Diverse HIV-1 Drug Resistance Profiles at Screening for ACTG A5288: A Study of People Experiencing Virologic Failure on Second-line ART in Resource Limited Settings.

BACKGROUND HIV drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well-defined among individuals on failing second-line ART in low- and middle-income countries (LMIC). METHODS Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (ACTG protocol 5288). Prior exposure to both NRTI and NNRTI and confirmed virologic failure on a PI-containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype and country were investigated. RESULTS Plasma HIV genotypes were analysed for 653 candidates screened; most had resistance (508 of 653 [78%]) to one or more drugs. Genotypes from 133 (20%) showed resistance to at least one drug in a drug class, 206 (32%) resistance to at least one drug in two drug classes, and 169 (26%) resistance to at least one drug in all three commonly available drug classes. Susceptibility to at least one second-line regimen was preserved in 59%, as was susceptibility to etravirine (78%) and darunavir/r (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell count, and those who had received LPV/r, but was lower among prior nevirapine recipients. CONCLUSIONS Highly-divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to three drug classes. These findings underscore the need for access to resistance testing and newer ARVs for optimal management of third-line ART in LMIC.

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