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More Early Failures With ddI, Tenofovir, and Efavirenz
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Mark Mascolini
October 31, 2004
A 36-person study reported earlier this year found a high rate of early virologic failure in treatment-naive people beginning once-daily didanosine (ddI), tenofovir (TDF), and efavirenz [1]. Now a larger study from Great Britain, unveiled at the 44th annual ICAAC in Washington, DC, confirms those results [2].
The new study, reported by Graeme Moyle and colleagues at London's Chelsea and Westminster Hospital, began as a 48-week randomized trial comparing two once-daily regimens:
o ddI/3TC/efavirenz
o ddI/TDF/efavirenz
The researchers stopped the study early when an unplanned interim analysis showed a substantially worse response among 44 people randomized to tenofovir compared with 36 randomized to 3TC. As in the earlier study, all poor responders had a high pretreatment viral load and low pretreatment CD4 count.
In the tenofovir group people weighing more than 60 kg took 250 mg of ddI daily with food. The 3TC group took 400 mg of ddI daily without food. Both regimens were taken once daily at night. The two groups began treatment with similar viral loads (around 100,000 copies/mL) and similar CD4 counts (medians of 158 cells/µL in the 3TC group and 174 cells/µL in the TDF group).
Despite high rates of adherence in both groups, after 4 weeks of treatment 4 people in the TDF group did not lower their viral load at least 10-fold or had a viral rebound. Whereas 24 of 34 people (71%) in the 3TC group had a viral load below 50 copies/mL at week 12, only 21 of 36 (61%) in the TDF group reached that mark. At the end of follow-up, Moyle counted no virologic failures in the 3TC group and 5 among 41 people (12%) in the TDF group, a significant difference (P < 0.05). All 5 people with a virologic failure had a CD4 count below 200 cells/µL and a viral load above 100,000 copies/mL before treatment.
The Chelsea and Westminster team concludes that ddI/TDF/efavirenz "has diminished efficacy" in people who start that regimen with a low CD4 count and a high viral load. They suggest that "a lower barrier to the development of resistance" may explain the high risk of early failure with this combination.
References
1. Podzamczer D, Ferrer E, Gatell JM, et al. Early virologic failure and occurrence of resistance in naive patients receiving tenofovir, didanosine and efavirenz. XIII International HIV Drug Resistance Workshop. June 8-12, 2004. Tenerife, Canary Islands. Abstract 156.
2. Moyle G, Maitland D, Hand J, et al. Early virological failure in persons with viral loads >100,000 cps/ml and CD4 counts <200/mm3 receiving ddI/tenofovir/efavirenz as initial therapy: results from a randomised comparative trial. 44th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). October 30-November 2, 2004. Washington, DC. Abstract H-566.
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