Showing papers by "Marie-Louise Newell published in 1998"

Mechanisms and timing of mother-to-child transmission of HIV-1

Abstract: A growing body of clinical and laboratory evidence supports several possible mechanisms of vertical HIV transmission including maternal disease state and viral load fetal exposure to infected maternal body fluids during pregnancy and delivery and breast feeding. More precise knowledge of the timing of maternal-infant transmission would help identify the periods of greatest risk and suggest approaches to reduce this risk. This article reviews the research literature on intrauterine transmission intrapartum transmission breast feeding and the hypothesized timing of HIV transmission. The research evidence suggests that transmission during late pregnancy and the intrapartum period contributes relatively more to the overall rate of vertical HIV transmission than the early intrauterine period even in populations where breast feeding is the norm and that postnatal transmission through breast feeding confers a substantial additional risk of infection.

A review of hepatitis C virus (HCV) vertical transmission: risks of transmission to infants born to mothers with and without HCV viraemia or human immunodeficiency virus infection

Abstract: Background Hepatitis C virus (HCV) vertical transmission studies have reported conflicting findings, possibly due to differences in HCV transmission risk factors among maternal populations, or to methodological differences. Methods Systematic review of worldwide published and unpublished HCV vertical transmission studies. Standardized diagnostic criteria were applied to minimize methodological differences, and transmission rates recalculated according to maternal HCV viraemic and human immunodeficiency virus (HIV) infection status. Results In all, 976 eligible infants from 28 studies were followed up sufficiently for recalculation of transmission rates. Overall transmission rates were less than 10% in 8/12 studies of HIV negative mothers, compared with 2/7 studies comprising at least 50% HIV-coinfected mothers. Rates from 409 viraemic mothers in 15 studies ranged from 0% to 41%, being less than 10% from HIV negative mothers in 6/13 studies and from HIV positive mothers in 1/6 studies. Nine studies measured maternal viraemia levels, with only 2/30 transmitting mothers having < 10 6 copies/ml of HCV RNA. Eight transmissions were identified overall from non-viraemic mothers. Significant transmission rate variation remained after accounting for maternal viraemia and HIV coinfection, possibly due to differences in other vertical transmission risk factors, in frequencies of postnatal transmission, or residual differences in study methodologies. Conclusions Overall, HCV transmission is largely restricted to infants born to HCV viraemic mothers, and low risks among most HIV negative mothers may be due to lower HCV viraemia levels. International agreement on standardized diagnostic criteria for HCV vertical transmission would facilitate pooling of individual findings, to allow more precise transmission estimates and further investigation of risk factors.

Acceptability of voluntary HIV testing by pregnant women in developing countries: an international survey. Ghent International Working Group on Mother-to-Child Transmission of HIV.

Abstract: Interventions such as the short-course regimen of zidovudine have been shown to reduce the perinatal transmission of HIV. However in order to benefit from such therapy pregnant women must know that they are infected with HIV. A low acceptability of voluntary counseling and HIV testing (VCT) services among such women may limit the uptake of therapy and services designed to reduce the mother-to-child transmission (MCT) of HIV. Findings are presented from an assessment of the acceptability of VCT among pregnant women in antenatal clinics in 11 cities of Burkina Faso Cote dIvoire Kenya Tanzania Malawi Zambia Zimbabwe South Africa and Thailand conducted through a postal survey in 1997. HIV prevalence among pregnant women was higher than 27% in 5 sites 9-18% in 7 sites and 2.3% in Bangkok. The median overall acceptance rate of VCT was 69% ranging from 33% to 95%. The overall acceptability of VCT most often depended upon return rates because acceptance rates were usually high. Where studies were conducted in parallel in the same city or country overall acceptability rates of HIV testing were generally comparable even if the intervention programs differed. Overall acceptability rates of VCT were high in antenatal clinics where a particular effort to implement VCT programs had been made. This survey shows that despite some obstacles VCT is both feasible and acceptable for pregnant women attempting to reduce their risk of transmitting HIV to their children.

