Onset of clinical signs in children with HIV-1 perinatal infection. Italian Register for HIV Infection in Children

OBJECTIVE: To investigate the timing of onset of each clinical sign in infants and children with HIV-1 perinatal infection. DESIGN AND METHODS: A total of 200 HIV-1-infected children followed-up from birth were studied. Failure and conditional probabilities were estimated by the Kaplan-Meier product-limit method. Cox proportional hazard analysis was used to evaluate independently associated factors. Results of 934 seroreverters were used to calculate reference values of CD4+ cell counts and predictivity of early signs. RESULTS: Median age at the onset of any sign was 5.2 months (range, 0.03-56 months). The probability of remaining asymptomatic was 19% [95% confidence interval (CI), 14-25.1] at 12 months and 6.1% (95% CI, 2.6-11.7) at 5 years. Lymphadenopathy (69.5%), splenomegaly (62.4%) and hepatomegaly (58.4%) were the most common signs in the first year of life. Peculiar to the first year of life (compared with subsequent ages) was the onset of primary HIV-1 hepatitis and diarrhoea (rate ratios, 23.3 and 15.2, respectively). When CD4+ cell counts in the asymptomatic stage (age, 2 months; range, 0.03-5.9 months) were below rather than above the fifth percentile in seroreverters, onset of signs was earlier [3 range, 0.03-19) versus 5 (range, 0.03-56) months]. Children manifesting signs before the 5.2-month breakpoint had a lower survival rate [74% (range, 65.9-82%) at 12 months and 45% (range, 32.9-57%) at 5 years] than children manifesting signs later [98% (range, 92.2-100%) at 12 months and 74% (range, 60.3-87.7%) at 5 years]. Children whose birthweight was < or = 2400 g had an earlier onset (24 months; range, 1-57 months) of severe conditions than children with higher birthweight (71 months; range, 1-71 months). Development of lymphadenopathy or hepatosplenomegaly within 3 months of life were reliable indicators of infection. CONCLUSIONS: This study describes the sequence of onset of signs in perinatal HIV-1 infection. Infection is shown to progress faster than in adults and in a different manner. Low birthweight, early decreased CD4+ cell counts, and early onset of signs are predictive of rapid progression.