A5288: Diverse Drug Resistance Profiles among People Experiencing Virologic Failure on Second-line ART in Resource Limited Settings

Clinical Infectious Diseases, November 2019

A5288 assessed third-line antiretroviral treatment (ART) in individuals who were failing second-line ART. This publication aimed to define resistance profiles among individuals failing second-line ART in low- and middle-income countries (LMIC), as this information is vital to optimize individual patient management and to develop treatment guidelines for this group. Of the 653 individuals screened for A5288, more than three-quarters (78%) had resistance to one or more drugs. One-fifth (20%) of participants showed resistance to at least one drug in a drug class, 32% showed resistance to at least one drug in two drug classes, and 26% showed 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% of individuals, 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, and was lower among prior nevirapine recipients.

Therefore, highly divergent HIV drug resistance profiles, ranging from no resistance to resistance to three drug classes, were seen among individuals failing second-line ART in LMIC.  These results underscore the need for ready access to resistance testing and newer antiretrovirals for optimal management of third-line ART in LMIC.

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.