Of the 4720 children enrolled in the Italian Register, 4554 were born to seropositive mothers. Of the latter, at the latest update 2989 (65.6%) had seroreverted, 440 (9.7%) were in indeterminate infection status, while 1125 (24.7%) were infected. Among these, 382 died of HIV-associated illnesses. The median age of those still alive was 82.5 months (range 1.4-192.8 months). The last survival curve highlighted an improvement in survival probability (51% at 130 months). The causes of death differed between infants and older children, with a higher proportion of Pneumocystis carinii pneumonia and cytomegalovirus (CMV) in the former. Only a fraction of infected children (< 3%) become long-term non-progressors (LTNPs). Immunological and clinical deterioration may occur at any age and in any child, including LTNPs. A targeted analysis revealed a poor prognostic indication of the clinical and immunological categories of the current CDC classification system for HIV infection in children. Both infected and uninfected exposed children are at high risk of separation from their family due to either parents' death or drug use. Given the high proportion of intravenous drug users among HIV-positive mothers, about three-quarters had hepatitis C virus (HCV) co-infection, and some of their children who escaped infection with HIV acquired HCV. An increasing proportion of HIV-infected children are approaching adolescence. This raises important new problems, such as when and how to communicate the diagnosis to these children, who need adequate psychological support to face the impact of knowing they are carriers of such an infection.
We assessed the long-term feasibility, safety, and tolerability of two regimens of aerosolized pentamidine (AP) as primary prophylaxis of Pneumocystis carinii pneumonia (PCP) in a large sample of infants and children with symptomatic HIV infection in 21 pediatric departments. One hundred forty children were assigned to receive 60 mg every 2 weeks (n = 60) or 120 mg every 4 weeks (n = 80) of AP, delivered by the ultrasonic nebulizer Fisoneb under the supervision of trained personnel. Children underwent monthly clinical and laboratory controls for toxicity and/or development of PCP for an 18-month period. Baseline characteristics were similar in the two treatment groups. The median age was 5 years. The feasibility of administering AP was excellent in 84 (60%) and good in 38 (27%) children, All children aged <2 years showed excellent or good feasibility. Long-term compliance was good with both regimens. No child had severe adverse reactions requiring discontinuation of the treatment. Cough, sneezing, and bronchospasm were the most frequent side effects occurring, respectively, in 12, 3.7, and 0.7% of the 60-mg treatments and in 19.1, 6.1, and 2.8% of 120-mg treatments (p < 0.05). Their incidence was not different in children younger or older than 5 years. Two episodes of PCP were observed in the group receiving 120 mg monthly, whereas none of the 60 children in the biweekly schedule had PCP (p = 0.20), AP can be safely administered to very young children with few adverse effects.
As of April 1992, 2337 children born to HIV-1-positive mothers were recorded by our multicentre study. Another 131 children were infected by contaminated blood products, while in 5 cases the risk factor remained unknown, as their personal history was lacking. The number of perinatally exposed children increased exponentially from 1981 to 1986, then stabilized. Of these, at last visit 624 were infected (531 P-2, 93 P-1), 463 were P-O and 1195 had seroreverted. Drug addiction continues to be the most frequent maternal risk factor, although infection acquired through sexual contact gradually increased up to 26.5% in 1991. Of the 762 first children identified at birth and older than 15 months of age, 132 (17.3%) acquired infection and seroconverted to HIV. A similar transmission rate was observed in 43 second-born children.
The Italian Register for HIV-1 infection in children was instituted in 1985 by the Italian Association of Pediatrics. As of March 1990, 1422 children (1321 born to seropositive mothers, 99 infected by blood products and 2 whose personal history was not available) were enrolled in our multicentre study. The number of perinatally exposed children was higher in industrialized areas and has been increasing over the years. Intravenous drug use (66.4%), sexual contacts with infected partner (14.5%) or both (15.6%) were the main mother's risk factors, with increasing proportion of those infected by sexual contacts (up to 21% in 1989). The mother-to-offspring transmission rate was 19.9%, when assessed in first born children prospectively followed-up from birth who remained seropositive after 18 months of age.Efficiency of infection was higher in children born to symptomatic mothers, whereas it was unaffected by mode of delivery, gestational age or birthweight. The role of breast-feeding remains doubtful. The risk of infection was not increased at second pregnancy (33 siblings studied) and infection status was disconcordant only in 1/10 twin pairs. Perinatally exposed population consisted of 396 infants whose infection status was still indeterminate (P-0), 388 infected children (93 P-1), including 31 antibody-negative, viral marker-positive subjects, and 295 P-2) and 537 uninfected children. 82.6% of infected seropositive children developed HIV-related clinical manifestations at a median age of 4 months. 69 (23.4%) P-2 patients have died at a median age of 12 months. Decreased CD4 + lymphocyte counts and increased serum immunoglobulin levels in the first months of life were indexes of disease progression rather than of infection status. Specific secondary infections, neurologic disorders, growth failure, fever, anemia and hepatitis were significantly and independently correlated to a poor prognosis. 688 doses of diphteria-tetanus vaccine, 476 of inactivated polyomielitis and 327 of attenuated live polyomielitis vaccine were administered in infected infants with no recorded side effects. Among bloodborne HIV-1 infections (48 haemophilics, 41 beta-thalassemics and 10 occasionally transfused children), only anecdotal cases have been recorded after 1985, when specific preventive measures were adopted. Clinical evolution was worse in perinatally infected children when compared to that of those who acquired infection through administration of blood products.HIV-1 infection in childhood has become a main problem in Italy. Diffusion by blood products has been widely restrained, but the increasing number of perinatally infected children indicates that further specific efforts and strategies in the field of public health are needed.