Clinical use of HIV-1 resistance genotyping.: Predictive factors of poor virological evolution in salvage treatments

OBJECTIVES. To describe the use of genotype resistance testing (GRT) for virological failure in clinical practice, and the long-term clinical and virological evolution in patients for whom it is requested. To identify the predictive factors of virological failure in patients with antiretroviral (ARV) salvage therapy. METHODS. Observational study in HIV-infected patients for whom GRT was requested for virological failure (VF) in the period of 1 October 1999 to 31 December 2001. Logistic regression analysis was used to determine the predictive factors of virological progression. RESULTS. Over the period studied, 196 patients required GRT for VF (15%) among those monitored in specific units. GRT was mainly requested for patients who had been extensively pretreated for a mean of 5 years and with a median of 5 ARV combinations. Half the patients presented 3 or more mutations associated with thymidine analogs (TAMs), mutations associated with non-nucleoside analogs (NNRTIs), and 5 or more mutations associated with protease inhibitors (Pis). In 143 (74%) patients, the RTV regimen was changed on the basis of GRT results. In the intent-to-treat analysis, the percentage of patients with plasma VL < 400 cop/mL at 6,12 and 18 months was 41%,29% and 17%, respectively. In the on-treatment analysis, the results were 50%,48% and 46%, respectively. Mean CD4 lymphocyte increase was 59.74 and 94 cells/mm(3). The variables predicting virological failure (plasma VL > 400 cop/ml) at 12 months were plasma VL > 30,000 cop/mL (OR 6,1.8-19.5) and accumulation of 3 or more TAMs (OR 4.4, 1.3-15) at the start of ARV salvage therapy. CONCLUSION. Even though in clinical practice GRT is requested for patients with various treatment failures, when ART salvage treatment was started, plasma VL was undetectable and immunological response persisted in 40% of patients followed-up for 18 months. The factors best predicting virological evolution were VL and the number of baseline TAMs.