IAS: DART trial shows AZT/3TC/tenofovir effective in majority after one year

A triple-nucleoside regimen of AZT, 3TC and tenofovir proved effective at controlling viral load in more than half of the participants in the African DART trial over 48 weeks of follow-up, according to findings presented last month at the Third International AIDS Society Conference on HIV Pathogenesis and Treatment in Rio de Janeiro, Brazil.

DART is a large study that has recruited over 3000 patients in Uganda and Zimbabwe to compare different approaches to treatment-monitoring and clinical management. Results from the main study are not expected for at least three years, but virological outcomes in 75% of patients in the study are being reported at regular intervals at international conferences. These patients are all taking AZT/3TC/tenofovir. The remainder of patients were originally randomised to either AZT/3TC/abacavir or AZT/3TC/nevirapine.

A triple-nucleoside regimen is especially attractive in settings such as Zimbabwe and Uganda, where tuberculosis (TB) is the most common AIDS-defining illness. The TB medicine rifampicin interacts with nevirapine and efavirenz, potentially reducing blood levels, so a regimen that has no interactions with rifampicin would therefore be advantageous.

The tenofovir-containing regimen has been watched carefully because of reports in the last 18 months of unusually high failure rates in patients receiving triple regimens combining tenofovir, 3TC and another nucleoside analogue (especially ddI). The combination of AZT, 3TC and tenofovir is thought to be less prone to failure because AZT protects against the development of the tenofovir resistance mutation K65R. However the DART trial is the first large-scale test of this regimen.

DART investigators presented 48 week results from a 300 person virology sub-study which is tracking virological suppression and the development of drug resistance in study participants. Participants in this study had advanced HIV disease at baseline (median CD4 cell count 100 cells/mm3); 30% had a baseline CD4 count below 50 cells/mm³ and three quarters had symptomatic HIV disease (WHO stages 3 or 4).

Baseline viral load was high in the study participants, at a median level of 279,000 copies/ml, and just over one in five (22%) had viral load above 700,000 copies/ml.

Results

After 48 weeks follow-up, an intent to treat (missing equals failure) analysis showed that 65% had viral load below 400 copies/ml and 55% had viral load below 50 copies/ml. Viral load rebound, defined as a viral load above 10,000 copies/ml, had occurred in 16% of participants by week 48.

The researchers also reported on week 24 resistance profiles in 18 out of 48 patients with viral load above 1000 copies/ml in whom it was possible to sequence reverse transcriptase. The predominant mutational patterns were associated with resistance to 3TC (14 patients) and nucleoside anlaogues (11). Three patients developed resistance to tenofovir.