shifts in formation date distributions were only observed with use of faster-evolving genes, while timing, frequency, and depth of sampling had minor or no significant effect on estimates.

Incidence of Health Facility Switching and Associations With HIV Viral Rebound Among Persons on Antiretroviral Therapy in Uganda: A Population-based Study.

BACKGROUND: A substantial proportion of persons on antiretroviral therapy (ART) considered lost to follow-up have actually transferred their human immunodeficiency virus (HIV) care to other facilities. However, the relationship between facility switching and virologic outcomes, including viral rebound, is poorly understood. METHODS: We used data from 40 communities (2015-2020) in the Rakai Community Cohort Study to estimate incidence of facility switching and viral rebound. Persons aged 15-49 years with serologically confirmed HIV who self-reported ART use and contributed ≥1 follow-up visit were included. Facility switching and virologic outcomes were assessed between 2 consecutive study visits (ie, index and follow-up visits, interval of approximately 18 months). Those who reported different HIV treatment facilities between index and follow-up study visits were classified as having switched facilities. Virologic outcomes included viral rebound among individuals initially suppressed (<200 copies/mL). Multivariable Poisson regression was used to estimate associations between facility switching and viral rebound. RESULTS: Overall, 2257 persons who self-reported ART use (median age, 35 years; 65% female, 92% initially suppressed) contributed 3335 visit-pairs and 5959 person-years to the analysis. Facility switching was common (4.8 per 100 person-years; 95% confidence interval [CI], 4.2-5.5) and most pronounced in persons aged <30 years and fishing community residents. Among persons suppressed at their index visit (n = 2076), incidence of viral rebound was more than twice as high in persons who switched facilities (adjusted incidence rate ratio = 2.27; 95% CI, 1.16-4.45). CONCLUSIONS: Facility switching was common and associated with viral rebound among persons initially suppressed. Investments in more agile, person-centered models for mobile clients are needed to address system inefficiencies and bottlenecks that can disrupt HIV care continuity.

Sexually transmitted infections and migration in Uganda: a population-based study.

OBJECTIVES: Migration is associated with increased risk of HIV infection in Africa, but evidence about non-HIV sexually transmitted infection (STI) burden among African migrants is limited. METHODS: We used data from the Sexually Transmitted Infection Prevalence Study, a cross-sectional population-based study of chlamydia, gonorrhoea, trichomoniasis, syphilis and herpes simplex virus type 2 prevalence in southern Uganda, to compare STI prevalence between adults aged 18 and 49 years with and without a recent history of migration. Migration status was determined using household census data, with a recent migration history defined as having moved into one's community of current residence within the last ~18 months. Unadjusted and adjusted modified Poisson regression models were used to compare individual STI prevalence risk by recent migration status with associations reported as adjusted prevalence risk ratios (adjPRRs) with 95% CIs. Adjusted models included participants' sex, age, community type, education, occupation and marital status. RESULTS: Among 1825 participants, 358 (19.6%) had a recent migration history. Overall, migrants exhibited a significantly higher combined prevalence of curable STIs (gonorrhoea, chlamydia, high-titre syphilis (rapid plasma regain ≥1:8) and trichomoniasis) as compared with long-term residents (34.4% vs 24.2%; adjPRR=1.23; 95% CI 1.03 to 1.47). Significant differences in curable STI prevalence by migration status were concentrated among persons living with HIV (49.4% prevalence in migrants vs 32.6% in long-term residents; adjPRR=1.42; 95% CI 1.10 to 1.85) and among women (38.8% in migrants vs 27.8% in long-term residents; adjPRR=1.26; 95% CI 1.01 to 1.58). High-titre syphilis prevalence was especially elevated among male migrants (11.2% in migrants vs 4.9% in long-term residents; adjPRR=1.82; 95% CI 1.06 to 3.13). CONCLUSIONS: The prevalence of non-HIV STIs is higher among migrants. Tailored outreach and service delivery approaches that address the needs of mobile populations are crucial for integrated HIV and STI epidemic control in Uganda to optimise resources and reduce transmission risks.

Motivational interviewing experiences from a community health worker-led HIV prevention and care intervention in rural Uganda: a qualitative study.

