In the JournalsPerspective

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.

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.

    Perspective
    Steven J. Reynolds

    Steven J. Reynolds

    Boender and colleagues present an interesting analysis from their Pan-African Studies to Evaluate Resistance Monitoring (PASER-M) collaboration looking at the impact of pre-treatment drug resistance in sub-Saharan Africa on ART switching and clinical outcomes over 36 months of follow-up. The researchers found a nearly fourfold increase in switches to second-line ART among participants harboring drug-resistant HIV before starting first-line ART. Pretreatment drug resistance was not associated with new AIDS-related events or excess mortality. The researchers also found that among patients switched to second-line regimens, 24% either had a viral load of less than 1,000 copies/mL or 1,000 copies/mL or more without evidence of drug resistance mutations. This is an important study given the current status of the ART role-out in sub-Saharan Africa, which is now entering its 12th year since expanded resources have saved millions of lives. This rapid expansion of ART has occurred in settings where the majority of individuals have limited access to viral load monitoring due to cost and complexity. This has raised concern that prolonged, undetected virologic failure may result in increasing rates of transmitted drug resistance, with some studies suggesting that these rates are rising. The study by Boender and colleagues highlights the importance of expanded access to virologic monitoring, which is now occurring in many countries across sub-Saharan Africa and a fundamental component of the latest WHO HIV treatment guidelines. Access to virologic monitoring will ensure that clients failing first-line ART are switched appropriately at the right time to avoid both the risk for transmitted drug resistance and the risk for morbidity and mortality from delayed switching and prolonged virologic failure. As the current ART programs in sub-Saharan Africa mature, attention will need to focus on the implementation challenges of viral-load monitoring, including clinician training on interpretation and timely switching as well as expanded access to affordable second-line ART regimens. This offers clinicians an opportunity to consolidate the tremendous gains made during the initial decade of the ART role-out and continue to offer our patients healthy and productive lives.

    • Steven J. Reynolds, MD, MPH, FRCPC
    • Senior clinician Division of intramural research, NIAID Associate professor of medicine and epidemiology Johns Hopkins University

    Disclosures: Reynolds reports no relevant financial disclosures.