Maternal antibody response at delivery and perinatal transmission of human immunodeficiency virus type 1 in African women.

Prospective cohort studies indicate that 13-45% of human immunodeficiency virus type 1 (HIV-1)-infected pregnant women transmit the virus to their infants. Although factors that influence perinatal transmission are not well understood, drug and immunotherapy trials to interrupt transmission are underway. The identification of women most at risk is essential for prevention, counselling, and medical intervention. We assessed 70 HIV-1-infected pregnant women enrolled in a prospective study of perinatal transmission in Brazzaville, Congo. The relations between maternal health status, antibody levels to selected HIV-1 structural antigens at delivery, and infant outcome were explored. Independent of clinical stage, higher maternal antibody titres to peptides corresponding to the V3 region of gp120 and the immunodominant domain of gp41 were correlated with a higher risk of perinatal transmission. In a logistic regression model, the predicted risk of transmission for symptom-free women whose antibody titres to V3 and gp41 were lowest was 0.02, whereas it was 0.88 for symptomatic women whose antibody titres to V3 and TMSP18 were highest. These associations may give new insight into the mechanisms of perinatal transmission and they may also provide a powerful means of identifying women who would most benefit from intervention trials to halt perinatal transmission.

Perinatal transmission of HIV in Africa.

PIP: Not all pregnant women who are infected with human immunodeficiency virus (HIV) transmit it to their children; in those cases where it is transmitted, the risk of infection and the mechanisms and factors affecting it are not well known. More is known about when infection occurs. The fetus can be infected at 8 weeks; it develops receptors, which allow penetration of cells by HIV, early. Because of the risk of direct contamination of the fetus, antenatal diagnosis is not possible and the exact frequency of early infection is unknown. Contamination by the mother's cells is difficult to rule out, since methods of detection are as sensitive as polymerase chain reaction (PCR). Although there is a significant increase in chorioamniotes in HIV-positive women and placental cells are infected with HIV in anatomo-pathological samples, the virus is absent in the embryo-fetus. The low level of sensitivity of PCRs and cultures in blood from the umbilical cord also indicate that the fetus is infected late during gestation. Studies on twins show infection often occurs during labor and delivery because the first-born is infected more often than the second. In a French study, results from viral cultures, PCR, and antibody profiles of samples showed that 60% of HIV-positive children were infected during birth. Although studies indicate there is risk of transmission during breast feeding, over half of the breastfed children will not be infected. In view of this, because of the high death rate among bottle-fed infants in developing countries, the World Health Organization recommends breastfeeding when risk-free bottle-feeding cannot be guaranteed.^ieng

Characteristics associated with HIV-1 infection in pregnant women in Brazzaville, Congo.

Maternal human immunodeficiency virus type 1 (HIV-1) infection in sub-Saharan Africa is a major public health concern because of the high prevalence among women of childbearing age and the poor prognosis for perinatally infected children. Characteristics associated with HIV seroprevalence were studied in a population of 1,833 pregnant women seen in two large mother-child clinics in Brazzaville, Congo. The prevalence of HIV infection was 3.9% (95% confidence interval, 3.0-4.9%) and differed significantly according to the district of residence, marital status, duration of the relationship with the current partner, number of sexual partners in the year prior to pregnancy, number of living and dead children, and history of blood transfusion and/or hospitalization. Logistic regression analysis identified six significant factors independently associated with seropositivity; age, history of blood transfusion and/or hospitalization, district of residence, duration of the relationship, number of living children, and number of decreased children. However, the predictive value of the model was poor: while 80% of the truly positive women were correctly predicted positive by the model, 50% of the truly negative women were misclassified. Among pregnant women attending these clinics it is therefore difficult to identify a subgroup at risk toward which specific actions could be targeted.

Bacillus Calmette-Guérin immunization in infants born to HIV-1-seropositive mothers.

During the prospective follow-up of 64 babies at risk for perinatal HIV-1 infection because their mothers were seropositive, and of 130 control babies whose mothers were seronegative, we studied the occurrence of complications of bacillus Calmette-Guérin (BCG) immunization and its ability to induce cutaneous reactivity to tuberculin. Babies born both to HIV-1-positive and HIV-1-negative mothers received BCG immunization during their first month of life according to the Expanded Programme on Immunization (EPI) recommendations. Local and regional complications of BCG vaccine were looked for at 3, 6 and 9 months after inoculation. A tuberculin skin test was performed at 6 or 9 months of age. Most babies born to HIV-1-positive mothers were later classified as infected or uninfected according to their clinical condition and/or serological status at 18 months of age. The mean duration of the follow-up was 36 months (range 30-40 months). No chronic or deep ulcerations at the site of injection or disseminated forms of BCG infection were observed. The frequency of BCG-related lymphadenitis in the group of HIV-1-infected children (24%) did not differ significantly from the group of uninfected children (19%; Fisher test: P = 0.73). In contrast, the tuberculin skin test responses were positive less often in the group of HIV-1-infected children (33%) than in the uninfected group (83%; Fisher test: P = 0.007). Because BCG vaccine appears to be safe--even when given to perinatally infected babies--continuation of the BCG immunization policies of the EPI is justified, especially in view of the growing incidence of tuberculosis as a complication of HIV infection.

Polymerase chain reaction for studies of mother to child transmission of HIV1 in Africa.

The feasibility and implications of the use of the polymerase chain reaction (PCR) assay in studies of HIV1 mother to child transmission in Africa were investigated. Uncultured leukocyte blood cells (PBL) obtained in Brazzaville (Congo) from newborns and infants (mean age = 27 weeks) of infected mothers were tested. HIV1 DNA sequences were identified in the PBL of six of eight newborns and 14 of 23 babies born to HIV1-positive mothers. In addition two of four babies, who at birth had been seropositive and subsequently were seronegative, were HIV1 DNA positive by PCR. This study demonstrates directly, therefore, a high rate of HIV1 transmission in Africa; it also indicates that PCR should be used for such epidemiological studies.

Mother-child transmission of HIV-1 and infant survival in Brazzaville, Congo.

The aim of this study was to compare the probability of survival of infants born to anti-HIV-1-positive and anti-HIV-1-negative mothers. One thousand, eight hundred and thirty-three pregnant women, recruited sequentially in two mother-child clinics in Brazzaville, were screened for anti-HIV-1 (by enzyme-linked immunosorbent assay with confirmation by Western blot). Each seropositive mother (71 out of 1833, 3.9%) was matched for age, presumed date of delivery and place of residence with two seronegative mothers. Sixty-four babies born to anti-HIV-1-positive mothers and 130 control babies born to anti-HIV-1-negative mothers were followed up for 12-22 months (mean, 18 months). The probabilities of survival were estimated by the Kaplan-Meier method. At birth, the two groups of babies did not differ with regard to rate of stillbirths, gestational age, sex ratio and weight. Among babies born to seropositive mothers, the probability of survival was 0.87 (s.d. 0.04) at 3 months, 0.71 (s.d. 0.06) at 6 months, 0.68 (s.d. 0.06) at 9 months and 0.61 (s.d. 0.06) at 12.5 months. In the controls the probability of survival was 0.98 (s.d. 0.01) at 3 months and 0.97 (s.d. 0.02) at 12 months. The excess of mortality in the babies born to anti-HIV-1-positive mothers is highly significant (P less than 0.001). The deaths occurred more frequently and earlier than in similar cohort studies performed in developed countries.