Quad Pill for HIV Appears Safe in Renal Disease (CME/CE)
HIV patients with mild to moderate renal impairment appear to tolerate treatment with a combination tablet that contains drugs known to impact kidney function, a phase III, open-label, two-cohort study found.
The treatment group receiving the four-drug combination of elvitegravir, cobicistat, tenofovir DF, and emtricitabine, branded as Stribild, saw a small impact on estimated creatinine clearance (eCCr), but the change rapidly plateaued and may not be clinically meaningful, Frank Post, MD, a reader in HIV at Kings College Hospital in London, told MedPage Today
Researchers saw no cases of proximal tubulopathy over the 24 weeks of the study, Post reported here during his poster presentation at the International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention.
Patients in the other cohort receiving cobicistat also saw minimal changes in eCCr from baseline to 24 weeks (reduction of 3.7 mL/min versus 5.2 mL/min for the Stribild cohort).
A total of 33 patients were in the Stribild group and 73 in the cobicistat group. Patients had an eCCr of 50-89 mL/min at baseline.
Stribild is licensed for use in treatment-naive HIV-infected patients with eCCr equal to or greater than 70 mL/min.
In the current phase III, open label, multicenter, two-cohort study, the four-drug tablet was given to treatment-naive patients, while cobicistat was given to virally suppressed patients receiving ritonavir-boosted atazanavir (Reyataz) or darunavir (Prezista) along with two reverse transcriptase inhibitors. The ritonavir was replaced with cobicistat.
Cobicistat used outside the "quad" pill is considered investigative use because it has not yet been approved by the FDA.
"Stribild and cobicistat -- as a replacement for ritonavir in various regimens -- may be an option for patients with baseline mild to moderate renal impairment," Post said.
Post noted that the drop in eCCr occurred almost immediately after the start of treatment with the drugs, and then remained constant.
A total of 14 patients had their actual glomerular filtration rate measured using iohexol clearance. Researchers saw no changes in the aGFR at 2, 4, and 24 weeks.
The patients on the four-drug regimen were about 50 years of age; 82% were men; 39% were of African descent.
The patients switched to cobicistat were about 54 years of age; 82% were men and 19% were of African descent.
Both tenofovir, an HIV nucleotide reverse transcriptase inhibitor, and cobicistat, a drug designed to boost bioavailability of the integrase inhibitor elvitegravir, are known to have impacts on renal function.
Ritonavir, in subtherapeutic doses, is also employed to boost integrase inhibitors and protease inhibitors in many HIV regimens.
"These are the patients who we should be most concerned about when treating with drugs such as tenofovir and cobicistat, and we are not seeing clinically meaningful changes in creatinine and glomerular filtration rate," Saye Khoo, MD, MBBS, a professor of translational medicine at the University of Liverpool, told MedPage Today
. "This study is reassuring."
However, Julio Montaner, MD, a professor of medicine at the University of British Columbia in Vancouver, cautioned, "Changes in renal function, although small, that have been observed with cobicistat in co-administration with tenofovir should not be dismissed."
He added that "optimal strategies for monitoring renal function in these patients needs to be defined further."
The study was sponsored by Gilead.
Khoo had no disclosures.
Montaner disclosed his center performs research for Gilead, Merck, GlaxoSmithKline, Bristol-Myers Squibb and multiple other pharmaceutical companies.
Post disclosed commercial relationships with Gilead, ViiV, Johnson & Johnson, Bristol-Myers Squibb, GlaxoSmithKline, and Merck.
Primary source: International AIDS Society
Source reference:
Post F, et al"Renal safety of elvitegravir/cobicistat/emtricitabine/tenofovir DF (STB) and cobicistat-boosted protease inhibitor regimens in HIV-1-infected patients with mild to moderate renal impairment" IAS
2013; Abstract TUPE280.
