When is breastfeeding not best? The dilemma facing HIV-infected women in resource-poor settings.
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Breast Feeding↗
Biomedical subjects
M G Fowler
Publications and source records attributed to M G Fowler.
Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team.
BACKGROUND: Maternal, obstetrical, and infant-related factors associated with the risk of perinatal transmission of human immunodeficiency virus type 1 (HIV-1) were identified before the widespread use of zidovudine therapy in pregnant women. The risk factors for transmission when women and infants receive zidovudine are not well characterized. METHODS: We examined the effects of maternal, obstetrical, and infant-related characteristics and maternal virologic and immunologic variables on the risk of perinatal transmission of HIV-1 among 480 women and their infants, all of whom received zidovudine. The women and infants were participating in a phase 3 trial of passive immunoprophylaxis for the prevention of perinatal transmission. RESULTS: In univariate analyses, the risk of perinatal transmission was associated with each of the following: decreased maternal CD4+ lymphocyte counts at base line; decreased maternal HIV p24 antibody levels at base line and delivery; increased maternal HIV-1 titer at base line and delivery; increased maternal HIV-1 RNA levels at base line and delivery; and the presence of chorioamnionitis at delivery. In multivariate analyses, the only independent risk factor was the maternal HIV-1 RNA level at base line (odds ratio for transmission, 2.4 per log increase in the number of copies; 95 percent confidence interval, 1.2 to 4.7; P=0.02) and at delivery (odds ratio, 3.4; 95 percent confidence interval, 1.7 to 6.8; P=0.001). There was no perinatal transmission of HIV-1 among the 84 women who had HIV-1 levels below the limit of detection (500 copies per milliliter) at base line or the 107 women who had undetectable levels at delivery. CONCLUSIONS: Among pregnant women and their infants, all treated with zidovudine, the maternal plasma HIV-1 RNA level was the best predictor of the risk of perinatal transmission of HIV-1. Antiretroviral therapy that reduces the HIV-1 RNA level to below 500 copies per milliliter appears to minimize the risk of perinatal transmission as well as improve the health of the women.
Analysis of Variance↗
Lack of tumors in infants with perinatal HIV-1 exposure and fetal/neonatal exposure to zidovudine.
Zidovudine (ZDV) therapy during pregnancy and to the neonate reduced perinatal HIV transmission by nearly 70% in Pediatric AIDS Clinical Trials Group (PACTG) protocol 076. ZDV has been reported as positive in several in vitro carcinogenicity screening tests. We evaluated the short-term risk for tumors in 727 children with known ZDV exposure enrolled into the PACTG 076/219 and the Women and Infants Transmission Study (WITS). ZDV exposure in utero (antepartum) occurred in 97% and 99% of infants in PACTG 076/219 or WITS, respectively. Mean follow-up was 38.3 months with 366.9 person years follow-up for PACTG 076/219 and 14.5 months with 743.7 person years follow-up for WITS. No tumors of any nature were observed; relative risk was 0 (95% confidence interval [CI], 0-17.6). These data are reassuring regarding the short-term lack of tumors for ZDV-exposed infants observed to date. Longitudinal, standardized follow-up for infants with in utero antiretroviral exposure is necessary to assess long-term carcinogenicity.
Anti-HIV Agents↗
A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006).
