Early versus deferred antiretroviral multidrug therapy in infants infected with HIV type 1.

BACKGROUND: The clinical impact of early antiretroviral multidrug therapy on the risk of early-onset severe human immunodeficiency virus (HIV) disease has not been evaluated on a large scale. METHODS: We evaluated the risk of early-onset events associated with acquired immunodeficiency syndrome (AIDS), particularly the risk of encephalopathy, among infants in the French Perinatal Cohort, according to whether antiretroviral multidrug therapy was initiated before or after the age of 6 months. RESULTS: Of 83 HIV-infected infants born in 1996 (when HAART became available) or later, 40 received early treatment on or before the age of 6 months, and 43 received deferred multidrug therapy after the age of 6 months. In the group that received early multidrug therapy, no child developed an opportunistic infection or an encephalopathy during the first 24 months of life. In the deferred multidrug therapy group, 6 infants presented with a total of 7 AIDS-associated events (P=.01), 3 of which were encephalopathies (P=.08). The small number of events prevented the identification of clinical and biological markers that accurately predict progression of early-onset severe HIV disease. CONCLUSION: In this observational study, infants who received multidrug therapy before 6 months of age did not have the early-onset severe form of childhood HIV disease. Further studies are needed to find accurate early markers of disease progression in this age group.

Early multitherapy including a protease inhibitor for human immunodeficiency virus type 1-infected infants.

BACKGROUND: To assess tolerance and efficacy of early multitherapy including a protease inhibitor for infants perinatally infected with HIV. METHODS: Observational study of tolerance and clinical and immunovirologic evolution in HIV-infected infants treated before the age of 1 year in the French Perinatal Study. RESULTS: Thirty-one infants were included. The median age was 3.7 months at initiation of multitherapy. Clinical stage was C (n = 8), B (n = 5) or A/N (n = 18). The median HIV RNA viral load was 5.8 log copies/ml, and the median CD4 cell percentage was 29%. Median follow-up of treatment was 27 months. Of 31 infants 15 experienced mild to moderate adverse events. No infant had clinical or immunologic progression. The median change in viral load was -2.7 log copies/ml after 3 months, -2.0 log after 12 months and -1.7 log after 24 months of treatment. The proportion of infants with a viral load below 500 copies/ml decreased from 53% at 6 months to 18% at 24 months of treatment. The virologic response was not correlated with viral load at baseline. However, the slope of the viral load decrease during the first month of treatment was predictive of the virologic response at 3 and 6 months. Fourteen infants with a viral load of >500 copies/ml after 6 months of treatment displayed viruses with antiretroviral resistance mutations in reverse transcriptase and/or protease genes. CONCLUSIONS: Despite the absence of clinical or immunologic progression, the high frequency of virologic failure associated with genotypic resistance reveals the difficulties associated with implementing antiretroviral multitherapy in infants. Suboptimal doses of protease inhibitor could be a factor contributing to treatment failure.