HIV-1 TRANSMISSION THROUGH BREAST-MILK - APPRAISAL OF RISK ACCORDING TO DURATION OF FEEDING

Objectives: To estimate the risk of HIV-1 transmission through breast-milk in children born to infected mothers, and to determine the relationship between duration of breast-feeding and risk. Design and methods: The study population included 168 breast-fed and 793 bottle-fed children born to seropositive mothers. All subjects were enrolled and followed-up in the Italian Register for HIV Infection in Children; HIV serostatus was defined in all children. Multivariate analysis was performed using a logistic regression model. Independent variables included biological factors (duration of breast-feeding, gestational age, clinical condition of mother at delivery, mode of delivery, birth-weight and sex). Year of birth and age when HIV infection was diagnosed were also considered in the analysis attempting to control for possible selection biases. Results: Breast-feeding increased the risk of HIV-1 transmission. The estimated adjusted odds ratio for 1 day of breast- versus bottle-feeding was 1.19 (95% confidence interval, 1.10-1.28). The infection odds ratio of breast- versus bottle-feeding increased with the natural logarithm of the duration of practice. Conclusions: These results are the first to provide an appraisal of the additional risk of HIV-1 transmission associated with a seropositive mother breast-feeding her child. Biological significance of this route of transmission was supported by demonstration of a relationship between duration of breast-feeding and risk of HIV-1 transmission

EPIDEMIOLOGY OF HIV-INFECTION IN CHILDREN IN ITALY

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

ITALIAN REGISTER FOR HIV-1 INFECTION IN CHILDREN - REPORT UP TO 30-3-1990 (1422 CHILDREN ENROLLED)

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

Predictive value of the HIV paediatric classification system for the long-term course of perinatally infected children

Background To compare the Centers for Disease Control and Prevention (CDC) paediatric classification system with the long-term course of perinatal human immunodeficiency virus type 1 (HIV-1) infection. Methods Prospective study on 366 perinatally infected children followed-up from birth and checked at least every 2 months. Survival, smoothed hazard, adjusted hazard ratio of death, and transition probabilities in clinical and immunological categories were outcome measures. Results Results Survival was 49% (95% CI : 40-58%) at 8 years. The risk of death was high before the age of 2, relatively low between ages 2 and 7, and contained thereafter. Children did not advance through the categories sequentially. Survival at 8 years was 61.7% (95% CI : 49.8-73.6%) in those children who had passed through clinical category A; the hazard ratio of death was 2.5 (95% CI : 1.7-3.8) for 175 (47.9%) children who skipped this category. Transition probability in clinical category B was 39.9% (95% CI : 32.3-45.6%) after one year, but 59.1% (95% CI : 51.4-66.8%) after 5 years. Before 2 years of age, the probability of entry into category C (40%; 95% CI: 35-45%) was higher than that of entry into immunological category 3 (28% 95% CI : 22-34%). Conclusions The classification system stands comparison with the clinical reality, but the CD4-positive cell thresholds in infancy should be adjusted and category B indicator diseases better distributed to improve their predictive value

HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 INFECTION AND BREAST-MILK

Major questions are whether mothers infected with the Human Immunodeficiency Virus type 1 (HIV-1) transmit the virus through breast milk and the magnitude of the additional transmission risk. The demonstration of a dose-response effect is an epidemiological method to demonstrate causality. Thus, a study was carried out by the Italian Register for HIV Infection in Children on 961 children of known infection status. Duration of breast-feeding was considered as the level of exposure in 168 ever breastfed children. Results showed that duration of practice significantly increased the risk of transmission. The adjusted infection odds ratio for one day of breast- versus exclusive formula-feeding was 1.19 with narrow confidence limits (1.10-1.28). In a second study by the Register on 556 children of known infection status and derived prospectively, an infection odds ratio of 2.55 (confidence interval: 1.03-6.37) was calculated in breast- versus exclusively formula-fed children. Several lines of evidence, including the above-mentioned data from the Italian Register for HIV Infection in Children, showed a contribution of breast-feeding to mother-to-child HIV-1 transmission. Thus, this practice is now discouraged in HIV-1 infected mothers living in industrialized societies where formula feeding is practical and attainable. Mode of feeding was known in 2183 children enrolled in the Register and born to HIV-1 infected mothers since 1981. It could be observed that feeding habits of at-risk infants changed in Italy in the middle 1980s, when a large majority of subjects was identified at birth. However, women infected exclusively by the sexual route are often unconscious of being infected or even being at risk from infection and consequently their children are less frequently identified at birth than are children of women with a history of intravenous drug use. In industrialized areas, the former children remain at risk from milk-borne HIV-1 infection

Human immunodeficiency virus type 1 infection and breast milk. The Italian Register for HIV Infection in Children.

Major questions are whether mothers infected with the Human Immunodeficiency Virus type 1 (HIV-1) transmit the virus through breast milk and the magnitude of the additional transmission risk. The demonstration of a dose-response effect is an epidemiological method to demonstrate causality. Thus, a study was carried out by the Italian Register for HIV Infection in Children on 961 children of known infection status. Duration of breast-feeding was considered as the level of exposure in 168 ever breast-fed children. Results showed that duration of practice significantly increased the risk of transmission. The adjusted infection odds ratio for one day of breast- versus exclusive formula-feeding was 1.19 with narrow confidence limits (1.10-1.28). In a second study by the Register on 556 children of known infection status and derived prospectively, an infection odds ratio of 2.55 (confidence interval: 1.03-6.37) was calculated in breast- versus exclusively formula-fed children. Several lines of evidence, including the above-mentioned data from the Italian Register for HIV Infection in Children, showed a contribution of breast-feeding to mother-to-child HIV-1 transmission. Thus, this practice is now discouraged in HIV-1 infected mothers living in industrialized societies where formula feeding is practical and attainable. Mode of feeding was known in 2183 children enrolled in the Register and born to HIV-1 infected mothers since 1981. It could be observed that feeding habits of at-risk infants changed in Italy in the middle 1980s, when a large majority of subjects was identified at birth

Italian guidelines for antiretroviral therapy in children with human immunodeficiency virus-type 1 infection. Italian Register for HIV Infection in Children.

Human immunodeficiency virus-type 1 (HIV-1) infection and its treatment are peculiar in children. Adherence and compliance must be carefully taken into account before initiating or changing therapy and in the choice of drugs. Even in the absence of paediatric-specific trial results and notwithstanding drug-labelling notations, all antiretroviral drugs should be used when indicated. A combined therapy is compulsory. Therapy is highly recommended in category C or category 3 and recommended in category B children. Indications in categories N1, N2, A1 or A2 are limited. A triple association is recommended in category C or category 3 children or in those with a high viral load, when compliance is guaranteed. A step-down strategy is not advisable. Infants' treatment should be inserted into controlled studies. Therapy should be changed when serious side effects or poor tolerance (choose drugs with a different toxicity and greater tolerance), poor compliance (individualize the motives) or treatment failure (evaluate progression and adherence) occurs