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… Click to show full 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 <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 percent (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 percent (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 to non-nucleoside 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.
               
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