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A single intrapartum dose of nevirapine for the prevention of mother-to-child transmission of human immunodeficiency virus (HIV) leads to the selection of resistance mutations. Whether there are clinically significant consequences in mothers who are subsequently treated with a nevirapine-containing regimen is unknown.We randomly assigned 1844 women in Thailand who received zidovudine during the third trimester of pregnancy to receive intrapartum nevirapine or placebo. In the postpartum period, 269 of the women with a CD4 count below 250 cells per cubic millimeter began a nevirapine-containing antiretroviral regimen. Plasma samples were obtained 10 days post partum and analyzed for resistance mutations. Plasma HIV type 1 (HIV-1) RNA was measured before the initiation of therapy and three and six months thereafter.After six months of therapy, the HIV-1 RNA level was less than 50 copies per milliliter in 49 percent of the women who had received intrapartum nevirapine, as compared with 68 percent of the women who had not received intrapartum nevirapine (P=0.03). Resistance mutations to nonnucleoside reverse-transcriptase inhibitors were detectable in blood samples obtained 10 days post partum from 32 percent of the women who had received intrapartum nevirapine; the most frequent mutations were K103N, G190A, and Y181C. Among the women who had received intrapartum nevirapine, viral suppression was achieved at six months in 38 percent of those with resistance mutations and 52 percent of those without resistance mutations (P=0.08). An HIV-1 RNA level at or above the median of 4.53 log10 copies per milliliter before therapy and intrapartum exposure to nevirapine were independently associated with virologic failure. After six months of therapy, there was no significant difference between groups in the CD4 count (P=0.65).Women who received intrapartum nevirapine were less likely to have virologic suppression after six months of postpartum treatment with a nevirapine-containing regimen. Our data suggest the need for strategies to maximize the benefits of both antiretroviral prophylaxis against mother-to-child transmission of HIV and antiretroviral therapy for mothers.

Although zidovudine prophylaxis decreases the rate of transmission of the human immunodeficiency virus (HIV) type 1 substantially, a large number of infants still become infected. We hypothesized that the administration, in addition to zidovudine, of a single dose of oral nevirapine to mothers during labor and to neonates would further reduce transmission of HIV.We conducted a randomized, double-blind trial of three treatment regimens in Thai women who were receiving zidovudine therapy during the third trimester of pregnancy. In one group, mothers and infants received a single dose of nevirapine (nevirapine-nevirapine regimen); in another, mothers and infants received nevirapine and placebo, respectively (nevirapine-placebo regimen); and in the last, mothers and infants received placebo (placebo-placebo regimen). The infants also received one week of zidovudine therapy and were formula-fed. The end point of the study was infection with HIV in the infants, established by virologic testing.Between January 15, 2001, and February 28, 2003, a total of 1844 Thai women were enrolled. At the first interim analysis, the independent data monitoring committee stopped enrollment in the placebo-placebo group. Among women who delivered before the interim analysis, the as-randomized Kaplan-Meier estimates of the transmission rates were 1.1 percent (95 percent confidence interval, 0.3 to 2.2) in the nevirapine-nevirapine group and 6.3 percent (95 percent confidence interval, 3.8 to 8.9) in the placebo-placebo group (P0.001). The final per-protocol transmission rate in the nevirapine-nevirapine group, 1.9 percent (95 percent confidence interval, 0.9 to 3.0), was not significantly inferior to the rate in the nevirapine-placebo group (2.8 percent; 95 percent confidence interval, 1.5 to 4.1). Nevirapine had an effect within subgroups defined by known risk factors such as viral load and CD4 count. No serious adverse effects were associated with nevirapine therapy.A single dose of nevirapine to the mother, with or without a dose of nevirapine to the infant, added to oral zidovudine prophylaxis starting at 28 weeks' gestation, is highly effective in reducing mother-to-child transmission of HIV.

The AIDS epidemic became visible in North America, Europe, and Africa at the beginning of the 1980s, but did not emerge in Asia until ten years later; some countries have only been experiencing the epidemic very recently. However, the lessons learned in countries which faced the epidemic 10 to 20 years ago seem to have had limited impact on the response to recent epidemics in Asia. In countries such as India, Myanmar, Cambodia, and Vietnam, the sad story of the HIV epidemic seems to be repeating itself. Thailand remains the exception.

