When people with HIV develop resistance to antiretroviral medications, their clinicians often prescribe previously-used nucleoside reverse transcriptase inhibitors (NRTIs), along with other drugs, in the new “salvage” regimen, reasoning that the NRTIs may improve the chances of treatment response. These extra drugs may result in side effects, however, and it is not certain if they’re necessary if other active medicines are included in the salvage regimen. In the OPTIONS trial (ACTG A5241), the AIDS Clinical Trials Group asked whether NRTIs are an essential component of salvage regimens if the regimen has other active medications.
The OPTIONS trial included more than 350 people with HIV who had received many different treatment regimens and developed resistance to a variety of medications before entering. The trial, which lasted almost 2 years, showed that clinicians do not need to add NRTIs to salvage regimens, as long as the new regimen has a cumulative activity of 2 or more active medicines from other drug classes. Salvage regimens that did not include NRTIs gave similar rates of durable virologic suppression as those that included NRTIs. This means that clinicians and people with HIV can be confident that they don’t need to add NRTIs as long as the rest of the regimen is strong enough. Fortunately, with newer and better antiretroviral medications, most people with HIV will have treatment options that result in successful control of the virus. By avoiding NRTIs when we don’t need them, we reduce the pill burden, side effects and the expense of extra medicines.
There were other important findings from the trial. The study found that younger people and those starting fewer new medications were less likely to achieve HIV suppression with salvage therapy. This means that we need to make extra efforts to make sure younger people and those who receive fewer new medicines are able to achieve successful control of their HIV. The study also used a questionnaire to assess participants’ quality of life scores before and during the study: participants in the trial had significant improvement in their scores, demonstrating the strong link between effective treatment and quality of life.
The participation of hundreds of people with HIV who took part in the OPTIONS trial, many of whom had received treatment for more than a decade before they joined, has already made a difference: treatment guidelines have changed thanks to the contribution of the study participants and the staff at the many ACTG sites in the OPTIONS trial.
Gandhi RT, Tashima KT, Smeaton LM, Vu V, Ritz J, Andrade A, Eron JJ, Hogg E, Fichtenbaum C. Long-term Outcomes in a Large Randomized Trial of HIV-1 Salvage Therapy: 96-week Results of AIDS Clinical Trials Group A5241 (OPTIONS). Journal of Infectious Diseases 2019 May 28
(Accompanying editorial: Hoenig M, Little S. Salvage Antiretroviral Therapy: Time for “DeNUKElearization”?)