Individuals taking salvage antiretroviral (ARV) regimens to treat HIV can safely leave out nucleoside reverse transcriptase inhibitors (NRTIs, or nukes), reports Aidsmed. Researchers conducted an open-label, multi-centre, randomised controlled trial including 360 individuals recruited between 2008 and 2011 from 62 clinics in the US.
A salvage regimen is treatment for HIV-positive individuals who have become resistant to multiple classes of antiretrovirals.
The participants all had ongoing viral replication despite being on a second- or third-line ARV regimen. All of them had taken a protease inhibitor (PI)–based regimen and had either taken or had resistance to both nukes and non-nucleoside reverse transcriptase inhibitors (NNRTIs, or non-nukes).
The participants were all switched onto salvage regimens that included at least two active ARVs from four drug classes, including non-nukes, boosted PIs, integrase inhibitors and entry inhibitors. They were then randomly assigned to either take nukes or leave them out.
93% of the participants completed a 48-week study. The cumulative probability that participants would fail their treatment regimen was 29.8% in the group that did not take nukes and 25.9% in the group that added nukes. There were no significant differences between the two groups in indications of drug safety or in the proportion of those with a fully suppressed viral load. There were no deaths in the group that did not take nukes, compared with seven deaths in the group that did take them.
The researchers concluded that leaving nukes out of a salvage regimen was safe and would also reduce pill burden and toxicities.
Nucleoside reverse transcriptase inhibitors (NRTIs) are often included in antiretroviral regimens in treatment-experienced patients in the absence of data from randomized trials.
To compare treatment success between participants who omit versus those who add NRTIs to an optimized antiretroviral regimen of 3 or more agents.
Multicenter, randomized, controlled trial. (ClinicalTrials.gov: NCT00537394).
Outpatient HIV clinics.
Treatment-experienced patients with HIV infection and viral resistance.
Open-label optimized regimens (not including NRTIs) were selected on the basis of treatment history and susceptibility testing. Participants were randomly assigned to omit or add NRTIs.
The primary efficacy outcome was regimen failure through 48 weeks using a noninferiority margin of 15%. The primary safety outcome was time to initial episode of a severe sign, symptom, or laboratory abnormality before discontinuation of NRTI assignment.
360 participants were randomly assigned, and 93% completed a 48-week visit. The cumulative probability of regimen failure was 29.8% in the omit-NRTIs group versus 25.9% in the add-NRTIs group (difference, 3.2 percentage points [95% CI, -6.1 to 12.5 percentage points]). No significant between-group differences were found in the primary safety end points or the proportion of participants with HIV RNA level less than 50 copies/mL. No deaths occurred in the omit-NRTIs group compared with 7 deaths in the add-NRTIs group.
Unblinded study design, and the study may not be applicable to resource-poor settings.
Treatment-experienced patients with HIV infection starting a new optimized regimen can safely omit NRTIs without compromising virologic efficacy. Omitting NRTIs will reduce pill burden, cost, and toxicity in this patient population.