Motivational Interviewing (MI) and Community Health Workers (CHWs) are increasingly utilized in global settings to improve HIV outcomes, yet research exploring implementation strategies using MI and CHWs is lacking. We examined the experiences of CHWs and their clients in a counseling intervention which used MI-informed counseling to increase engagement in HIV prevention and treatment. This study was nested within the mLAKE cluster-randomized trial in a high HIV prevalence fishing community in rural Rakai District, Uganda. We conducted in-depth interviews with purposively-sampled CHWs (n = 8) and clients (n = 51). Transcripts were analyzed thematically to characterize CHWs' implementation of the intervention. Main themes identified included use of specific MI strategies (including evocation, guidance towards positive behavior change, active listening, and open-ended questions), and MI spirit (including collaboration, power-sharing, trust, and non-judgmental relationship building). Through these specific MI mechanisms, CHWs supported client behavior change to facilitate engagement with HIV services. This study provides evidence from a low-resource setting that CHWs with no previous experience in MI can successfully implement MI-informed counseling that is well-received by clients. CHW-led MI-informed counseling appears to be a feasible and effective approach to increase uptake of HIV prevention and care services in low-resource, HIV endemic regions.

The potential promise and pitfalls of point-of-care viral load monitoring to expedite HIV treatment decision-making in rural Uganda: a qualitative study.

BACKGROUND: HIV treatment programs in Africa have implemented centralized testing for routine viral load monitoring (VLM), which may result in specimen processing delays inhibiting timely return of viral load results. Decentralized, point-of-care (PoC) VLM is a promising tool for expediting HIV clinical decision-making but remains unavailable in most African settings. We qualitatively explored the perceived feasibility and appropriateness of PoC VLM to address gaps along the viral load monitoring continuum in rural Uganda. METHODS: Between May and September 2022, we conducted 15 in-depth interviews with HIV clinicians (facility in-charges, clinical officers, nurses, counselors) and six focus group discussions with 47 peer health workers from three south-central Ugandan districts. Topics explored centralized VLM implementation and opportunities/challenges to optimizing routine VLM implementation with PoC testing platforms. We explored perspectives on PoC VLM suitability and feasibility using iterative thematic analysis. Applying the Framework Method, we then mapped salient constraints and enablers of PoC VLM to constructs from the Consolidated Framework for Implementation Research. RESULTS: Clinicians and peers alike emphasized centralized viral load monitoring's resource-intensiveness and susceptibility to procedural/infrastructural bottlenecks (e.g., supply stockouts, testing backlogs, community tracing of clients with delayed VLM results), inhibiting timely clinical decision-making. Participants reacted enthusiastically to the prospect of PoC VLM, anticipating accelerated turnarounds in specimen processing, shorter and/or fewer client encounters with treatment services, and streamlined efficiencies in HIV care provision (including expedited VLM-driven clinical decision-making). Anticipated constraints to PoC VLM implementation included human resource requirements for processing large quantities of specimens (especially when machinery require repair), procurement and maintenance costs, training needs in the existing health workforce for operating point-of-care technology, and insufficient space in lower-tier health facilities to accommodate installation of new laboratory equipment. CONCLUSIONS: Anticipated implementation challenges, primarily clustering around resource requirements, did not diminish enthusiasm for PoC VLM monitoring among rural Ugandan clinicians and peer health workers, who perceived PoC platforms as potential solutions to existing inefficiencies within the centralized VLM ecosystem. Prioritizing PoC VLM rollout in facilities with available resources for optimal implementation (e.g., adequate physical and fiscal infrastructure, capacity to manage high specimen volumes) could help overcome anticipated barriers to decentralizing viral load monitoring.

