Philippe Gaillard

Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis.

BACKGROUND HIV contributes substantially to child mortality, but factors underlying these deaths are inadequately described. With individual data from seven randomised mother-to-child transmission (MTCT) intervention trials, we estimate mortality in African children born to HIV-infected mothers and analyse selected risk factors. METHODS Early HIV infection was defined as a positive HIV-PCR test before 4 weeks of age; and late infection by a negative PCR test at or after 4 weeks of age, followed by a positive test. Mortality rate was expressed per 1000 child-years. We investigated the effect of maternal health, infant HIV infection, feeding practices, and age at acquisition of infection on mortality assessed with Cox proportional hazards models, and allowed for random effects for trials grouped geographically. FINDINGS 378 (11%) of 3468 children died. By age 1 year, an estimated 35.2% infected and 4.9% uninfected children will have died; by 2 years of age, 52.5% and 7.6% will have died, respectively. Mortality varied by geographical region, and was associated with maternal death (adjusted odds ratio 2.27, 95% CI 1.62-3.19), CD4+ cell counts <200 per microL (1.91, 1.39-2.62), and infant HIV infection (8.16, 6.43-10.33). Mortality was not associated with either ever breastfeeding and never breastfeeding in either infected or uninfected children. In infected children, mortality was significantly lower for those with late infection than those with early infection (0.52, 0.39-0.70). This effect was also seen in analyses of survival from the age at infection (0.74, 0.55-0.99). INTERPRETATION These findings highlight the necessity for timely antiretroviral care, for support for HIV-infected women and children in developing countries, and for assessment of prophylactic programmes to prevent MTCT, including child mortality and infection averted.

Vulnerability of women in an African setting: lessons for mother-to-child HIV transmission prevention programmes.

After discussing advantages and risks, only a third of the 290 HIV-infected women included in an intervention study to reduce mother-to-child transmission of HIV in Mombasa, Kenya, informed their partners of their results. Despite careful counselling, 10% subsequently experienced violence or disruption of their relationship. To increase the uptake of interventions to reduce perinatal HIV transmission safely, we recommend the involvement of partners in HIV testing. In addition, the counselling of women has to address methods and skills to deal with violence.

Use of antiretroviral drugs to prevent HIV-1 transmission through breast-feeding: from animal studies to randomized clinical trials.

The major remaining challenge in the prevention of mother-to-child transmission is the reduction of the risk in settings where breast-feeding is common. This review gives an update on ongoing or planned antiretroviral intervention studies in resource-limited settings that are aimed at reducing the risk of mother-to-infant HIV transmission during lactation. These strategies include antiretroviral therapy given to the mother to reduce viral load in plasma and breast milk as well as antiretroviral regimens providing prophylaxis to uninfected infants during the period of breast-feeding. The rationale for the interventions based on animal models and human studies is described as well as the study designs of clinical trials. Potential risks and benefits of these interventions to mothers and infants are also highlighted. Laboratory studies nested within several of these trials will provide a better understanding of the pathogenesis of postnatal HIV transmission and its potential prevention using antiretroviral drugs.

Vaginal lavage with chlorhexidine during labour to reduce mother-to-child HIV transmission: clinical trial in Mombasa Kenya.

ObjectivesTo evaluate the effect of vaginal lavage with diluted chlorhexidine on mother-to child transmission of HIV (MTCT) in a breastfeeding population. MethodsThis prospective clinical trial was conducted in a governmental hospital in Mombasa, Kenya. On alternating weeks, women were allocated to non-intervention or to intervention consisting of vaginal lavage with 120 ml 0.2% chlorhexidine, later increased to 0.4%, repeated every 3 h from admission to delivery. Infants were tested for HIV by DNA polymerase chain reaction within 48 h and at 6 and 14 weeks of life. ResultsEnrolment and follow-up data were available for 297 and 309 HIV-positive women, respectively, in the non-lavage and the lavage groups. There was no evidence of a difference in intrapartum MTCT (17.2 versus 15.9%, OR 0.9, 95% CI 0.6–1.4) between the groups. Lavage solely before rupture of the membranes tended towards lower MTCT with chlorhexidine 0.2% (OR O.6, 95% CI 0.3–1.1), and even more with chlorhexidine 0.4% (OR 0.1, 95% CI 0.0–0.9). ConclusionThe need remains for interventions reducing MTCT without HIV testing, often unavailable in countries with a high prevalence of HIV. Vaginal lavage with diluted chlorhexidine during delivery did not show a global effect on MTCT in our study. However, the data suggest that lavage before the membranes are ruptured might be associated with a reduction of MTCT, especially with higher concentrations of chlorhexidine.

