Pretreatment HIV drug resistance leads patients to switch to second-line ART
Recent data suggested that pretreatment 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.
“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 pretreatment 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 analyzed for viral load and genotypic resistance testing.
A pretreatment genotype was available for 2,579 patients, including 5.5% who had pretreatment drug resistance, defined as decreased susceptibility to one or more prescribed drugs.
Researchers found that pretreatment 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 pretreatment drug resistance in adjusted analyses.
At 3-year follow-up, 4.1% of patients had switched to second-line therapy; of these patients, 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 programs,” the researchers wrote.
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. – by Tina DiMarcantonio
Disclosure: The researchers report no relevant financial disclosures.