Early ART-initiation and longer ART duration reduces HIV-1 proviral DNA levels in children from the CHER trial

Abstract

Background Reduction of the reservoir of latent HIV-infected cells might increase the possibility of long-term remission in individuals living with HIV. We investigated factors associated with HIV-1 proviral DNA levels in children receiving different antiretroviral therapy (ART) strategies in the children with HIV early antiretroviral therapy (CHER) trial. Methods Infants with HIV \u2009< \u200912\xa0weeks old with CD4% \u2009≥ \u200925% were randomized in the CHER trial to early limited ART for 40 or 96\xa0weeks (ART-40\xa0W, ART-96\xa0W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40\xa0W/ART-96\xa0W, ART was started/re-started for clinical progression or CD4% \u2009<\u2009 25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received \u2009≥\u2009 24\xa0weeks ART and two consecutive undetectable HIV-1 RNA 12–24\xa0weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96\xa0W at week 96, and in all arms at week 248. Factors associated with HIV-1 proviral DNA levels were evaluated using linear regression. Findings Longer duration of ART was significantly associated with lower HIV-1 proviral DNA at both 96 (p\u2009 =\u2009 0.0003) and 248\xa0weeks (p\u2009 = \u20090.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p \u2009= \u20090.0225) and 248\xa0weeks (p\u2009 = \u20090.0398). Week 248 HIV-1 proviral DNA was significantly higher in those with positive HIV-1 serology at week 84 than those with negative serology (p\u2009 =\u2009 0.0042). Intepretation Longer ART duration is key to HIV-1 proviral DNA reduction. Further understanding is needed of the effects of “immune-attenuation” through early HIV-1 exposure. Funding Wellcome Trust, National Institutes of Health, Medical Research Council.