Gestational age determination and prevention of HIV perinatal transmission.

OBJECTIVE: To compare different methods of gestational age (GA) measurement for ensuring effective zidovudine (ZDV) prophylaxis to prevent mother-to-child transmission of HIV. METHODS: For 1398 HIV-infected women enrolled in a perinatal prevention trial, gestation durations were calculated based on GA estimated using ultrasound (US), date of last menstruation period (LMP), first fundal height (FH(1)), and a specific algorithm was developed to provide a "reference" GA. The performance of each GA estimate was evaluated by the percentage of women who would have received > or =8 weeks ZDV, if prophylaxis was initiated at 28 weeks. RESULTS: The performances of the algorithm, US, LMP, and FH(1) were 95.5%, 94.8%, 88.4%, and 83.7%, respectively. US and FH(1) were significantly better when estimated before and after 24 weeks, respectively. CONCLUSION: In situations where no US is available and LMP is not or imprecisely known, FH(1) can be used after 24 weeks to schedule ZDV initiation date.

[HIV-1 transmission from mother to child and its prevention]. / Transmission du VIH-1 de la mère à l'enfant et sa prévention.

Mother-to-child transmission of HIV-1 can occur during pregnancy, labor/delivery, or breastfeeding. Without intervention HIV infection occurs in about 35% of infants born to HIV-infected women: 10% during pregnancy, 15% during labor/delivery, and 10% during breastfeeding. As early as 1994, the PACTG 076-ANRS 024 study documented the remarkable effectiveness of AZT in reducing mother-to-child HIV transmission from 26% to 8% in women who did not breastfeed. Since then, AZT or multiple antiretroviral therapies has been widely used in pregnant HIV-infected women in industrialized countries resulting in decline of the transmission rate to less than 3%. In developing countries where most perinatal transmissions occur, preventive treatment is more difficult to implement. Abbreviated treatment using AZT or nevirapine (NVP) in a single dose to the mother during delivery and to the newborn reduces perinatal transmission but to a lesser extent in comparison with standard treatment. Combination treatment using AZT + 3TC or AZT + NVP is more effective. Elective cesarean section has also been proposed but is not recommended in developing countries. To date the only alternative of proven efficacy for reducing transmission during breastfeeding is formula feeding, but this method may be hazardous if sanitary conditions are poor. Studies are currently under way to test the efficacy of antiretrovirals administered to the mother and/or infant in reducing HIV transmission during breastfeeding.

Infant feeding practices and attitudes among women with HIV infection in northern Thailand.

Knowledge and attitudes towards infant feeding among women in northern Thailand were examined. Face-to-face interviews using structured questionnaires were undertaken in three districts of Chiang Rai province. Subjects included postnatal women with HIV infection (group 1, n=80), antenatal women with HIV infection (group 2, n=36) and antenatal women with unknown HIV status (group 3, n=86). Advantages of breastfeeding and formula feeding according to several characteristics (convenience, cleanliness, cheapness and safety) were rated using a four-point (0-3) scale. Overall, breastfeeding was rated much higher (11.4/12) than formula feeding (6.1/12)(p < 0.0005). Formula feeding rating was highest among postnatal women with HIV infection (6.8/12); however, it was lower than the rating for breastfeeding (11.3/12). The vast majority of women with HIV infection were either formula feeding (group 1, 94%) or intended to formula feed (group 2, 72%) their infants. In contrast, the vast majority of antenatal women of unknown HIV status planned to breastfeed (group 3, 83%). All women, regardless of HIV status, consider breastfeeding to be more advantageous than formula feeding. However, once women with HIV infection are informed of the risk of HIV transmission through breastfeeding, they are able to make their own decision to follow the Thai Ministry of Public Health's recommendation to formula feed.

A trial of shortened zidovudine regimens to prevent mother-to-child transmission of human immunodeficiency virus type 1. Perinatal HIV Prevention Trial (Thailand) Investigators.

