High-Dose ART Not Efficacious for Neurocognitive Impairment in Patients With HIV

High-dosage antiretroviral (ART) is not an effective treatment strategy for neurocognitive impairment (NCI) in individuals with HIV who take suppressive ART, according to study findings published in the journal Clinical Infectious Diseases

Although ART in individuals with HIV suppresses HIV below the lower limit of quantification, a substantial amount of those affected have concurrent NCI. Recent studies have shown that NCI is present in up to 69.5% of individuals with HIV, which includes those taking ART. As findings are inconclusive to whether or not ART drugs, which distribute more widely in the central nervous system, can reduce NCI, researchers aimed to assess the efficacy of adding 2 antiretroviral drugs, dolutegravir and maraviroc, to those already on ART.

Integrase and Maraviroc Intensification in Neurocognitive Dysfunction (InMIND; ClinicalTrials.gov Identifier: NCT02519777) is a phase 4, randomized, double-blinded, placebo-controlled trial where the researchers assessed whether ART intensification improved neurocognitive performance in individuals with HIV on suppressive ART. Inclusion criteria consisted of patients with HIV who were taking an ART regiment for at least 6 months that did not contain an integrase inhibitor and had plasma HIV RNA <50 copies/mL, as well as testing ≥1 standard deviation below the mean on ≥2 separate neurocognitive tests. Individuals who had severe neuropsychiatric conditions were excluded from the study.

Primary outcome was change in z-scores over a set of 6 cognitive domains (attention/working memory, executive function, fine motor skills, speed of information processing, verbal learning, verbal memory) over a timeframe of 48 weeks, compared with baseline. Neurocognitive performance change at 96 weeks from baseline was the secondary endpoint. 

A total of 191 individuals participated in the study and enrolled from April 2016 to November 2018. Most individuals were men (71%); average age, 52.

At baseline, the most used ART drugs were:

• emtricitabine (83%),
• tenofovir disoproxil fumarate (63%),
• efavirenz (32%),
• tenofovir alafenamide (27%), and
• darunavir (24%).

At baseline, all participants met criteria for NCI with an average of >4 comorbid conditions, notably:

• hypertension (74; 39%),
• hyperlipidemia (29; 15%),
• asthma (23; 12%),
• osteoarthritis (23; 12%), and
• type 2 diabetes mellitus (18; 9%).

Improvement of z-score was found from baseline to primary outcome endpoint (mean 0.25; 95% C, 0.16-0.34) across all arms of the trial.

No difference was noted between treatment and control arms (dolutegravir + placebo vs dual-placebo: P =.60, dolutegravir + maraviroc vs dual-placebo: P =.33).

Additionally, secondary endpoint found no change as well (dolutegravir + placebo vs dual-placebo: P =0.79, dolutegravir + maraviroc vs dual-placebo: P =.95). Of note, results were unchanged when adjusted for age, sex, education, study site, baseline z-score, or efavirenz use (P >.10).

In reference to intervention effect on soluble biomarkers, change in biomarkers over time did not differ by treatment arm.

Post hoc analysis on body mass index (BMI) found an increase at 96 weeks for the entire cohort (integrase effect on weight), however minimal (mean 0.32 kg/m2; 95% CI, 0.11-.074 kg/m2).

Study limitations included insufficient power of test, as well as the possibility of intervention being only beneficial in the subgroup (individuals with higher cell-associated HIV DNA or cerebrospinal fluid viral escape less likely to benefit).

The researchers concluded, “the negative findings do not support the use of ART intensification to treat this condition in PWH [persons with HIV] who are already taking stable, suppressive ART.”

Disclosures: Several study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.