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 < 12 weeks old with CD4% ≥ 25% were randomized in the CHER trial to early limited ART for 40 or 96 weeks (ART-40 W, ART-96 W), or deferred ART (ART-Def). For ART-Def infants or following ART interruption in ART-40 W/ART-96 W, ART was started/re-started for clinical progression or CD4% < 25%. In 229 participants, HIV-1 proviral DNA was quantified by PCR from stored peripheral blood mononuclear cells from children who had received ≥ 24 weeks ART and two consecutive undetectable HIV-1 RNA 12–24 weeks apart. HIV-1 proviral DNA was compared between ART-Def and ART-96 W 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 = 0.0003) and 248 weeks (p = 0.0011). Higher total CD8 count at ART initiation was associated with lower HIV-1 proviral DNA at both 96 (p = 0.0225) and 248 weeks (p = 0.0398). 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 = 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.

Persistence of Unintegrated HIV DNA Associates With Ongoing NK Cell Activation and CD34+DNAM-1brightCXCR4+ Precursor Turnover in Vertically Infected Patients Despite Successful Antiretroviral Treatment

“…As expected, no association was observed between HIV reservoir and the time to any ART, including monotherapy in early years (p=0.443 for tDNA and ρ =-0.079; p=0.8567 for uDNA). These findings suggest that shades of delay in ART initiation in this cohort associate with tDNA levels and are in line with previous reports in PHIV ( 50 , 51 ). Interestingly, however, there was no relationship between uDNA levels and time to ART, suggesting that factors other than ART influence presence/absence of uDNA.…”

Weight gain in children from birth to 10 years on antiretroviral treatment

“…These results are in agreement with the findings of other studies in Africa. 34,35 Statistically significant improvements in weight gain over the 24-month research period and at each six-month follow-up visit since ART was initiated was observed. Although the focus was on changes in WAZ, there was consistent improvement in both WAZ and L/HAZ, with more rapid increases in weight as opposed to gradual increases in length or height.…”

Virological failure and its predictors among human immunodeficiency virus infected individuals on second line antiretroviral treatment in North‐East Ethiopia, 2021

“…The possible justification might be being on ART for a longer duration may expose individuals to better HIV‐related knowledge, 52 which may further improve their adherence level 53 and could result in a good viral suppression rate. A similar study indicated longer ART duration is key to HIV‐ DNA reduction 54 . Whereas, a study conducted in Mekelle showed that the duration of ART was not significantly related to SLART failure 41 .…”

“…A similar study indicated longer ART duration is key to HIV-DNA reduction. 54 Whereas, a study conducted in Mekelle showed that the duration of ART was not significantly related to SLART failure. 41 Against the result of this study, evidence from South Africa showed that as the duration of ART increases the likelihood of TF increases.…”