Pre-treatment HIV drug resistance

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Recent data suggested that pre-treatment HIV drug resistance in sub-Saharan Africa was associated with a nearly fourfold increase in switching to second-line ART, but did not influence mortality or Aids-related events, reports Healio. “The expanding exposure to antiretroviral drugs at a population level will lead to increased transmission of drug-resistant viruses,” the researchers wrote. “As a consequence, ART programs will be confronted with increasing numbers of patients that already carry drug strains before starting standard first-line ART.”

In a multinational cohort study of adult patients beginning standard first-line ART, researchers evaluated the effect of pre-treatment drug resistance on switching ART regimens after presumed treatment failure, as well as its effect on clinical outcomes including all-cause mortality and new Aids events. Additionally, plasma samples collected before ART and at 12, 24 and 36 months were analysed for viral load and genotypic resistance testing.

A pre-treatment genotype was available for 2,579 patients, including 5.5% who had pre-treatment drug resistance, defined as decreased susceptibility to one or more prescribed drugs. Researchers found that pre-treatment drug resistance was associated with an increased risk for regimen switching (P = .005), but the mortality rate and the incidence of new Aids events did not significantly differ for patients with and without pre-treatment drug resistance in adjusted analyses.

At 3-year follow-up, 4.1% of patients had switched to second-line therapy; of these patients. Of them, 17% had a viral load of less than 1,000 copies/mL, 6.6% had a viral load of 1,000 copies/mL or greater and no drug resistance mutations, and 43.4% had a viral load of 1,000 copies/mL or greater and one or more drug resistance mutations.

Researchers expressed concern that 23.6% of patients who were switched to second-line therapy had a viral load of less than 1,000 copies/mL or a viral load of 1,000 copies/mL or greater without the presence of drug resistance mutations. This finding indicated that these patients may have benefited from remaining on first-line ART.

“Unnecessary switching to more costly and toxic second-line therapy, as reported in previous studies, impairs the efficiency in the use of scarce resources available in ART programmes,” the researchers are quoted in the report as saying. The researchers called for expanded access to second-line ART and recommended that viral load monitoring be used to improve accuracy of failure detection and efficiency of switching practices.

Abstract
Background.After the scale-up of antiretroviral therapy (ART) in Africa, increasing numbers of patients have pretreatment HIV drug resistance. This study assessed the effect of pretreatment drug resistance on ART regimen switching and clinical outcomes.
Methods.In a large multi-country cohort of patients starting standard first-line ART in six African countries, pol genotyping was retrospectively performed if viral load (VL) ≥1,000 cps/ml. Pretreatment drug resistance was defined as a decreased susceptibility to ≥1 prescribed drug. We assessed the effect of PDR on all-cause mortality, new AIDS-events and switch to second-line ART due to presumed treatment failure, using Cox models.
Results.Among 2,579 participants for whom a pretreatment genotype was available, 5.5% had pretreatment drug resistance. Pretreatment drug resistance was associated with an increased risk of regimen switch (aHR 3.80; 95%CI 1.49-9.68; p=0.005) but was not associated with mortality (aHR 0.75, 95%CI 0.24-2.35; p=0.617) or new AIDS events (aHR 1.06, 95%CI 0.68-1.64; p=0.807). During three years of follow up, 106 (4.1%) participants switched to second-line, of whom 18 (17.0%) switched with VL <1,000 cps/ml, 7 (6.6%) with VL≥1,000 cps/ml and no drug resistance mutations, 46 (43.4%) with VL≥1,000 cps/ml and ≥1 drug resistance mutations; no HIV RNA data was available for 32 (30.2%) participants.
Conclusions: Given rising pretreatment drug resistance levels in sub-Saharan Africa, these findings underscore the need for expanded access to second-line ART. Viral load monitoring can improve the accuracy of failure detection and efficiency of switching practices.

Full Healio report
Clinical Infectious Diseases abstract


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