Both baseline HIV-1 drug resistance and antiretroviral drug levels are associated with short-term virologic responses to salvage therapy

Background: To determine the impact of HIV-1 drug resistance at baseline and antiretroviral drug levels (DL) during follow-up on virologic response to the next antiretroviral regimen. Methods: Baseline genotypic and phenotypic susceptibility was obtained for plasma virus from patients failing a protease inhibitor-containing regimen. Untimed plasma antiretroviral DL were performed and the distribution of DL after 12 weeks of follow-up was classified as above (DL_High) or below (DL_Low) the median. Inhibitory quotients [IQ = (DL at week 12)/(fold change in IC₅₀ to wild-type)] were determined for each drug in the regimen. Primary outcome was change in log₁₀ plasma HIV-1 RNA viral load (ΔVL) from baseline to 12 weeks. Results: There were 137 patients who had baseline resistance data available for the antiretroviral drugs used in the salvage regimen, and DL at week 12. Each drug with DL_High was associated with ΔVL = -0.40 (P = 0.0002) while each drug with DL_Low had ΔVL = -0.1 6 (P = 0.11). In multivariate models ΔVL associated with each active drug (defined by genotype) with DL_High was -0.48 log₁₀ (P < 0.0001), and with each active drug with DL_Low was -0.22 (P = 0.03). The ΔVL was -0.18 if no drugs in the regimen had an IQ > median, compared to -0.58 for one drug, -1.06 for two drugs, -0.86 for three drugs, and -1.44 for four or five drugs with IQ > median (P < 0.0001 for trend). Conclusions: In salvage therapy, both the number of active drugs and the DL for each drug in the new regimen determine the antiviral response.