The need to achieve ≥95 % adherence to HAART for treatment effectiveness may be a barrier for universal initiation at early stages of HIV. Using longitudinal data collected from 2006 to 2011 from cohort studies of MSM (MACS) and IDUs (ALIVE study), we estimated the minimum adherence needed to achieve HIV RNA suppression (<50 copies/mL), defined as the level at which at least 80 % were virally suppressed, and the odds of suppression was not significantly different than that observed with ≥95 % adherence. In the MACS, ≥80 % suppression was observed with 80-84 % adherence and the odds ratio for suppression (vs. ≥95 % adherence) was 1.43 (0.61, 3.33). In the ALIVE study where <35 % were on newer drugs, only 71.4 % were suppressed among those who reported ≥95 % adherence. Although IDUs on older HAART regimens may need to be ≥95 % adherent, concerns related to non-adherence may be less of a barrier to initiation of modern HAART regimens.

Background

Neurocognitive impairment (NCI) in people with HIV (PWH) on antiretroviral therapy (ART) is common and may result from persistent HIV replication in the central nervous system.

Methods

A5324 was a randomized, double-blind, placebo-controlled, 96-week trial of ART intensification with dolutegravir (DTG) + MVC, DTG + Placebo, or Dual - Placebo in PWH with plasma HIV RNA <50 copies/mL on ART and NCI. The primary outcome was the change on the normalized total z score (ie, the mean of individual NC test z scores) at week 48.

Results

Of 357 screened, 191 enrolled: 71% male, 51% Black race, 22% Hispanic ethnicity; mean age 52 years; mean CD4+ T-cells 681 cells/µL. Most (65%) had symptomatic HIV-associated NC disorder. Study drug was discontinued due to an adverse event in 15 (8%) and did not differ between arms (P = .17). Total z score, depressive symptoms, and daily functioning improved over time in all arms with no significant differences between them at week 48 or later. Adjusting for age, sex, race, study site, efavirenz use, or baseline z score did not alter the results. Body mass index modestly increased over 96 weeks (mean increase 0.32 kg/m2, P = .006) and did not differ between arms (P > .10).

Conclusions

This is the largest, randomized, placebo-controlled trial of ART intensification for NCI in PWH. The findings do not support empiric ART intensification as a treatment for NCI in PWH on suppressive ART. They also do not support that DTG adversely affects cognition, mood, or weight.