Review 2: "Age and Gender Profiles of HIV Infection Burden and Viraemia: Novel Metrics for HIV Epidemic Control in African Populations with High Antiretroviral Therapy Coverage"

RR:C19 Evidence Scale rating by reviewer:

• Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.

***************************************

Review: In this manuscript by Brizzi et al, the authors estimate population HIV prevalence and HIV viremia over subsequent rounds of household-based HIV screening surveys from 2013 to 2019 in inland and fishing communities (on Lake Victoria) in the Rakai Community Cohort Study in southcentral Uganda. The objectives of the analysis were: a) to evaluate changes in estimated HIV seroprevalence and HIV viremia by age and gender strata, accounting for the underlying population structures of the communities, over a time period in which universal HIV treatment (antiretroviral therapy regardless of CD4 cell count) was implemented following adoption of universal HIV treatment in Ugandan national guidelines in 2016; and b) to determine the burden profile of HIV prevalence and HIV viremia by age and gender strata over the same time period. The authors present the “burden profiles” as alternative metrics that account for the contribution of each gender and age subgroup to the total number of individuals either with HIV or exhibiting viremia.

The results show a decline in population HIV viremia from the 2013-2015 testing round to the 2019 round in both inland and fishing communities, and across gender and age strata, reflecting progress in implementation of universal testing and treatment in these communities from 2016 onward. The results of the burden profile estimates for HIV viremia show that a) despite higher proportion of persons with HIV achieving viral suppression, the burden profile of HIV viremia in fishing communities remained higher than inland communities, due to higher HIV prevalence; and b) groups that were furthest from achieving 95-95-95 UNAIDS targets (e.g., 15-19-year-old women in inland communities), did not contribute the greatest number of people with viremia: rather older age groups (e.g., women aged 20-29 years) made up a greater proportion of people with viremia despite being close to or exceeding 95-95-95 targets. 

The main conclusions of the manuscript are well supported by the data and analyses presented and provide a useful, alternative lens to consider progress in HIV control and elimination efforts by accounting for underlying population structures. One limitation of the analyses presented is that, though the authors describe the number and proportion of adults reached in their homes who accept testing, the proportion of census-enumerated adults reached in each survey round is not provided in the manuscript. Additional limitations are largely accounted for by the authors in the Discussion, including limiting the analysis to adults 15-49 (and not capturing the contribution of older adults, ≥50 years) and the assumption that first-time participants in the survey were representative of non-participants. Despite these limitations, the conclusions are supported by the results presented, in this well-written manuscript.