Polly Clayden, HIV i-Base

A poster authored by Megan Palmer and coworkers from the United States and South Africa presented findings from PACTG 1020A. This is a phase I/II study of atazanavir (ATV) with or without ritonavir (r) with 2 NRTI (excluding tenofovir [TDF]) in HIV-positive treatment-naïve children aged 91 days to 21 years.

This poster showed data from treatment-naïve South African children participating in the dose-finding study, for age (<2 years, 2 to 13 years, >13 years) and formulation (powder vs capsule) groups.

Each group started with a dose of 310 mg/m2 of ATV, which was adjusted based on day 7 24-hour, intensive PK and week 4 safety data. Acceptable PK and safety dose criteria were:  AUC >/=30 ug*hour/mL and C24 >/=60 ng/mL in 4 of 5 children; no AUC <15 ug*hour/mL; and median AUC for 5 children </=60 ug*hour/mL and </=1 of 5 children with >/= grade 3 adverse events, none life-threatening.

Guided by these criteria, the investigators either enrolled an additional 5 children at the starting dose or the starting dose was adjusted. An optimal dose was based on >=10 evaluable children with acceptable PK and safety results.

The study has enrolled 183 children to date of this evaluation; 62 from South Africa.

This report showed 48-week treatment outcomes for 57 South African children receiving unboosted (n=22) and boosted (n=35) ATV. Approximately half (29/57) of the children were girls.

At baseline, the children were a median of 6 years of age
(91 days to 21 years); CD4 count, 411 cells/mm3 (24 to 2192); CD4%, 13% (1 to 35); log10 viral load, 5.0 (3.6 to 5); and mean height z-score, –2.09 (–4.56 to 0.73) and weight z-score, –1.98 (–5.80 to 0.91).

The investigators reported that 35/48 of the children (73%, 95%CI 58% to 85%) had viral load <400 copies/mL at 48 weeks, in an intent-to-treat analysis. Weight and height z-score improved significantly at the same time point; mean change in height z-score +0.27 (p=0.04) and mean change in weight z-score +0.79 (p<0.0001).

11 children discontinued ATV, of these, 5 were due to toxicity (hyperbilirubinemia, LFT increase, or QT interval changes), 1 due to death (unrelated, pneumonia), and 5 for other reasons (eg lost to follow-up, need for protocol disallowed medications).

The investigators noted that RTV boosting of the capsule significantly improved PK parameters of ATV. The dose of 310 mg/m2 for powder and 205 mg/m2 for capsule plus RTV passed protocol defined safety parameters.

They also found in this South African cohort children were severely malnourished at baseline and weight and height z-scores improved significantly.

Ref:
Meyers T, Rutstein R, Samson P et al. Treatment responses to atazanavir-containing HAART in a drug-naïve paediatric population in South Africa. 15th CROI. February 2008. Boston, Mass, USA. Poster abstract 582.