Predictors of intact HIV DNA levels among children in Kenya

Abstract

Objective: We determined predictors of both intact (estimate of replication-competent) and total (intact and defective) HIV DNA in the reservoir among children with HIV. Design: HIV DNA in the reservoir was quantified longitudinally in children who initiated antiretroviral therapy (ART) at less than 1 year of age using a novel cross-subtype intact proviral DNA assay that measures both intact and total proviruses. Quantitative PCR was used to measure pre-ART cytomegalovirus (CMV) viral load. Linear mixed effects models were used to determine predictors of intact and total HIV DNA levels (log10copies/million). Results: Among 65 children, median age at ART initiation was 5 months and median follow-up was 5.2 years; 86% of children had CMV viremia pre-ART. Lower pre-ART CD4+ percentage [adjusted relative risk (aRR): 0.87, 95% confidence intervals (95% CI): 0.79–0.97; P = 0.009] and higher HIV RNA (aRR: 1.21, 95% CI: 1.06–1.39; P = 0.004) predicted higher levels of total HIV DNA during ART. Pre-ART CD4+ percentage (aRR: 0.76, 95% CI: 0.65–0.89; P < 0.001), CMV viral load (aRR: 1.16, 95% CI: 1.01–1.34; P = 0.041), and first-line protease inhibitor-based regimens compared with nonnucleoside reverse transcriptase-based regimens (aRR: 1.36, 95% CI: 1.04–1.77; P = 0.025) predicted higher levels of intact HIV DNA. Conclusion: Pre-ART immunosuppression, first-line ART regimen, and CMV viral load may influence establishment and sustainment of intact HIV DNA in the reservoir.

Increased frequency and quantity of mucosal and plasma cytomegalovirus replication among Ugandan Adults Living with HIV

“…Indeed, CMV viremia is an independent risk factor for death among PLWH receiving ART [7,8]. Rates of congenital CMV among HIV-exposed infants remain elevated despite ART and early CMV replication in infants can negatively impact the establishment of the HIV reservoir in cases where they are HIV-infected [37,38]. Thus, medications to control CMV replication, such as valganciclovir or letermovir, or prevention of CMV infection through vaccination would likely be particularly valuable for PLWH.…”