HLA-G 14 bp deletion/insertion polymorphism and mother-to-child transmission of HIV.

The human leukocyte antigen HLA-G, highly expressed at the maternal-fetal interface, has a pivotal role in mediating immune tolerance. In this study we investigated the influence of HLA-G 14 bp insertion polymorphism in human immunodeficiency virus (HIV)-1 mother-to-child HIV-1 transmission. The 14 bp insertion polymorphism was analyzed among 99 HIV-1 positive mothers and 329 infants born to HIV-positive mothers in Zambia, among whom vertical transmission status and timing had been determined. HLA-G 14 bp insertion polymorphism was detected using a custom TaqMan single nucleotide polymorphisms (SNPs) genotyping assay. Logistic regression was conducted to examine the associations between HLA-G alleles and the risk of HIV transmission. The 14 bp insertion allele was more frequent in HIV exposed-uninfected (EU) infants than in infected infants, and was associated with reduced risk of both in utero (IU) and intrapartum (IP) HIV transmission, after adjusting for maternal cluster of differentiation 4 (CD4) cell count and plasma viral load. Maternal HLA-G 14 bp insertion genotype and HLA-G concordance between mother and child were not associated with the risk of perinatal HIV transmission. The presence of the 14 bp insertion associates with protection toward IU and IP HIV infection in children from Zambia, suggesting that HLA-G could be involved in the vertical transmission of HIV.

Value of chest radiography in predicting treatment response in children aged 3-59 months with severe pneumonia.

SETTING: International multicentric study at nine tertiary care centres. OBJECTIVE: The World Health Organization (WHO) currently does not recommend chest radiographs (CXRs) for routine management of pneumonia. We evaluated the use of CXR for the prediction of treatment failure in children with severe pneumonia. DESIGN: We used WHO vaccine trials radiographic assessment, clinical and nasopharyngeal microbiological data from 1121 3-59-month-old children recruited using the WHO definition of severe pneumonia in the Amoxicillin Penicillin Pneumonia International Study (APPIS). Using Poisson regression, we estimated the relative risk of developing clinical treatment failure and predictive preventive benefit of the CXR and examined the concordance of the CXR findings with the nasopharyngeal microbiological data. RESULTS: A CXR with 'significant pathology' (defined by the WHO algorithm as end-point consolidation, pleural fluid and other infiltrates) was associated with a high risk of treatment failure, especially in children who received penicillin as compared to oral amoxicillin. Significant pathology was also associated with nasopharyngeal isolation of penicillin-resistant Streptococcus pneumoniae. Children with a normal CXR had a reduced risk of clinical treatment failure. CONCLUSIONS: CXR with significant pathology independently and additively predicts clinical treatment failure. If CXR and the WHO tool are available, they can be used in the management of severe pneumonia.

Impact of human immunodeficiency virus infection on Streptococcus pneumoniae colonization and seroepidemiology among Zambian women.

Nasopharyngeal colonization with Streptococcus pneumoniae precedes invasive pneumococcal disease. Human immunodeficiency virus (HIV) infection increases rates of invasive pneumococcal disease, and its effect on colonization is unknown. In a longitudinal cohort of Zambian mothers with or without HIV infection, HIV infection increased the risk of colonization (risk ratio [RR], 1.9; 95% confidence interval [CI], 1.3-2.8) and repeat colonization (RR, 2.4; 95% CI, 1.1-5.3) and reduced the time to new colonization (P = .01). Repeat colonization with homologous sero/factor types occurred only among HIV-positive mothers. Pediatric serotypes 6, 19, and 23 accounted for excess colonization among HIV-positive mothers. HIV infection significantly increases the risk of pneumococcal colonization. Increased rates of colonization by pediatric serotypes suggest a potential role for the 7-valent pneumococcal vaccine in HIV-infected adults.

Effect of presumptive co-trimoxazole prophylaxis on pneumococcal colonization rates, seroepidemiology and antibiotic resistance in Zambian infants: a longitudinal cohort study.

