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Stavudine or zidovudine in three-drug combination therapy for initial treatment of HIV infection in antiretroviral-naïve individuals.

Abstract

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).

OBJECTIVES

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.

SEARCH STRATEGY

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

SELECTION CRITERIA

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.

DATA COLLECTION AND ANALYSIS

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

MAIN 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.

AUTHORS' 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.

Authors+Show Affiliations

University of Minnesota, Minneapolis, Minnesota, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

20687097

Citation

Spaulding, Alicen, et al. "Stavudine or Zidovudine in Three-drug Combination Therapy for Initial Treatment of HIV Infection in Antiretroviral-naïve Individuals." The Cochrane Database of Systematic Reviews, 2010, p. CD008651.
Spaulding A, Rutherford GW, Siegfried N. Stavudine or zidovudine in three-drug combination therapy for initial treatment of HIV infection in antiretroviral-naïve individuals. Cochrane Database Syst Rev. 2010.
Spaulding, A., Rutherford, G. W., & Siegfried, N. (2010). Stavudine or zidovudine in three-drug combination therapy for initial treatment of HIV infection in antiretroviral-naïve individuals. The Cochrane Database of Systematic Reviews, (8), CD008651. https://doi.org/10.1002/14651858.CD008651
Spaulding A, Rutherford GW, Siegfried N. Stavudine or Zidovudine in Three-drug Combination Therapy for Initial Treatment of HIV Infection in Antiretroviral-naïve Individuals. Cochrane Database Syst Rev. 2010 Aug 4;(8)CD008651. PubMed PMID: 20687097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stavudine or zidovudine in three-drug combination therapy for initial treatment of HIV infection in antiretroviral-naïve individuals. AU - Spaulding,Alicen, AU - Rutherford,George W, AU - Siegfried,Nandi, Y1 - 2010/08/04/ PY - 2010/8/6/entrez PY - 2010/8/6/pubmed PY - 2010/8/26/medline SP - CD008651 EP - CD008651 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 8 N2 - 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). OBJECTIVES: 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. SEARCH STRATEGY: Standard Cochrane methods were used to search electronic databases and conference proceedings with relevant search terms without limits to language. SELECTION CRITERIA: 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. DATA COLLECTION AND ANALYSIS: Two authors assessed each reference for inclusion and exclusion criteria established a priori. Data were abstracted independently using a standardised abstraction form. MAIN 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. AUTHORS' 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. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/20687097/Stavudine_or_zidovudine_in_three_drug_combination_therapy_for_initial_treatment_of_HIV_infection_in_antiretroviral_naïve_individuals_ L2 - https://doi.org/10.1002/14651858.CD008651 DB - PRIME DP - Unbound Medicine ER -