Evidence supports once-daily pill for HIV-infected teens

By Marilynn Larkin

NEW YORK - A small study of treatment-naïve adolescents with HIV infection helped pave the way for approval in the U.S. and elsewhere of the once-daily Genvoya tablet for HIV-infected adults and children age 12 and older, researchers say.

Genvoya, marketed in the U.S. by Gilead Sciences, is a fixed-dose combination of elvitegravir, cobicistat, emtricitabine and tenofovir alafenamide. It was approved by the U.S. Food and Drug Administration a year ago and selected by the U.S. Department of Health and Human Services pediatric HIV treatment guidelines panel as a preferred first-line regimen for adolescents, according to a report in The Lancet HIV, online October 17.

Coauthor Dr. Aditya Gaur of St. Jude Children's Research Hospital in Memphis, Tennessee told Reuters Health, "Finding simple to take, safe and effective options for treatment of HIV is important . . . for adults but critical for children and adolescents. The development of this single-tablet, once a day regimen for HIV-1 infected adolescents 12 to 18 years old is an important milestone in the field of pediatric HIV infection."

"Given some concerns around tenofovir disoproxil fumarate (TDF) use in pediatric patients related to possible bone and renal toxicity, tenofovir alafenamide, with its improved bone and renal safety profile, is particularly pertinent to pediatric patients who are in the midst of peak bone growth," he said by email.

"In addition, integrase inhibitors are now part of most initial guideline-recommended regimens for adults," he observed. "(This tablet) is the first integrase inhibitor-containing (elvitegravir) single-tablet regimen for pediatric patients."

Before testing the regimen, Dr. Guar and colleagues searched PubMed for randomized clinical trials of tenofovir alafenamide in HIV and found that the prodrug is as effective as TDF, but safer from the standpoint of renal and bone toxicity.

From 2013 to 2014, the team conducted a 48-week single-arm, open-label trial in 50 treatment-naive adolescents with HIV from hospital clinics in the U.S., South Africa, Thailand and Uganda. Eligible participants were 12 to 18 years old and had plasma HIV-1 RNA of at least 1000 copies/mL, a CD4 count of at least 100 cells/uL, an estimated glomerular filtration rate of at least 90 mL/min/1.73m2 by the Schwartz formula, weighed at least 35 kg, and had an HIV-1 genotype showing sensitivity to the treatment components.

Participants took the single-tablet regimen containing 150 mg elvitegravir, 150 mg cobicistat, 200 mg emtricitabine, and 10 mg tenofovir alafenamide once daily with food, and visited the clinic regularly over the course of the trial.

Forty-eight patients completed the trial (one withdrew consent and the other was lost to follow up). The regimen was well tolerated, and no patients stopped treatment due to adverse events.

Four participants (8%) had a serious adverse event, one of which (intermediate uveitis) was deemed related to the study regimen but resolved without interrupting treatment. The most common drug-related adverse events were nausea (10 participants), abdominal pain (six) and vomiting (five).

Dr. Gaur observed, "The results from this study have prompted an ongoing study looking at this same, single-tablet, once a day, treatment regimen in younger HIV-infected children, six to 12 years of age."

He concluded, "It is important that such drug-development efforts for children and adolescents occur at the same pace as studies in adults and inform the safe access to these medications to the pediatric population."

Dr. David Burger of Radboud University Medical Center in Nijmegen, The Netherlands, coauthor of a related editorial, told Reuters Health the findings are "good news, as now this regimen has been approved for adolescents." But he questions "the necessity of separate studies in adolescents when data from adults are already available."

"From a pharmacokinetics perspective, one could state that adolescents are similar to adults. There is no single antiretroviral agent that needs to be dosed differently in children weighing more than 35 kg versus adults," he said by email. "Safety may not be similar, if children are more vulnerable, but one can question whether a short, small, non-comparative study gives sufficient answers."

By contrast, "There is an enormous and unacceptable delay in acquiring pharmacokinetic and pharmacodynamic data in the youngest groups, where often an unmet medical need resides," he said.

The study was funded by Gilead Sciences. Seven coauthors are Gilead employees. Dr. Guar received grants from Gilead during the study and outside the submitted work. One other coauthor reported research support from Gilead.

SOURCE: http://bit.ly/2eHBwZO and http://bit.ly/2dSp8a5

Lancet HIV 2016.

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