Higher in utero and perinatal HIV infection risk in girls than boys

OBJECTIVE: This study analyzed mother-to-child HIV transmission rates by sex and exposure time for babies born to HIV-infected, untreated African women. METHODS: Data were analyzed from 2 independent studies done in Malawi during the 1990s. Infections were established by polymerase chain reaction on blood samples. Odds ratios (ORs) for transmission were examined by period at risk: in utero (infected in umbilical cord blood), perinatal (infected in 1st postnatal blood > or =4 weeks), and postnatal (later postnatal infection). RESULTS: Among 1394 singleton births, girls were more likely to become infected than boys. For in utero transmission, the OR was 1.4 (95% CI: 0.9 to 2.2). For transmission during early life (umbilical cord blood not available) the OR was 2.7 (95% CI: 1.5 to 4.9). However, transmission risks in the perinatal and postnatal infection periods did not differ in boys and girls. Among 303 tested twin-birth pairs, girls were at higher risk than boys for in utero (OR: 2.6; 95% CI: 1.2 to 5.8) and perinatal (OR: 1.9; 95% CI: 1.0 to 3.7) infection. Recognized mother-to-child transmission risk factors did not explain the higher risk of infection in girls. CONCLUSIONS: Girls were at higher risk of early (in utero and perinatal) HIV infection than boys. It is proposed that minor histocompatibility reactions between maternal lymphocytes and infant Y chromosome-derived antigens reduce the risk of HIV transmission in boys.     

HIV-1 viral load and other risk factors for mother-to-child transmission of HIV-1 in a breast-feeding population in Cote d'Ivoire

Short-course antiretroviral regimens have been evaluated to reduce mother-to-child transmission of HIV in resource-limited settings. This report from Abidjan, Cote d'Ivoire, examines the risk factors for HIV transmission by 1 and 24 months among breast-feeding women. Eligible HIV-1-seropositive pregnant women enrolled in this randomized double-blind clinical trial were randomly assigned to receive either oral zidovudine (ZDV) (n = 126) prophylaxis or placebo (n = 124). Maternal prophylaxis began at 36 weeks of gestation (300 mg ZDV twice daily antepartum and 300 mg every 3 hours intrapartum); there was no neonatal prophylaxis component. The cumulative risk of transmission in the treatment group was 11.9% and 22.1% by 1 and 24 months, respectively. In adjusted analyses, viral load at enrollment was the strongest predictor of transmission (per log increment: odds ratio [OR] = 4.8, 95% confidence interval [CI]: 2.5-9.5 at 1 month; OR = 5.7; 95% CI: 3.1-10.8 at 24 months). Overall, ZDV prophylaxis was not significantly protective for infection at 1 or 24 months. Comparing ZDV with placebo following dichotomization of viral load (<50,000 vs. > or =50,000 copies/mL) at enrollment, however, there was a significant effect of ZDV seen only among those women with a low viral load at enrollment. The substantial risk of transmission despite ZDV prophylaxis, particularly among those with higher viral loads, underscores the need to find more effective regimens appropriate for use in resource-limited settings.     

High incidence of HIV-associated mortality among black and Hispanic infants and women of childbearing age in the United States 1990-2001

This study examined HIV-associated mortality in infants and in women of childbearing age (15-44 years) in the United States from 1990-2001. HIV-associated deaths were identified from national vital records using multiple cause-of-death data. HIV-associated mortality was higher in black and Hispanic women than in white women (rate ratio(black) = 13.5, 95% CI = 13.2-13.8; rate ratio(Hispanic) = 2.4, 95% CI = 1.9-3.2). Racial/ethnic trends in infant mortality rates from HIV reflected trends observed in women (rate ratio(black) = 16.3, 95% CI = 13.5-19.7; rate ratio(Hispanic) = 3.4, 95% CI = 3.3-3.5). HIV-associated mortality decreased in infants and in women of childbearing age following the availability of highly active antiretroviral therapy, but the decrease was considerably less marked in black women than in women of other racial/ethnic groups. Our findings indicate the need for increased emphasis on prevention of HIV mortality in black and Hispanic women and infants. Reduction of HIV prevalence in young women may also prevent infant mortality from HIV by reducing mother-to-child transmission.     

