Antiretroviral therapy intensification with dolutegravir and/or maraviroc did not affect HIV-1 cell-associated DNA, RNA, and 2-LTR circles over twelve weeks

Background Neurocognitive impairment (NCI) among people living with HIV (PWH) on antiretroviral therapy (ART) may result from residual viral replication. The A5324 trial found ART intensification with dolutegravir (DTG) +/- maraviroc (MVC) did not affect NCI in PWH. We evaluated the impact of ART intensification on peripheral virological measures during the first 12 weeks of intensification. Methods A5324 was a randomized, double-blind, placebo-controlled, 96-week trial of ART intensification with either dual placebo (PBO), DTG+PBO, or DTG+MVC in PWH with NCI on ART that were naïve to integrase strand transfer inhibitors (INSTI) and MVC. At baseline and weeks 2, 4, and 12, HIV-1 RNA was measured in plasma by a low-copy assay, while HIV-1 cell-associated DNA (caDNA), cell-associated unspliced RNA (caRNA), and cell-associated 2-LTR circles (ca2LTR) were quantified from PBMC by ddPCR. Results 171 participants were randomized as follows: 59 dual PBO, 57 DTG+PBO, and 55 DTG+MVC. Changes in caDNA and caRNA and detection of plasma RNA did not differ between arms over 12 weeks (p > 0.05). Detection of ca2LTR was less frequent at weeks 2-4 in the DTG+MVC arm (40.4%) compared to the dual PBO (70.7%, p=0.02) or DTG+PBO (68.4%, p=0.03) arms. However, this difference diminished by week 12, and baseline ca2LTR detection in the DTG+MVC arm was lower than in the other groups. Conclusions DTG intensification had no effect on peripheral markers of HIV-1 persistence. DTG+MVC intensification reduced ca2LTR detection at weeks 2-4, though this effect did not persist to week 12. These findings indicate minimal impact of intensification on the HIV-1 peripheral reservoir, aligning with prior studies.