OBJECTIVE: To determine the safety, pharmacokinetics, tolerance, antiretroviral activity, and infant HIV infection status after giving a single dose of nevirapine to HIV-1-infected pregnant women during labor and their newborns during the first week of life. DESIGN: An open label phase I/II study. SETTING: Tertiary care hospital, Kampala, Uganda. PATIENTS AND INTERVENTIONS: Nevirapine, 200 mg, was given as a single dose during labor to 21 HIV-1-infected pregnant Ugandan women. In cohort 1, eight infants did not receive nevirapine whereas in cohort 2, 13 infants received a single dose of nevirapine, 2 mg/kg, at 72 h of age. OUTCOMES: The number and type of adverse events; nevirapine concentrations in the plasma and breast milk; maternal plasma HIV-1 RNA copy number before and up to 6 weeks after delivery; and HIV-1 infection status of the infants were monitored. RESULTS: Nevirapine was well tolerated by women and infants; no serious adverse events that were related to nevirapine were observed. Median nevirapine concentration in the women at delivery was 1623 ng/ml (range 238-2356 ng/ml); median cord/maternal blood ratio of 0.75 (0.37-0.93). The median half-life in women was 61.3 h (27-90 h) and the transplacental nevirapine half-life in infants who did not receive a neonatal dose was 54 h. The median half-life after a single dose at 72 h in infants was 46.5 h. During the first week of life, the median colostrum/breast milk to maternal plasma nevirapine concentration was 60.5% (25-122%). The median nevirapine concentration in breast milk 1 week after delivery was 103 ng/ml (25-309 ng/ml). Plasma nevirapine concentrations were above 100 ng/ml in all infants from both cohorts tested at age 7 days. Maternal HIV-1 RNA levels decreased by a median of 1.3 logs at 1 week postpartum, and returned to baseline by 6 weeks postpartum. Detectable plasma HIV-1 RNA was observed in one out of 22 (4.5%) infants at birth; three out of 21 (14%) at 6 weeks; and four out of 21 (19%) at 6 months of age. CONCLUSION: The administration of a single dose of nevirapine to women during labor and to their newborns at 72 h was well tolerated and showed potent antiretroviral activity in the women at 1 week after dosing without rebound above baseline 6 weeks after a single dose. The nevirapine concentration was maintained above the target of 100 ng/ml in infants at age 7 days, even in those infants not receiving a neonatal dose. This regimen has promise as prophylaxis against intrapartum and early breast milk transmission in a breastfeeding population.
Anti-HIV Agents↗
Cervical dysplasia on cervicovaginal Papanicolaou smear among HIV-1-infected pregnant and nonpregnant women. Women and Infants Transmission Study.
OBJECTIVE: To assess the association of squamous intraepithelial lesions (SIL) on cervicovaginal Papanicolaou (Pap) smear among women infected with HIV-1 and their pregnancy status, and historical and clinical factors. METHODS: Study enrollment Pap smears of 452 pregnant and 126 nonpregnant HIV-infected women had cytologic evaluation. The rates of SIL were compared with pregnancy status, immunosuppression, presence of sexually transmitted diseases (STDs) and demographic features. RESULTS: Rates of low grade SIL were similar for pregnant and nonpregnant HIV-1-infected women (17% and 23.8%, respectively; p = .09). Of them, 12 women, 9 pregnant and 3 nonpregnant, had high grade SIL. None had invasive cervical cancer. Low CD4 percentage (odds ratio, [OR] = 3.8; 95% confidence interval [CI], 2.0-7.3) and inflammation (OR = 2.8; 95% CI, 1.8-4.3) were associated with SIL. An association between herpes simplex and SIL (OR = 3.3; 95% CI, 1.1-9.5) was less certain due to clinical diagnosis and low prevalence of herpes simplex (17 of 456 women). CONCLUSIONS: Pap smears for a cohort of HIV-infected pregnant and nonpregnant women revealed a high prevalence of LGSIL but a low prevalence of HGSIL and no cases of cervical cancer. Although pregnancy may not affect the rate of Pap smear abnormalities, SIL is associated with immunosuppression, cervical inflammation, and herpes simplex. Closer surveillance of HIV-1-infected women with these risk factors may be warranted.
Adolescent↗
Vitamin A deficiency and other nutritional indices during pregnancy in human immunodeficiency virus infection: prevalence, clinical correlates, and outcome. Women and Infants Transmission Study Group.
Vitamin A levels in plasma and other nutritional indices were measured during pregnancy for 449 women enrolled in a multicenter cohort study of mother-to-infant transmission of human immunodeficiency virus type 1 (HIV-1). During the third trimester, 29.6% of the women had low (20 to <30 microg/dL) and 11.1% had very low (<20 microg/dL) vitamin A levels. Vitamin A and body mass index, serum albumin levels, and hemoglobin levels were weakly correlated. After adjustment for other covariates, women with low and very low vitamin A levels before the third trimester were more likely to deliver infants with low birth weight (<2500 g) than were those with higher levels (odds ratio [OR], 4.58; 95% confidence interval [CI], 1.57-13.4; and OR, 6.99; 95% CI, 1.09-45.0, respectively). However, there was no statistically significant association between vitamin A level and mother-to-infant transmission of HIV-1. Anemia and low body mass index before the third trimester were associated with an increased risk of transmission in univariate analyses but not in multivariate analyses.
Adult↗
Interruption of materno-fetal transmission.
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Anti-HIV Agents↗
Predictive value of quantitative plasma HIV RNA and CD4+ lymphocyte count in HIV-infected infants and children.