Breastfeeding, genetic, obstetric and other risk factors associated with mother-to-child transmission of HIV-1 in Sao Paulo State, Brazil. Sao Paulo Collaborative Study for Vertical Transmission of HIV-1

Abstract: OBJECTIVES: To evaluate the effect of maternal, obstetric, neonatal and post-natal factors on the risk of vertical transmission of HIV-1. DESIGN: Multicentre retrospective cohort study. SETTING: Obstetric and paediatric clinics in four cities in Sao Paulo State, Brazil. MAIN OUTCOME: Child's HIV-1 infection status. METHODS: Data were collected by standardized record abstraction and interview on 553 children born to women identified as HIV-1-infected before or at delivery. Paediatric infection was determined by immunoglobulin G anti-HIV-1 tests at age 18 months or by AIDS diagnosis at any age. Multivariate logistic regression was used to assess the effect of potential risk factors on vertical transmission of HIV-1. RESULTS: HIV-1 infection status was determined for 434 children (follow-up rate of 78%); 69 were classified as HIV-1-infected [transmission risk, 16%; 95% confidence interval (CI), 13-20%]. In multivariate analysis, advanced maternal HIV-1 disease [odds ratio (OR), 4.5; 95% CI, 2.1-9.5], ever breastfed (OR, 2.2; 95% CI, 1.2-4.2), child's negative Rhesus blood group (OR, 2.5; 95% CI, 1.2-5.5), third trimester amniocentesis (OR, 4.1; 95% CI, 1.2-13.5) and black racial group (OR, 0.3; 95% CI, 0.1-0.9) were independently and significantly associated with mother-to-child transmission of HIV-1. Transmission was increased marginally with prematurity, more than 10 lifetime sexual partners and prolonged duration of membrane rupture. No association was found between child's HIV-1 infection and mode of delivery or serological evidence of syphilis during pregnancy. CONCLUSION: These findings support the importance of severity of maternal HIV-1 disease in the risk of vertical transmission of HIV-1, indicate measures to reduce transmission by avoiding amniocentesis and breastfeeding and suggest that race and Rhesus blood type may be markers for genetic susceptibility to infection.

Infant feeding and risk of mother-to-child transmission of HIV-1 in São Paulo State, Brazil

Abstract: Although vertical transmission of HIV-1 can occur through breast-feeding, little is known about the effect of colostrum, duration of breast-feeding, mixing feeding, and nipple pathology. We used retrospective cohort data to examine the association between breast-feeding-related factors and transmission of HIV-1 from mother to child in Sao Paulo State, Brazil. Information on maternal and postnatal factors was collected by medical record review and interview. Infection status was determined for 434 children by anti-HIV-1 tests performed beyond 18 months of age or diagnosis of AIDS at any age. Among 168 breast-fed children, the risk of transmission of HIV-1 was 21%, compared with 13% (p = .01) among 264 children artificially fed. Breast-feeding was independently and significantly associated with mother-to-child transmission of HIV-1 after controlling for stage of maternal HIV-1 disease (odds ratio [OR] = 2.2; 95% confidence interval [CI], 1.3-3.8). A trend was shown toward an increased risk of transmission with longer duration of breast-feeding, a history of bleeding nipples, and introduction of other liquid food before weaning, but these associations were not statistically significant. History of colostrum intake or cracked nipples without bleeding were not associated with transmission. Most of the women who breast-fed were unaware of their HIV-1 infection status at the time of delivery. Avoidance of mixed feeding and withholding of breast-feeding in the presence of bleeding nipples should be considered in further research as strategies to reduce postnatal transmission of HIV-1 in settings in which safe and sustainable alternatives for breast-feeding are not yet available.

