Meta-Analysis of Truvada vs Epzicom Backbones Used with Boosted Protease Inhibitors for First-line Antiretroviral Therapy

First-line antiretroviral therapy (ART) that includes a nucleoside/nucleotide backbone of tenofovir/emtricitabine (the drugs in the Truvada coformulation) was more effective than regimens containing abacavir/lamivudine (the drugs in the Epzicom coformulation) for HIV patients with high pre-treatment viral load, according to a meta-analysis published in the October 2009 issue of HIV Medicine.

Both tenofovir/emtricitabine and abacavir/lamivudine are widely used as nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) backbones with ritonavir-boosted protease inhibitors (PIs) as first-line antiretroviral therapy, but there is conflicting evidence about their relative efficacy.

The ACTG 5202 and BICOMBO trials suggested that tenofovir/emtricitabine had higher efficacy, particularly for patients with high baseline viral load, whereas the HEAT trial showed no difference in efficacy between the 2 NRTI backbones.

In the present study, researchers conducted a systematic search of the MEDLINE medical literature database. They identified 21 treatment arms in 12 clinical trials, including a total of 5168 antiretroviral-naive patients, in which tenofovir/emtricitabine (n=3399) or abacavir/lamivudine (n=1769) was used with boosted PIs.

For each NRTI backbone and boosted PI, the percentage of patients with viral load < 50 HIV RNA copies/mL at week 48 using a standardized intent-to-treat Time to Loss of Virological Response (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 trials, HIV RNA suppression rates were significantly higher for patients with baseline viral load < 100,000 copies/mL (77.2%) versus > 100,000 copies/mL (70.9%) (P=0.0005).
• For trials using lopinavir/ritonavir (Kaletra), boosted atazanavir (Reyataz), or boosted fosamprenavir/ritonavir (Lexiva), virological responses were significantly lower when abacavir/lamivudine was used, relative to tenofovir/emtricitabine, for all patients (P = 0.0015).
• Virological responses were also significantly lower with abacavir/lamivudine for patients with baseline viral load < 100,000 copies/mL (70.1% vs 80.6%; P=0.0161).
• Virological responses were also lower with abacavir/lamivudine, but with only borderline statistical significance, for patients with viral load > 100,000 copies/mL (67.5% vs 71.5%; P = 0.0523).

Based on these findings, the study authors wrote, "This systematic meta-regression analysis suggests higher efficacy for first-line use of a [tenofovir/emtricitabine] NRTI backbone with boosted PIs, relative to use of [abacavir/lamivudine].”

They noted, however, "This effect may be confounded by differences between the trials in terms of baseline characteristics, patient management or adherence."

Pharmacology Research Laboratories, University of Liverpool, Liverpool, UK; Department of Statistics, MetaVirology Ltd, London, UK.

10/09/09

Reference

A Hill 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 10(9): 527-535. October 2009. Abstract.