CONTEXT: Pediatric human immunodeficiency virus (HIV) infection has unique viral pathogenetic features that preclude routine extrapolation from adult studies and require specific analysis. OBJECTIVES: To evaluate the prognostic value of 2 key laboratory markers-plasma RNA and CD4+ lymphocyte count-for HIV disease progression in infants and children and to establish targeted values for optimal outcome. DESIGN: Data from a cohort of 566 infants and children who participated in a randomized, placebo-controlled trial of nucleoside reverse transcriptase inhibitors (ACTG 152) were analyzed. The trial was conducted between 1991 and 1995 and enrolled a heterogeneous cohort of antiretroviral therapy-naive children (age, 3 months to 18 years); patients had a median follow-up of 32 months. MAIN OUTCOME MEASURES: The trial clinical end points consisted of time to first HIV disease progression (growth failure, decline in neurologic or neurodevelopmental function, opportunistic infections) or death. RESULTS: Baseline plasma RNA levels were high (age group medians, 5 x 10(4) to >10(6) copies/mL), and both baseline RNA and CD4+ lymphocyte count were independently predictive of subsequent clinical course. Risk reduction for disease progression between 49% and 64% was observed for each log10 reduction in baseline RNA and was linear without suggestion of a threshold or age effect. Disease progression predictive power was enhanced by the combined use of plasma RNA and CD4+ cell count. Marker values of less than 10000 copies/mL for plasma RNA and greater than 500 x 10(6)/L (<6.5 years of age) or greater than 200 x 10(6)/L (>6.5 years) for CD4+ cell count were associated with a 2-year disease progression rate of less than 5%. CONCLUSIONS: Two key laboratory markers--plasma RNA and CD4+ lymphocyte count-are independent predictors of clinical course among HIV-infected infants and children. The linear, age-independent relationship between log10 plasma RNA and relative risk of disease progression strongly supports therapeutic efforts to achieve plasma virus levels as low as possible.
Adolescent↗
The immunogenicity of Haemophilus influenzae type b conjugate vaccines in children born to human immunodeficiency virus-infected women. Women and Infants Transmission Study Group.
BACKGROUND: Immunocompromise caused by HIV-1 infection increases the importance of receipt of routine childhood vaccines to prevent infections such as invasive Haemophilus influenzae type B (Hib) disease. The objectives of the study were to evaluate the immunogenicity of Hib conjugate vaccines among HIV-infected children according to clinical and immunologic disease progression as well as viral load. METHODS: The concentration of antibody to polyribosylribitol phosphate (PRP) was measured at approximately 9 and 24 months of age in plasma specimens from children of HIV-infected women enrolled in the Women and Infants Transmission Study. RESULTS: Among 227 children (35 HIV-infected, 192 uninfected) at the 9-month study visit who were known to have received age-appropriate immunization with CRM197 mutant Corynebacterium diphtheriae protein-conjugated Hib vaccine, geometric mean antibody concentrations were lower among HIV-infected children (1.64 microg/ml) than among uninfected children (2.70 microg/ml), although the difference was not statistically significant. Anti-PRP antibody concentrations did not vary significantly among these HIV-infected children with predominantly mild-moderate disease progression according to clinical category, immunologic stage or viral load (P > or = 0.48). The proportion of children with antibody concentrations > or = 1.0 microg/ml did not vary significantly according to HIV infection status (73% uninfected, 74% infected) or, if infected, clinical or immunologic disease progression or viral load. Similar results were obtained among 127 children (17 HIV-infected, 110 uninfected) eligible for analysis at the 24-month study visit. Changes in antibody concentrations over time (between 9 and 24 months of age) did not differ significantly among 10 HIV-infected as compared with 72 uninfected children (P=0.81). CONCLUSIONS: These results suggest that HIV-infected children with predominantly mild-moderate disease progression respond reasonably well in terms of a quantitative antibody response to Hib conjugate vaccines during the first 2 years of life. Research to further characterize the immune response to Hib conjugate vaccines and to further delineate the "durability" of anti-PRP antibody concentrations beyond 2 years of life should be pursued.
Antibodies, Bacterial↗
Elevated CD8+DR+ lymphocytes in HIV-exposed infants with early positive HIV cultures: a possible early marker of intrauterine transmission. Women and Infants Transmission Study Group.