BACKGROUND: The optimal duration of zidovudine administration to prevent perinatal transmission of human immunodeficiency virus type 1 (HIV-1) should be determined to facilitate its use in areas where resources are limited. METHODS: We conducted a randomized, double-blind equivalence trial of zidovudine starting in the mother at 28 weeks' gestation, with 6 weeks of treatment in the infant (the long-long regimen), which is similar to protocol 076; zidovudine starting at 35 weeks' gestation, with 3 days of treatment in the infant (the short-short regimen); a long-short regimen; and a short-long regimen. The mothers received zidovudine orally during labor. The infants were fed formula and were tested for HIV DNA at 1, 45, 120, and 180 days. After the first interim analysis, the short-short regimen was stopped. RESULTS: A total of 1437 women were enrolled. At the first interim analysis, the rates of HIV transmission were 4.1 percent for the long-long regimen and 10.5 percent for the short-short regimen (P=0.004). For the entire study period, the transmission rates were 6.5 percent (95 percent confidence interval, 4.1 to 8.9 percent) for the long-long regimen, 4.7 percent (95 percent confidence interval, 2.4 to 7.0 percent) for the long-short regimen, and 8.6 percent (95 percent confidence interval, 5.6 to 11.6 percent) for the short-long regimen. The rate of in utero transmission was significantly higher with the two regimens with shorter maternal treatment (5.1 percent) than with the two with longer maternal treatment (1.6 percent). CONCLUSIONS: The short-short zidovudine regimen is inferior to the long-long regimen and leads to a higher rate of perinatal HIV transmission. The long-short, short-long, and long-long regimens had equivalent efficacy. However, the higher rate of in utero transmission with the short-long regimen suggests that longer treatment of the infant cannot substitute for longer treatment of the mother.

Contribution of AIDS to the general mortality in Central Africa: evidence from a morgue-based study in Brazzaville, Congo.

OBJECTIVE: To accurately measure AIDS-related mortality relative to other causes and its impact on life expectancy in Brazzaville, Congo. DESIGN: Investigation of all deaths during a 1-month period in Brazzaville. METHODS: From 10 July to 9 August 1996, all bodies handled by Brazzaville's three morgues were examined by a physician. Relatives were interviewed on the circumstances of death, while additional clinical data were gathered from hospital files. Blood samples were systematically drawn from the bodies in two of the three morgues and tested for HIV antibodies. RESULTS: Amongst the 756 bodies examined at the three morgues, 149 (19.7%) AIDS cases were identified. HIV-1 prevalence was 26.2% (38 out of 145) amongst the subjects in the two morgues where HIV serology was systematically performed. AIDS was the leading cause of death in adults (age > or = 15 years), with 25.1% (122 out of 487) of the adults diagnosed with AIDS. The proportion of adult female AIDS cases was significantly higher than the proportion of male cases (30.2 versus 21.0%; P < 0.05). Moreover, female AIDS cases were significantly younger than male cases (median age, 32 versus 42 years; P < 0.00001). Overall AIDS mortality rate amongst adults was 2.8 per 1000 for men and 3.2 per 1000 for women. The impact of AIDS on life expectancy at birth is 4.3 years for women and 3.3 years for men. CONCLUSION: Our study provides a direct measure of AIDS contribution to mortality relative to other causes, using a rapid, low cost, reliable and replicable method. Clearly, the impact of AIDS is strongest on female life expectancy.

PIP: As of December 1997, UNAIDS estimated that 20.8 million people were infected with HIV in sub-Saharan Africa. Brazzaville, Congo, has an estimated population of 850,000, according to the 1996 national census, and an estimated HIV-1 prevalence rate of approximately 5% in the general reproductive-age population. Findings are presented from a study conducted to accurately measure AIDS-related mortality relative to other causes and its impact upon life expectancy in Brazzaville, Congo. From July 10 to August 9, 1996, all bodies handled by Brazzaville's 3 morgues were examined by a physician. Relatives were interviewed on the circumstances of death and additional clinical data were collected from hospital files. Blood samples were systematically drawn from the bodies in 2 of the 3 morgues and tested for HIV antibodies. 149 of the 756 bodies (19.7%) examined at the morgues had AIDS. 38 of the 145 (26.2%) subjects in the 2 morgues in which HIV serology was systematically performed were infected with HIV-1. AIDS was the leading cause of death among people aged 15 years and older, with 122 of the 487 (25.1%) adults diagnosed with AIDS. 30.2% of the adult female deaths were due to AIDS, compared to only 21.0% of the male cases. The median age of female AIDS cases was 32 years, compared to 42 years for male cases, a highly significant difference. The overall AIDS mortality rate among adults was 2.8/1000 for men and 3.2/1000 for women. The impact of AIDS upon life expectancy at birth is 4.3 years for women and 3.3 years for men.

