Similar neurocognitive outcomes after 48 weeks in HIV-1-infected participants randomized to continue tenofovir/emtricitabine + atazanavir/ritonavir or simplify to abacavir/lamivudine + atazanavir

Human immunodeficiency virus (HIV)-associated neurocognitive disorders can persist in many patients despite achieving viral suppression while on antiretroviral therapy (ART). Neurocognitive function over 48 weeks was evaluated using a Cogstate test battery assessing psychomotor function, attention, learning, and working memory in 293 HIV-1-infected, ART-experienced, and virologically suppressed adults. The ASSURE study randomized participants 1:2 to remain on tenofovir/emtricitabine (TDF/FTC) and ritonavir-boosted atazanavir (ATV/r) or simplify to abacavir/lamivudine + atazanavir (ABC/3TC + ATV). Neurocognitive z-scores were computed using demographically adjusted normative data and were classified as “impaired” (defined as either a z-score ≤ − 2 or having 2 or more standardized individual test z-scores ≤ − 1); while higher scores (equaling better performance) were classified as “normal”. By z-scores, 54.7% of participants had impaired neurocognition at baseline and 50.2% at week 48. There were no significant differences (p < 0.05) in the baseline-adjusted performance between treatment groups for any individual test or by z-score. Specific demographic and medical risk factors were evaluated by univariate analysis for impact on neurocognitive performance. Factors with p < 0.10 were evaluated by backwards regression analysis to identify neurocognition-correlated factors after accounting for treatment, assessment, and baseline. Four risk factors at baseline for impaired neurocognition were initially identified: lower CD4 nadir lymphocyte counts, higher Framingham risk scores, and interleukin-6 levels, and a history of psychiatric disorder not otherwise specified, however none were found to moderate the effect of treatment on neurocognition. In this aviremic, treatment-experienced population, baseline-adjusted neurocognitive function remained stable and equivalent over 48 weeks with both TDF/FTC + ATV/r-treated and in the ART-simplified ABC/3TC + ATV treatment groups

The ASSURE study: HIV-1 suppression is maintained with bone and renal biomarker improvement 48 weeks after ritonavir discontinuation and randomized switch to abacavir/lamivudine+atazanavir

Objectives: HIV treatment guidelines endorse switching or simplification of antiretroviral therapy in therapy-experienced patients with suppressed viraemia; ritonavir discontinuation may also enhance tolerability and reduce long-term adverse events (AEs). This open-label, multicentre, noninferiority study enrolled HIV-1-infected, treatment-experienced adults with confirmed HIV-1 RNA≤75 HIV-1 RNA copies/mL currently receiving tenofovir/emtricitabine+atazanavir/ritonavir (TDF/FTC+ATV/r) for ≥6 months with no reported history of virological failure. Methods: Participants were randomized 1:2 to continue current treatment or switch to abacavir/lamivudine + atazanavir (ABC/3TC+ATV). Endpoints included the proportion of participants with HIV-1 RNA<50 copies/mL by time to loss of virological response (TLOVR), AEs, fasting lipids, and inflammatory, coagulation, bone and renal biomarkers. Results: After 48 weeks, 76% (152 of 199) of ABC/3TC+ATV-treated and 79% (77 of 97) of TDF/FTC+ATV/r-treated participants had HIV-1 RNA<50 copies/mL (TLOVR; P=0.564). Other efficacy analyses yielded similar results. Rates of new grade 2-4 AEs were 45% in both groups, but an excess of hyperbilirubinaemia made the rate of treatment-emergent grade 3-4 laboratory abnormalities higher with TDF/FTC+ATV/r (36%) compared with ABC/3TC+ATV (19%). Most fasting lipid levels remained stable over time; high-density lipoprotein (HDL) cholesterol increased modestly in ABC/3TC+ATV-treated participants. Bone and renal biomarkers improved significantly between baseline and week 48 in participants taking ABC/3TC+ATV and were stable in participants taking TDF/FTC+ATV/r. No significant changes occurred in any inflammatory or coagulation biomarker within or between treatment groups. Conclusions: The ABC/3TC+ATV treatment-switch group had similar viral suppression rates up to 48 weeks to the TDF/FTC+ATV/r comparator group, with lower rates of moderate- to high-grade hyperbilirubinaemia and improvements in bone and renal biomarkers