Tenofovir Alafenamide Plus Emtricitabine Non-Inferior to Abacavir Plus Lamivudine in Specific HIV Patients

Alan Winston, MD, Imperial College of London

Alan Winston, MD

Tenofovir alafenamide plus emtricitabine, which belongs in the class of nucleoside reverse transcriptase inhibitors, poses little risk for bone or renal toxicity in virologically suppressed patients with HIV, and this therapy regimen can be safely used as an alternative to abacavir plus lamivudine in these patients, according to findings from a randomized, double-blind, phase 3 trial reported in a recent issue of the Lancet HIV.¹

“To the best of our knowledge, this randomized, double-blind, multicentre, active-controlled, non-inferiority trial is the first to provide a head-to-head comparison of regimens containing tenofovir alafenamide plus emtricitabine with those containing abacavir plus lamivudine,” stated the study investigators Alan Winston, MD, et al. “Bone and renal safety profiles of tenofovir alafenamide plus emtricitabine and abacavir plus lamivudine were similar, reinforcing the evidence for improved bone and renal safety profile of tenofovir alafenamide compared with tenofovir disoproxil fumarate.”

Investigators screened a total of 501 HIV-1-positive adults at 79 sites across North America and Europe. All participants were virologically suppressed, as identified by HIV-1 RNA <50 copies per mL, and were on a stable 3-drug regimen comprised of abacavir and lamivudine.

The investigators randomized (1:1) participants to switch to fixed-dose tablets of 10 mg or 25 mg tenofovir alafenamide plus 200 mg emtricitabine (n= 253) or to remain on 600 mg abacavir plus 300 mg lamivudine with matching placebo (n= 248). The proportion of patients with virological suppression at 48-week follow-up comprised the primary endpoint.

Virological suppression was sustained in 90% (n= 227) of participants randomized to tenofovir alafenamide plus emtricitabine vs. 93% (n= 230) among those randomized to abacavir plus lamivudine (difference -3.0%, 95% CI -8.2 to 2.0).

In addition, a switch to tenofovir alafenamide plus emtricitabine was associated with non-inferiority in relation to 48-week virological failure (2% vs. 1%; difference 0.8%, 95% CI -1.5 to 3.3; P =.69). At week 48, the mean CD4 count changes were -29 cells per μL (SD 153.5) in the tenofovir alafenamide plus emtricitabine group vs 1 cell per μL (177.3) in the abacavir plus lamivudine group (P= .063).

Adverse events were similar between those randomized to tenofovir alafenamide plus emtricitabine vs abacavir plus lamivudine (4% vs. 3%, respectively). No significant or major differences existed between the 2 groups in regard to changes from baseline to 48 weeks in hip or lumbar spine mineral density. Fractures that did occur were considered related to trauma vs. therapy, and no therapy discontinuations related to fractures occurred.

Considering patients who were tolerating abacavir were enrolled in this study, the findings could have been biased in favor of those receiving this drug. Additionally, the findings from this study may not be generalizable to population groups other than the group presented in this study, which primarily consisted of white men who have sex with men.

“In combination with various third drugs, the fixed-dose combination of tenofovir alafenamide plus emtricitabine was well tolerated and had high efficacy, with rare emergence of drug resistance,” concluded the study investigators. “In patients with creatinine clearance >50 mL/min who are virologically suppressed, tenofovir alafenamide plus emtricitabine could be an alternative to abacavir plus lamivudine, without concern for new onset of renal or bone toxicities or hyperlipidemia.”

REFERENCE

1. Winston A, Post FA, DeJesus E, et al. Tenofovir alafenamide plus emtricitabine versus abacavir plus lamivudine for treatment of virologically suppressed HIV-1-infected adults: a randomised, double-blind, active-controlled, non-inferiority phase 3 trial [published online February 20, 2018]. Lancet HIV. doi: 10.1016/S2352-3018(18)30010-9.