PROTEASE INHIBITOR THERAPY IN CHILDREN WITH PERINATALLY ACQUIRED HIV-INFECTION

Objective: To review the short-term response and safety of protease in hibitor therapy in HIV-infected children. Design: Retrospective chart review of open-label protease inhibitor-containing combination therapy . Setting: Two urban pediatric HIV centers. Patients: Twenty-eight HIV -infected children were prescribed 30 protease inhibitor-containing an tiretroviral therapy combinations. The median age at initiation of pro tease inhibitor antiretroviral therapy was 79 months. Patients had bee n on previous antiretroviral therapy for a mean of 45.5 months. Result s: Of the 28 children who completed at least 1 month of therapy, 26 ex perienced marked virologic and immunologic improvement (mean maximal d ecrease in viral load 1.90 log(10) copies/ml; SD, 0.8; mean maximal ri se in CD4+ lymphocytes of 279x10(6)/l; SD, 300 x10(6)/l). Eleven patie nts achieved a viral nadir of < 400 copies/ml, and seven sustained thi s level of viral suppression for a mean of 6 months. Indinavir use was associated with a high incidence of renal side-effects, including two patients who developed interstitial nephritis. Two patients on ritona vir experienced a significant elevation of liver enzymes. Conclusions: Protease inhibitor therapy was associated with substantial short-term virologic and immunologic improvement in this primarily heavily pretr eated cohort, with 25% maintaining a viral load of < 400 copies/ml aft er 6 months of therapy. There was a significant rate of adverse events . Pharmacokinetic and safety data are needed to guide aggressive antir etroviral therapy in HIV-infected children, and further treatment opti ons are required for those failing or intolerant to the available prot ease inhibitors.