OBJECTIVE: To ascertain the microbiological consequences of WHO's recommendation for presumptive co-trimoxazole prophylaxis for infants with perinatal HIV exposure. METHODS: Using a longitudinal cohort design, we followed HIV-exposed and HIV-unexposed infants trimonthly for up to 18 months per infant. HIV-exposed infants received daily co-trimoxazole prophylaxis from 6 weeks to > or = 12 months of age. Using Streptococcus pneumoniae as our sentinel pathogen, we measured how co-trimoxazole altered nasopharyngeal colonization, pneumococcal resistance to antibiotics and serotype distribution as a function of co-trimoxazole exposure. FINDINGS: From 260 infants followed for 3096 patient-months, we detected pneumococci in 360/1394 (25.8%) samples. HIV-exposed infants were colonized more frequently than HIV-unexposed infants (risk ratio, RR: 1.4; 95% confidence interval, CI: 1.0-1.9, P = 0.04). Co-trimoxazole prophylaxis reduced colonization by ca 7% but increased the risk of colonization with co-trimoxazole-resistant pneumococci within 6 weeks of starting prophylaxis (RR: 3.2; 95% CI: 1.3-7.8, P = 0.04). Prophylaxis with co-trimoxazole led to a small but statistically significant increase of nasopharyngeal colonization with pneumococci not susceptible to clindamycin (RR: 1.6; 95% CI: 1.0-2.6, P = 0.04) but did not increase the risk of non-susceptibility to penicillin (RR: 1.1; 95% CI: 0.7-1.7), erythromycin (RR: 1.0; 95% CI: 0.6-1.7), tetracycline (RR: 0.9; 95% CI: 0.6-1.5) or chloramphenicol (RR: 0.8; 95% CI: 0.3-2.3). Co-trimoxazole prophylaxis did not cause the prevailing pneumococcal serotypes to differ from those that are targeted by the 7-valent conjugate pneumococcal vaccine (RR: 1.0; 95% CI: 0.7-1.6). CONCLUSION: Co-trimoxazole prophylaxis modestly suppresses pneumococcal colonization but accelerates infant acquisition of co-trimoxazole- and clindamycin-resistant pneumococci. Co-trimoxazole prophylaxis appears unlikely to compromise the future efficacy of conjugate vaccines.

Inferiority of single-dose sulfadoxine-pyrimethamine intermittent preventive therapy for malaria during pregnancy among HIV-positive Zambian women.

BACKGROUND: The World Health Organization advocates 2-3 doses of sulfadoxine-pyrimethamine (SP) for intermittent preventive treatment of malaria (SP IPTp). The optimal number of doses and the consequences of single-dose therapy remain unclear. METHODS: Data were from a randomized, controlled study of human immunodeficiency virus-positive Zambian women comparing monthly versus 2-dose SP IPTp. We compared maternal and neonatal birth outcomes as a function of how many doses the mothers received (1 to > or =4 doses). RESULTS: Of 387 deliveries, 34 received 1 dose of SP. Single-dose SP was significantly associated with higher proportions of maternal anemia, peripheral and cord blood parasitemia, infant prematurity, and low birth weight. SP conferred dose-dependent benefits, particularly in the transition from 1 to 2 doses of SP. Women randomized to the standard 2-dose regimen were much more likely to receive only 1 dose than were women randomized to monthly IPT (relative risk, 16.4 [95% confidence interval, 4.0-68.3]). CONCLUSIONS: Single-dose SP was a common result of trying to implement the standard 2-dose regimen and was inferior to all other dosing regimens. At a programmatic level, this implies that monthly SP IPTp may ultimately be more effective than the standard regimen by reducing the risk of inadvertently underdosing mothers.

Quantitation of human immunodeficiency virus type 1 in breast milk.

