Cost-Effective Alternative to Drug-Resistant HIV Genotyping

Antiretroviral therapy (ART) has led to remarkable improvements in HIV-infected individuals. By suppressing HIV RNA to <50 copies/mL, ART has changed the disease trajectory and lengthened expected survival.

CD4+ cells have resilient memories, which is 1 reason why HIV is so difficult to treat. Even if ART is effective, CD4+ cells can archive drug resistance mutations (DRMs) in resting memory.

Researchers have identified DRMs using sequencing-extracted DNA from buffy coat, whole blood, or peripheral blood mononuclear cells. Clinically, RNA genotyping is the gold standard for HIV drug resistance testing, but it is costly.

Recently, a research team developed a method to sequence pol gene from proviral DNA in order to identify DRMs in viremic and suppressed patients. In the study, which was published in PLOS One, 120 HIV-infected individuals from the Peninsula AIDS Research Cohort study in California’s San Mateo and San Francisco counties were monitored for 2 years.

At baseline, the researchers completed HIV-1 pol genotyping via bulk sequencing on both DNA and RNA from 38 viremic patients. They performed HIV-1 pol genotyping DNA on only 82 suppressed patients.

Among the participants, 81% had received ART for a median time of 7 years. Thirty-two viremic patients (84%) possessed concordant RNA and DNA genotypes, while the remainder had discordant profiles, which was likely to be seen in those with low-level viremia.

Among suppressed patients with <50 HIV RNA copies/mL, 26% had proviral DNA DRMs with potential resistance to 1, 2, or 3 ARV classes in 16, 4, and 1 samples, respectively. DRMs in this population elevate risk for transmission of drug-resistant virus when there is virologic failure, treatment interruption, or decreased adherence.

The clinical relevance of the high level of genotype concordance between DNA and RNA in viremic patients indicates that DNA genotyping might be used to assess drug resistance. This less costly DNA genotyping could prove advantageous for resource-limited settings, though the researchers stressed that further investigation is needed.