What to Do After Virologic Failure on First-Line Therapy with a Nonnucleoside Reverse Transcriptase Inhibitor?

Until recently, most people living with HIV in resource-limited settings initially received antiretroviral regimens anchored by nonnucleoside reverse transcriptase inhibitors (NNRTIs), typically efavirenz. When virologic failure occurs with these regimens, especially in the absence of genotypic resistance testing, what can clinicians do?

In the noninferiority D²EFT trial, 828 people (54% female) who had initial treatment failure with NNRTIs were randomized to receive the recommended standard of care (ritonavir-boosted darunavir [DRV/r] plus two nucleoside reverse transcriptase inhibitors [NRTIs]) or one of two dolutegravir regimens:

• Dolutegravir plus boosted darunavir (DTG+DRV/r)

• Dolutegravir plus tenofovir disoproxil fumarate plus either lami…