The distribution and stability of human immunodeficiency virus type 1 (HIV-1) in breast milk (BM) components remain largely unknown. Inhibitory effects, if any, of BM on HIV RNA and DNA PCR amplification are poorly understood. We have addressed these issues by using virus-spiked BM samples from HIV-negative women. BM samples from HIV-negative women were spiked with HIV-1 virions or cells containing a single integrated copy of HIV DNA (8E5/LAV). After incubation under different experimental conditions, viral RNA was detected by the Roche Amplicor UltraSensitive assay in whole-milk, skim milk, and lipid fractions. We found excellent correlation between HIV-1 input copy and recovery in whole milk (r = 0.965, P < 0.0001), skim milk (r = 0.972, P < 0.0001), and the lipid fraction (r = 0.905, P < 0.001). PCR inhibition was observed in less than 10% of the spiked samples. Similar levels of inhibition were noted in BM samples collected from HIV-infected women. HIV proviral DNA was detected in BM samples using real-time PCR (linear correlation between the threshold cycle versus log DNA copy number, >0.982). The effects of incubation duration and temperature and repeated freeze-thaw cycles on HIV RNA recovery were analyzed. HIV RNA levels were remarkably stable in whole milk after three freeze-thaw cycles and for up to 30 h at room temperature. Our findings improve the understanding of the dynamics of HIV detection in BM and the conditions for BM sample collection, storage, and processing.

Early detection of reverse transcriptase activity in plasma of neonates infected with HIV-1: a comparative analysis with RNA-based and DNA-based testing using polymerase chain reaction.

Plasma viral load from 71 HIV-1-infected neonates was measured by using Amp-RT, an ultrasensitive quantitative reverse transcriptase (RT) assay and by nucleic acid sequence-based amplification (NASBA), an RNA-based quantitative assay. Results were then compared with those obtained from detection of proviral DNA in peripheral blood mononuclear cells (PBMCs) by polymerase chain reaction (PCR) using Turnbull analysis. At 5 days of life, 50% of neonates were positive by Amp-RT, 30% were NASBA positive, and 20% were DNA-PCR positive. Through the first 12 days of life, Amp-RT was more sensitive than either NASBA or DNA-PCR in detecting HIV-1 infection. Amp-RT values correlated well with NASBA RNA values, with an overall Pearson's r = 0.63 (95% confidence interval [CI], 0.40-0.78). In proportional hazards analysis of infants aged 14 to 61 days (N = 31), a one-log increase in RNA-based viral load was associated with a > fivefold risk of disease progression when using the U.S. Centers for Disease Control and Prevention (CDC) clinical Category C (CDC-C) or death as an endpoint (p =.014). Kaplan-Meier analysis of these data found that RNA viral loads were able to predict disease progression using CDC-C/death as an endpoint (p = .013). Early quantitative viral load measurements may assist clinicians in diagnosing HIV-1 infection, stratifying risk of disease progression, and implementing a treatment plan using highly active antiretroviral therapy for infants within the first few weeks of life.

Relative influences of sex, race, environment, and HIV infection on body composition in adults.

BACKGROUND: The factors that control body composition in disease are uncertain. OBJECTIVE: We planned to compare the relative influences of HIV infection, sex, race, and environment on body composition. METHODS: We analyzed results of body composition studies performed by bioelectrical impedance analysis in 1415 adults from 2 cohorts: white and African American men and women from the United States, and African men and women (279 HIV-infected and 1136 control). The effects of sex and HIV infection on weight, body cell mass, and fat-free mass were analyzed by using both unadjusted and age-, weight-, and height-adjusted data. RESULTS: Control men weighed more and had more body cell mass and fat-free mass than did control women, although control women had more fat. The strongest correlates with body composition were height and weight, followed by sex. HIV infection, age, environment, and race. Control men and women weighed more and had more body cell mass, fat-free mass, and fat than did HIV-infected men. However, differences in body composition between HIV-infected and control groups were strongly influenced by sex. Of the differences in weight between HIV-infected and uninfected subjects, fat-free mass accounted for 51% in men but only 18% in women, in whom the remainder was fat. Sex effects were similar in African and American groups. CONCLUSIONS: Sex has a marked effect on the changes in body composition during HIV infection, with women losing disproportionately more fat than men. Sex-related differences in body composition were narrower in the HIV-infected groups. Race and environment had smaller effects than sex and HIV infection.

Distinct risk factors for intrauterine and intrapartum human immunodeficiency virus transmission and consequences for disease progression in infected children. Perinatal AIDS Collaborative Transmission Study.