Direct estimation of maternal mortality in Africa.

PIP: Direct estimation of maternal mortality is facilitated in Brazzaville, Congo, by a law requiring that all bodies be delivered to a mortuary before burial. The authors investigated all bodies handled by the city's 3 mortuaries in a 4-week period in 1996. 15 maternal deaths were identified among the 138 female adult bodies. Based on the number of live births (27,888) in a 12-month period in 1995-96 and on the age distribution of the mothers, a maternal mortality rate of 645/100,000 was calculated. The lifetime risk for maternal mortality was estimated as 1 in 25 women. This rate is unexpectedly high since 90% of women in Brazzaville have access to prenatal care and most births occur in maternity hospitals. The excess maternal mortality is attributable, in part, to the high number of abortion-related deaths in young women. In this series, 6 deaths were due to abortion-related septicemia or hemorrhage. Maternal mortality is unlikely to decrease in African cities until more safe reproductive choices are available.^ieng

[Clinical experimentation with HIV vaccines: scientific and ethical dilemmas]. / Expérimentation clinique des vaccins contre le VIH: dilemmes scientifiques et éthiques.

Developing a vaccine against HIV is one of the greatest challenges the scientific community faces today. Several vaccine candidates have undergone preliminary safety and immunogenicity studies in humans. Research teams are ready to test these vaccines in the field, yet the scientific community is divided as to whether efficacy trial should begin. This paper addresses the complex scientific and ethical issues raised by clinical trials. Considering the pressure to act rapidly to solve the crisis, scientists need to hold to the fundamental principles that guide decisions in biomedical research: respect for persons, beneficence and justice. Because these studies need to enroll a large number of subjects, prospective vaccines will need to be tested in developing, as well as industrial countries. The international community needs to work to ensure that the populations that accept the risk of the research receive the full benefit of that research and, that the vaccine proven successful, be made accessible and affordable to people in less economically developed situation.

Mother-to-child transmission of HIV-1 in Congo, central Africa. Congolese Research Group on Mother-to-Child Transmission of HIV.

OBJECTIVE: To assess the risk of mother-to-child transmission of HIV-1 in a central African population and to study maternal factors associated with perinatal transmission. DESIGN: Prospective cohort study of infants born to HIV-1-positive women and controls born to HIV-1-negative women enrolled sequentially in two prenatal clinics and one maternity hospital in Brazzaville, Congo. SUBJECTS AND METHODS: A total of 118 exposed and 208 control infants were followed from birth for at least 2 years. Assessment of infection in children and computation of transmission rate were made according to the European Economic Community/World Health Organization Ghent guidelines (1992). RESULTS: The transmission rate was 40.4% [95% confidence interval (CI), 30.7-50.1]. Maternal age, parity, history of adverse pregnancy outcome or history of decreased children were not associated with transmission. However, independently, women whose relationship with their infant's father was less than 1 year, or women who had symptoms of HIV-1 during pregnancy had an increased risk of transmission [adjusted odds ratios, 11.1 (95% CI, 2.4-50.2) and 10.3 (95% CI, 2.9-37.1), respectively]. CONCLUSION: The transmission rate observed in Congo is in the upper range of the rates reported in Africa. The uneven distribution of cofactors for perinatal transmission, such as the presence of symptoms of HIV disease during pregnancy, may explain some of the variation observed across studies.

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.