Maternal viral load, CD4 cell count and vertical transmission of HIV-1

Abstract: HIV load and CD4 cell numbers were measured among 95 HIV infected women during pregnancy in order to determine their value as prognostic markers for transmission of virus from mother to infant. Among the 94 live births, 13 children were infected with HIV, 69 were uninfected and 12 were of unknown infection status. HIV RNA levels, as measured by nucleic acid sequence based amplification, were significantly higher (P < 0.001) in women who transmitted virus than among those who did not transmit and maternal viral load was a stronger predictor of transmission than CD4 cell number. The predicted rate of transmission relative to maternal HIV RNA was 2% at 1,000 copies, 11% at 10,000 copies and 40% at 100,000 copies/ml. Little variation in viral load occurred during pregnancy and there was an association between viral load and prematurity, the mean gestation at delivery decreasing by 1.3 weeks for every 10-fold increase in maternal HIV RNA (P = 0.007). This study demonstrates that a high level of maternal HIV RNA is a risk factor for transmission of virus to the infant and maternal viral load is of more value as a prognostic marker for transmission risk than CD4 cell number. High viral load is also associated with premature delivery. Maternal viral load is therefore a useful marker on which to base management decisions during pregnancy.

Administration of Imiquimod, an Interferon Inducer, in Asymptomatic Human Immunodeficiency Virus—Infected Persons to Determine Safety and Biologic Response Modification

Abstract: A phase I study to determine safety, maximum tolerated dose, and biologic response during multiple once-a-week administration of oral imiquimod, an immune response modifier, was conducted in 12 adults with early human immunodeficiency virus (HIV) infection. All completed the dose-escalation phase of weekly dosing at 100-mg increments and received at least one maintenance dose, 100 mg below the patient's toxic dose, for 12 weeks. Dose-limiting toxicity occurred in 3 patients at 200-mg, 5 at 300-mg, and 3 at 400-mg dose levels. One tolerated the 500-mg dose without dose-limiting toxicity. Dose-limiting toxicities included fatigue, fever, malaise, increased transaminases, hypotension, vomiting, and depression. Seven of 12 completed 12 weeks of maintenance. At > or = 200 mg of imiquimod, all patients had biologic responses, measured by elevations in serum interferon, beta2-microglobulin, and neopterin levels. Imiquimod induced pronounced levels of circulating interferon in asymptomatic HIV-infected persons, with variable effect on virus load.

Cost-effectiveness and cost-benefit in the prevention of mother-to-child transmission of HIV in developing countries. Ghent International Working Group on Mother-to-Child Transmission of HIV.

Abstract: Approximately 25-30% of infants born to HIV-infected mothers in developing countries are infected with HIV. A range of approaches exists to reduce the rate of mother-to-child transmission (MCT). Currently however the only therapeutic approach proven to reduce such vertical transmission is the administration of zidovudine therapy during pregnancy delivery and the neonatal period in the absence of breast-feeding. The authors review economic evaluation as an approach to help guide the development of policies on preventing MCT in developing countries drawing from studies evaluating anti-retroviral therapy in sub-Saharan Africa and Thailand. Principles of economic evaluation are discussed followed by a review of available evidence and the consideration of the sensitivity of estimates to parameter variation the reliability of parameter estimates model completeness and comparability and affordability. Future evaluations of MCT interventions should include economic evaluation to determine whether the intervention if found to be effective can or should be implemented as a public health measure. Such economic evaluations should be clear and include a sensitivity analysis of the most important variables thought to influence effectiveness and costs. Affordability should also be considered and multiple outcome measures and frames of reference used.

Is zidovudine therapy in pregnant HIV-infected women associated with gestational age and birthweight?

