AEGiS-04CROI: Prevalence of protease inhibitor (PRI) and reverse transcriptase inhibitor (RTI) drug-resistance mutations in a rural Iowa HIV+- population: implication for treatment.

4th Conference on Retroviruses and Opportunistic Infections

Washington, DC - January 22-26, 1997

Prevalence of protease inhibitor (PRI) and reverse transcriptase inhibitor (RTI) drug-resistance mutations in a rural Iowa HIV+- population: implication for treatment.

Conf Retroviruses Opportunistic Infect 1997 Jan 22-26; 4th:66 (abstract no. 9)

Kozal M, Leahy N, Ross J, Swack N, Stapleton J; University of Iowa, Iowa City, IA.

Objective: To determine the prevalence of PRI and RTI drug-resistant mutations & polymorphisms (polys) in a rural HIV-infected population and to investigate the effect preexisting mutations & polys within PR gene have on the frequency, rapidity and patterns of emergence of PR mutations in HIV+ patients in relation to patients beginning PRI therapy without any PRI resistance mutations. Design/Measurements: Retrospective, cross-sectional analysis of viral isolates, and a prospective, observational, longitudinal analysis of Pol gene sequences from patients who were drug naïve or RTI experienced and were changed to an alternate Rx (including Saquinavir, Indinavir or Ritonavir). All Pol genes were sequenced using both automated sequencing (ABI) and DNAChips (Affymetrix) using methods previously published (Kozal et.al Nature Med 1996, 2:753).

Results: Pol genes from HIV-1 isolates from 72 PRI-naïve patients were sequenced. Mutations known to confer resistance to all 3 licensed PRIs were identified. 26% of patients had changes within the PR gene associated with PRI resistance, specifically at codons 10/20/24/45/54/63/71/82. 21% of patients harbored viruses with multiple PR mutations. 25% of patients contained RTI drug-resistant mutations (58% AZT, 17% 3TC, 25% ddN). Of newly Dx HIV- infected patients (n=60) 3% harbored RTI-resistant mutations. Longitudinal results from patients with and without PRI mutations at the start of RTI+PRI therapy will be presented.

Conclusion: PRI mutations associated with PRI drug-resistance were prevalent in this rural PRI-naïve patient cohort. RTI drug-resistant mutations were also prevalent in patients both RTI-naïve newly Dx and RTI-experienced. The high frequency with which drug-resistance mutations occur suggests that Rx based on blind algorithms of drug switching may lead to patients being switched or started on Rx regimens for which their HIV-1 isolates are already resistant.

Keywords: AEGIS, Reverse Transcriptase Inhibitors, Protease Inhibitors, HIV-1, Anti-HIV Agents, HIV Protease Inhibitors, HIV-1 Reverse Transcriptase, Mutation, Saquinavir, Genes, pol, Ritonavir, Indinavir, Prevalence, Zidovudine, Drug Resistance, Drug Resistance, Microbial, Cross-Sectional Studies, Retrospective Studies, Iowa, Human, therapy, epidemiology, genetics, drug therapy, AIDS

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Copyright © 1980, 1997 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed through AIDSLINE, National Library of Medicine.