Predictors of nonadherence to single-dose nevirapine therapy for the prevention of mother-to-child HIV transmission

BACKGROUND: Adequate adherence is required for prevention of mother-to-child transmission of HIV (pMTCT) programs to be effective. We investigated predictors and extent of nonadherence to single-dose nevirapine. METHODS: Data on nevirapine intake and possible predictors were collected among 760 HIV-positive women with liveborn babies enrolled in a study in Lusaka, Zambia. RESULTS: Most (94%) women took nevirapine before delivery, and most (91%) newborns received it soon after delivery. Maternal nonadherence was associated with home births (odds ratio [OR]: 3.2; 95% confidence interval [CI]: 1.3 to 7.4), no high school education (OR: 2.4; 95% CI: 1.1 to 5.3), and low newborn birth weight (OR: 4.6; 95% CI: 1.3 to 20.1). Disclosure of HIV status and couples counseling was only associated with adherence among home births. Failure to administer nevirapine to the newborn was associated with birth at the tertiary hospital (OR: 7.2; 95% CI: 3.7 to 13.8), lower 5-minute Apgar scores (OR: 0.5; 95% CI: 0.4 to 0.7), and neonatal death (OR: 5.8; 95% CI: 2.0 to 16.3). CONCLUSIONS: Excellent adherence to single-dose nevirapine for pMTCT can be achieved. Nonadherence seems to be affected by place of birth and by poor health status of the newborn. Procedures to ensure that viable yet ill neonates receive nevirapine should be part of clinical protocols and training within pMTCT programs.     

Placental inflammation and perinatal transmission of HIV-1

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 baby's 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.     

Impact of human immunodeficiency virus infection in pregnant women on variant-specific immunity to malaria

Human immunodeficiency virus (HIV) increases susceptibility to Plasmodium falciparum infection, and this has most clearly been demonstrated in pregnant women. Variant surface antigens on the surfaces of erythrocytes infected with P. falciparum are major targets of protective immunity. We studied the impact of HIV infection on pregnant women's humoral immunity to variant surface antigens expressed by placental and pediatric isolates of P. falciparum. By flow cytometry, sera from HIV-infected women more frequently lacked antibodies to these antigens than sera from HIV-uninfected women. This difference was similar in magnitude for pediatric isolates (unadjusted odds ratio [OR] = 6.36; 95% confidence interval [CI] = 1.14, 35.32; P < 0.05) and placental isolates (unadjusted OR = 6.47; 95% CI = 0.75, 55.64; P < 0.10). We divided women into high and low responders on the basis of their antibody levels. After adjustment for CD4 count, maternal age, and gravidity, we found that HIV-infected women more frequently had low responses to both pediatric isolates (OR = 5.34; 95% CI = 1.23, 23.16; P = 0.025) and placental isolates (OR = 4.14; 95% CI = 1.71, 10.02; P = 0.002). The relative quantity of antibodies to both pediatric isolates (P = 0.035) and placental isolates (P = 0.005) was lower in HIV-infected women than in HIV-uninfected women. HIV infection has a broad impact on variant-specific immunity, which may explain the susceptibility of infected individuals to clinical malaria episodes.     