Abstract: OBJECTIVE Prophylactic zidovudine during pregnancy and labour reduces maternal viral load and, with neonatal therapy, has been shown to reduce vertical transmission. However, zidovudine may have additional effects. Advanced HIV disease is associated with premature delivery, which in turn results in increased vertical transmission. Data from the European Collaborative Study (ECS) were analysed to investigate whether zidovudine could be associated with decreased prematurity risk and/or with a reduced frequency of low birthweight. METHODS HIV-infected pregnant women enrolled in the ECS were followed prospectively according to a standard protocol. Gestational age was assessed by ultrasound, prematurity was defined as delivery before 37 weeks and the cut-off for low birthweight was 2500 g. We calculated odds ratios (OR) to estimate the effect of zidovudine on the risk of premature of low birthweight delivery. RESULTS In 2299 mothers, zidovudine taken to reduce the risk of vertical transmission decreased the odds of premature delivery by a quarter (OR = 0.76, 95% confidence interval (CI) 0.53-1.09), and the odds of low birthweight by nearly half (OR = 0.55, 95% CI 0.39-0.79). Allowing for CD4 count and mode of delivery did not greatly alter these OR values. A multivariate analysis suggested that prophylactic zidovudine and prematurity were independently associated with risk of transmission. CONCLUSION Our findings suggest an additional health benefit of zidovudine. Even if most vertical transmission occurs around the time of delivery, therapy earlier in pregnancy could have an indirect effect on transmission rates through delaying delivery. This hypothesis needs to be confirmed or refuted by more appropriate studies.

Social care of children born to HIV-infected mothers in Europe. European Collaborative Study.

Abstract: Children of HIV-infected women are likely to be profoundly affected by their mothers' infection, regardless of their own infection status and their number will increase with the spread of infection among women in Europe. This article describes the family circumstances and social care of 1,123 children born to HIV-infected women enrolled in the European Collaborative Study and followed prospectively from birth. Most mothers were white, married or cohabiting, asymptomatic and had a history of drug use, with 45% currently using injecting drugs at the time of enrollment. Seventy percent of children were cared for by their mothers and/or fathers consistently in their first four years of life, but by age eight an estimated 60% will have lived away from their parents (i.e. with foster or adoptive parents, other relatives or in an institution). Whether or not a child was infected did not influence the likelihood of living in alternative care. Maternal injecting drug use, single parenthood and health status were the major reasons necessitating alternative care. The type of alternative care varied according to maternal characteristics, child's age and geographic location. The mothers of 98 children had died and average age at maternal death was four years.

Routine vaccination and vaccine‐preventable infections in children born to human immunodeficiency virus‐infected mothers

Abstract: Information on vaccinations and vaccine-preventable infections collected in a prospective study of children born to human immunodeficiency virus (HIV)-infected mothers was analysed for reports of adverse reactions and to estimate the clinical efficacy of vaccines. No vaccinated, HIV-infected child developed measles (56 child-years' follow-up), mumps (33), rubella (33) or pertussis (239), and only one adverse reaction - to Bacillus Calmette-Guerin (BCG) - was reported. These findings provide limited evidence of the safety and efficacy of routine vaccination of HIV-infected children.

Routine vaccination and vaccine-preventable infections in children born to human immunodeficiency virus-infected mothers. European Collaborative Study.

Abstract: Information on vaccinations and vaccine-preventable infections collected in a prospective study of children born to human immunodeficiency virus (HIV)-infected mothers was analysed for reports of adverse reactions and to estimate the clinical efficacy of vaccines. No vaccinated, HIV-infected child developed measles (56 child-years' follow-up), mumps (33), rubella (33) or pertussis (239), and only one adverse reaction - to Bacillus Calmette-Guerin (BCG) - was reported. These findings provide limited evidence of the safety and efficacy of routine vaccination of HIV-infected children.

Mother-to-child transmission of hepatitis B infection

Abstract: Most transmission of hepatitis B virus (HBV) infection occurs around the time of delivery through contact with contaminated vaginal secretions or blood. Hence, interventions to reduce vertical transmission of HBV depend on identification of the infected woman during pregnancy so that the newborn infant exposed to infection can be given immunoglobulin immediately after birth, and a course of immunization can be started.