Predictors and prognosis of intrauterine and intrapartum human immunodeficiency virus (HIV) transmission were investigated among 432 children of HIV-infected women in the Perinatal AIDS Collaborative Transmission Study. Timing of transmission was inferred from polymerase chain reaction or viral culture within 2 days of birth. Proportions of infections due to intrauterine transmission were similar among women using (29%) or not using zidovudine (30%). Preterm delivery was strongly associated with intrapartum transmission (relative risk, 3.7; 95% confidence interval [CI], 2.2-6.1), particularly among infants delivered longer after membrane rupture, but was not associated with intrauterine transmission. Progression to AIDS or death increased 2.5-fold (95% CI, 1.1-5.8) among intrauterine infected children, adjusting for preterm delivery, and maternal CD4 cell count. Early transmission appears unlikely to explain instances of zidovudine failure. Preterm infants may be more vulnerable to HIV acquisition at delivery, especially if membrane rupture is prolonged. Intrauterine infection does not appear to increase risk of preterm delivery.

Sensitivity and specificity of a qualitative RNA detection assay to diagnose HIV infection in young infants. Perinatal AIDS Collaborative Transmission Study.

OBJECTIVE: To evaluate the sensitivity and specificity of an RNA detection assay for diagnosing perinatal HIV infection. METHODS: Plasma and serum specimens taken during the first 3 months of life from HIV-infected and uninfected children enrolled in a cohort study were assayed for HIV RNA using the qualitative nucleic acid sequence-based amplification (NASBA) kit. Sensitivity, specificity, and predictive values were calculated. NASBA results from infected children were compared with DNA PCR results from the same blood samples. Autoantibody patterns of suspected false-positive specimens were compared with those of subsequent specimens from the same child to exclude specimen labelling errors. RESULTS: Amongst 131 specimens from 105 HIV-infected children, the sensitivity of the qualitative NASBA assay was 13 out of 34 [38%; 95% confidence interval (CI), 22-56] at < 7 days, 56 out of 58 (97%; 95% CI, 88-100) at 7-41 days, and 37 out of 39 (95%; 95% CI, 83-99) at 42-93 days of life. Of 252 specimens from 206 uninfected children, six tested positive and one tested indeterminate by NASBA. Four of these positive specimens had discordant autoantibody patterns suggesting mislabelling; excluding these, the test specificity was 245 out of 248 (99%; 95% CI, 97-100). Amongst 128 paired specimens from infected children, NASBA results were more often positive than those from DNA PCR (103 versus 92; P=0.01). Amongst infants with specimens drawn in the first week of life, the proportion born after > 4 h of membrane rupture was greater amongst those testing negative (81%) than those testing positive (46%; P=0.05). CONCLUSIONS: The qualitative NASBA RNA assay is highly specific and more sensitive than DNA PCR. Qualitative RNA assays may be useful for diagnosing and excluding perinatal HIV infection in children after the first week of life for such purposes as initiating antiretroviral therapy and other treatment, resolving parental uncertainty, determining timing of transmission, and providing endpoints for intervention trials.

Association of human immunodeficiency virus (HIV) load early in life with disease progression among HIV-infected infants. New York City Perinatal HIV Transmission Collaborative Study Group.

The utility of RNA virus load to predict progression of human immunodeficiency virus (HIV)-1 disease was assessed in 89 HIV-1-infected children. Of 22 virus load values during week 1 of life, 17 were below the detection threshold. Geometric mean virus load increased to approximately 7 x 10(5) copies/mL by week 4, was sustained throughout the first 6 months of life, and then declined to 1.6 x 10(5) copies/mL during the third year. Samples from week 1 of life had little predictive value, but virus load during days 7-30 strongly predicted progression to CDC-3 classification or death (P = .024; risk ratio = 1.6), and virus load during months 2-3 predicted progression to CDC-C or death within the first 6 months of life (P = .002, risk ratio = 11). Virus load was highly associated with imminent vulnerability to CDC-C or death (P = .002) during the first 18 months of life. Except for values from the first week of life, virus load at any age through 18 months is strongly associated with risk of HIV disease progression.