Age Patterns of HSV-2 Incidence and Prevalence in Two Ugandan Communities: A Catalytic Incidence Model Applied to Population-Based Seroprevalence Data.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) is an incurable sexually transmitted infection associated with increased risk of acquiring and transmitting human immunodeficiency virus (HIV). HSV-2 is highly prevalent in sub-Saharan Africa, but population-level estimates of incidence are sparse. METHODS: We measured HSV-2 prevalence from cross-sectional serological data among adults aged 18-49 years in 2 south-central Uganda communities (fishing, inland). We identified risk factors for seropositivity, then inferred age patterns of HSV-2 with a Bayesian catalytic model. RESULTS: HSV-2 prevalence was 53.6% (n = 975/1819; 95% confidence interval, 51.3%-55.9%). Prevalence increased with age, was higher in the fishing community, and among women, reaching 93.6% (95% credible interval, 90.2%-96.6%) by age 49 years. Factors associated with HSV-2 seropositivity included more lifetime sexual partners, HIV positive status, and lower education. HSV-2 incidence peakied at age 18 years for women and 19-20 years for men. HIV prevalence was up to 10-fold higher in HSV-2-positive individuals. CONCLUSIONS: HSV-2 prevalence and incidence were extremely high, with most infections occurring in late adolescence. Interventions against HSV-2, such as future vaccines or therapeutics, must target young populations. Remarkably higher HIV prevalence among HSV-2-positive individuals underscores this population as a priority for HIV prevention.

Exploring HIV/AIDS investigator perceptions of equity within research partnerships between low-and middle-income and high-income countries: a pilot survey.

BACKGROUND: Recommendations for research partnerships between low- and middle-income countries (LMICs) and high-income countries (HICs) stress the importance of equity within the collaboration. However, there is limited knowledge of the practical challenges and successes involved in establishing equitable research practices. This study describes the results of a pilot survey assessing key issues on LMIC/HIC partnership equity within HIV/AIDS research collaborations and compares perspectives of these issues between LMIC- and HIC-based investigators. METHODS: Survey participants were selected using clustered, random sampling and snowball sampling. Responses were compared between LMIC and HIC respondents using standard descriptive statistics. Qualitative respondent feedback was analyzed using a combination of exploratory and confirmatory thematic analysis. RESULTS: The majority of categories within four themes (research interests and resources; leadership, trust, and communication; cultural and ethical competence; representation and benefits) demonstrated relative consensus between LMIC and HIC respondents except for 'lack of trust within the partnership' which was rated as a more pronounced challenge by LMIC respondents. However, subcategories within some of the themes had significant differences between respondent groups including: equitable setting of the research agenda, compromise within a partnership, the role of regulatory bodies in monitoring partnerships for equity, and post-study access to research technology. CONCLUSIONS: These efforts serve as a proof-of-concept survey characterizing contemporary issues around international research partnership equity. The frequency and severity of specific equity issues can be assessed, highlighting similarities versus differences in experiences between LMIC and HIC partners as potential targets for further discussion and evaluation.

HIV Prevention and Treatment Behavior Change and the Situated Information Motivation Behavioral Skills (sIMB) Model: A Qualitative Evaluation of a Community Health Worker Intervention in Rakai, Uganda.

A community health worker (CHW) model can promote HIV prevention and treatment behaviors, especially in highly mobile populations. In a fishing community in Rakai, Uganda, the Rakai Health Sciences Program implemented a CHW HIV intervention called Health Scouts. The situated Information, Motivation, and Behavioral Skills (sIMB) framework informed the design and a qualitative evaluation of the intervention. We interviewed 51 intervention clients and coded transcripts informed by sIMB framework dimensions. Clients reported that Health Scouts provided information about HIV prevention and treatment behaviors and helped them manage personal and social motivations to carry out health-promoting behavior. Prominent barriers which moved clients away from behavior change included daily pill burdens, anticipated stigma, serostatus disclosure, substance use at social gatherings, and anticipated reactions of partners. Our study adds to the evidence establishing CHWs as facilitators of behavior change, positioned to offer supportive encouragement and navigate contextualized circumstances.

Prevalence and Predictors of Persistent Human Immunodeficiency Virus Viremia and Viral Rebound After Universal Test and Treat: A Population-Based Study.

