Simplification to atazanavir/ritonavir monotherapy for HIV-1 treated individuals on virological suppression: 48-week efficacy and safety results.

Abstract

OBJECTIVES:

The objective of this study was to assess the 48-week virological efficacy of atazanavir/ritonavir (ATV/r) monotherapy vs. ATV/r along with two nucleoside reverse transcriptase (NRTIs) in HIV-1 treated individuals with HIV-RNA less than 50 copies/ml.

METHODS:

A multicentre, randomized, open-label, noninferiority trial. HIV-1 treated individuals on ATV/r 300/100 mg along with two NRTIs were randomized to receive ATV/r monotherapy or to maintain their antiretroviral regimen. The primary endpoint was the confirmed viral rebound (CVR: two consecutive HIV-RNA >50 copies/ml) or treatment discontinuation for any reason. Individuals who experienced CVR on ATV/r monotherapy reintroduced NRTIs and discontinued the study if HIV-RNA was more than 50 copies/ml after 12 weeks since reintensification.

RESULTS:

One hundred and three patients enrolled. By week 48, 11 patients in ATV/r arm and two in ATV/r along with two NRTIs experienced CVR; four (8%) patients in ATV/r and eight (15%) in ATV/r along with two NRTIs discontinued. At the 48-week primary efficacy analysis (re-intensification = failure), treatment success was 73% in ATV/r arm and 85% in ATV/r along with two NRTIs [difference -12.1%, 95% confidence interval (95% CI) -27.8 to 2.1]. According to the analysis considering re-intensification is equal to success, treatment success was 92% in ATV/r arm and 85% in the ATV/r along with two NRTIs arm (difference 7.5%, 95% CI -4.7 to 19.8). At CVR, no mutation was observed in ATV/r arm and reintensification with NRTIs was effective in all individuals. Overall, Grade 3-4 (P = 0.003) and grade 3-4 drug-related (P = 0.027) adverse events were less frequent in ATV/r arm. A significant increase in total and low-density lipoprotein (LDL)-cholesterol was observed as well as a significant improvement in high-density lipoprotein (HDL)-cholesterol, fasting glucose, liver fibrosis and alkaline phosphatase was observed in ATV/r monotherapy in comparison with ATV/r along with two NRTIs.

CONCLUSION:

ATV/r monotherapy treatment simplification showed lower virological efficacy in comparison with maintaining triple therapy; NRTIs reintroduction was effective in all the individuals.

• Authors: Antonella Castagna, Vincenzo Spagnuolo, Laura Galli, Concetta Vinci, Silvia Nozza, Elisabetta Carini, Antonella D'Arminio Monforte, Francesco Montella, Andrea Antinori, Antonio Di Biagio, Stefano Rusconi, Adriano Lazzarin, MODAt Study Group
• Journal: AIDS (London, England) (AIDS) Vol. 28 Issue 15 Pg. 2269-79 (Sep 24 2014) ISSN: 1473-5571 [Electronic] England
• PMID: 25058680 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Oligopeptides
• Pyridines
• Atazanavir Sulfate
• Ritonavir

Topics

• Adult
• Anti-HIV Agents (adverse effects, therapeutic use)
• Antiretroviral Therapy, Highly Active (adverse effects, methods)
• Atazanavir Sulfate
• Drug-Related Side Effects and Adverse Reactions (epidemiology)
• Female
• HIV Infections (drug therapy)
• HIV-1 (isolation & purification)
• Humans
• Male
• Middle Aged
• Oligopeptides (adverse effects, therapeutic use)
• Pyridines (adverse effects, therapeutic use)
• Ritonavir (adverse effects, therapeutic use)
• Treatment Outcome
• Viral Load