Incubation period of HIV-1 in perinatally infected children. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVES: To estimate the distribution of the incubation period of HIV-1 among perinatally infected children and to test the hypothesis that this distribution has been changing over time. DESIGN: An analysis of 190 perinatally HIV-1-infected children born between 1986 and 1997 in eight medical centers in New York City to women enrolled in a prospective cohort study. METHODS: Non-parametric Kaplan-Meier method and parametric survival analysis. RESULTS: Using the Kaplan-Meier method it was estimated that among perinatally HIV-1-infected children, 48% [95% confidence interval (CI), 41-56] developed AIDS by 3 years of age after which the rate was less than 3% per year. Using a parametric survival analysis for extrapolation, it was predicted that 33% (95% CI, 23-43) would remain AIDS-free at 13 years of age. Median age at onset of AIDS was estimated to be 4.1 years (95% CI, 1.9-6.4) by parametric survival analysis. The year of birth was significantly associated with AIDS-free survival, suggesting an increase in the time to AIDS over the years. This association remained significant (P=0.03) after adjustment for those maternal characteristics that have also changed over time: timing of enrollment (prepartum versus postpartum), zidovudine, alcohol, and hard drug (heroin, cocaine or methadone) use during pregnancy. CONCLUSIONS: Although a substantial proportion of perinatally HIV-1-infected children develop AIDS very early in life, a significant and increasing percentage of them are expected to survive into adolescence without developing AIDS. Further research is needed to determine the factors associated with the lengthening survival to AIDS.

Genetic evaluation of suspected cases of transient HIV-1 infection of infants.

Detection of human immunodeficiency virus-type 1 (HIV-1) on only one or a few occasions in infants born to infected mothers has been interpreted to indicate that infection may be transient rather than persistent. Forty-two cases of suspected transient HIV-1 viremia among 1562 perinatally exposed seroreverting infants and one mother were reanalyzed. HIV-1 env sequences were not found in specimens from 20; in specimens from 6, somatic genetic analysis revealed that specimens were mistakenly attributed to an infant; and in specimens from 17, phylogenetic analysis failed to demonstrate the expected linkage between the infant's and the mother's virus. These findings argue that transient HIV-1 infection, if it exists, will only rarely be satisfactorily documented.

Neutralizing antibody and perinatal transmission of human immunodeficiency virus type 1. New York City Perinatal HIV Transmission Collaborative Study Group.

The major immunologic determinants for perinatal transmission of human immunodeficiency virus type 1 (HIV-1) remain largely unknown. The presence of maternal neutralizing antibodies has been proposed as an explanation for why the majority of infants born to untreated HIV-1-infected women do not become infected. Using maternal and infant specimens collected as part of a longitudinal cohort study of perinatal transmission in New York City between 1991 and 1995, we successfully obtained primary viral isolates from 10 of 20 perinatally nontransmitting (NTR) women, 14 of 20 perinatally transmitting (TR) women, and 13 of 13 of their HIV-1-infected infants. Neutralizing antibody titers were then determined using a titer reduction assay. TR and NTR women did not differ in their ability to neutralize autologous virus or laboratory strains LAI and MN. Infant viruses were not less sensitive to neutralization by maternal sera than autologous viruses. Similarly, TR and NTR isolates were neutralized equally well using a reference serum with broad neutralizing ability. Finally, a heteroduplex tracking assay (HTA) was used to analyze the degree of viral homology within 13 TR maternal-infant pairs. In eight pairs, maternal and infant isolates were highly homologous. In five pairs, lesser degrees of homology were observed, consistent with perinatal transmission of a minor species. However, these isolates were no more or less resistant to maternal sera than were homologous isolates. Thus we found no association between the presence of neutralizing antibody in maternal sera as measured by a titer reduction neutralization (inactivation) assay and perinatal transmission of HIV-1.

Effect of maternal CD4+ cell count, acquired immunodeficiency syndrome, and viral load on disease progression in infants with perinatally acquired human immunodeficiency virus type 1 infection. New York City Perinatal HIV Transmission Collaborative Study Group.

