Maternal clinical factors influencing HIV-1 transmission.

The complex puzzle of maternal factors involved in mother-to-child human immunodeficiency virus type 1 (HIV-1) transmission is being put together. The risk of perinatal infection increases with mother's disease progression, but it remains stable in women seroconverting to HIV-1 during pregnancy and in consecutive pregnancies. Thus, transmission correlates with the HIV-1 progression rather than the duration of infection in the mother. Nutritional alterations such as vitamin A deficiency may also have a significant impact, whereas geographic origin and mode of maternal infection are of no influence. Placenta membrane inflammation and concurrent sexually transmitted diseases are other significant covariates. The rate of transmission appears directly correlated with maternal age and inversely with length of gestation. A protective effect of caesarean section has been reported in some observational studies but, being controversial, these results need to be corroborated by randomized trials.

Airway resistance and spirometry in children with perinatally acquired human immunodeficiency virus-type 1 infection.

Airway resistance was measured by the interrupter technique in 54 children [aged 63.8 months (range: 9.1-131.6 months)], with perinatal human immunodeficiency virus-type 1 (HIV-1) infection and in a control group of 315 gender, height, and race-matched healthy children. In addition, 14 HIV-infected children, aged 75-131 months, had spirometry performed. Resistance was significantly higher in infected children than in controls (0.84 +/- 0.3 vs 0.64 +/- 0.08 kPa x l(-1) x s; t = 9.991; P < 0.0001). Resistance decreased with age in controls (r = -0.95; P < 0.001), but not in infected children (r= -0.22; P = 0.105). Resistance did not correlate with mothers' intravenous drug addiction, perinatal data, T-cell subset numbers, treatment, clinical course, or presence of respiratory complications. Resistance was higher (t = 3.103; P < 0.003) in p24 antigen-positive than in negative children. Thirty-nine children underwent a second evaluation 12.3 months (range 11.1-14 months) after the first. Resistance was higher (t = 3.960; P < 0.0001) at the second evaluation compared to the first. Eight of 14 children had abnormal spirometric measurements. We conclude that perinatal HIV-1 infection is associated with increased airway resistance and often abnormal spirometry. The degree of abnormalities in resistance depends on the duration of the infection rather than on HIV-1-related respiratory complications.

Mode of delivery and gestational age influence perinatal HIV-1 transmission. Italian Register for HIV Infection in Children.

Some data suggest that cesarean section reduces mother-to-child HIV-1 transmission. To assess the influence of mode of delivery and other maternal and infant factors on the rate of transmission, we analyzed the data of 1,624 children prospectively followed from birth. Of these, at the last visit 1,033 were > 18 months of age or would have been had they not died of HIV-related illness. Among the 975 first singleton children, 180 [18.5%; 95% confidence limits (CL), 16.1-20.9] acquired infection, as did 8 of 56 (14.3%; 95% CL, 5.1-23.5) second-born children. Multivariate stepwise analysis showed that vaginal delivery and development of symptoms in the mother were significantly and independently associated with a higher transmission rate (vaginal delivery; odds ratio, 1.69; 95% CL, 1.14-2.5; symptoms: odds ratio, 1.61; 95% CL, 1.12-2.3). In contrast, a history of maternal drug use, birth weight, breast-feeding (only 37 infants were breast-fed), and child's sex did not have a significant impact on viral transmission. The percentage of infected children was highest (30.7%) among very premature infants (< or = 32 weeks of gestation); this significant trend subsequently decreased to 11.9% at the week 42 (p < 0.001), suggesting a parallel reduction in peripartum transmission. The reduced rate of infection observed in infants born by cesarean section underlines the urgent need for randomized controlled trials to evaluate the protective role of surgical delivery in preventing perinatal HIV-1 transmission.

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.