678   Evaluation of Toxicity, Tolerability and Antiviral Activity of Early d4T + ddI + Nelfinavir (NFV) Therapy in HIV-1 Vertically Infected Infants: 24-Week Preliminary Results from the PENTA 7 Study.

A. Faye*¹, A. Compagnucci², and Y. Saidi²for the PENTA 7 Executive Committee.
¹Hôp. Robert Debré, Paris, and²INSERM SC10, Villejuif, France.

Background:Early potent antiretroviral therapy in HIV-1-infected infants may prevent severe clinical progression and immunological deterioration and may achieve long-term suppression of HIV-1 replication. Few data concerning the safety and antiviral efficacy of triple therapy in HIV-1-infected infants are available. The objectives of this study were to evaluate the toxicity, tolerability and antiviral activity of early triple antiretroviral therapy (ART) with d4T + ddI + NFV in HIV-1-infected infants.

Methods:An international multi-centre, phase I/II open, noncomparative study of infants<12 weeks (wks) of age, without AIDS, receiving d4T + ddI + NFV was performed. NFV was initially given at a dose of 120 mg/kg/ day but increased to 150 mg/kg/day after PK results showed low AUCs in the first 4 infants. If mothers had received these drugs in pregnancy, resistance testing of the baby was required to show sensitivity to the regimen.

Results:Sixteen infants were enrolled from 5 European countries. Median age at initiation of ART was 11 wks (range 4 —20). CDC stage was N (9), A (6), or B (1). Median (IQR) viral load (VL) at baseline was 5.67 log₁₀copies/ml (5.45—6.24). Median (IQR) CD4% was 38 (24—48). Twelve children reached wk 24. Four infants who were started on NFV powder and were switched to tablets given BID because of poor tolerability. Four serious adverse events (AE) and 11 minor AE were reported. Only 3 minor AE were considered to be related to ART. Treatment was stopped at wk 12 in one infant due to poor adherence and mild diarrhoea and in another infant for virologic rebound. Median (IQR) VL reduction from baseline was -1.97 (-3.72 to -1.30) log₁₀cps/ml at wk 24. VL was <400 cps/ml in 50% of children and <50 cps/ml in 25% at wk 24. Median (IQR) changes in CD4 % and CD4 Z score (CD4 adjusted for age) from baseline to wk 24 were respectively 0 (-7—16) and 0.86 (-0.52—1.74). No clinical progressions were observed.

Conclusions:Early triple therapy with d4T + ddI + NFV was tolerated by all infants. Preliminary data on virologic response suggest that attaining undetectable viral load may be difficult in infants. PK, resistance and compliance studies are underway to help to better understand the virologic failures.