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Effects of nucleoside reverse transcriptase inhibitor backbone on the efficacy of first-line boosted highly active antiretroviral therapy based on protease inhibitors: meta-regression analysis of 12 clinical trials in 5168 patients.
HIV Med. 2009 Oct; 10(9):527-35.HM

Abstract

OBJECTIVES

Tenofovir/emtricitabine (TDF/FTC) and abacavir/lamivudine (ABC/3TC) are widely used with ritonavir (RTV)-boosted protease inhibitors (PIs) as first-line highly active antiretroviral therapy (HAART), but there is conflicting evidence on their relative efficacy. The ACTG 5202 and BICOMBO trials suggested higher efficacy for TDF/FTC, whereas the HEAT trial showed no efficacy difference between the nucleoside reverse transcriptase inhibitor (NRTI) backbones.

METHODS

A systematic MEDLINE search identified 21 treatment arms in 12 clinical trials of 5168 antiretroviral-naïve patients, where TDF/FTC (n=3399) or ABC/3TC (n=1769) was used with RTV-boosted PI. For each NRTI backbone and RTV-boosted PI, the percentage of patients with viral load <50 HIV-1 RNA copies/mL at week 48 by standardized Intent to Treat, Time to Loss of Virological Failure (ITT TLOVR) analysis were combined using inverse-variance weighting. The effect of baseline HIV RNA, CD4 cell count and choice of NRTI backbone were examined using a weighted analysis of covariance.

RESULTS

Across all the trials, HIV RNA suppression rates were significantly higher for those with baseline viral load below 100,000 copies/mL (77.2%) vs. above 100,000 copies/mL (70.9%) (P=0.0005). For the trials of lopinavir/ritonavir (LPV/r), atazanavir/ritonavir (ATV/r) and fosamprenavir/ritonavir (FAPV/r) using either TDF/FTC or ABC/3TC, the HIV RNA responses were significantly lower when ABC/3TC was used, relative to TDF/FTC, for all patients (P=0.0015) and for patients with baseline viral load <100,000 copies/mL (70.1%vs. 80.6%, P=0.0161), and was borderline for those with viral load >100,000 copies/mL (67.5%vs. 71.5%, P=0.0523).

CONCLUSIONS

This systematic meta-regression analysis suggests higher efficacy for first-line use of a TDF/FTC NRTI backbone with boosted PIs, relative to use of ABC/3TC. However, this effect may be confounded by differences between the trials in terms of baseline characteristics, patient management or adherence.

Authors+Show Affiliations

Pharmacology Research Laboratories, University of Liverpool, Liverpool, UK. microhaart@aol.comNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Review

Language

eng

PubMed ID

19785663

Citation

Hill, A, and W Sawyer. "Effects of Nucleoside Reverse Transcriptase Inhibitor Backbone On the Efficacy of First-line Boosted Highly Active Antiretroviral Therapy Based On Protease Inhibitors: Meta-regression Analysis of 12 Clinical Trials in 5168 Patients." HIV Medicine, vol. 10, no. 9, 2009, pp. 527-35.
Hill A, Sawyer W. Effects of nucleoside reverse transcriptase inhibitor backbone on the efficacy of first-line boosted highly active antiretroviral therapy based on protease inhibitors: meta-regression analysis of 12 clinical trials in 5168 patients. HIV Med. 2009;10(9):527-35.
Hill, A., & Sawyer, W. (2009). Effects of nucleoside reverse transcriptase inhibitor backbone on the efficacy of first-line boosted highly active antiretroviral therapy based on protease inhibitors: meta-regression analysis of 12 clinical trials in 5168 patients. HIV Medicine, 10(9), 527-35. https://doi.org/10.1111/j.1468-1293.2009.00724.x
Hill A, Sawyer W. Effects of Nucleoside Reverse Transcriptase Inhibitor Backbone On the Efficacy of First-line Boosted Highly Active Antiretroviral Therapy Based On Protease Inhibitors: Meta-regression Analysis of 12 Clinical Trials in 5168 Patients. HIV Med. 2009;10(9):527-35. PubMed PMID: 19785663.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of nucleoside reverse transcriptase inhibitor backbone on the efficacy of first-line boosted highly active antiretroviral therapy based on protease inhibitors: meta-regression analysis of 12 clinical trials in 5168 patients. AU - Hill,A, AU - Sawyer,W, PY - 2009/9/30/entrez PY - 2009/9/30/pubmed PY - 2010/7/22/medline SP - 527 EP - 35 JF - HIV medicine JO - HIV Med VL - 10 IS - 9 N2 - OBJECTIVES: Tenofovir/emtricitabine (TDF/FTC) and abacavir/lamivudine (ABC/3TC) are widely used with ritonavir (RTV)-boosted protease inhibitors (PIs) as first-line highly active antiretroviral therapy (HAART), but there is conflicting evidence on their relative efficacy. The ACTG 5202 and BICOMBO trials suggested higher efficacy for TDF/FTC, whereas the HEAT trial showed no efficacy difference between the nucleoside reverse transcriptase inhibitor (NRTI) backbones. METHODS: A systematic MEDLINE search identified 21 treatment arms in 12 clinical trials of 5168 antiretroviral-naïve patients, where TDF/FTC (n=3399) or ABC/3TC (n=1769) was used with RTV-boosted PI. For each NRTI backbone and RTV-boosted PI, the percentage of patients with viral load <50 HIV-1 RNA copies/mL at week 48 by standardized Intent to Treat, Time to Loss of Virological Failure (ITT TLOVR) analysis were combined using inverse-variance weighting. The effect of baseline HIV RNA, CD4 cell count and choice of NRTI backbone were examined using a weighted analysis of covariance. RESULTS: Across all the trials, HIV RNA suppression rates were significantly higher for those with baseline viral load below 100,000 copies/mL (77.2%) vs. above 100,000 copies/mL (70.9%) (P=0.0005). For the trials of lopinavir/ritonavir (LPV/r), atazanavir/ritonavir (ATV/r) and fosamprenavir/ritonavir (FAPV/r) using either TDF/FTC or ABC/3TC, the HIV RNA responses were significantly lower when ABC/3TC was used, relative to TDF/FTC, for all patients (P=0.0015) and for patients with baseline viral load <100,000 copies/mL (70.1%vs. 80.6%, P=0.0161), and was borderline for those with viral load >100,000 copies/mL (67.5%vs. 71.5%, P=0.0523). CONCLUSIONS: This systematic meta-regression analysis suggests higher efficacy for first-line use of a TDF/FTC NRTI backbone with boosted PIs, relative to use of ABC/3TC. However, this effect may be confounded by differences between the trials in terms of baseline characteristics, patient management or adherence. SN - 1468-1293 UR - https://www.unboundmedicine.com/medline/citation/19785663/Effects_of_nucleoside_reverse_transcriptase_inhibitor_backbone_on_the_efficacy_of_first_line_boosted_highly_active_antiretroviral_therapy_based_on_protease_inhibitors:_meta_regression_analysis_of_12_clinical_trials_in_5168_patients_ L2 - https://doi.org/10.1111/j.1468-1293.2009.00724.x DB - PRIME DP - Unbound Medicine ER -