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.