ONSET OF CLINICAL SIGNS IN CHILDREN WITH HIV-1 PERINATAL INFECTION

Objective: To investigate the timing of onset of each clinical sign in infants and children with HIV-1 perinatal infection. Design and metho ds: A total of 200 HIV-l-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 wa s used to evaluate independently associated factors. Results of 934 se roreverters were used to calculate reference values of CD4+ cell count s 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 r emaining 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 co mmon signs in the first year of life. Peculiar to the first year of li fe (compared with subsequent ages) was the onset of primary HIV-1 hepa titis and diarrhoea (rate ratios, 23.3 and 15.2, respectively). When C D4+ cell counts in the asymptomatic stage (age, 2 months; range, 0.03- 5.9 months) were below rather than above the fifth percentile in seror everters, onset of signs was earlier [3 (range, 0.03-19) versus 5 (ran ge, 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 mont hs and 45% (range, 32.9-57%) at 5 years] than children manifesting sig ns later [98% (range, 92.2-100%) at 12 months and 74% (range, 60.3-87. 7%) at 5 years]. Children whose birthweight was less than or equal to 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 withi n 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 coun ts, and early onset of signs are predictive of rapid progression.