The associations among timing of maternal-fetal human immunodeficiency virus (HIV) transmission, infant age at first positive HIV culture, and CD8+ lymphocyte activation were examined for 74 perinatally infected infants. Nineteen of the infected infants had positive HIV cultures at < or =7 days of life, and 55 had negative HIV cultures at < or =7 days but were positive later. Of the infants with early positive HIV-1 cultures, 15 of the 17 tested with DNA polymerase chain reaction methods had concordant results. The percentage of CD8+ and HLA-DR+ lymphocytes (CD8+DR+%) during the first week of life was significantly higher in infants with early compared with late positive cultures (median CD8+DR+% of 5.0% versus 2.0%, p = 0.0006). The CD8+DR+% was similar between uninfected infants and infants with late positive cultures during the first week of life (median 2%) but increased in infants with late positive cultures to 6% by 1 month. The CD4+% during the first 6 months of life was not different between infants with early or with late positive cultures, but infants with the highest CD8+DR+% at < or =7 days of life had significantly lower CD4+% at < or =7 days and at 1, 2, and 4 months of age. These data show that early CD8+ lymphocyte activation is associated with early positive HIV cultures and lower CD4+ percentages during early infancy and are consistent with the hypothesis that early positive cultures positivity may indicate in utero HIV infection.
Biomarkers↗
Zidovudine, didanosine, or both as the initial treatment for symptomatic HIV-infected children. AIDS Clinical Trials Group (ACTG) Study 152 Team.
BACKGROUND: Zidovudine has been the drug of choice for the initial treatment of symptomatic children infected with the human immunodeficiency virus (HIV). This trial was designed to assess the efficacy and safety of treatment with zidovudine alone as compared with either didanosine alone or combination therapy with zidovudine plus didanosine. METHODS: In this multicenter, double-blind study, symptomatic HIV-infected children 3 months through 18 years of age were stratified according to age (<30 months or > or =30 months) and randomly assigned to receive zidovudine, didanosine, or zidovudine plus didanosine. The primary end point was length of time to death or to progression of HIV disease. RESULTS: Of the 831 children who could be evaluated, 92 percent had never received antiretroviral therapy and 90 percent had acquired HIV perinatally. An interim analysis (median follow-up, 23 months) showed a significantly higher risk of HIV-disease progression or death in patients receiving zidovudine alone than in those receiving combination therapy (relative risk, 0.61; 95 percent confidence interval, 0.42 to 0.88; P=0.007). The study arm with zidovudine alone was stopped and unblinded; the other two treatment arms were continued. At the end of the study, didanosine alone had an efficacy similar to that of zidovudine plus didanosine (median follow-up, 32 months) (relative risk of disease progression or death, 0.98; 95 percent confidence interval, 0.70 to 1.37; P=0.91). A significantly lower risk of anemia or neutropenia was seen in patients receiving didanosine alone (P=0.036). CONCLUSIONS: In symptomatic HIV-infected children, treatment with either didanosine alone or zidovudine plus didanosine was more effective than treatment with zidovudine alone. The efficacy of didanosine alone was similar to that of the combination therapy and was associated with less hematologic toxicity.
Adolescent↗
Lymphocyte phenotyping in infants: maturation of lymphocyte subpopulations and the effects of HIV infection.
Changes in the distribution of lymphocyte subpopulations in infants with perinatally acquired HIV infection are confounded by the rapid changes that are the result of normal maturation of the immune system. We describe the changes in seven lymphocyte phenotypes (CD3+ CD4+, CD3+ CD8+, CD8+ HLA- DR+, CD8+ CD38+, CD8+ CD57+, CD3-/ CD16+ 56+, and CD19+) over the first 2 years of life in 390 HIV-1 exposed but uninfected and 98 HIV-1-infected infants enrolled in the Women and Infants Transmission Study. The greatest changes in uninfected infants were declines in the CD3+ CD4+ lymphocytes and increases in CD8+ HLA- DR+ and CD19+ lymphocytes. All phenotypes were affected by HIV infection but the greatest changes were declines in the CD3+ CD4+ subset and increases in the CD3+ CD8+ and CD8+ HLA- DR+ subsets. Thus, this study provides reference data for the maturational changes in lymphocyte phenotypes in HIV-exposed but uninfected infants and describes the overall changes that occur with perinatally acquired HIV infection.
Adult↗
Women and HIV. Epidemiology and global overview.
