Efficacy and safety of nucleoside reverse transcriptase inhibitor-sparing salvage therapy for multidrug-resistant HIV-1 infection based on new-class and new-generation antiretrovirals.

Abstract

BACKGROUND:

The advent of new antiretrovirals has expanded the therapeutic options for multiple drug-resistant HIV-1 infection. The role of recycled nucleoside reverse transcriptase inhibitors (NRTIs) in this scenario remains uncertain.

METHODS:

Observational study of 122 consecutive patients with prior triple-class failure and multidrug-resistant HIV infection who started a salvage regimen with at least three of the new antiretrovirals darunavir, etravirine, raltegravir and maraviroc. Virological, immunological and clinical outcomes were compared according to the inclusion or not of NRTIs in the regimen, after 48 weeks of follow-up.

RESULTS:

All patients received at least two and 65% received three fully active drugs in the salvage regimen. In 63 patients recycled NRTIs were added to new drugs (NRTI-containing group) and 59 patients did not receive NRTIs (NRTI-sparing group). Both groups were comparable at baseline regarding the number of prior failures, resistance profile, CD4 cell count and HIV plasma viral load. The rates of HIV-1 RNA suppression below 50 copies/mL at week 48 (intent-to-treat analysis) were similar in the two groups: 46/59 [78%, 95% confidence interval (CI) 67%-88%] in the NRTI-sparing group and 49/63 (78%, 95% CI 67%-88%) in the NRTI-containing group. No significant differences were found in CD4 cell count increases. Drug-related adverse events leading to drug discontinuations only occurred in the NRTI-containing group (5 of 63, NRTI-related in 3 cases).

CONCLUSIONS:

The addition of NRTIs with reduced activity, according to genotypic resistance tests, does not seem to improve the efficacy of salvage regimens containing three of the new antiretrovirals in patients with multidrug-resistant HIV-1 infection.

• Authors: Arkaitz Imaz, Josep M Llibre, Marta Mora, Gracia Mateo, Angela Camacho, José R Blanco, Adrian Curran, José R Santos, Estrella Caballero, Isabel Bravo, Francisco Gayá, Pere Domingo, Antonio Rivero, Vicenç Falcó, Bonaventura Clotet, Esteban Ribera
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 66 Issue 2 Pg. 358-62 (Feb 2011) ISSN: 1460-2091 [Electronic] England
• PMID: 21172789 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-HIV Agents
• Nucleosides
• Reverse Transcriptase Inhibitors
• RNA-Directed DNA Polymerase

Topics

• Adult
• Anti-HIV Agents (adverse effects, pharmacology, therapeutic use)
• CD4 Lymphocyte Count
• CD4-Positive T-Lymphocytes (drug effects)
• Drug Resistance, Multiple, Viral
• Female
• HIV Infections (drug therapy)
• HIV-1 (drug effects)
• Humans
• Male
• Middle Aged
• Nucleosides (therapeutic use)
• RNA-Directed DNA Polymerase (metabolism)
• Reverse Transcriptase Inhibitors (adverse effects, pharmacology, therapeutic use)
• Salvage Therapy
• Viral Load (drug effects)