BACKGROUND:
Short-term (48-week) results of the OPTIONS trial showed that nucleoside reverse transcriptase inhibitors (NRTIs) can be safely omitted from salvage therapy as long as the regimen has a cumulative activity of >2 active antiretroviral (ARV) medications. The long-term durability of this approach and outcomes in persons who have more-extensive HIV-1 drug resistance are uncertain.

METHODS:
Participants with virologic failure and anticipated ARV susceptibility received an optimized regimen and were randomized to Omit or Add NRTIs. A separate group with more resistance (cumulative activity ≤2 active agents) received an optimized regimen including NRTIs.

RESULTS:
At week 96, among 360 participants randomized to Omit or Add NRTIs, 70% and 65% had HIV-1 RNA <200 copies/mL, respectively. Virologic failure was uncommon after week 48. Younger age and starting fewer new antiretroviral medications were associated with higher odds of virologic failure. In the Highly Resistant group, 53% had HIV-1 RNA <200 copies/mL at week 96.

CONCLUSIONS:
HIV-1 salvage therapy can safely omit NRTIs without compromising efficacy or durability of response as long as the new regimen has a cumulative activity of >2 active drugs. Younger people and those receiving fewer new ARVs require careful monitoring. Even among individuals with more-extensive resistance, most achieve virologic suppression.