Genotypic resistance and immunologic outcomes among HIV-1-infected women with viral failure

Objectives: To describe the prevalence of specific protease inhibitor (PI) and nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations and the relationship between the presence of these mutations and immunologic outcomes following PI/NNRTI initiation among a cohort of HTV-1-infected women. Methods: Viral genotypic resistance testing was done for 366 women enrolled in the Women's Interagency HIV Study at the visit immediately prior to 1st reported use of PI or NNRTI (baseline) and at the visit approximately 1 year after PI/NNRTI initiation. We modeled the changes in CD4⁺ T-cell counts and HIV RNA levels approximately 1 year after therapy initiation as a function of baseline and follow-up markers, type of antiretroviral therapy used, and resistance mutations. Results: At baseline, 52% of women showed only nucleoside reverse transcriptase inhibitor (NRTI) mutations, 38% showed no mutations, and 10% showed PI or NNRTI mutations. Only 40% of women showed viral response (HIV-1 RNA ≤ 80 copies/mL) 1 year after initiating a PI or NNRTI. Among those without a viral response, 54% developed PI or NNRTI mutations. NNRTI (among those with baseline NRTI mutations) and PI resistance mutations were associated with better CD4⁺ cell count changes (mean increase of 118 cells/mm³ and 64 cells/mm³, respectively, as compared with viral nonresponders with no PI or NNRTI mutations). Conclusions: In this population-based cohort, virologic failure with PI or NNRTI resistance was common. Viremia with these resistance mutations was associated with preserved CD4⁺ T-cell count responses, providing evidence of reduced virulence or viral fitness.