BACKGROUND: There are limited data on individual human immunodeficiency virus (HIV) viral load (VL) trajectories at the population-level after the introduction of universal test and treat (UTT) in sub-Saharan Africa. METHODS: Human immunodeficiency virus VLs were assessed among HIV-positive participants through 3 population-based surveys in 4 Ugandan fishing communities surveyed between November 2011 and August 2017. The unit of analysis was a visit-pair (2 consecutive person-visits), which were categorized as exhibiting durable VL suppression, new/renewed VL suppression, viral rebound, or persistent viremia. Adjusted relative risks (adjRRs) and 95% confidence intervals (CIs) of persistent viremia were estimated using multivariate Poisson regression. RESULTS: There were 1346 HIV-positive participants (n = 1883 visit-pairs). The population-level prevalence of durable VL suppression increased from 29.7% to 67.9% during UTT rollout, viral rebound declined from 4.4% to 2.7%, and persistent viremia declined from 20.8% to 13.3%. Younger age (15-29 vs 40-49 years; adjRR = 1.80; 95% CI = 1.19-2.71), male sex (adjRR = 2.09, 95% CI = 1.47-2.95), never being married (vs currently married; adjRR = 1.88, 95% CI = 1.34-2.62), and recent migration to the community (vs long-term resident; adjRR = 1.91, 95% CI = 1.34-2.73) were factors associated with persistent viremia. CONCLUSIONS: Despite increases in durable VL suppression during roll out of UTT in hyperendemic communities, a substantial fraction of the population, whose risk profile tended to be younger, male, and mobile, remained persistently viremic.

Effectiveness of Voluntary Medical Male Circumcision for Human Immunodeficiency Virus Prevention in Rakai, Uganda.

BACKGROUND: The efficacy of voluntary male medical circumcision (VMMC) for human immunodeficiency virus (HIV) prevention in men was demonstrated in 3 randomized trials. This led to the adoption of VMMC as an integral component of the United States President's Emergency Plan for AIDS Relief (PEPFAR) combination HIV prevention program in sub-Saharan Africa. However, evidence on the individual-level effectiveness of VMMC programs in real-world, programmatic settings is limited. METHODS: A cohort of initially uncircumcised, non-Muslim, HIV-uninfected men in the Rakai Community Cohort Study in Uganda was followed between 2009 and 2016 during VMMC scale-up. Self-reported VMMC status was collected and HIV tests performed at surveys conducted every 18 months. Multivariable Poisson regression was used to estimate the incidence rate ratio (IRR) of HIV acquisition in newly circumcised vs uncircumcised men. RESULTS: A total of 3916 non-Muslim men were followed for 17 088 person-years (PY). There were 1338 newly reported VMMCs (9.8/100 PY). Over the study period, the median age of men adopting VMMC declined from 28 years (interquartile range [IQR], 21-35 years) to 22 years (IQR, 18-29 years) (P for trend < .001). HIV incidence was 0.40/100 PY (20/4992.8 PY) among newly circumcised men and 0.98/100 PY (118/12 095.1 PY) among uncircumcised men with an adjusted IRR of 0.47 (95% confidence interval, .28-.78). The effectiveness of VMMC was sustained with increasing time from surgery and was similar across age groups and calendar time. CONCLUSIONS: VMMC programs are highly effective in preventing HIV acquisition in men. The observed effectiveness is consistent with efficacy in clinical trials and supports current recommendations that VMMC is a key component of programs to reduce HIV incidence.

Novel community health worker strategy for HIV service engagement in a hyperendemic community in Rakai, Uganda: A pragmatic, cluster-randomized trial.

