Pre-treatment resistance and virologic failure

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Pre-treatment resistance and HIV-1 sub-type appear to be independently linked to virologic failure in HIV patients undergoing treatment with ART in resource-limited settings, according to results from the PEARLS trial, says a Healio report.

“Resource-limited settings disproportionately bear the global burden of HIV,” researchers wrote. “The development and transmission of antiretroviral (ARV) drug resistance are major hurdles to HIV care. As ARV therapy (ART) becomes more accessible in (resource-limited settings), it is essential to investigate ARV drug resistance in diverse HIV-1 sub-types and settings to guide clinical care.”

In the phase 4, randomised, open-label clinical trial, researchers evaluated 1,571 adult HIV patients with CD4 cell counts lower than 300 cells/µL and no previous ART. Participants were randomly assigned to one of the following three treatment arms: Sustiva (efavirenz, Bristol-Myers Squibb; EFV) plus co-formulated Combivir (lamivudine/zidovudine, ViiV Healthcare; n = 519); Reyataz (atazanavir, Bristol-Myers Squibb) plus Videx (didanosine, Bristol-Myers Squibb) and Emtriva (emtricitabine, Gilead Sciences; FTC; n = 526); or EFV plus co-formulated Truvada (tenofovir/FTC, Gilead Sciences; n = 526).

The researchers conducted pol genotyping on a sub-cohort of 261 randomly selected participants, of whom 51 failed ART, as well as a case group of 218 additional participants who failed treatment. Viral load and CD4 cell count were measured at enrolment and every 8 weeks throughout the study. Virologic failure was defined as having a viral load greater than 1,000 copies/mL. The researchers also examined associations between pre-treatment resistance and treatment failure.

Results showed a 4.2% rate of baseline resistance, which occurred evenly across treatment arms and sub-types. In the sub-cohort and case groups combined, baseline resistance was seen in 7.1% (9.4% with virologic failure and 4.3% without virologic failure). A significant association was seen between baseline resistance and shorter time to virologic failure (HR = 2.03; 95% CI, 1.05-3.92), and this independent association persisted after adjusting for sex, treatment arm, sex-treatment arm interaction, pre-treatment CD4 cell count, baseline viral load and sub-type (HR = 2.1; 95% CI, 1-4.6). Compared with sub-type B, sub-type C infection was related to a higher risk for virologic failure (HR = 1.57; 95% CI, 1.04-2.35), while infection with non-B/C sub-type was related to longer time to virologic failure (HR = 0.47; 95% CI, 0.22-0.98).

The researchers said the findings support the use of pre-ART genotyping in resource-limited settings. “With expected increases in the prevalence of transmitted resistance worldwide, this study will help inform policy decisions related to the use of resistance testing in clinical practice in (resource-limited settings),” they wrote. “The findings in the report support use of genotyping prior to ART initiation in (resource-limited settings), when feasible.”

Full Healio report
Clinical Infectious Diseases abstract

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