For patients infected with HIV-1, tenofovir alafenamide plus emtricitabine has a renal and bone safety profile similar to that of abacavir plus lamivudine, according to results of a study led by Dr Martin Shree at Gilead Sciences.
A tenofovir alafenamide plus emtricitabine regimen could be an alternative for patients with virologic suppression who are concerned about the new onset of renal or bone toxicities or hyperlipidemia.
The randomised, double-blind, active-controlled, non-inferiority phase 3 trial included adults who were HIV-1 positive from 79 sites in 11 countries across North America and Europe.
Participants had virologic suppression (<50 RNA copies/mL) and were on a stable 3-drug regimen containing abacavir plus lamivudine. Participants were randomly assigned to switch to fixed-dose tablets of tenofovir alafenamide (10 mg or 25 mg) plus 200 mg emtricitabine (n=253) or to remain on 600 mg abacavir plus 300 mg lamivudine (n=248). The primary outcome was the proportion of participants with virologic suppression (<50 RNA copies/mL) at week 48 with a predefined 10% noninferiority margin.
At week 48, 90% (227) of the participants in the tenofovir alafenamide group maintained virologic suppression compared with 93% (230) of participants in the abacavir group.
Several participants discontinued treatment because of adverse events: 4% of participants in the tenofovir alafenamide group and 3% of participants in the abacavir group.
Among both groups, 3 participants had serious treatment-related adverse events. In the tenofovir alafenamide group, 1 participant had renal colic and 1 had neutropenia. In the abacavir group, 1 participant had myocardial infarction. There were no treatment-related deaths.
“The results of our study suggest that, in the population we studied, tenofovir alafenamide was no different to abacavir from a renal and bone safety standpoint, and tenofovir alafenamide does not seem to be associated with bone or renal toxicity,” concluded the study authors.
Background: Abacavir and tenofovir alafenamide offer reduced bone toxicity compared with tenofovir disoproxil fumarate. We aimed to compare safety and efficacy of tenofovir alafenamide plus emtricitabine with that of abacavir plus lamivudine.
Methods: In this randomised, double-blind, active-controlled, non-inferiority phase 3 trial, HIV-1-positive adults (≥18 years) were screened at 79 sites in 11 countries in North America and Europe. Eligible participants were virologically suppressed (HIV-1 RNA <50 copies per mL) and on a stable three-drug regimen containing abacavir plus lamivudine. Participants were randomly assigned (1:1) by a computer-generated allocation sequence (block size 4) to switch to fixed-dose tablets of tenofovir alafenamide (10 mg or 25 mg) plus emtricitabine (200 mg) or remain on abacavir (600 mg) plus lamivudine (300 mg), with matching placebo, while continuing to take the third drug. Randomisation was stratified by the third drug (boosted protease inhibitor vs other drug) at screening. Investigators, participants, and study staff giving treatment, assessing outcomes, and collecting data were masked to treatment group. The primary endpoint was the proportion of participants with virological suppression (HIV-1 RNA <50 copies per mL) at week 48 (assessed by snapshot algorithm), with a 10% non-inferiority margin. We analysed the primary endpoint in participants enrolled before May 23, 2016 (when target sample size was reached), and we analysed safety in all enrolled participants who received at least one dose of study drug (including patients enrolled after these dates). This study was registered with ClinicalTrials.gov, number NCT02469246.
Findings: Study enrolment began on June 29, 2015, and the cutoff enrolment date for the week 48 primary endpoint analysis was May 23, 2016. 501 participants were randomly assigned and treated. At week 48, virological suppression was maintained in 227 (90%) of 253 participants receiving tenofovir alafenamide plus emtricitabine compared with 230 (93%) of 248 receiving abacavir plus lamivudine (difference −3·0%, 95% CI −8·2 to 2·0), showing non-inferiority. Few participants discontinued treatment because of adverse events: 12 (4%) of 280 participants in the tenofovir alafenimide plus emtricitabine group and nine (3%) of 276 in the abacavir plus lamivudine group. Three participants had serious, treatment-related adverse events: one each with renal colic and neutropenia in the tenofovir alafenamide plus emtricitabine group, and one myocardial infarction in the abacavir plus lamivudine group. There were no treatment-related deaths.
Interpretation: Tenofovir alafenamide, in combination with emtricitabine and various third drugs, maintained high efficacy with a renal and bone safety profile similar to that of abacavir. In virologically suppressed patients, a regimen containing tenofovir alafenamide could be an alternative to those containing abacavir, without concern for new onset of renal or bone toxicities or hyperlipidaemia.
Alan Winston, Frank A Post, Edwin DeJesus, Daniel Podzamczer, Giovanni Di Perri, Vicente Estrada, François Raffi, Peter Ruane, Paula Peyrani, Gordon Crofoot, Patrick W G Mallon, Francesco Castelli, Mingjin Yan, Stephanie Cox, Moupali Das, Andrew Cheng, Martin S Rhee