Four-drug Combo Pill for HIV an Option in Chronic Dialysis Patients

By Reuters Staff

December 21, 2018

NEW YORK (Reuters Health) - A daily single-tablet regimen of coformulated elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide, approved in the U.S. and elsewhere for HIV-1-infected patients with mild-to-moderate chronic kidney disease, may also work well in those with end-stage renal disease on chronic hemodialysis, a new study suggests.

This regimen may provide a "tolerable and convenient" option for ongoing treatment of HIV infection in this patient population, the study team says in The Lancet HIV, online December 13.

The "quad" elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide pill is marketed in the U.S. as Genvoya by Gilead Sciences, which funded the study.

The open-label, single-arm, phase 3b trial was conducted at 26 outpatient clinics in Europe and the U.S. and included 55 HIV-1-infected adults with end-stage renal disease (creatinine clearance <15 mL/min) on hemodialysis. All patients were switched from previous antiretroviral therapy (ART) regimens to Genvoya, taken once daily after hemodialysis for up to 96 weeks.

Genvoya was judged safe and effective in this patient population through 48 weeks, with an overall "low incidence" of adverse events considered related to treatment, report Dr. Joseph Eron, Jr., of the University of North Carolina School of Medicine in Chapel Hill and colleagues.

Although 18 of 55 patients (33%) had an adverse event of grade 3 or higher on treatment (the primary endpoint), only three (5%) stopped it due to adverse events, and 82% maintained virological suppression at 48 weeks, they note.

The frequency of treatment-emergent grade 3+ adverse events in the study was substantially higher than would be expected in a study of otherwise healthy adults living with HIV, they point out. But this is not surprising or "unexpected" in a group of HIV-infected adults on chronic dialysis, "nearly all of whom had hypertension, approximately half had cardiovascular disease or hyperlipidemia, and a quarter had diabetes," they note.

"This trial is an important proof of concept which might change clinical practice guidelines for ART in this setting," Dr. Juan Ambrosioni and Dr. Jose Miro of the University of Barcelona, Spain, write in a linked comment.

"However, the study had two substantial limitations with regards to assessing mid-term to long-term safety," they note. "First, no bone densitometry studies were done. Although tenofovir alafenamide in patients with chronic HIV infection is usually safe in terms of bone toxicity, dialysis is a different scenario and bone density should be monitored in these patients over a longer follow-up. Second, mitochondrial toxicity was not assessed. Although tenofovir, lamivudine and emtricitabine have lower affinities for mitochondrial DNA polymerase, this study cannot exclude the long-term toxicity. Therefore, conclusions must be cautious."

"Drug-drug interactions are an additional issue," caution Drs. Ambrosioni and Miro. "Patients on hemodialysis frequently take many co-medications, some possibly interacting with cobicistat. Thus, careful dose adjustments should be made."

"Finally, despite the encouraging results from Eron and colleagues’ study, dialysis remains only a bridge to kidney transplantation, which has been shown to be safe and to offer a much better prognosis and quality of life than hemodialysis for HIV-infected individuals. While awaiting transplantation, however, a simpler, effective, and safe single-tablet regimen is more than welcome for HIV-positive patients on hemodialysis," they conclude.

Gilead Sciences had the lead role in study design, data collection, data analysis, data interpretation and (along with Dr. Eron) writing of the manuscript. Dr. Eron had full access to all the data in the study and had final responsibility for the decision to submit for publication.

SOURCE: https://bit.ly/2CmmjdG and https://bit.ly/2CjHUmZ

Lancet HIV 2018.

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