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

Abstract

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.

Figure 1.

Participant disposition. Abbreviation: NRTI, nucleoside reverse transcriptase inhibitor.

Figure 2.

Cumulative probability of virologic failure over time by treatment group. Abbreviation: NRTI, nucleoside reverse transcriptase inhibitor.

Figure 3.

Mean quality of life score and change in quality of life score over time by treatment group. Quality of life was assessed using the general health score, which uses a visual analog scale that ranges from 0 (worst possible health) to 100 (perfect health). Abbreviation: NRTI, nucleoside reverse transcriptase inhibitor.