BACKGROUND: Effective implementation strategies are needed to increase engagement in HIV services in hyperendemic settings. We conducted a pragmatic cluster-randomized trial in a high-risk, highly mobile fishing community (HIV prevalence: approximately 38%) in Rakai, Uganda, to assess the impact of a community health worker-delivered, theory-based (situated Information, Motivation, and Behavior Skills), motivational interviewing-informed, and mobile phone application-supported counseling strategy called "Health Scouts" to promote engagement in HIV treatment and prevention services. METHODS AND FINDINGS: The study community was divided into 40 contiguous, randomly allocated clusters (20 intervention clusters, n = 1,054 participants at baseline; 20 control clusters, n = 1,094 participants at baseline). From September 2015 to December 2018, the Health Scouts were deployed in intervention clusters. Community-wide, cross-sectional surveys of consenting 15 to 49-year-old residents were conducted at approximately 15 months (mid-study) and at approximately 39 months (end-study) assessing the primary programmatic outcomes of self-reported linkage to HIV care, antiretroviral therapy (ART) use, and male circumcision, and the primary biologic outcome of HIV viral suppression (<400 copies/mL). Secondary outcomes included HIV testing coverage, HIV incidence, and consistent condom use. The primary intent-to-treat analysis used log-linear binomial regression with generalized estimating equation to estimate prevalence risk ratios (PRR) in the intervention versus control arm. A total of 2,533 (45% female, mean age: 31 years) and 1,903 (46% female; mean age 32 years) residents completed the mid-study and end-study surveys, respectively. At mid-study, there were no differences in outcomes between arms. At end-study, self-reported receipt of the Health Scouts intervention was 38% in the intervention arm and 23% in the control arm, suggesting moderate intervention uptake in the intervention arm and substantial contamination in the control arm. At end-study, intention-to-treat analysis found higher HIV care coverage (PRR: 1.06, 95% CI: 1.01 to 1.10, p = 0.011) and ART coverage (PRR: 1.05, 95% CI: 1.01 to 1.10, p = 0.028) among HIV-positive participants in the intervention compared with the control arm. Male circumcision coverage among all men (PRR: 1.05, 95% CI: 0.96 to 1.14, p = 0.31) and HIV viral suppression among HIV-positive participants (PRR: 1.04, 95% CI: 0.98 to 1.12, p = 0.20) were higher in the intervention arm, but differences were not statistically significant. No differences were seen in secondary outcomes. Study limitations include reliance on self-report for programmatic outcomes and substantial contamination which may have diluted estimates of effect. CONCLUSIONS: A novel community health worker intervention improved HIV care and ART coverage in an HIV hyperendemic setting but did not clearly improve male circumcision coverage or HIV viral suppression. This community-based, implementation strategy may be a useful component in some settings for HIV epidemic control. TRIAL REGISTRATION: ClinicalTrials.gov NCT02556957.

HIV care and treatment models and their association with medication possession ratio among treatment-experienced adults in three African countries.

OBJECTIVE: How clinics structure the delivery of antiretroviral therapy (ART) services may influence patient adherence. We assessed the relationship between models of HIV care delivery and adherence as measured by medication possession ratio (MPR) among treatment-experienced adults in Tanzania, Uganda and Zambia. METHODS: Eighteen clinics were grouped into three models of HIV care. Model 1-Traditional and Model 2-Mixed represented task-sharing of clinical services between physicians and clinical officers, distinguished by whether nurses played a role in clinical care; in Model 3-Task-Shifted, clinical officers and nurses shared clinical responsibilities without physicians. We assessed MPR among 3,419 patients and calculated clinic-level MPR summaries. We then calculated the mean differences of percentages and adjusted residual ratio (aRR) of the association between models of care and incomplete adherence, defined as a MPR <90%, adjusting for individual-level characteristics. RESULTS: In the adjusted analysis, patients in Model 1-Traditional were more likely than patients in Model 2-Mixed to have MPR <90% (aRR = 1.60, 95% CI 1-2.48). Patients in Model 1-Traditional were no more likely than patients in Model 3-Task-Shifted to have a MPR <90% (aRR = 1.58, 95% 0.88-2.85). There was no evidence of differences in MPR <90% between Model 2-Mixed and Model 3-Task-Shifted (aRR = 0.99, 95% CI 0.59-1.66). CONCLUSION: Non-physician-led ART programmes were associated with adherence levels as good as or better than physician-led ART programmes. Additional research is needed to optimise models of care to support patients on lifelong treatment.

Qualitative Assessment of Barriers and Facilitators of PrEP Use Before and After Rollout of a PrEP Program for Priority Populations in South-central Uganda.

Uganda piloted HIV pre-exposure prophylaxis (PrEP) for priority populations (sex workers, fishermen, truck drivers, discordant couples) in 2017. To assess facilitators and barriers to PrEP uptake and adherence, we explored perceptions of PrEP before and experiences after rollout among community members and providers in south-central Uganda. We conducted 75 in-depth interviews and 12 focus group discussions. We analyzed transcripts using a team-based thematic framework approach. Partners, family, peers, and experienced PrEP users provided adherence support. Occupational factors hindered adherence for sex workers and fishermen, particularly related to mobility. Pre-rollout concerns about unskilled/untrained volunteers distributing PrEP and price-gouging were mitigated. After rollout, awareness of high community HIV risk and trust in PrEP effectiveness facilitated uptake. PrEP stigma and unexpected migration persisted as barriers. Community-initiated, tailored communication with successful PrEP users may optimize future engagement by addressing fears and rumors, while flexible delivery and refill models may facilitate PrEP continuation and adherence.

