# Antiretroviral Therapy Intensification With Dolutegravir and/or Maraviroc Did Not Affect HIV-1 Cell-Associated DNA, RNA, and 2­–LTR Circles Over 12 Weeks

## TL;DR

Adding dolutegravir and maraviroc to HIV treatment did not significantly reduce viral markers in people with HIV and neurocognitive issues.

## Contribution

Demonstrated that ART intensification with DTG and/or MVC does not significantly impact HIV-1 reservoir markers over 12 weeks.

## Key findings

- Changes in caDNA and caRNA did not differ between treatment arms over 12 weeks.
- DTG + MVC reduced ca2LTR detection at weeks 2–4 but not by week 12.
- ART intensification had minimal impact on the HIV-1 peripheral reservoir.

## Abstract

Neurocognitive impairment (NCI) among people living with human immunodeficiency virus (HIV; PWH) on antiretroviral therapy (ART) may result from residual viral replication. The A5324 trial found that ART intensification with dolutegravir (DTG) with or without 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.

The A5324 study was a randomized, double-blind, placebo (PBO)–controlled, 96-week trial of ART intensification with either dual PBO, DTG + PBO, or DTG + MVC in PWH with NCI on ART who were naive to integrase strand transfer inhibitors and MVC. At baseline and weeks 2, 4, and 12, HIV-1 RNA was measured in plasma with a low-copy assay, while HIV-1 cell-associated DNA (caDNA), cell-associated unspliced RNA (caRNA), and cell-associated 2-long terminal repeat circles (ca2LTR) were quantified from peripheral blood mononuclear cells using droplet digital polymerase chain reaction.

Of the 171 participants, 59 were randomized to dual PBO, 57 to DTG + PBO, and 55 to DTG + MVC. Changes in caDNA and caRNA and detection of plasma RNA did not differ between treatment arms over 12 weeks (P > 0.05). Detection of ca2LTR was less frequent at weeks 2–4 in the DTG + MVC arm (40.4%) than in the dual-PBO (70.7%; P =0 .02) and 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.

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 through week 12. These findings indicate the minimal impact of intensification on the HIV-1 peripheral reservoir, consistent with prior studies.

In people with HIV-1 and with neurocognitive impairment, the A5324 trial tested the effect of antiretroviral therapy (ART) intensification with either dolutegravir or dolutegravir + maraviroc. ART intensification did not significantly affect virological measures of the HIV-1 peripheral reservoir.