Stavudine or zidovudine in three-drug combination therapy for initial treatment of HIV infection in antiretroviral-naïve individuals.
BACKGROUND
The introduction of highly active antiretroviral therapy (ART) as treatment for HIV infection has greatly improved mortality and morbidity for adults and children living with HIV around the world. Two common medications given in first-line antiretroviral therapy are the nucleoside reverse transcriptase inhibitors (NRTI) stavudine (d4T) or zidovudine (AZT).


OBJECTIVE
To assess the efficacy of d4T compared to AZT in combination with one NRTI and one non-nucleoside reverse transcriptase inhibitor (NNRTI), two additional NNRTIs, or one NRTI and one protease inhibitor (PI), as part of first-line ART for HIV-infected people in low-resource settings.


METHODS
Standard Cochrane methods were used to search electronic databases and conference proceedings with relevant search terms without limits to language.


METHODS
Randomised controlled trials of HIV-infected patients 5 years of age and older were included. Primary outcomes of interest included mortality, severe adverse events, virologic response to ART, and adherence/tolerance/retention. Secondary outcomes included immunologic response to ART, development of ART drug resistance, and prevention of sexual transmission of HIV.


METHODS
Two authors assessed each reference for inclusion and exclusion criteria established a priori. Data were abstracted independently using a standardised abstraction form.


RESULTS
Nine randomised controlled trials were identified as meeting the inclusion criteria. The nine trials enrolled 2,159 participants but looked at a multiplicity of drug combinations. Despite this, a reasonably robust literature suggests no statistically significant difference between the two drug combinations, including severe adverse events and adherence/tolerance/retention. The quality of the literature was found overall to be low to very low for all key outcomes. Only one study reported on drug resistance, and no studies reported on sexual transmission of HIV. The length of follow-up time and study settings varied greatly.


CONCLUSIONS
While ideally future research would focus on direct comparison of standard therapeutic combinations of d4T+3TC+an NNRTI and AZT+3TC+an NNRTI to compare these regimens more directly, it is unlikely that additional trials will be mounted. Observational studies should focus on understanding outcomes, including toxicity and tolerability, in low- and middle-income countries.
Spaulding
Alicen
A
University of Minnesota, Minneapolis, Minnesota, USA.
Rutherford
George W
GW
Siegfried
Nandi
N
D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination / Q000379:methods; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D016032:Randomized Controlled Trials as Topic; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D018119:Stavudine / Q000627:therapeutic use; D055815:Young Adult; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine; D018119:Stavudine