RESUMEN: En 2017, Uganda introdujo profilaxis pre-exposición (PrEP), dirigida a las populaciones con alto riesgo de contraer al VIH (trabajadoras sexuales, pescadores, camioneros, parejas sero-discordantes). Para investigar facilitadores y barreras para la adopción y la adherencia a la PrEP, exploramos percepciones de PrEP antes y después de su introducción en Uganda. Realizamos 75 entrevistas y 12 grupos focales con miembros de la comunidad y trabajadores de salud. Analizamos las transcripciones temáticamente usando un marco de referencia. Parejas, familias, compañeros, y clientes usando PrEP apoyaron a los demás mantener adherencia. Movilidad fue una barrera para la adherencia a la PrEP para trabajadoras sexuales y pescadores. Preocupaciones sobre el entrenamiento de los distribuidores de PrEP y la especulación de precios no fueron realizadas. Percepciones del riesgo del VIH y confianza en la eficacia de PrEP facilitaron su adopción. Estigma y migración inesperada persistieron como barreras para la adopción de PrEP. Comunicaciones manejadas por clientes usando PrEP pueden motivar interés en PrEP y abordar rumores. Sistemas flexibles del entrego y la recarga de medicinas pueden permitir continuación de, y adherencia a, la PrEP.

The Promise and Peril of Mobile Phones for Youth in Rural Uganda: Multimethod Study of Implications for Health and HIV.

BACKGROUND: In East Africa, where landlines are used by 1% of the population and access to the internet is limited, owning a cell phone is rapidly becoming essential for acquiring information and resources. Our analysis illuminates the perils and potential promise of mobile phones with implications for future interventions to promote the health of adolescents and young adults (AYAs) and to prevent HIV infection. OBJECTIVE: The aim of this study is to describe the current state of AYAs' phone use in the region and trace out the implications for mobile health interventions. METHODS: We identified 2 trading centers that were representative of southern Uganda in terms of key demographics, proportion of cell phone ownership, and community HIV prevalence. We stratified the sample of potential informants by age group (15-19 years and 20-24 years), gender, and phone ownership and randomly sampled 31 key informant interview participants within these categories. In addition, we conducted 24 ethnographic participant observations among AYAs in the communities of study. RESULTS: AYA frequently reported barriers to using their phones, such as difficulty accessing electricity. Nearly all AYAs used mobile phones to participate in the local economy and communicate with sexual partners. Phone use was frequently a point of contention between sexual partners, with many AYAs reporting that their sexual partners associated phone use with infidelity. Few AYAs reported using their phones for health-related purposes, with most getting health information in person from health workers. However, most AYAs reported an instance when they used their phone in an emergency, with childbirth-related emergencies being the most common. Finally, most AYAs reported that they would like to use their phones for health purposes and specifically stated that they would like to use their mobile phones to access current HIV prevention information. CONCLUSIONS: This study demonstrates how mobile phones are related to income-generating practices in the region and communication with sexual partners but not access to health and HIV information. Our analysis offers some explanation for our previous study, which suggested an association between mobile phone ownership, having multiple sexual partners, and HIV risk. Mobile phones have untapped potential to serve as tools for health promotion and HIV prevention.

Adaptive Viral Load Monitoring Frequency to Facilitate Differentiated Care: A Modeling Study From Rakai, Uganda.

