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More research needed to determine risks of efavirenz treatment among children
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Although there is evidence of the safety and efficacy of efavirenz treatment among children with HIV-1, more research is needed to determine the actual risks of treating children with efavirenz, according to a review in the Journal of Pediatric Health, Medicine and Therapeutics.
The FDA approved efavirenz (Sustiva, Bristol-Myers Squibb) for use among children following study findings from the Pediatric AIDS Clinical Trials Group, which indicated efavirenz in combination with nelfinavir (Viracept, Agouron) was well tolerated and led to sustained virologic suppression in most children older than 3 years.
Since then, additional studies have shown efavirenz to be an effective treatment option for both treatment-naive and heavily pretreated children with HIV, leading to an extension of the FDA approval to children as young as 3 months. However, these studies are limited by their small cohorts and/or small follow-up periods and highlights a need for multisite studies of long-term outcomes and toxicities of efavirenz among children, according to Beatriz Larru, MD, PhD, of the Children’s Hospital of Philadelphia, and colleagues, who wrote the review.
Recent data has shown better outcomes in adults taking efavirenz compared with nevirapine (Viramune, Boehringer Ingelheim), the other WHO-recommended antiretroviral therapy regimen. Pediatric research has yielded similar evidence, according to researchers.
Nevirapine has been associated with a higher risk for non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations than efavirenz, which the researchers said may be problematic among adolescents, who have the poorest adherence rates compared with adults and young children.
Efavirenz may be considered more user-friendly, as it is taken once daily, whereas nevirapine is taken twice daily and requires a lead-in-period of about 2 weeks. However, the cost of efavirenz is higher than nevirapine.
There are few studies that evaluate the pharmacokinetics of efavirenz, but existing evidence shows a high prevalence of virological failure with a plasma efavirenz concentration less than 1 mg/L.
The most common toxicities of efavirenz are neuropsychiatric adverse reactions, such as dizziness, sleep disturbances, vivid dreams, nightmares, impaired concentration, and hallucinations. About 50% of adult patients experience these side effects. It is difficult to evaluate the prevalence of neuropsychiatric side effects among children, because they are typically unable to report such problems. Other common side effects of efavirenz are skin rashes. About 5% to 20% of adults develop a skin rash during the first 2 weeks of treatment, about half the incidence reported with nevirapine. Rashes are more common among children using efavirenz and occur in up to one-third of patients. Gynecomastia is an increasingly recognized side effect of efavirenz in prepubertal and pubertal children.
Concerns of teratogenicity have limited the use of efavirenz among females of reproductive age. Further research regarding these concerns is essential, according to researchers, because highly active ART therapy is becoming more popular in low-resource settings, in an effort to prevent mother-to-child HIV transmission.
Long-term side effects need to be better quantified among children, especially those with extensive experience and with higher doses.
“The development of prospective surveillance systems to allow systematic recording of birth outcomes for women receiving ART during pregnancy is essential,” the researchers concluded. “Further research is also needed to determine the role of efavirenz in children exposed perinatally to nevirapine and efavirenz.”
Disclosure: The researchers report no relevant financial disclosures.
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