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 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. 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. 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. One concern with increased use of ARVs in sub-Saharan Africa is the extent by which viral resistance will develop over time among the non-clade B HIV-1-infected individuals. In a study done in collaboration with our colleagues at the University of Cape Town, baseline drug resistance among pregnant women initiating ART was low, observed in 12/167 (7%) of women. However, viremia post-treatment initiation was common in these women, and by measuring antiretroviral drug levels prior to viremia we were able to show that 90% of viremic episodes were due to non-adherence to ART in this population as opposed to pre-treatment drug resistance suggesting that public health efforts to support drug adherence as opposed to screening for pre-treatment drug resistance would be more important in this 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. Examining the prevalence and predictors of persistent HIV viremia and viral rebound during the current test and treat era, we found that persistent viremia declined from 20.7 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. Despite increases in durable VL suppression during roll-out of test and treat in hyperendemic communities, a substantial fraction of the population, whose risk profile tended to be younger, male, and mobile, remained persistently viremic. Effective implementation strategies are needed to increase engagement in HIV services to achieve maximum HIV epidemic control. We conducted a cluster randomized trial to assess the impact of community health workers equipped with a novel mobile phone-based counseling strategy to improve uptake of HIV treatment and prevention services. Despite improvements in HIV care and ART service uptake, the intervention did not clearly improve male circumcision coverage or HIV suppression. Early mortality in the first year of ART therapy continues to challenge the health benefits of treatment particularly among patients presenting with late change disease. We hypothesized that as treatment guidelines changed in Uganda to earlier initiation, significant mortality declines would occur. We conducted a retrospective cohort analysis on 6800 HIV-infected adults aged 18+ years who started ART between 2005 and 2016 at the urban-based Mengo Hospital HIV clinic to examine trends in mortality over time. The proportion of patients initiating ART with CD4 count 100 cells/ul decreased from 46% to 27% (p <0.001) and those initiating with WHO stage III or IV disease significantly decreased from 50% to 22% (p<0.001) over this time. Mortality in the first year of ART decreased by 70% over this corresponding time period, from 8.7/100 person-years to 2.5/100 person-years (p<0.001). Changing treatment guidelines and strategies to implement earlier initiation of ART have had a dramatic impact on early mortality in our setting.