BACKGROUND: After scale-up of antiretroviral therapy (ART), routine annual viral load monitoring has been adopted by most countries, but reduced frequency of viral load monitoring may offer cost savings in resource-limited settings. We investigated if viral load monitoring frequency could be reduced while maintaining detection of treatment failure. METHODS: The Rakai Health Sciences Program performed routine, biannual viral load monitoring on 2489 people living with human immunodeficiency virus (age ≥15 years). On the basis of these data, we built a 2-stage simulation model to compare different viral load monitoring schemes. We fit Weibull regression models for time to viral load >1000 copies/mL (treatment failure), and simulated data for 10 000 individuals over 5 years to compare 5 monitoring schemes to the current viral load testing every 6 months and every 12 months. RESULTS: Among 7 monitoring schemes tested, monitoring every 6 months for all subjects had the fewest months of undetected failure but also had the highest number of viral load tests. Adaptive schemes using previous viral load measurements to inform future monitoring significantly decreased the number of viral load tests without markedly increasing the number of months of undetected failure. The best adaptive monitoring scheme resulted in a 67% reduction in viral load measurements, while increasing the months of undetected failure by <20%. CONCLUSIONS: Adaptive viral load monitoring based on previous viral load measurements may be optimal for maintaining patient care while reducing costs, allowing more patients to be treated and monitored. Future empirical studies to evaluate differentiated monitoring are warranted.

HIV Prevention Efforts and Incidence of HIV in Uganda.

BACKGROUND: To assess the effect of a combination strategy for prevention of human immunodeficiency virus (HIV) on the incidence of HIV infection, we analyzed the association between the incidence of HIV and the scale-up of antiretroviral therapy (ART) and medical male circumcision in Rakai, Uganda. Changes in population-level viral-load suppression and sexual behaviors were also examined. METHODS: Between 1999 and 2016, data were collected from 30 communities with the use of 12 surveys in the Rakai Community Cohort Study, an open, population-based cohort of persons 15 to 49 years of age. We assessed trends in the incidence of HIV on the basis of observed seroconversion data, participant-reported use of ART, participant-reported male circumcision, viral-load suppression, and sexual behaviors. RESULTS: In total, 33,937 study participants contributed 103,011 person-visits. A total of 17,870 persons who were initially HIV-negative were followed for 94,427 person-years; among these persons, 931 seroconversions were observed. ART was introduced in 2004, and by 2016, ART coverage was 69% (72% among women vs. 61% among men, P<0.001). HIV viral-load suppression among all HIV-positive persons increased from 42% in 2009 to 75% by 2016 (P<0.001). Male circumcision coverage increased from 15% in 1999 to 59% by 2016 (P<0.001). The percentage of adolescents 15 to 19 years of age who reported never having initiated sex (i.e., delayed sexual debut) increased from 30% in 1999 to 55% in 2016 (P<0.001). By 2016, the mean incidence of HIV infection had declined by 42% relative to the period before 2006 (i.e., before the scale-up of the combination strategy for HIV prevention) - from 1.17 cases per 100 person-years to 0.66 cases per 100 person-years (adjusted incidence rate ratio, 0.58; 95% confidence interval [CI], 0.45 to 0.76); declines were greater among men (adjusted incidence rate ratio, 0.46; 95% CI, 0.29 to 0.73) than among women (adjusted incidence rate ratio, 0.68; 95% CI, 0.50 to 0.94). CONCLUSIONS: In this longitudinal study, the incidence of HIV infection declined significantly with the scale-up of a combination strategy for HIV prevention, which provides empirical evidence that interventions for HIV prevention can have a population-level effect. However, additional efforts are needed to overcome disparities according to sex and to achieve greater reductions in the incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others.).

Cell Phones, Sexual Behaviors and HIV Prevalence in Rakai, Uganda: A Cross Sectional Analysis of Longitudinal Data.

Cell phones have increased communication and connection across the globe and particularly in sub-Saharan Africa-with potential consequences for the HIV epidemic. We examined the association among ownership of cell phones, sexual behaviors (number of sexual partners, alcohol use before sex, inconsistent condom use), and HIV prevalence. Data were from four rounds (2010-2016) of the Rakai Community Cohort Study (N = 58,275). Sexual behaviors and HIV prevalence were compared between people who owned a cell phone to people who did not own a cell phone. We stratified analysis by younger (15-24 years) and older (25+ years) age groups and by gender. Using logistic regression and after adjusting for sociodemographic characteristics, we found cell phone ownership was independently associated with increased odds of having two or more sexual partners in the past 12 months across age and gender groups (young men AOR 1.67, 95% CI 1.47-1.90; young women AOR 1.28 95% CI 1.08-1.53; older men AOR 1.54 95% CI 1.41-1.69; older women AOR 1.44 95% CI 1.26-1.65). Interestingly, young men who owned cell phones had decreased odds of using condoms inconsistently (AOR 0.66, 95% CI 0.57-0.75). For young women, cell phone ownership was associated with increased odds of using alcohol before sex (AOR 1.38 95% CI 1.17-1.63) and increased odds of inconsistent condom use (AOR 1.40, 95% 1.17-1.67). After adjusting for sociodemographic characteristics, only young women who owned cell phones had increased odds of being HIV positive (AOR 1.27 95% CI 1.07-1.50). This association was not mediated by sexual behaviors (Adjusted for sociodemographic characteristics and sexual behaviors AOR 1.24, 95% CI 1.05-1.46). While cell phone ownership appears to be associated with increased HIV risk for young women, we also see a potential opportunity for future cell phone-based health interventions.

