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

AIDS. 2007 Apr 23;21(7):825-34. doi: 10.1097/QAD.0b013e32805e8764.

Abstract

Background: HIV-1 triple-class antiretroviral drug resistance (TC-DR) may substantially limit therapeutic options and compromise clinical outcomes.

Objective: To estimate TC-DR prevalence and incidence, and identify risk factors for TC-DR acquisition.

Methods: 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.

Results: 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.

Conclusion: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Anti-HIV Agents / administration & dosage
  • Antiretroviral Therapy, Highly Active
  • CD4 Lymphocyte Count
  • Drug Administration Schedule
  • Drug Resistance, Multiple, Viral* / genetics
  • Female
  • Follow-Up Studies
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / immunology
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Risk Factors
  • Viral Load

Substances

  • Anti-HIV Agents