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Transmitted drug resistance mutations increase in HIV

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March 3, 2017

Transmitted drug-resistance mutations in HIV increased among ARTnaive patients from 2000 to 2013, according to findings published in The Journal of Infectious Diseases.

“The research and discovery of chemical entities targeting HIV replication have provided the medical community with an arsenal of drugs to combat the advance of the AIDS epidemic,” Nicolas A. Margot, MA, of the department of biology at Gilead Sciences, and colleagues wrote. “However, concurrent to the use of ART with suboptimal viral suppression and owing to the error-prone replication of HIV reverse transcriptase, drug-resistant strains of HIV have emerged.”

Researchers conducted resistance testing in 5,990 ARTnaive patients who had participated in nine clinical studies performed by Gilead between 2000 and 2013. Across all nine studies, median age ranged from 34 to 38 years. The most common subtype was HIV-1 subtype B.

During the study period, the incidence of transmitted drug-resistance mutations increased from 5.2% to 11.4%, the researchers reported. This was driven mainly by non-nucleoside RT inhibitor resistance mutations, which increased incidence from 0.3% to 7.1%. K103N/S mutations in particular rose from 0.3% to 5.3%.

NRTI mutations occurred in 3.1% of patients, Margot and colleagues wrote. A small percentage of patients had at least one thymidine mutations: 0.07% had T215Y/F mutations and 2.7% had T215 revertant mutations. Those patients who had a combination of M41L+L210W+T215 revertant mutations showed full suppression when treated with a TDF or tenofovir alafenamide-containing regimen, the researchers reported.

“In summary, we have shown that the presence of common transmitted drug-resistance mutations, particularly the T215 revertant mutations, in ARTnaive patients had no measurable impact on treatment response to TDF or tenofovir alafenamide-based regimens,” Margot and colleagues wrote. “This further suggests that the presence of T215 revertant mutations should not be a factor in the estimation of genotypic resistance to TDF or tenofovir alafenamide.” – by Andy Polhamus

Disclosure: All researchers are employees and stockholders of Gilead Sciences.

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