Impact of dolutegravir and efavirenz on immune recovery markers: results from a randomized clinical trial

Abstract

Objectives: CD4/CD8 ratio and CD4⁺ T-cell percentage (CD4%) predicts the risk of AIDS and non-AIDS events. Multiple T-cell marker recovery (MTMR) has been proposed as the most complete level of immune reconstitution. We quantified differences in the CD4/CD8 ratio, CD4% recovery and MTMR after starting HIV-1 treatment with dolutegravir/abacavir/lamivudine vs. efavirenz (EFV)/tenofovir (TDF)/emtricitabine (FTC).

Methods: Exploratory post hoc analysis of the SINGLE study, a randomized double-blind, clinical trial. Percentage differences and corresponding precision based on 95% confidence intervals, and p values were calculated for CD4/CD8 ratio normalization, CD4% normalization and the achievement of MTMR. Cox models taking into account competing risks were used to estimate sub-hazard ratios when comparing the times to normalization of the CD4/CD8 ratio and the CD4% by treatment arm.

Results: Data from 833 participants were analysed (414 in the dolutegravir/abacavir/lamivudine arm). There were no statistically significant differences in the proportion of patients who reached a CD4/CD8 ratio ≥0.5 at weeks 48 and 96. However, at week 96, the proportion of patients with a CD4/CD8 ratio ≥1 was higher in the EFV-TDF-FTC group (difference, 11.70; 95% confidence interval, 4.49-18.91; p 0.002). The decrease from baseline in CD8⁺ cell count was consistently greater in the EFV-TDF-FTC arm. Analysis of CD4⁺ percentages showed no significant differences during the study. The proportion of patients attaining a MTMR was higher in the EFV-TDF-FTC group, although the difference was only statistically significant at week 96 (p 0.001).

Conclusions: EFV-TDF-FTC showed significantly greater increases in CD4/CD8 ratio ≥1.0 or MTMR beyond treatment week 96. Additional studies are necessary to better understand the impact of these findings.

Keywords: Antiretroviral therapy; CD4 T-cell count; CD4 percentage; CD4/CD8 ratio; dolutegravir; efavirenz.