Among a cohort of 152 infants perinatally infected with human immunodeficiency virus type 1, and their mothers, we correlated infant outcome with material CD4+ lymphocyte count and the presence of maternal acquired immunodeficiency syndrome near delivery. In a subset of 50 mother-infant pairs, we also correlated infant outcome with maternal quantitative viral burden as measured by the nucleic acid sequence based amplification system. We found that low maternal CD4+ cell count and high viral burden were associated with decreased time to category C disease or death in infants infected with human immunodeficiency virus type 1. In a multivariate analysis, high maternal viral load and maternal acquired immunodeficiency syndrome were independently associated with shorter time to category C disease or death in infants with human immunodeficiency virus type 1 infection. High viral load in pregnant women, independent of the presence of advanced maternal disease, appears to increase the risk of rapidly progressive disease in their infected offspring.

Early detection of perinatal human immunodeficiency virus (HIV) type 1 infection using HIV RNA amplification and detection. New York City Perinatal HIV Transmission Collaborative Study.

Early diagnosis of perinatally transmitted human immunodeficiency virus type 1 (HIV) infection can guide early interventions. HIV coculture and DNA polymerase chain reaction (DNA-PCR) detect few HIV-infected infants at birth and 90%-100% by age 3 months. Because extracellular HIV RNA may appear soon after infection, a plasma HIV RNA assay was compared with DNA-PCR for early detection of perinatally infected infants. Blood-draw specimens (108) obtained at the same time from 49 HIV-infected infants and 10 specimens from 8 uninfected infants were tested. HIV RNA and DNA-PCR positivity rates were 56% and 33%, respectively, in 36 specimens from 36 infants <28 days of age (binomial test, P = .001). Among 81 specimens obtained after age 14 days, 79 (98%) were positive by HIV RNA testing. No HIV-infected infant specimens were DNA-PCR-positive and HIV RNA-negative. All specimens from 8 uninfected infants were HIV RNA-negative. These results suggest that plasma HIV RNA was detectable earlier and more reliably than HIV DNA in perinatal infection.

Timing of maternal-infant HIV transmission: associations between intrapartum factors and early polymerase chain reaction results. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To investigate the hypothesis that labour and delivery events, perinatal characteristics, and maternal factors are only associated with intrapartum HIV transmission, and not with intrauterine HIV transmission. METHODS: In the New York City Perinatal HIV Transmission Collaborative Study 276 infants of HIV-infected women were followed prospectively and had results of early polymerase chain reaction (PCR) tests available. Among infected children, intrauterine infection was presumed if HIV DNA was detected by PCR in samples collected from children aged < or = 3 days, and intrapartum infection was presumed if HIV DNA was not detected in these early samples. The proportion of infants with presumed intrauterine and intrapartum infections were compared by selected intrapartum, perinatal and maternal characteristics. RESULTS: Presumed intrapartum infection was found in 7% of infants delivered by Cesarean section and, among infants delivered vaginally, those with longer duration of membrane rupture (> 4 h) were significantly more likely to have presumed intrapartum HIV infection (22%) than those with shorter duration (9%; P = 0.02). There were no differences in presumed intrauterine HIV infection by mode of delivery or longer duration of membrane rupture. Infants born preterm and small for gestational age had significantly higher risks of presumed intrapartum infection, but only those who were small for gestational age had higher risks of intrauterine infection. CONCLUSION: Our results support the notion that selected intrapartum conditions, long duration of membrane rupture prior to delivery in particular, are independent risk factors for maternal-infant transmission, and suggest that preterm infants may be especially vulnerable to intrapartum HIV exposure.

The effect of maternal viral load on the risk of perinatal transmission of HIV-1. New York City Perinatal HIV Transmission Collaborative Study Group.

