Cancer Consortium, and P30 AI027757 CFAR New During HIV infection, a reservoir of long-lived latently infected cells is established that persists during antiretroviral therapy (ART) and is the source of virus replication after treatment cessation. A better understanding of when viruses enter the HIV reservoir (reservoir seeding) will aid efforts to target these long-lived HIV infected cells during their establishment. We studied women infected at two different times with two genetically distinct HIV strains (called superinfection), and assessed the genetic relationship between sequences of the HIV strains that circulated throughout infection (pre-ART HIV RNA sequences) and the HIV strains that persisted in reservoir cells (HIV DNA sequences during ART). We estimated when HIV DNA sequences entered the reservoir by identifying the time the most genetically related HIV RNA sequence was detected. In most cases we observed that viruses in the reservoir included both the initial and superinfecting lineages, suggesting reservoir seeding occurs throughout HIV infection. However, the majority of HIV sequences entered the reservoir near the time of ART initiation, suggesting that novel strategies that aim to reduce reservoir size should focus on times immediately prior to ART.

We compared change in HIV reservoir DNA following continued antiretroviral therapy (ART) vs short treatment interruption (TI) in early ART-treated Kenyan infants. While HIV DNA in the reservoir decayed with continued ART, HIV DNA levels were similar to pre-TI HIV DNA reservoir levels in most children after short TI.

Identifying determinants of HIV reservoir levels may inform novel viral eradication strategies. Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) co-infections were assessed as predictors of HIV proviral DNA level in 26 HIV RNA-suppressed Kenyan children starting antiretroviral therapy (ART) before 7 months of age. Earlier acquisition of CMV and EBV, and higher cumulative burden of systemic EBV DNA viremia were each associated with higher HIV DNA level in the reservoir after 24 months of ART, independent of HIV RNA levels over time. These data suggest delaying or containing CMV and EBV viremia may be novel strategies to limit HIV reservoir formation.