Diversity of the Human Immunodeficiency Virus Type 1 (HIV-1) env Sequence after Vertical Transmission in Mother-Child Pairs Infected with HIV-1 Subtype A

ABSTRACT Although several virologic and immunologic factors associated with an increased risk of perinatal human immunodeficiency virus type 1 (HIV-1) transmission have been described, the mechanism of mother-to-child transmission is still unclear. More specifically, the question of whether selective pressures influence the transmission remains unanswered. The aim of this study was to assess the genetic diversity of the transmitted virus after in utero transmission and after peripartum transmission and to compare the viral heterogeneity in the child with the viral heterogeneity in the mother. To allow a very accurate characterization of the viral heterogeneity in a single sample, limiting-dilution sequencing of a 1,016-bp fragment of the env gene was performed. Thirteen children were tested, including 6 with in utero infections and 7 with peripartum infections. Samples were taken the day after birth and at the ages of 6 and 14 weeks. A homogeneous virus population was seen in six (46.2%) infants, of whom two were infected in utero and four were infected peripartum. A more heterogeneous virus population was detected in seven infants (53.8%), four infected in utero and three infected peripartum. The phylogenetic trees of the mother-child pairs presented a whole range of different tree topologies and showed infection of the child by one or more maternal variants. In conclusion, after HIV-1 transmission from mother to child a heterogeneous virus population was detected in approximately one-half of the children examined. Heterogeneous virus populations were found after peripartum infection as well as after in utero infection. Phylogenetic tree topologies argue against selection processes as the major mechanism driving mother-to-child transmission but support the hypothesis that virus variability is mainly driven by the inoculum level and/or exposure time.

Placental Malaria and Perinatal Transmission of Human Immunodeficiency Virus Type 1

Prevalence of placental malaria in human immunodeficiency virus (HIV) type 1-infected and -uninfected women and the effect of placental malaria on genital shedding and perinatal transmission of HIV-1 were examined. Genital samples for HIV-1 DNA RNA were collected during labor. Infants were tested for HIV-1 at 1 day and 6 weeks postpartum. Placental malaria was diagnosed by histopathological examination: 372 placentas of HIV-1-infected women and 277 of HIV-1-uninfected women were processed. A higher prevalence of placental malaria was seen in HIV-1-infected women. No association was found between placental malaria and either maternal virus load, genital HIV-1 DNA, or HIV-1 RNA. Placental malaria did not correlate with in utero or peripartal transmission of HIV-1.

Placental inflammation and perinatal transmission of HIV-1.

&NA; The effect of placental membrane inflammation on mother‐to‐child transmission (MTCT) of HIV‐1 is reported. Placentas from HIV‐1‐infected women were examined as part of a perinatal HIV‐1 project in Mombasa. Kenya. Polymerase chain reaction analysis was used to test for HIV‐1 in the infants at birth and at 6 weeks. The maternal HIV‐1 seroprevalence was 13.3% (298 of 2,235). The overall rate of MTCT of HIV‐1 was 25.4%; polymerase chain reaction analysis revealed that of the 201 infants 6.0% (12) were already HIV‐1‐positive at birth (intrauterine transmission) and 19.4% (39) were infected during the peripartum period or in early neonatal life (perinatal transmission). The prevalence of acute chorioamnionitis was 8.8%, that of deciduitis was 10.8%, and that of villitis was 1.6%. Acute chorioamnionitis was independently associated with peripartum HIV‐1 transmission but not with in utero MTCT (17.9% vs. 6.7%, respectively; adjusted odds ratio, 3.9; 95% confidence interval, 1.2‐12.5; p = .025). Other correlates of perinatal MTCT were presence of HIV in the genital tract and in the babys oral cavity and a high maternal viral load in peripheral blood. The adjusted population attributable fraction of 12.8% (95% confidence interval, 1.5%‐22.8%) indicated that approximately 3% of MTCT could be prevented if acute chorioamnionitis was eliminated. We suggest that further research on the role of antimicrobial treatment in the prevention of chorioamnionitis and the reduction of peripartum MTCT needs to be performed.

Exposure to HIV-1 during delivery and mother-to-child transmission.

