Kids maintain HIV suppression on low-dose, quad-combo pill
At a lower dose, the single-pill drug that combines elvitegravir (EVG), cobicistat, emtricitabine, and tenofovir alafenamide (TAF) has an acceptable safety profile and maintains virological suppression in HIV-infected children, according to the results of a single-arm, open label trial.
Safety and efficacy of the low-dose quad pill in young children are consistent with its full‐strength efficacy in older populations, the investigators said. Furthermore, drug exposures in the paediatric population appear to be within range of adult historical data.
Presented at the virtual meeting of the 23rd International AIDS Conference, the trial enrolled 27 children with HIV‐1 RNA <50 copies/mL for ≥6 months and CD4 count of ≥200 cells/μL. The median age was 6 years (range, 3–9), and the median weight was 19 kg (range, 15–24). Sixty-three percent of the children were girls, and 89 percent were black. The median CD4 count was 1,061 cells/μL (range, 383–2,401).
All children were given the quad-combo drug once daily, with each tablet containing 90-mg EVG, 90-mg cobicistat, 120-mg emtricitabine, and 6-mg TAF. Over 24 weeks of treatment, six patients developed upper respiratory tract infection (22 percent), five had cough (19 percent), and four showed decreased appetite (15 percent). All adverse events were mild to moderate in severity, and none of the children discontinued treatment due to these events. [AIDS 2020, abstract OABLB0101]
HIV remained suppressed in all children at week 16 and in 10 of 11 (91 percent) at week 24. One patient had HIV‐1 RNA between 200 to <400 copies/mL. CD4 count decreased by a mean of 95 cells/mL (0.3 percent) from baseline at the final follow-up.
Pharmacokinetic analysis revealed that compared with adults treated with the standard-dose combination (150-mg EVG, 150-mg cobicistat, 200-mg emtricitabine, and 10-mg TAF), total exposure levels to both low-dose EVG and TAF (as indicated by area under the curves) in children were modestly higher—less than twofold. Exposures of all analytes stayed within range of historical data.
Swallowability, acceptability, and palatability of the low-dose quad-combo drug were favourable at all timepoints assessed for most children.
The standard-dose quad-combo pill is approved as a complete antiretroviral therapy (ART) regimen in children aged ≥6 years weighing ≥25 kg. It can be used in ART-naïve children and to replace the current ART regimen in those who have been virologically suppressed. The drug is said to carry a lower risk of bone and renal toxicity as compared with regimens containing tenofovir disoproxil fumarate. [https://aidsinfo.nih.gov/contentfiles/lvguidelines/glchunk/glchunk_279.pdf]