How Stable Are Transmitted Drug-Resistance Mutations?

Clinicians routinely test for transmitted drug-resistance mutations in patients with newly diagnosed HIV infection. But relatively few data address the question of how stable these mutations are without drug pressure — in other words, the likelihood that a transmitted drug-resistant virus will revert to wild type in a patient who is not on treatment.

Researchers in the U.K. compiled data from 313 adult patients with confirmed drug-resistant virus who had genotype testing repeated while still antiretroviral therapy–naive, 10 to 96 weeks after initial testing. Most participants were men who have sex with men, were infected with subtype B virus, and had well-preserved CD4-cell counts; only 47 (15%) were known to have had the first genotype test performed within 18 months of initial infection.

Overall, only 24% of mutations revealed by the first test were undetectable on the second: 22% of nucleoside reverse transcriptase inhibitor mutations, 24% of nonnucleoside reverse transcriptase inhibitor mutations, and 27% of protease inhibitor mutations. Among the most likely mutations to disappear were K70R (7/14 patients), M184V (16/34), T215Y (13/25), and Y181C (10/20). Among the least likely to disappear were D67N (4/27) and T215 “revertants” (9/106), associated with thymidine-analogue resistance.

Multivariate analysis showed that mutations in non–subtype B infections disappeared more quickly than those in subtype B infections. CD4-cell count, viral load, recent infection, and number of mutations had no clear effect on the rate or pattern of mutation loss.