The global HIV-1 epidemic in women continues to expand at an alarming rate. More than 11 million women are currently estimated to be HIV-infected, with the majority living in sub-Saharan Africa. The primary risk factor for HIV infection in women is unprotected heterosexual intercourse. Several cofactors may influence a woman's risk for HIV acquisition. These include the presence of other STDs, the prevalence of HIV in the population, engagement in high-risk sexual behaviors at a young age, an increased number of sexual partners, HIV illness severity in an infected partner, host immunogenetic responses, hormonal and other local effects in the female genital tract, and viral characteristics. The general clinical findings in women with HIV disease are similar to those in HIV-infected men. Some studies have noted higher rates of esophageal candidiasis and decreased rates of Kaposi's sarcoma in women when compared with men. Overall disease progression and survival in women and men are similar once an adjustment is made for other important risk factors such as the time of seroconversion, the receipt of antiretrovirals, and baseline CD4 cell counts. Women with HIV have a high frequency of a number of diseases of the reproductive tract, including low-grade cervical dysplasia and vulvovaginal candidiasis. Despite progress in understanding the risk factors for HIV transmission to women and the variables related to disease progression, major research questions remain. These include the role of hormonal contraceptives in the risk for HIV acquisition, the primary mechanism of infection, and host systemic as well as local hormonal and immune responses in the female reproductive tract that may alter the risk of HIV infection. Over the next decade, it is anticipated that the quality of life and length of survival will improve dramatically for both HIV-infected women and men in settings in which new highly active combination antiretroviral therapy is available and affordable. Unfortunately, in most of the world, these antiretroviral drugs are not available for the treatment of the vast numbers of individuals infected by HIV. Therefore, development of successful strategies for primary prevention of HIV infection in women must be a top public health priority.
AIDS-Related Opportunistic Infections↗
Evaluation of pharmacokinetics, safety, tolerance, and activity of combination of zalcitabine and zidovudine in stable, zidovudine-treated pediatric patients with human immunodeficiency virus infection. AIDS Clinical Trials Group Protocol 190 Team.
A double-blind phase II trial compared zalcitabine (0.03 mg/kg/day) in combination with zidovudine (720 mg/m2/day) and zidovudine monotherapy in 250 clinically stable, previously zidovudine-treated, human immunodeficiency virus-infected children. The combination was well-tolerated except for an increased incidence of neutropenia (14%) compared with that in children receiving monotherapy (5%). No differences were noted for time to first AIDS-defining illness or death, neuropsychologic status, or weight Z scores. In patients in the combination arm, the CD4 cell count decline was slower (13% per year) than in patients receiving monotherapy (25% per year) (P = .03), and quantitative peripheral blood mononuclear cell virus load remained lower at all time points (P = .08). Deaths were fewer in patients receiving combination therapy (4) compared with those in patients receiving monotherapy (10) (P = .083). Thus, administration of zidovudine with zalcitabine to children with prior zidovudine treatment did not result in a significant increase in toxicity compared with that resulting from zidovudine monotherapy and demonstrated improvement in immunologic and virologic surrogate markers.
AIDS-Related Opportunistic Infections↗
Maternal immunologic and virologic risk factors for infant human immunodeficiency virus type 1 infection: findings from the Women and Infants Transmission Study.
Maternal virus load of human immunodeficiency virus 1 (HIV-1) and maternal immunity are both associated with risk of an infected infant. The interrelationship of these two variables in describing that risk was assessed in a multisite study of 475 mother-infant pairs. Infant infection was associated with low CD4 cell percentage, high CD8, CD8/CD38, and CD8/DR cell percentages, persistently positive HIV-1 cultures, and high HIV-1 titer (P < .001, .001, .005, .006, .001, and .013, respectively). The association of CD4 cell percentage and increased CD8, CD8/CD38, and CD8/DR cell percentages with transmission was restricted to the 42% of women whose HIV-1 cultures were not persistently positive (all P < .001). Women with at least 1 negative culture and high CD4 cell percentage or low CD8 cell percentage were at very low risk (0-4%) of transmitting HIV-1, while those with always positive cultures transmitted at a high rate (18%-27%), regardless of immune status.
Adolescent↗
Progress in prevention of perinatal HIV-1.
