of Truvada vs Epzicom Backbones Used with Boosted Protease Inhibitors
for First-line Antiretroviral Therapy |
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.
||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.
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(09)): 527-535. October 2009. (Abstract).