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)(p0.0005). 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.

To accurately measure AIDS-related mortality relative to other causes and its impact on life expectancy in Brazzaville, Congo.Investigation of all deaths during a 1-month period in Brazzaville.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.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 (ageor = 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%; P0.05). Moreover, female AIDS cases were significantly younger than male cases (median age, 32 versus 42 years; P0.00001). 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.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.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.

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.

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.

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–Guerin (BCC) 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.

ss Open Acce Oral presentation O222 Treatment interruption in children with chronic HIV-infection: the results of the paediatric European network for treatment of AIDS (PENTA) 11 trial DM Gibb*1, A Compagnucci2, H Green3, M Lallemant4, Y Saidi2, N NgoGiang-Huong4, C Taylor3, L Mofenson5, F Monpoux6, MIG Tome7, M Marczynska8, D Nadal9, U Wintergerst10, S Kanjavanit11, H Lyall12, C Giaquinto13 and J Moye4

Address: 1Institut de Recherche pour le Developpement UMI 174/Programs for HIV Prevention and Treatment (PHPT), Chiang Mai, Thailand, 50100, 2Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand, 50200, 3Harvard School of Public Health, Harvard University, Boston, MA 02115, USA, 4Harvard Medical School, Harvard University, Boston, MA 02115, USA, 5Lamphun Hospital, Lamphun, Thailand, 51000, 6Health Promotion Hospital Regional Center I, Bangkok, Thailand, 10210, 7Somdej Pranangchao Sirikit Hospital, Chonburi, Thailand, 20000 and 8Buddhachinaraj Hospital, Pitsanuloke, Thailand, 65000 * Corresponding author

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.

Recommendations from the meeting on prevention of mother-to-infant transmission of HIV by the use ofantiretrovirals. World Health Organization. Geneva, 1994. International Ethical Guidelines for Biomedical Research Involving Human Subjects. Council for International Organizations of Medical Sciences and the World Health Organisation. Geneva, 1993. Halsey NA, Sommer A, Henderson DA et al, 1997. Ethics and international research (editorial). BMJ. 3157114. Prabhakaran S, 1997. Mothers give support to placebo trials. Mail and Guardian. 1 October, Johannesburg.

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.

The lack of serum haptoglobin in Africans has been investigated in the Congo, Central Africa, where HpO prevalence is about 30%. This study shows that it is possible to suppress ahaptoglobinaemia within a few weeks by antimalarial chemoprophylaxis, that it does not occur in protected individuals, that ahaptoglobinaemia reappears at its original incidence levels after interruption of chemoprophylaxis, and that some individuals are more susceptible in relation to Hp2 gene. Malaria is the only significant cause of ahaptoglobinaemia in subjects both with and without detectable parasitaemia. The possible mechanisms involved are discussed.

An epidemiologic study of hearing loss was undertaken on a small Caribbean island and revealed a high frequency of abnormal audiograms among the population of French origin. Since there is no clear-cu

Several studies have shown that the early virus population present in HIV-1 infected infants usually is homogeneous when compared to the highly diversified viral population present at delivery in their mothers. We explored the antigenic and functional properties of pseudotyped viruses expressing gp120 encoded by env clones issued from four mother–infant pairs infected by CRF01_AE viruses. We compared their sensitivity to neutralization and to entry inhibitors, their infectivity levels and the Env processing and incorporation levels. We found that both transmitted viruses present in infants and the variants present in their chronically infected mothers display a wide spectrum of biological properties that could not distinguish between them. In contrast, we found that all the transmitted viruses in the infants were more sensitive to neutralization by PG9 and PG16 than the maternal variants, an observation that may have implications for the development of prophylactic strategies to prevent mother-to-child transmission.

Address: 1IRD 174/PHPT, Chiang Mai, Thailand, 2Chiang Mai University, Faculty of Associated Medical Sciences, Chiang Mai, Thailand, 3UMR 196 CEPED (INED-IRD-Universite Paris Descartes), Paris, France, 4Nakornping Hospital, Chiang Mai, Thailand, 5Lamphun Hospital, Lamphun, Thailand, 6Chiang Kham Hospital, Chiang Kham, Thailand and 7Laboratoire de Virologie, INSERM ERI 19, and Centre National de Reference pour le VIH, Universite F Rabelais, Tours, France * Corresponding author