Nucleoside reverse transcriptase inhibitors in combination therapy for HIV patients: systematic review and meta-analysis.
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.
Chowers
M
M
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. chowersm@post.tau.ac.il
Gottesman
B-S
BS
Leibovici
L
L
Schapiro
J M
JM
Paul
M
M
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
D019380:Anti-HIV Agents; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors; D054303:HIV Reverse Transcriptase
AIDS. 2000 Jul 28;14(11):1601-10
10983647
Clin Infect Dis. 2004 Oct 1;39(7):1038-46
15472858
Clin Infect Dis. 2001 Dec 1;33(11):1931-7
11692306
AIDS. 2009 Jan 28;23(3):343-53; discussion 355-6
19114855
N Engl J Med. 2006 Jan 19;354(3):251-60
16421366
JAMA. 2006 Aug 16;296(7):769-81
16905783
JAMA. 2004 Jul 14;292(2):180-9
15249567
Lancet. 2008 Apr 26;371(9622):1417-26
18387667
J Acquir Immune Defic Syndr. 2007 Feb 1;44(2):139-47
17106274
Antivir Ther. 2003 Aug;8(4):339-46
14518703
Ann Intern Med. 2000 Jul 4;133(1):21-30
10877736
Int J STD AIDS. 2005 Jun;16(6):427-9
15969777
J Acquir Immune Defic Syndr. 2008 Jan 1;47(1):74-8
17971715
AIDS. 2000 Jul 28;14(11):1591-600
10983646
HIV Med. 2008 Feb;9(2):65-71
18257769
Clin Infect Dis. 2005 Jan 1;40(1):148-57
15614705
AIDS. 2000 Apr 14;14(6):671-81
10807190
AIDS. 2000 Jun 16;14(9):1171-80
10894281
JAMA. 2004 Jul 14;292(2):191-201
15249568
J Antimicrob Chemother. 2005 Feb;55(2):246-51
15608053
J Acquir Immune Defic Syndr. 2002 Dec 1;31(4):399-403
12447010
HIV Clin Trials. 2004 Nov-Dec;5(6):361-70
15682349
AIDS. 2008 May 11;22(8):997-8
18453864
Lancet. 2002 Jul 6;360(9326):81-5
12114062
Clin Infect Dis. 2008 Oct 15;47(8):1083-92
18781872
HIV Med. 2006 Mar;7(2):85-98
16420253
HIV Clin Trials. 2002 May-Jun;3(3):177-85
12032876
N Engl J Med. 2003 Dec 11;349(24):2304-15
14668456
AIDS. 2008 Sep 12;22(14):F17-24
18753925
Pharmacotherapy. 2005 Aug;25(8):1044-54
16207094
AIDS. 2006 Oct 24;20(16):2051-64
17053351
BMJ. 2003 Sep 6;327(7414):557-60
12958120