• Infectious Disease Clinical Trials
• HIV & AIDS

• Infectious Disease Clinical Trials
• Infectious Disease
• HIV & AIDS

The first single-tablet regimen containing an integrase inhibitor for the treatment of human immunodeficiency virus (HIV) demonstrated high rates of virologic suppression, safety, and tolerability at 144 weeks in treatment-naïve patients. Richard Elion, MD, Whitman Walker Health, Washington, DC, USA, presented the results of the prespecified pooled analysis from 2 double-blind, active-control phase 3 studies of first-line treatment.

Elvitegravir (EVG; 150 mg), cobicistat (COBI; 150 mg), emtricitabine (FTC; 200 mg), and tenofovir DF (TDF; 300 mg) compose the single tablet (EVG/COBI/FTC/TDF). A previous study demonstrated that EVG/COBI/FTC/TDF was noninferior at 48 weeks when compared with coformulated efavirenz (EFV), FTC, and TDF (EFV/FTC/TDF) as initial therapy [Sax P et al. Lancet. 2012]. Another study showed that EVG/COBI/FTC/TDF, when compared with the ritonavir-boosted (RTV) protease inhibitor regimen of atazanavir (ATV) plus coformulated FTC/TDF (RTV-ATV/FTC/TDF) for initial therapy, was noninferior for the primary outcome of HIV RNA concentration of ≤ 50 copies/mL at 48 weeks [DeJesus E et al. Lancet. 2012]. The comparators in both studies are treatments recommended by guidelines [Gunthard HF et al. Lancet. 2014].

The present pooled analysis included treatment-naïve patients with HIV-1 RNA ≥ 5000 copies/mL and an estimated glomerular filtration rate ≥ 70 mL/min randomized to either EVG/COBI/FTC/TDF once daily (n = 701), a fixed-dose combination pill containing EFV/FTC/TDF every night at bedtime (n = 352), or RTV-ATV/FTC/TDF once daily (n = 355). The patients were followed for 144 weeks.

The majority of patients were men (90%); the mean age was 38 years; and most (82% to 84%) had an asymptomatic HIV infection. The median baseline HIV-1 RNA level was 4.8 log₁₀ copies/mL, and the median GFR was 114 mL/min. The mean CD4 count was 377, 382, and 375 cells/mm³ in the EVG/COBI/FTC/TDF, EFV/FTC/TDF, and RTV-ATV/FTC/TDFgroups, respectively. Approximately 37% of the patients had viral loads > 100 000 copies/mL, and 45% had CD4 counts ≤ 350 cells/mm³.

The primary efficacy end point was virologic suppression (HIV-1 RNA < 50 copies/mL) at week 48, which was achieved in 89%, 84%, and 87% of the EVG/COBI/FTC/TDF, EFV/FTC/TDF, and RTV-ATV/FTC/TDF groups, respectively. These rates were 79%, 75%, and 75% at week 144, respectively. Outcomes were consistent across demographics and baseline HIV-1 RNA and CD4 levels. Increases in CD4 counts were robust and comparable in each group (about 300 cells/mm³) at week 144.

Emergent resistance was low and occurred in 2.6%, 4.0%, and 0.6% of the EVG/COBI/FTC/TDF, EFV/FTC/TDF, and RTV-ATV/FTC/TDF groups, respectively, at 144 weeks. Most of the resistance occurred in the first 24 to 48 weeks. There were relatively few adverse events (AEs). Diarrhea, upper respiratory infection, and nausea were the most frequent AEs. AEs leading to discontinuation were similar among the groups (about 7%), and discontinuation due to renal toxicity was infrequent. There were no new cases of proximal tubulopathy and no further increases in serum creatinine. Increases in creatinine usually occurred in the first 4 to 6 weeks. Patients in the EVG/COBI/FTC/TDF group had lower rates of drug-related central nervous system and psychiatric AEs.

Dr Elion stated that the overall efficacy, safety, and tolerability of EVG/COBI/FTC/TDF support its use as a first-line regimen in treatment-naïve patients.

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