Long-Term Responses to Treatment Including Ritonavir or Nelfinavir in HIV-1-Infected Children

Summary

Background: Knowledge concerning the long-term antiretriviral and immunological efficacy of protease inhibitors in children is limited.

Patients and Methods: An open-label, prospective, multicenter clinical trial was conducted over a period of 72 weeks in Switzerland. 60 HIV-1 infected children (aged 0.3–16.9 years) naive to protease inhibitors were enrolled. Ritonavir or nelfinavir and at least one new nucleoside reverse transcriptase inhibitor were introduced into the durrent treatment regimen. HIV-1 RNA levels and CD4 cell counts were monitored after introducing the protease inhibitor, and the tolerability and safety of the drugs were assessed.

Results: Dictated by chronological availability, 37 children received ritonavir and 23 nelfinavir. At baseline, children given ritonavir had higher mean plasma HIV-1 RNA levels (5.03 vs 4.63 log₁₀ copies/ml; p = 0.001) and lower mean CD4 cell counts (277 vs 555 cells/μl; p = 0.009) than children given nelfinavir. Antiretroviral treatment (ART) naive children showed higher mean plasma HIV-1 RNA levels than non-naive (5.18 vs 4.64 log₁₀ copies/ml; p = 0.02). The decline in plasma HIV-1 RNA levels 72 weeks after treatment with ritonavir and nelfinavir was −2.17 and −1.30 log₁₀ copies/ml, respectively (p = 0.006) and in ART-naive vs non-naive patietns −2.70 vs − 1.39 log₁₀ copies/ml (p ≤ 0.01). 69% of ART-naive patients and 32% of non-naive patients achieved sustained plasma HIV-1 RNA levels < 400 copies/ml. Increases in CD4 cells were higher in ART naive compared to non-naive patients (p < 0.04).

Conclusion: The antiretroviral and immunologic benefits of protease inhibitors are more profound in ART-naive than in non-naive children.