677   Early Therapy with Ritonavir (RTV), ZDV and 3TC in HIV-1-Infected Children 1—24 Months of Age.

E. G. Chadwick*¹, P. Palumbo², J. Rodman³, K. Luzuriagia⁴, P. Britto⁵, and R. Yogev¹.
¹Northwestern Univ. Med. Sch., Chicago, IL;²New Jersey Med. Sch., Newark, NJ;³St. Jude's Children's Res. Hosp., Memphis, TN;⁴Univ. of Massachusetts Med. Sch., Worcester; and⁵Harvard Sch. of Publ. Health, Boston, MA.

Background:Data on RTV safety, pharmacokinetics and efficacy are lacking in HIV-1-infected children <24 months of age.

Methods:Two dosing cohorts (C1 and C2) were treated with 350 mg/m²or 450 mg/m²of RTV q12h in combination with ZDV and 3TC. Study endpoints (E) included grade 3-4 toxicity, 16-wk HIV-1 plasma RNA level (VL) >400 copies/ml, rebound VL >400 after 16 wks, or CD4% decline of >50% from baseline.

Results:Data through 48 wks or study endpoint are available for 17 (C1) and 22 (C2) subjects. There were no grade 3 or 4 toxicities related to Rx. Median RTV concentrations in C1 were 16—57% lower than predicted from adult data. By week 16, 6/17 (35%) in C1 and 5/22 (23%) in C2 failed study treatment (Rx), 4 for virologic E and 2 for intolerance in C1 and 4 for virologic E and 1 for intolerance in C2. Among subjects who tolerated RTV, 11/ 15 (73%) C1 and 17/21 (81%) C2 subjects had VL <400 at 16 wks and 10/11 (91%) C1 and 7/17 (41%) C2 subjects had VL <400 at 48 wks; most virologic E were due to poor adherence. CD4% increased from 0—8% at 48 weeks; however, this gain was not statistically significant.

Conclusions:For infants <24 mos who tolerated therapy, the combination of RTV, ZDV and 3TC was safe and efficacious, even though the 350 mg/m²dose of RTV produced lower than predicted concentrations. Considering the age-related natural decline in CD4%, the observed modest increase in CD% suggests preservation of CD4 cells.