Superior efficacy of dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) fixed dose combination (FDC) compared with ritonavir (RTV) boosted atazanavir (ATV) plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in treatment-naïve women with HIV-1 infection (ARIA Study)

INTRODUCTION: The FDC of DTG/ABC/3TC is built upon an unboosted integrase-strand transfer inhibitor (INSTI) and may offer a simplified regimen for the treatment of HIV-1 infection. To gain additional data for women on this regimen, we conducted ARIA, an international, randomized, open-label study to evaluate the safety and efficacy of DTG/ABC/3TC versus ATV + RTV + FTC/TDF (ClinicalTrials.gov: NCT01910402). METHODS: Treatment-naïve adult women, with HIV-1 RNA ≥500 copies (c)/mL were randomized (1:1, stratified by plasma HIV-1 RNA and CD4+ count) to 48 weeks of treatment with DTG/ABC/3TC or ATV + RTV + FTC/TDF once daily. The primary endpoint was the proportion of women achieving an HIV-1 RNA <50 c/mL at week 48 (Snapshot algorithm). Women who became pregnant were withdrawn, and where possible offered an option to enter a DTG/ABC/3TC pregnancy study. RESULTS: 495 women were randomized and treated. Median age was 37 years. Subjects were well matched for demographic and baseline (BL) characteristics. DTG/ABC/3TC was superior to ATV + RTV + FTC/TDF, with 82% and 71%, respectively, achieving HIV-1 RNA <50 c/mL at week 48 (adjusted difference 10.5%, 95% CI: 3.1%–17.8%, p = 0.005). Differences were driven by lower rates of both discontinuations due to adverse events (AEs) and Snapshot virologic failures in the DTG/ABC/3TC group. Increases in CD4+ count were similar between treatment groups. The safety profile of DTG/ABC/3TC was favourable compared to ATV + RTV + TDF/FTC, with fewer drug-related AEs reported in the DTG/ABC/3TC group. Of six DTG/ABC/3TC subjects who met protocol-defined virologic withdrawal criteria, none had treatment-emergent primary INSTI or ABC/3TC resistance mutations, compared with four ATV + RTV + TDF/FTC subjects who met virologic withdrawal criteria of which one had an emergent NRTI mutation, M184M/I/V. CONCLUSIONS: DTG/ABC/3TC demonstrated superior efficacy and a favourable safety profile compared with ATV + RTV + FTC/TDF in treatment-naïve women after 48 weeks of treatment. The study provides important information to help guide treatment decisions for women.