Nucleoside reverse transcriptase inhibitors in combination therapy for HIV patients: systematic review and meta-analysis.

Abstract

Treatment guidelines recommend dual nucleoside reverse transcriptase inhibitors (NRTI ) as a part of combination antiretroviral therapy. The objective of this study was to assess the relative efficacy and toxicity of the dual NRTI part of the regimen in antiretroviral-naïve HIV-1-infected adults. A systematic review and meta-analysis of randomized controlled trials assessing highly active antiretroviral therapy (HAART) for treatment-naïve HIV-infected adults with a 48-week follow-up were done. We searched the PubMed, CENTRAL, and EMBASE electronic databases up to April 2009. Proceedings from conferences were reviewed. Data were extracted independently by two reviewers. Primary outcome was viral suppression at 48 weeks. The odds ratio (OR) is reported with its corresponding 95% confidence interval (CI). Twenty-two randomized controlled trials, including 8,184 HIV-treatment-naïve patients, were included. The combination didanosine + lamivudine/emtricitabine (four trials, 1,148 patients) was more effective (OR 0.53, 95% CI 0.41-0.68) for viral load (VL) >50 copies/ml and less toxic (OR 0.52, 95% CI 0.36-0.76) for discontinuation due to adverse events (AE) than its comparators. The combination tenofovir + lamivudine/emtricitabine was more effective and less toxic (OR 0.75, 95% CI 0.58-0.96) only in the 144-week follow-up data (two trials, 1,119 patients). Abacavir + lamivudine had similar efficacy to its comparators (OR 0.81, 95% CI 0.8-1.1), but more AIDS-defining events (OR 3.22, 95% CI 1.24, 8.40). The once-daily combination didanosine + lamivudine/emtricitabine was found to be effective and tolerable. This combination, soon to be generic, should be compared to the current standard of care in a large randomized trial. An effective, safe, and inexpensive alternative to current options is needed.

• Authors: M Chowers, B-S Gottesman, L Leibovici, J M Schapiro, M Paul
• Journal: European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology (Eur J Clin Microbiol Infect Dis) Vol. 29 Issue 7 Pg. 779-86 (Jul 2010) ISSN: 1435-4373 [Electronic] Germany
• PMID: 20449621 (Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)

Chemical References

• Anti-HIV Agents
• Nucleosides
• Reverse Transcriptase Inhibitors
• HIV Reverse Transcriptase

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Anti-HIV Agents (adverse effects, therapeutic use)
• Antiretroviral Therapy, Highly Active (methods)
• HIV Infections (drug therapy)
• HIV Reverse Transcriptase (antagonists & inhibitors)
• Humans
• Middle Aged
• Nucleosides (adverse effects, therapeutic use)
• Randomized Controlled Trials as Topic
• Reverse Transcriptase Inhibitors (adverse effects, therapeutic use)
• Treatment Outcome
• Withholding Treatment
• Young Adult