title: 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.affiliation: Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. chowersm@post.tau.ac.il
authors.forename: M
authors.initials: M
authors.lastname: Chowers
authors.forename: B-S
authors.initials: BS
authors.lastname: Gottesman
authors.forename: L
authors.initials: L
authors.lastname: Leibovici
authors.forename: J M
authors.initials: JM
authors.lastname: Schapiro
authors.forename: M
authors.initials: M
authors.lastname: Paul
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors; D006801:Humans; D008875:Middle Aged; D009705:Nucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D028761:Withholding Treatment; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase
references.citation: AIDS. 2000 Jul 28;14(11):1601-10
references.pmid: 10983647
references.citation: Clin Infect Dis. 2004 Oct 1;39(7):1038-46
references.pmid: 15472858
references.citation: Clin Infect Dis. 2001 Dec 1;33(11):1931-7
references.pmid: 11692306
references.citation: AIDS. 2009 Jan 28;23(3):343-53; discussion 355-6
references.pmid: 19114855
references.citation: N Engl J Med. 2006 Jan 19;354(3):251-60
references.pmid: 16421366
references.citation: JAMA. 2006 Aug 16;296(7):769-81
references.pmid: 16905783
references.citation: JAMA. 2004 Jul 14;292(2):180-9
references.pmid: 15249567
references.citation: Lancet. 2008 Apr 26;371(9622):1417-26
references.pmid: 18387667
references.citation: J Acquir Immune Defic Syndr. 2007 Feb 1;44(2):139-47
references.pmid: 17106274
references.citation: Antivir Ther. 2003 Aug;8(4):339-46
references.pmid: 14518703
references.citation: Ann Intern Med. 2000 Jul 4;133(1):21-30
references.pmid: 10877736
references.citation: Int J STD AIDS. 2005 Jun;16(6):427-9
references.pmid: 15969777
references.citation: J Acquir Immune Defic Syndr. 2008 Jan 1;47(1):74-8
references.pmid: 17971715
references.citation: AIDS. 2000 Jul 28;14(11):1591-600
references.pmid: 10983646
references.citation: HIV Med. 2008 Feb;9(2):65-71
references.pmid: 18257769
references.citation: Clin Infect Dis. 2005 Jan 1;40(1):148-57
references.pmid: 15614705
references.citation: AIDS. 2000 Apr 14;14(6):671-81
references.pmid: 10807190
references.citation: AIDS. 2000 Jun 16;14(9):1171-80
references.pmid: 10894281
references.citation: JAMA. 2004 Jul 14;292(2):191-201
references.pmid: 15249568
references.citation: J Antimicrob Chemother. 2005 Feb;55(2):246-51
references.pmid: 15608053
references.citation: J Acquir Immune Defic Syndr. 2002 Dec 1;31(4):399-403
references.pmid: 12447010
references.citation: HIV Clin Trials. 2004 Nov-Dec;5(6):361-70
references.pmid: 15682349
references.citation: AIDS. 2008 May 11;22(8):997-8
references.pmid: 18453864
references.citation: Lancet. 2002 Jul 6;360(9326):81-5
references.pmid: 12114062
references.citation: Clin Infect Dis. 2008 Oct 15;47(8):1083-92
references.pmid: 18781872
references.citation: HIV Med. 2006 Mar;7(2):85-98
references.pmid: 16420253
references.citation: HIV Clin Trials. 2002 May-Jun;3(3):177-85
references.pmid: 12032876
references.citation: N Engl J Med. 2003 Dec 11;349(24):2304-15
references.pmid: 14668456
references.citation: AIDS. 2008 Sep 12;22(14):F17-24
references.pmid: 18753925
references.citation: Pharmacotherapy. 2005 Aug;25(8):1044-54
references.pmid: 16207094
references.citation: AIDS. 2006 Oct 24;20(16):2051-64
references.pmid: 17053351
references.citation: BMJ. 2003 Sep 6;327(7414):557-60
references.pmid: 12958120