ABSTRACT: Objective: To assess the prognostic significance of drug-associated mutations in the protease and reverse transcriptase (RT) genes on virological response to salvage therapy.
Patients: All patients from four centres of the Swiss HIV Cohort Study who, following failure of HAART (HIV-1 RNA > 1000 copies/ml after >3 months), were switched to nelfinavir plus other antiretroviral drugs between February and October 1997.
Methods: Direct sequencing of RT and protease genes derived from plasma RNA was performed in 62 patients before salvage therapy. Baseline predictors (drug resistance mutations, drug exposure, clinical and biological parameters) of virological response after 4012 weeks of therapy were assessed by linear regression analyses.
Results: Patients had been treated with RT inhibitors and protease inhibitors (PI) for a median duration of 35.6 and 12.2 months, respectively. Baseline median CD4 count was 113 cells/mm3 and HIV-1 RNA was 5.16 log10 copies/ml. The medial decrease of HIV-1 RNA was 0.38 log10 and 32% of the patients showed a >1 log10 decrease. At baseline, 90% of the patients had RT inhibitor resistance mutations with a median number of four (range 0-7) per patient. Primary and secondary PI resistance mutations were detected in 69% and 89% of the patients, respectively. The median number of total PI resistance mutations per patient was four (range 0-9). In univariate analysis, virological response to salvage therapy was associated with the number of RT inhibitors, primary and secondary PI resistance mutations, history of PI use (duration and number), but not with clinical stage, HIV-1 RNA level or CD4 cell count. After adjustment for all variables, the number of RT inhibitor plus PI resistance mutations was the only independent predictor.
Conclusions: In patients with advanced HIV infection, the virological response to salvage therapy containing nelfinavir is best predicted by the number of baseline RT inhibitor plus PI resistance mutations.