The findings of a recent human immunodeficiency (HIV-1) prevention trial in the USA demonstrated that administration of an antiretroviral drug, zidovudine, to mothers during the prenatal and intrapartum periods, and to their neonates for 6 weeks, resulted in a two-thirds reduction in risk of perinatal transmission from 25.5% to 8.3%. These results were rapidly disseminated both in the USA and internationally. Since the release of these clinical trial results in the spring of 1994, several observational studies have documented a sharp increase in maternal and neonatal zidovudine use, as well as a significant decrease in perinatal HIV-1 transmission, with rates of about 8% being observed in non-clinical trial settings. Internationally, the results have led to the development of a variety of perinatal prevention trials that build on the success of the U.S. perinatal prevention trial but use modified strategies that can feasibly be carried out in developing countries.
Anti-HIV Agents↗
Update: transmission of HIV-1 from mother to child.
Mother-to-child transmission near the time of birth is the primary route of HIV-1 infection among infants and young children. Throughout the world, 1000 babies a day become infected with HIV, and cumulative global estimates are that 3 million children have been infected since the HIV pandemic began. Although major advances have been made in reducing mother-to-child transmission of HIV-1 in the USA and Europe through the use of an intensive regimen of zidovudine, many research questions remain unresolved. These include (1) viral and host characteristics which hinder or facilitate perinatal HIV transmission (i.e. the role played by viral load, the placenta and obstetric risk factors); (2) the proportion of transmission occurring in utero, intrapartum or during the breast feeding period; and (3) the mode of action of the successful zidovudine regimen. Studies published within the past year have shed light on several of these research topics. In 1996-1997 a number of important studies were published which support a general correlation between maternal viral load and infant HIV infection. The most recent studies do not, however, support the theory that there is a threshold below which transmission cannot occur, and also indicate that zidovudine, given according to the US Public Health Service guidelines, can significantly reduce the risk of transmission across all levels of maternal viral load. Analyses of viral load data from the successful clinical trial with zidovudine (AIDS Clinical Trial Group 076) suggest that its primary action is not by reducing the viral load, and raise the possibility that administering antiretroviral prophylaxis to the infant at the time of highest exposure may be another reason for the reduction in transmission. Obstetric risk factors for mother-to-child HIV transmission have been evaluated in several large cohort studies. A duration of membrane rupture of more than 4 h, and procedures such as amniocentesis, preterm labor, and the presence of sexually transmitted diseases during pregnancy were found to be significant risk factors. Still unresolved is the potential protective effect of cesarean section in reducing the risk of transmission. Likewise, the role played by the placenta in preventing or facilitating perinatal transmission is not well understood, and requires further research. This year did see the publication of consistent findings from diverse geographical regions regarding the probable timing of perinatal HIV transmission. On the basis of the timing of the first infant positive polymerase chain reaction or culture, most transmission would appear to occur around the intrapartum or very late prenatal period, and only approximately 12-14% is related to breast feeding. These advances should help focus and refine future research efforts to reduce mother-to-child HIV transmission worldwide.
Breast Feeding↗
Obstetrical factors and the transmission of human immunodeficiency virus type 1 from mother to child. The Women and Infants Transmission Study.
BACKGROUND: A substantial proportion of perinatally acquired infections with the human immunodeficiency virus type 1 (HIV-1) occur at or near delivery, which suggests that obstetrical factors may have an important influence on transmission. We evaluated the relation of such factors and other variables to the perinatal transmission of HIV-1. METHODS: The Women and Infants Transmission Study is a prospective, observational study of HIV-1-infected women who were enrolled during pregnancy and followed with their infants for three years after delivery. We studied obstetrical, clinical, immunologic, and virologic data on 525 women who delivered live singleton infants whose HIV-1-infection status was known as of August 31, 1994. RESULTS: Among mothers with membranes that ruptured more than four hours before delivery, the rate of transmission of HIV-1 to the infants was 25 percent, as compared with 14 percent among mothers with membranes that ruptured four hours or less before delivery. In a multivariate analysis, the presence of ruptured membranes for more than four hours nearly doubled the risk of transmission (odds ratio, 1.82; 95 percent confidence interval, 1.10 to 3.00; P = 0.02), regardless of the mode of delivery. The other maternal factors independently associated with transmission were illicit-drug use during pregnancy (odds ratio, 1.90; 95 percent confidence interval, 1.14 to 3.16; P = 0.01), low antenatal CD4+ lymphocyte count (<29 percent of total lymphocytes) (odds ratio, 2.82; 1.67 to 4.76; P<0.001), and birth weight <2500 g (odds ratio, 1.86; 1.03 to 3.34; P = 0.04). CONCLUSIONS: The risk of transmission of HIV-1 from mother to infant increases when the fetal membranes rupture more than four hours before delivery.
Adult↗