Lamivudine and indinavir/ritonavir maintenance therapy in highly pretreated HIV-infected patients (Vista ANRS 109)

Objective: In patients with extensive HIV resistance, one option is to delay salvage therapy until new drugs become available. We hypothesized that this delay period could be based on a simplified treatment, which would reduce drug toxicity, stabilize resistance, and prevent resurgence of wild-type virus. Methods: A prospective 24-week treatment simplification study in HIV-1-infected patients having failed several lines of antiretroviral therapy, with CD4(+) T-cell counts >= 100 cells/ml, plasma HIV RNA (viral load [VL]) >= 4 log(10) copies/ml and a resistance genotype predicting less than two active drugs. Treatment associated ritonavir-boosted low-dose indinavir (200 mg twice daily) and lamivudine (150 mg twice daily). The primary endpoint was a decrease in CD4(+) T-cell counts >= 25% or increase in VL >= 0.7 log copies/ml relative to baseline. Results; Twenty-six patients were included. Baseline median VL was 4.5 log(10) copies/ml and median CD4(+) T-cell count was 290 cells/ml. During the study, 10/26 patients (38%, 95% confidence interval=20.2-59.4) reached the primary endpoint. No patient had an AIDS-defining event. At week 24, the median change in plasma VL was +0.2 log(10) opies/ml (interquartile range (IQR): 0-0.5; P=0.003). The median change in CD4(+) T-cell counts was -49 cells/ml (IOR: -14 to -93, P < 0.001), with a median decline slope of 10 cells/ml/month, which was not different from that measured under full highly active antiretroviral therapy during the 6 months preceding inclusion. There were no significant changes in HIV-1 protease and reverse transcriptase genotypes during the study. Conclusions: In patients with advanced resistance, treatment simplification prevented resurgence of wild-type HIV, reduced drug burden, but failed to stabilize progression of the immune deficiency.