BackgroundThe correlation between the presence of HIV-1 in maternal cervico-vaginal secretions and in the infants oro-pharyngal secretions at birth, and mother-to-child HIV transmission (MTCT) were examined to obtain a better understanding of its mechanism. MethodsWomen without medical and obstetrical complications, living within a reasonable distance of the government hospital in Mombasa, Kenya, were recruited after informed consent. Maternal and infant characteristics were collected. Polymerase chain reaction was used to detect HIV-1 in cervico-vaginal and oro-pharyngal secretions. Infants were tested for HIV-1 by polymerase chain reaction within 48 h and at 6 weeks after delivery. ResultsBetween April 1998 and April 1999, 228 woman–infant pairs were included in the study. HIV-1 DNA in cervico-vaginal secretions was independently associated with HIV-1 maternal viral load and with infant birth-weight, whereas HIV-1 RNA was associated with maternal viral load and maternal age. HIV-1 DNA in the oro-pharyngal secretions was also independently associated with maternal viral load. MTCT rate at the age of 6 weeks was 23.6%. Intrapartum and early postpartum HIV transmission was independently associated with maternal viral load [adjusted odds ratio (OR), 1.6; 95% confidence interval (CI),1.0–2.7], detection of HIV-1 RNA in cervico-vaginal secretions (adjusted OR, 3.2; 95% CI, 1.5–7.3) and of HIV-1 DNA in oro-pharyngal secretions (adjusted OR, 3.2; 95% CI, 1.1–9.0). DiscussionAs far as is known, this is the first study showing that infant exposure to HIV-1 in the birth canal and the presence of HIV-infected cells in the infants oro-pharyngal cavity are independently associated with intrapartum and early postpartum MTCT. It supports the hypothesis that MTCT could occur through the oral route.

Placental inflammation and perinatal outcome.

OBJECTIVE To examine the role of placental inflammation in adverse obstetrical outcome (AOO). METHODS Analysis of perinatal data of 701 randomly selected mothers of singleton infants, Mombasa, Kenya. RESULTS There were 661 (94.3%) live infants and 40 (5.7%) stillbirths. Out of the live born infants, 78 (12.4%) had a low birth weight (LBW < 2500g); 33 of them were preterm and 41 small for gestational age (SGA). The incidence of neonatal sepsis and post partum endometritis was 3.6 and 19.8%, respectively. The perinatal death rate was estimated to be 7.3% (51/701). The prevalence of acute placental inflammation was 19.6%. Acute placental inflammation was independently associated with preterm low birth weight (ARR=3.8, 95% CI=1.7-8.9, P<0.01), stillbirth (ARR=2.3, 95% CI=1.1-5.0, P=0.03) and perinatal death (ARR=2.8, 95% CI=1.4-5.4, P<0.01). Women with acute placental inflammation had a two-fold higher risk for AOO (32.6 versus 15.2%, respectively, ARR=2.5, 95% CI=1.3-4.8, P<0.01). Other risk factors for AOO were bad obstetrical history, low haemoglobin level and leucocytosis. CONCLUSIONS The incidence of adverse obstetrical outcome defined as low birth weight, low Apgar score, perinatal mortality and post partum endometritis, was high in this population. Acute placental inflammation was associated with preterm birth, stillbirth and perinatal death. More research is needed to study the role of infection in adverse obstetrical outcome, and to design interventions to decrease infectious morbidity and mortality in pregnancy.

Changes in sexual behaviour among HIV-infected women in west and east Africa in the first 24 months after delivery.

Objective:Describe changes in sexual behaviour and determinants of unsafe sex among HIV-infected women in the 24 months after delivery. Design:Cohort analysis nested within a prevention of mother-to-child transmission trial in Burkina Faso (n = 339) and Kenya (n = 432). Methods:Women were followed during pregnancy and until 12–24 months after delivery. At each visit, structured questionnaires were administered about sexual activity and condom use, and risk-reduction counselling and condoms were provided. Results:At study entry, a median 2 months after HIV testing (interquartile range = 1–4), 411/770 (53.4%) of women reported partner disclosure, increasing to 284/392 (71.9%) at the final visit. Although most partners were supportive following disclosure, between 5 and 10% of disclosed women experienced hostile or unsupportive partner responses during follow-up visits. At each visit, about a third of sexually active women reported unsafe sex (unprotected sex with HIV-uninfected or unknown status partner). In multivariable logistic regression, unsafe sex was 1.70-fold more likely in Kenyan than in Burkinabe women [95% confidence interval (95% CI) = 1.14–2.54], and in those with less advanced HIV disease or aged 16–24 years. Compared with women who disclosed their status to partners and others, unsafe sex was over six-fold higher in nondisclosers (95% CI = 3.31–12.11), the effect size reducing with increasing disclosure. Conclusion:HIV-infected women who recently delivered have a high potential for further HIV transmission, especially as HIV discordance is common in Africa. Longitudinal care for women, including positive-prevention interventions, is needed within new services providing antiretroviral prophylaxis during breastfeeding – this repeated interface with services could focus on reducing unsafe sex. Much remains unknown about how to facilitate beneficial disclosure.