Triple-class antiretroviral drug resistance : risk and predictors among HIV-1-infected patients

HIV-1 triple-class antiretroviral drug resistance (TC-DR) may substantially limit therapeutic options and compromise clinical outcomes. To estimate TC-DR prevalence and incidence, and identify risk factors for TC-DR acquisition. We identified patients in the University of North Carolina HIV Cohort Study with TC-DR HIV-1 variants. Nucleos(t)ide reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and major protease inhibitor (PI) mutations, were based on the International AIDS Society - USA guidelines. Prevalence was estimated with the exact binomial distribution, incidence with the exact Poisson distribution, and multivariable analyses were performed using logistic regression. Of 1587 patients, half initiated therapy with HAART (N = 789), 20% (N = 320) with non-HAART combination therapy, and 30% (N = 478) with one NRTI. The median time on therapy was 5.7 years [interquartile range (IQR) 2.9, 8.6], the median number of previous antiretroviral agents was six (IQR 4, 8), and 47% (N = 752) were exposed to at least one NRTI, NNRTI and PI. Assuming patients without genotypes did not harbor TC-DR virus, the prevalence of TC-DR among all antiretroviral-experienced patients was 8% [95% confidence interval (CI) 6%, 9%]. The prevalence was 3% (95% CI 2%, 4%) and 12% (95% CI 10%, 15%) among patients treated initially with HAART and non-HAART, respectively. The number of antiretroviral agents received and initiating therapy with non-HAART or an unboosted PI, increased TC-DR risk in multivariable analyses. The majority of patients with TC-DR have extensive antiretroviral exposure, particularly to non-HAART regimens, whereas HAART initiators are at low risk of acquiring TC-DR during a median of 4 years of follow-up.