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

National Institute Of Allergy And Infectious Diseases

Investigators

Linked publications, trials & patents

Abstract

The introduction of 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 assessed the effectiveness of our VMMC program outside of the clinical trial setting and showed that effectiveness was sustained with increasing time from surgery and was similar across age groups. We assessed migration patterns using data collected between August 2011 and January 2015 from the RCCS. 29% (n=6718) of participants who migrated over 2 years were significantly more likely to be young and female. Compared to long-term residents, risk of HIV-infection was significantly elevated in women and men in the first two years following migration (women: adjIRR=1.92, 95%CI: 1.52-2.43; men: adjIRR=1.75, 95%CI: 1.33-2.33). While HIV incidence significantly declined among residents and non-recent in-migrants with scale-up of combination HIV prevention, it did not decline among recent in-migrants. HIV-infected migrants, largely women, are less likely to use ART and differentially move into hotspot fishing communities. We find that migrants moving into hotspots (prevalence 40%) had significantly higher HIV prevalence than migrants moving elsewhere, but that out-migrants from hotspots dispersed broadly, contributing minimally to HIV burden in individual destination locations. The COVID-19 pandemic presented a challenge to continuity of HIV prevention and treatment services with a risk of halting the gains made in reducing HIV incidence. We examined population trends in HIV service delivery, viral suppression and incidence before and during the COVID-19 era in Rakai. We found a slight decrease in HIV testing during the COVID-19 era but ART use and male circumcision rates increased while viral load suppression remained high above 90%. HIV incidence continued to decline from 0.48/100 person years immediately before Covid to 0.35/100 person years during Covid. In our setting, community based outreach strategies contributed to sustained HIV service delivery and continued success in HIV prevention programs. Pre-exposure prophylaxis (PrEP) is a key component of our HIV combination prevention strategy among high-risk HIV uninfected clients. During the early phase of our PrEP rollout among key populations (fisher folk, commercial sex workers, adolescent girls and truck drivers) we observed high uptake of PrEP services with 92.2% of eligible clients enrolled and started on PrEP. Despite this uptake, retention was poor with a medium retention of 45.4 days overall with male clients being at higher risk of discontinuation of PrEP In a follow-up qualitative study among PrEP users, we found that PrEP stigma and unexpected migration issues among clients were major barriers to continuation with PrEP Flexible community led delivery models may improve PrEP retention among these highly mobile clients. PrEP programs have focused on key populations at highest risk of HIV for maximum impact, however, we assessed PrEP eligibility among our general population in Rakai and found a high rate (29%) of eligibility which was also associated with an elevated HIV incidence in our general population. Wider access to PrEP in our setting will be key to achieving HIV epidemic control. PrEP eligibility was highly dynamic among HIV-negative men and women of reproductive age (15-49 years) in rural Uganda, providing some of the first empirical evidence of PrEP eligibility changes in sub-Saharan Africa. Individuals transitioned through periods of acquisition, discontinuation, and resumption of PrEP eligibility. Our findings highlight the importance of adapting PrEP delivery strategies to the changing HIV risk profiles among clients targeted for HIV prevention strategies. Hotspots of HIV transmission have been thought to be a source of ongoing spread of HIV and potentially an important target for HIV prevention efforts. Using phylogenetic analysis, we were able to infer partial HIV transmission networks including the directionality of transmission. Using RCCS residence and migration data, HIV transmission flows were quantified between high and low prevalence areas. Most transmissions (89.2%) occurred within inland low prevalence settings while a minority (5.7%) occurred within high prevalence fishing communities. Contrary to what was hypothesized, more transmissions were documented going from low prevalence inland areas to high prevalence fishing communities (3.7%) while only 1.3% of transmissions were observed going from high prevalence fishing communities to low prevalence inland areas. Our findings suggest that geographic focus on HIV hotspots may not achieve epidemic control and wider prevention efforts are needed. 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. Redefining viral load suppression (VLS) using lower cutpoints could impact progress towards the UNAIDS 95-95-95 targets. We assessed impacts of lowering the VLS cutpoint on achieving the 95-95-95 VLS target in the Rakai Community Cohort Study. Population VLS fell from 86% to 84% and 76%, respectively, after lowering VLS cutpoints from <1,000 to <200 and <50 copies/mL. The fraction of viremic persons increased by 17% after lowering the VLS cutpoint from <1,000 to <200 copies/mL.Our findings suggest that lowering VLS cutpoints would result in a substantial population-level increase in the number of individuals requiring enhanced clinical monitoring (e.g., intensive ART adherence support, increased care appointment frequency). Long-acting injfectable (LAI) ART is a new tool on the horizon for both treatment and prevention in Uganda. We conducted a study among clients and healthcare workers to assess the acceptability of LAI ART in our treatment cohort. LAI ART has great potential as an additional ART option for people living with HIV. It may be particularly beneficial for those who have challenges with adherence to a daily pill regimen and who are virally unsuppressed. We found that virally unsuppressed individuals and health workers were generally enthusiastic about the potential benefits of LA ART, while also noting potential barriers to use. Given the challenges with oral ART, future research and programmatic efforts should explore whether and how to offer LAI ART to virally unsuppressed individuals. We hope our findings can help program planners anticipate and address potential challenges as LAI ART options are considered in Uganda and similar settings. Rollout of combination HIV interventions (CHIs) has led to significant declines in HIV incidence in sub-Saharan Africa; however, population-level data on non-HIV STI burden in the context of CHIs is rare. We measured population prevalence of Chlamydia trachomatis (chlamydia), Neisseria gonorrhoeae (gonorrhea), Trichomonas vaginalis (trichomoniasis), syphilis, and