Long-term Outcomes in a Large Randomized Trial of HIV-1 Salvage Therapy: 96-Week Results of AIDS Clinical Trials Group A5241 (OPTIONS)

J Infect Dis. 2020 Apr 7;221(9):1407-1415. doi: 10.1093/infdis/jiz281.


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 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 antiretroviral 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 antiretrovirals require careful monitoring. Even among individuals with more-extensive resistance, most achieve virologic suppression.

Clinical trials registration: NCT00537394.

Keywords: HIV-1; antiretroviral therapy; drug resistance; randomized controlled trial; salvage therapy; treatment-experienced participants.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy*
  • Acquired Immunodeficiency Syndrome / virology
  • Adult
  • Anti-HIV Agents / therapeutic use*
  • CD4 Lymphocyte Count
  • Drug Resistance, Viral*
  • Drug Therapy, Combination
  • Female
  • HIV-1 / genetics
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • RNA, Viral / blood
  • Reverse Transcriptase Inhibitors / therapeutic use*
  • Salvage Therapy*
  • Sustained Virologic Response


  • Anti-HIV Agents
  • RNA, Viral
  • Reverse Transcriptase Inhibitors

Associated data

  • ClinicalTrials.gov/NCT00537394