Efficacy and Durability of Dolutegravir- or Darunavir-Based Regimens in ART-Naïve AIDS- or Late-Presenting HIV-Infected Patients

Abstract

Background: Since limited data are available, we aimed to compare the efficacy and durability of dolutegravir and darunavir in advanced naïve patients.

Methods: Retrospective multicenter study including AIDS- or late-presenting (def. CD4 ≤ 200/µL) HIV-infected patients starting dolutegravir or ritonavir/cobicistat-boosted darunavir+2NRTIs. Patients were followed from the date of first-line therapy initiation (baseline, BL) to the discontinuation of darunavir or dolutegravir, or for a maximum of 36 months of follow-up.

Results: Overall 308 patients (79.2% males, median age 43 years, 40.3% AIDS-presenters, median CD4 66 cells/µL) were enrolled; 181 (58.8%) and 127 (41.2%) were treated with dolutegravir and darunavir, respectively. Incidence of treatment discontinuation (TD), virological failure (VF, defined as a single HIV-RNA > 1000 cp/mL or two consecutive HIV-RNA > 50 cp/mL after 6 months of therapy or after virological suppression had been achieved), treatment failure (the first of TD or VF), and optimal immunological recovery (defined as CD4 ≥ 500/µL + CD4 ≥ 30% + CD4/CD8 ≥ 1) were 21.9, 5.2, 25.6 and 1.4 per 100 person-years of follow-up, respectively, without significant differences between dolutegravir and darunavir (p > 0.05 for all outcomes). However, a higher estimated probability of TD for central nervous system (CNS) toxicity (at 36 months: 11.7% vs. 0%, p = 0.002) was observed for dolutegravir, whereas darunavir showed a higher probability of TD for simplification (at 36 months: 21.3% vs. 5.7%, p = 0.046).

Conclusions: Dolutegravir and darunavir showed similar efficacy in AIDS- and late-presenting patients. A higher risk of TD due to CNS toxicity was observed with dolutegravir, and a higher probability of treatment simplification with darunavir.

Keywords: HIV-1; advanced naïve; antiretroviral therapy; integrase inhibitors; protease inhibitors; treatment discontinuation; virological failure.

Figure 1

Kaplan–Meier estimates of treatment discontinuation (TD). (A) TD over the entire follow-up; (B) TD when censoring follow-up at 12 months; (C) TD when considering only patients still on first-line treatment at 12 months. Abbreviations: ART, antiretroviral therapy; DRV, darunavir; DTG, dolutegravir; TD, treatment discontinuation.

Figure 2

Kaplan–Meier estimates of time to treatment discontinuation (TD) for different reasons. (A) TD for overall toxicity; (B) TD for central nervous system toxicity; (C) TD for simplification; (D) TD for drug–drug interactions. Abbreviations: ART, antiretroviral therapy; TD, treatment discontinuation; TD-CNS, TD for central nervous system toxicity; TD-DDI, TD for drug–drug interactions; TD-S, TD for simplification.

Figure 3

Kaplan–Meier estimates of time to virological failure (A), treatment failure (B), and optimal immunological recovery (C). Abbreviations: ART, antiretroviral therapy; OIR, optimal immunological recovery; TF, treatment failure; VF, virological failure.