OBJECTIVE: To determine the effect of maternal viral load at delivery on the risk of perinatal transmission of HIV-1. DESIGN: A nested case-control study within a prospectively followed cohort of HIV-1-infected pregnant women and their infants. SETTING: The multicenter New York City Perinatal HIV Transmission Collaborative Study. PARTICIPANTS: Fifty-one women who gave birth to HIV-1 infected infants were frequency-matched within CD4+ cell count quintiles with 54 non-transmitting mothers. MAIN OUTCOME MEASURES: Maternal quantity of HIV-1 viral RNA was assayed in plasma obtained near delivery using the nucleic acid sequence-based amplification assay system. RESULTS: Viral RNA was detected in 73 (70%) out of 105 women and the median viral load was 16,000 RNA copies/ml in transmitters and 6,600 in non-transmitters (P < 0.01). When adjusted for maternal CD4+ count near delivery, women with measurable viral load were nearly sixfold more likely to transmit HIV-1 than women with viral load below detection [adjusted odds ratio (AOR), 5.8; 95% confidence interval (CI), 2.2 15.5]. The odds ratio for perinatal transmission of log10 viral load, adjusted for CD4 count was 2.7 (95% CI, 1.5-5.1). When stratified by the stage of HIV-1 disease, the only group with significant association between log10 viral load and transmission were AIDS-free women with CD4+ count > 500 x 10(6)/l (AOR, 9.1; 95% CI, 2.6-31.5). CONCLUSIONS: High maternal viral load increases the likelihood of perinatal transmission of HIV-1 in women without AIDS and advanced immunosuppression. HIV-1 infected pregnant women without advanced disease, shown by others to have the lowest risk of perinatal transmission, may benefit the most from efforts to identify and decrease viral load at delivery.

Vitamin A deficiency and maternal-infant transmissions of HIV in two metropolitan areas in the United States.

OBJECTIVE: To determine whether vitamin A deficiency is associated with maternal-infant HIV transmission among HIV-infected pregnant women in two United States cities. METHODS: Third trimester serum vitamin A levels were evaluated using high-performance liquid chromatography in 133 HIV-infected women who delivered livebirths during May 1986 to May 1994 and whose infants had known HIV infection status. RESULTS: Sixteen per cent (seven out of 44) of the transmitting mothers and 6% (five out of 89) of the non-transmitting mothers had severe vitamin A deficiency (< 0.70 mumol/l; P = 0.05). Maternal-infant transmission was also associated with prematurity < 37 weeks gestation (P = 0.02), and Cesarean section delivery (P = 0.04), CD4 percentage (P = 0.03) and marginally associated with duration of membrane rupture of > or = 4 h (P = 0.06) by univariate analysis. In a multivariate logistic regression model, severe vitamin A deficiency [adjusted odds ratio (AOR), 5.05; 95% confidence interval (CI), 1.20-21.24], Cesarean section delivery (AOR, 3.75; 95% CI, 1.10-12.87), and prematurity (AOR, 2.25; 95% CI, 1.22-4.13) were associated with transmission after adjusting for CD4+ percentage, and duration of membrane rupture. CONCLUSION: Increased risk of maternal-infant transmission was associated with severe vitamin A deficiency among non-breastfeeding women in these cohorts from the United States.

Lack of increased risk for perinatal human immunodeficiency virus transmission to subsequent children born to infected women.

BACKGROUND: Little is known about whether a woman's risk of transmitting HIV perinatally increases over time and whether the infection outcome of a previous child affects the risk of transmitting HIV to subsequent children. METHODS: We analyzed data from 114 prospectively followed women who gave birth to at least 2 children after becoming infected with HIV to determine the risk for perinatal HIV transmission to these sibling pairs. RESULTS: The median interval between sibling births was 19 months. HIV infection occurred in 19 (17%) older siblings and 20 (18%) younger siblings (P = 0.87). Two (11%) of the 19 children with infected older siblings were infected compared with 18 (19%) of the 95 children with uninfected older siblings (P = 0.86). The risk for transmission to younger siblings was not associated with the interval between deliveries of the two siblings. CONCLUSIONS: These data do not demonstrate that an HIV-infected woman's risk of transmitting HIV perinatally increases with time, although the observed interpregnancy interval was relatively short. The risk for perinatal transmission does not appear to be affected by the infection outcome of previous children. These findings may be useful for counseling HIV-infected women about their risk of transmitting HIV perinatally.