Qualitative insights into implementation, processes, and outcomes of a randomized trial on peer support and HIV care engagement in Rakai, Uganda.

BACKGROUND: People living with human immunodeficiency virus (HIV) who have not yet initiated antiretroviral therapy (ART) can benefit from being engaged in care and utilizing preventive interventions. Community-based peer support may be an effective approach to promote these important HIV services. METHODS: After conducting a randomized trial of the impact of peer support on pre-ART outcomes, we conducted a qualitative evaluation to better understand trial implementation, processes, and results. Overall, 75 participants, including trial participants (clients), peer supporters, and clinic staff, participated in 41 in-depth interviews and 6 focus group discussions. A situated Information Motivation, and Behavioral skills model of behavior change was used to develop semi-structured interview and focus group guides. Transcripts were coded and thematically synthesized. RESULTS: We found that participant narratives were generally consistent with the theoretical model, indicating that peer support improved information, motivation, and behavioral skills, leading to increased engagement in pre-ART care. Clients described how peer supporters reinforced health messages and helped them better understand complicated health information. Peer supporters also helped clients navigate the health system, develop support networks, and identify strategies for remembering medication and clinic appointments. Some peer supporters adopted roles beyond visiting patients, serving as a bridge between the client and his or her family, community, and health system. Qualitative results demonstrated plausible processes by which peer support improved client engagement in care, cotrimoxazole use, and safe water vessel use. Challenges identified included insufficient messaging surrounding ART initiation, lack of care continuity after ART initiation, rare breaches in confidentiality, and structural challenges. CONCLUSIONS: The evaluation found largely positive perceptions of the peer intervention across stakeholders and provided valuable information to inform uptake and scalability of the intervention. Study findings also suggest several areas for improvement for future implementation of pre-ART peer support programs. TRIAL REGISTRATION: NCT01366690 . Registered June 2, 2011.

Identifying models of HIV care and treatment service delivery in Tanzania, Uganda, and Zambia using cluster analysis and Delphi survey.

BACKGROUND: Organization of HIV care and treatment services, including clinic staffing and services, may shape clinical and financial outcomes, yet there has been little attempt to describe different models of HIV care in sub-Saharan Africa (SSA). Information about the relative benefits and drawbacks of different models could inform the scale-up of antiretroviral therapy (ART) and associated services in resource-limited settings (RLS), especially in light of expanded client populations with country adoption of WHO's test and treat recommendation. METHODS: We characterized task-shifting/task-sharing practices in 19 diverse ART clinics in Tanzania, Uganda, and Zambia and used cluster analysis to identify unique models of service provision. We ran descriptive statistics to explore how the clusters varied by environmental factors and programmatic characteristics. Finally, we employed the Delphi Method to make systematic use of expert opinions to ensure that the cluster variables were meaningful in the context of actual task-shifting of ART services in SSA. RESULTS: The cluster analysis identified three task-shifting/task-sharing models. The main differences across models were the availability of medical doctors, the scope of clinical responsibility assigned to nurses, and the use of lay health care workers. Patterns of healthcare staffing in HIV service delivery were associated with different environmental factors (e.g., health facility levels, urban vs. rural settings) and programme characteristics (e.g., community ART distribution or integrated tuberculosis treatment on-site). CONCLUSIONS: Understanding the relative advantages and disadvantages of different models of care can help national programmes adapt to increased client load, select optimal adherence strategies within decentralized models of care, and identify differentiated models of care for clients to meet the growing needs of long-term ART patients who require more complicated treatment management.