Continuous vs intermittent treatment with triple nuke combination of AZT/3TC/tenofovir in Africa: early results from DART study

DART is a large five year clinical trial of HIV treatment in Africa that will enroll 3,300 patients with advanced HIV disease or AIDS, conducted in Uganda and Zimbabwe.

The trial is to investigate whether or not antiretrovirals can be given in the absence of routine laboratory tests (relying on clinical monitoring alone) and whether the drugs be given intermittently rather than continuously.

The majority of patients enrolled received AZT/3TC/tenofovir as first line therapy a regimen for which there are limited data and none on a large scale. A smaller group received AZT/3TC/abacavir or AZT/3TC/nevirapine. Results from the main study will not be available for at least three years.

Charles Gilks, on behalf of the DART investigators, presented 48-week data from a virology sub-study of 300 patients. The median age of the patients was 37.3 years (range 20-62 years) and 66% were women. The median baseline CD4 was 100 cells/mm³ (IQR: 37-150 cells/mm³) and 30% of patients were <50 cells/mm³. The median baseline viral load was 262,100 cells/mm³ (IQR: 93,400-625,300).

At 48 weeks, using an ITT, missing=failure analysis, 55% of patients had a viral load <50 copies/ml and 63% <400 copies/mL compared to 56% and 74% at 24 weeks. The mean CD4 increases were 103 and 127 cells/mm³ at 24 and 48 weeks respectively.

At 48 weeks 16% of patients had viral load >10,000 copies/mL but no patient switched to second line therapy according to clinical criteria within the period of evaluation.

The investigators also looked at resistance in 20/38 samples obtained at 24 weeks from patients with viral load >1000 copies/mL. Of the remaining 18 samples which could not amplify 12 had viral load >5000 copies/mL.

Mutations were found in 18/20 samples: 14 had M184V, 11 with additional NAMS; one had NAMS alone and 3 had K65R, one with T215Y, one with Y115F and one alone. Additionally they reported 2/14 with M184V had NNRTI mutations despite no documented treatment with this class. The investigators summarised: TAMS was the most common route to resistance whereas K65R was identified infrequently.

Kaleebu P, DART trial team. 48 week virological response to triple nucleoside/nucleotide analogue regimen in adults with HIV infection in Africa within the DART trial. 3rd IAS Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, 2005. Abstract WeOaLB0203.