International Center for Excellence in Research (ICER) in Uganda: Impact of ARVs

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications & trials

Abstract

The expanded access to HIV antiretroviral medication (ARVs) in Africa has resulted in substantial reductions in morbidity and mortality. This project is studying the impact of ARVs on community level incidence in the Rakai Community Cohort Study (RCCS) in Uganda and using phylogenetics to identify hotspots of HIV transmission and areas where HIV prevention efforts need to be intensified. We have shown complete elimination of transmission among discordant couples on ARVs and continue to scale up treatment as prevention. Our combination prevention study has proven the impact of effectively implemented programs on HIV incidence in the general Rakai population. Our study was the first to provide evidence of the beneficial impact of combination prevention on rural communities in sub-Saharan Africa. Despite this success, challenges remain at achieving epidemic control and we continue to describe important implementation challenges as we scale up combination prevention. We have previously highlighted the high prevalence of migration among rural populations in Uganda which has implications for those enrolled in HIV care at fixed facilities. We used data from 40 communities (2015-2020) in the Rakai Community Cohort Study to estimate incidence of facility switching and viral rebound. 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. We also examined the impact of migration at the household level in Rakai and observed that non-migrating members of households where other members migrated to outside communities had higher HIV prevalence compared to households where no members migrated highlighting the importance of incorporating migration risk into HIV prevention efforts. 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. In our research population, migrants exhibited a significantly higher combined prevalence of curable STIs (gonorrhoea, chlamydia, high-titre syphilis and trichomoniasis) as compared with long-term residents (34.4% vs 24.2%). 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; and among women (38.8% in migrants vs 27.8% in long-term residents highlighting the importance of migration on the risk of both HIV and non-HIV STIs in our setting. HIV incidence in eastern and southern Africa has historically been concentrated among girls and women aged 15–24 years. As new cases decline with HIV interventions, population-level infection dynamics may shift by age and gender. We integrated population-based surveillance in the Rakai Community Cohort Study and longitudinal deep-sequence viral phylogenetics to assess how HIV incidence and population groups driving transmission have changed from 2003 to 2018 in Uganda. We observed 1,117 individuals in the incidence cohort and 1,978 individuals in the transmission cohort. HIV viral suppression increased more rapidly in women than men, however incidence declined more slowly in women than men. We found that age-specific transmission flows shifted: whereas HIV transmission to girls and women (aged 15–24 years) from older men declined by about one-third, transmission to women (aged 25–34 years) from men that were 0–6 years older increased by half in 2003 to 2018. Based on changes in transmission flows, we estimated that closing the gender gap in viral suppression could have reduced HIV incidence in women by half in 2018. This study suggests that HIV programmes to increase HIV suppression in men are critical to reduce incidence in women, close gender gaps in infection burden and improve men’s health in Africa. Pre-exposure prophylaxis (PrEP) is a key component of our HIV combination prevention strategy among high-risk HIV uninfected clients. PrEP programs in Uganda continue to mature with improved knowledge and flexible delivery services which our group has been monitoring for impact. We assessed the PrEP care continuum in a high HIV prevalence fishing community on the shores of Lake Victoria and found that over 85% of participants were aware of PrEP. Despite this high awareness, only 14.5% of participants reported ever using PrEP highlighting the critical importance of promoting PrEP delivery in these high risk communities. Preventing new HIV infections among adolescents and young adults is a critical focus for HIV prevention programs. We examined PrEP awareness and use among 15-24 year olds in south central Uganda between 2018 and 2023 and observed that 62.4% were aware of PrEP but less than 2% had ever taken PrEP. Efforts to reduce barriers to PrEP access, particularly among adolescents and young adults, are critical for reducing HIV incidence in this population. While antiretroviral therapy (ART) reduces AIDS-related morbidity and mortality, it is unclear if prolonged ART use among people living with HIV (PLHIV) increases the risk of hypertension. After controlling for age, sex, and body mass index, the prevalence of having all stages of high BP was increased by at least 42% in participants with more than five years of ART use with even greater risks observed for severe hypertension or hypertensive crisis developing. PLHIV on long-term ART have a higher burden of hypertension, highlighting the need for enhanced screening and integrated management in HIV programs. Tuberculosis (TB) continues to be a major challenge facing HIV treatment programs with high rates of co-infections. We examined the incidence of TB in our rural treatment population in Rakai and observed that the incidence of TB among PLHIV on ART was low in our population who started ART at an early clinical stage and continues to decrease with increasing duration on ART highlighting the importance of continued efforts to initiate ART early during the course of HIV. The antiretroviral therapy (ART) initiation policy in Uganda recommends that ART is initiated on the same day of HIV diagnosis to those who do not have contraindications. We assessed determinants of retention in ART care at the first follow-up (FFU) after same-day ART initiation and retention in long-term care beyond the FFU visit. We found that clients initiated on ART at outreach facilities had a higher risk of loss to follow-up compared to those starting ART at a facility. Retention-strengthening strategies for clients initiated on ART from outreach/mobile health service settings in tandem with same-day ART initiation efforts might improve overall identification, linkage and retention in care in our setting. Viral load monitoring (VLM) is currently being scaled up in Uganda after a decade of relying on immunologic and clinical monitoring. This provides a unique tool to investigate adherence challenges and also improve on the quality of care delivery by focusing resources on those most in need. Point of care technologies offer an opportunity to move this important monitoring tool to rural hard to reach populations such as where we work in Rakai. We qualitatively explored the perceived feasibility and appropriateness of PoC VLM to address gaps along the viral load monitoring continuum in rural Uganda. 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 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).