Intensifying antiretroviral therapy (ART) with dolutegravir (DTG), with or without maraviroc (MVC), does not improve neurocognitive symptoms more than placebo in virally suppressed people living with HIV (PLWH), a U.S. study has found.
About This Study
“Antiretroviral Therapy Intensification for Neurocognitive Impairment in HIV” was published online on May 15, 2023, in Clinical Infectious Diseases. The lead author is Scott L. Letendre, M.D., of the University of California-San Diego. One study author is from ViiV Healthcare, the manufacturer of the study drugs.
Key Research Findings
The A5324 Phase 4, randomized, double-blind, placebo-controlled trial assessed the impact of adding DTG, with or without MVC, to the baseline regimens of virally suppressed PLWH with neurocognitive impairment (NCI). One hundred ninety-one participants were randomized to one of three arms: adding DTG+MVC (61 participants), DTG only (67 participants), or nothing (63 participants). Placebos replaced MVC and/or DTG in the last two arms.
Most participants were Black men (71% men, 51% Black) with a mean age of 52 years. Sixty-five percent of participants had HIV-associated neurocognitive disorder (HAND) symptoms. The study was conducted in the U.S. (n=156), Brazil (n=5), South Africa, and Thailand (n=15 each). Neurocognitive tests were adjusted for cultural relevance in each country.
The verbal learning and memory domains improved more in the DTG+MVC arm than in the other two arms, but total z-scores—a composite measure of neurocognitive impairment—improved across all study arms. Verbal tests varied across study visits, but other tests remained static. Repeat tests measured attention/working memory, executive function, fine motor skills, and information processing speed.
Discussion Highlights and Implications for Practice
The authors summarized their results by stating that they “provide strong evidence that ART intensification with currently available ART drugs is not an effective strategy to treat existing NCI in PWH who are already taking suppressive therapy.”
However, they also described study limitations that included low statistical power; study drugs that may only have worked for a subgroup of participants; non-uniform neurocognitive testing; and potential practice effects that may have affected the non-verbal domain tests.
Possible explanations reported for the findings include a lack of further suppression of neurotoxic viral products beyond what is achieved by viral suppression; comorbidities more common in PLWH causing NCI; irreversible brain injury from HIV prior to starting ART; and poor choice of study drugs—i.e., perhaps other antiretroviral drugs may be better suited for the purpose.
The study authors wrote that they plan to test stored specimen for drug concentrations and HIV RNA and DNA to determine whether these markers affected study results.