Pretreatment Drug Resistance Testing Optimizes Antiretroviral Therapy in INSTI Regimens

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The most frequently prescribed INSTI was raltegravir, followed by dolutegravir, and elvitegravir/cobicistat.
The most frequently prescribed INSTI was raltegravir, followed by dolutegravir, and elvitegravir/cobicistat.

Nucleoside reverse transcriptase inhibitor (NRTI) resistance genotyping may be beneficial for people with HIV who have transmitted drug resistance and are beginning integrase strand transfer inhibitor (INSTI) first-line antiretroviral therapy, according to a study published in the Journal of Antimicrobial Chemotherapy.

The researchers identified 1365 individuals with HIV-1 from the Antiviral Response Cohort Analysis (ARCA) who were “drug-naive patients starting [2] NRTIs and either an INSTI or a [boosted protease inhibitors], with an available pre-[antiretroviral therapy] resistance genotype.” The study reviewed sequences present in the ARCA database dated from January 2008 to June 2016. Of the total participants, 1205 were in the boosted protease inhibitors (bPI) group and 160 were in the INSTI group. The study end point was virological failure, which study investigators defined as a plasma HIV-1 RNA >200 copies/mL after week 24.

At the 48-week median follow-up mark, investigators performed survival analyses for each group using Kaplan-Meier curves. In the bPI group, 195 people experienced virological failure, compared with 11 in the INSTI group. The estimated cumulative probability of failure in the bPI group was 11%; the probability in the INSTI group was 7.7%. Baseline resistance was not an influencing factor for virological failure in the bPI group. However, for people classified as having transmitted drug resistance mutations present and “at least low-level resistance to at least one prescribed drug” in the INSTI group, the estimated probability of virological failure at 48 weeks was significant (50%).

The researchers note the study findings are “reassuring, suggesting that even in the presence of [transmitted drug resistance], INSTI-based first-line regimens are effective when fully active accompanying drugs are selected based on the resistance test result.” They believe the study results “support the need for pretreatment drug resistance testing of NRTIs in order to optimize antiretroviral therapy in patients starting first-line INSTI-based regimens.”

Disclosures: Multiple authors declared affiliations with the pharmaceutical industry. Please refer to the reference for a complete list of authors' disclosures.

Reference

Spertilli CS, Rossetti B, Paglicci L, et al. Impact of transmitted HIV-1 drug resistance on the efficacy of first-line antiretroviral therapy with two nucleos(t)ide reverse transcriptase inhibitors plus an integrase inhibitor or a protease inhibitor [published online June 25, 2018]. J Antimicrob Chemother. doi:10.1093/jac/dky211

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