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HIV9: More Data Demonstrate Similar Efficacy of Abacavir and Tenofovir

As previously reported, ACTG study 5202 was partially halted this past March after interim results showed that among treatment-naive patients with a high baseline HIV viral load (> 100,000 copies/mL), abacavir/lamivudine (the drugs in the Epzicom coformulation pill) did not suppress HIV as well as tenofovir/emtricitabine (the drugs in the Truvada pill) when both were used in combination with either efavirenz (Sustiva) or ritonavir-boosted atazanavir (Reyataz). Four cohort studies presented at the recent 9th International Congress on Drug Therapy in HIV Infection in Glasgow provided further evidence regarding the relative efficacy of the abacavir/lamivudine and tenofovir/emtricitabine backbones. 

At the XVII International AIDS Conference this summer, the ACTG 5202 investigators reported data from the high viral load arm showing that time to virological failure was significantly shorter in the abacavir/lamivudine arm than in the tenofovir/emtricitabine arm, and patients taking abacavir/lamivudine were more likely to modify their regimen. But in GlaxoSmithKline's HEAT study -- a head-to-head comparison of Epzicom versus Truvada combined with lopinavir/ritonavir (Kaletra) -- both regimens demonstrated comparable virological efficacy and safety through 96 weeks. (Neither study used the HLA-B*5701 genetic screening test to exclude patients susceptible to abacavir hypersensitivity reactions.)

In the German STAR cohort, 113 treatment-naive patients started Epzicom and 563 started Truvada, both in combination with lopinavir/ritonavir (similar to HEAT). Among participants with baseline HIV RNA > 100,000 copies/mL, rates of virological suppression < 50 copies/mL at 24 weeks were similar in the Epzicom and Truvada arms in both an intent-to-treat analysis (57% vs. 51%) and an as-treated analysis (57% vs 54%).

In the U.K. TEAL study, 120 participants started abacavir/lamivudine and 140 started tenofovir/emtricitabine, usually with a NNRTI; more people in the latter arm had high baseline viral load. Among treatment-experienced patients in the study, similar proportions in the 2 arms achieved HIV RNA < 50 copies/mL at 48 weeks in an intent-to-treat analysis (87% vs 76%; not a statistically significant difference). Among treatment-naive participants, the intent-to-treat response rate was significantly higher in the tenofovir/emtricitabine arm (94% vs 76%), although virological failure occurred in 4% of patients in both arms. But response rates were similar in an as-treated analysis, reflecting the fact that more patients discontinued therapy in the abacavir/lamivudine arm.

Another U.K. study looked at 87 treatment-naive patients starting Epzicom or Truvada with a NNRTI (usually efavirenz) or a protease inhibitor (usually atazanavir/ritonavir or lopinavir/ritonavir). At 24 weeks, as-treated response rates were similar in the Epzicom and Truvada arms among participants with a baseline viral load < 10,000 copies/mL (91% vs 83%), 10,000-100,000 copies/mL (90% vs 91%), or > 100,000 copies/mL (91% vs 80%).

Finally, the TOKEN study looked at treatment outcomes in predominantly black African patients with relatively advanced disease (mean CD4 count 172 cells/mm3) starting treatment for the first time. A total of 58 HLA-B* 5701 negative individuals started regimens containing Epzicom, while 81 started Truvada regimens. In an intent-to-treat analysis at 48 weeks, 85% taking Epzicom and 83% taking Truvada achieved HIV RNA < 40 copies/mL (not a significant difference), and response did not differ according to baseline viral load.

Although these studies were not randomized, controlled trials designed to compare the 2 NRTI backbones, they nevertheless offer further evidence that abacavir/lamivudine and tenofovir/emtricitabine may be functionally equivalent in terms of efficacy, especially if patients are pre-screen to exclude those susceptible to abacavir hypersensitivity.

12/12/08

References

E Wolf, A Trein, W Schmidt, and others. Similar virological response rates for ART-naïve subjects starting KVX + LPV/r or TVD+ LPV/r. Data from the prospective observational STAR cohort. 9th International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland. November 9-13, 2008. Journal of the International AIDS Society 11(Suppl 1): P7. November 10, 2008.

KJ Eccleston, A Bambumba, CS Babu, and others. Efficacy and safety of tenofovir/emtricitabine compared to abacavir/lamivudine in HIV-1 infected patients in clinical setting. The TEAL study. 9th International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland. November 9-13, 2008. Journal of the International AIDS Society 11(Suppl 1): P79. November 10, 2008.

RH Daniels, BG Gazzard, P Holmes, and others. Comparing the efficacy of Truvada and Kivexa combination therapy in HAART-naive individuals with different viral loads. 9th International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland. November 9-13, 2008. Journal of the International AIDS Society 11(Suppl 1): P14. November 10, 2008.

S Das, J Arumainayagam, B Kumari, and others. The TOKEN study: safety and efficacy of Truvada or Kivexa in combination with efavirenz in treatment-naïve predominantly black African HIV patients. 9th International Congress on Drug Therapy in HIV Infection. Glasgow, Scotland. November 9-13, 2008. Journal of the International AIDS Society 11(Suppl 1): P15. November 10, 2008.