Wasting during pregnancy increases the risk of mother-to-child HIV-1 transmission

OBJECTIVES: To examine whether wasting during pregnancy, as measured by weight loss and low weight gain, is associated with increased mother-to-child transmission (MTCT) of HIV-1. METHODS: This was a cohort study in Dar es Salaam, Tanzania, among 957 HIV-1-infected pregnant women. Weight was measured at the first prenatal visit and every month thereafter until delivery. Weight loss was defined as a weekly rate of weight gain 0 and /=167 g/wk, weight loss during pregnancy was related to higher risk of intrauterine MTCT (adjusted relative risk [RR] = 2.32, 95% CI = 1.23-4.36, P = 0.009), HIV positive at birth or fetal death (RR = 2.13, 95% CI = 1.40-3.24, P = 0.0004), and HIV positive at birth or early neonatal death (RR = 1.96, 95% CI = 1.26-3.07, P = 0.003). The rate of weight gain during the 3rd trimester was inversely related to the risk of intrapartum/early breast-feeding transmission (adjusted P value, test for trend = 0.05). CONCLUSIONS: Weight loss during pregnancy increases the risk of early MTCT. Identifying causes of wasting during pregnancy may provide clues for new strategies to prevent MTCT.     

Maternal characteristics associated with antenatal, intrapartum, and neonatal zidovudine use in four US cities, 1994-1998

OBJECTIVES: To evaluate implementation of 1994 United States Public Health Service guidelines for zidovudine (ZDV) use in HIV-infected women and their newborns by describing the prevalence of use of perinatal ZDV and other antiretrovirals and by investigating determinants of not receiving perinatal ZDV. DESIGN/METHODS: The Perinatal AIDS Collaborative Transmission Study is a prospective cohort study designed to collect information related to mother-to-child HIV transmission that was conducted in New York City (NY), Newark (NJ), Baltimore (MD), and Atlanta (GA), U.S.A. The current analysis was restricted to infants born between July 1994 and June 1998. RESULTS: Utilization rates for antenatal, intrapartum, and neonatal ZDV increased from 41% to 70% during the 4-year period. Use of combination antiretrovirals increased from fewer than 2% of women in 1994 to 1995 to 35% in 1997 to 1998. Antenatal and neonatal ZDV use increased each year, but intrapartum ZDV use reached a plateau after 1996. Mother-infant pairs with the following characteristics were less likely to have received a complete 3-part ZDV regimen: older maternal age, CD4 count >500 cells/microl, preterm birth, cocaine or heroin use during pregnancy, positive newborn drug screen test result, and smoking or alcohol use during pregnancy. By multivariate logistic regression adjusted for hospital and year of birth, cocaine or heroin use during pregnancy (odds ratio [OR], 2.3; 95% confidence interval [CI], 1.6-3.3), maternal CD4 count (OR, 0.4; 95% CI, 0.2-0.8; comparing <200 with >500 cells/microl), and preterm birth (OR, 1.6; 95% CI, 1.1-2.5) remained independently associated with not receiving the complete ZDV regimen. CONCLUSIONS: ZDV use by pregnant HIV-infected women and their infants has increased dramatically since publication of the 1994 guidelines. Nevertheless, women who abuse substances, give birth preterm, or have less advanced immunosuppression, were at substantial risk of not receiving the complete ZDV regimen.     

Effect of maternal HIV and malaria infection on pregnancy and perinatal outcome in Zimbabwe

OBJECTIVE: To investigate the effect of isolated or concomitant infection with malaria and HIV on pregnancy and neonatal outcome. METHODS: Data were collected on pregnant women admitted during the rainy seasons in the obstetric division of a district referral hospital in northern Zimbabwe in 2000 and 2001. The effects of malaria and HIV infection were determined by multivariate analysis. RESULTS: The prevalence of HIV seropositivity and symptomatic malaria in 986 pregnant women was 8.3% and 14.7%, respectively. HIV-infected women were more likely to develop malaria attacks during pregnancy than seronegative women (odds ratio [OR] = 3.96, 95% confidence interval (CI): 2.42-6.46). Malaria and HIV infections were associated with increased risk of stillbirth (OR = 4.74, 95% CI: 1.34-16.78) and preterm delivery (OR = 4.10, 95% CI: 2.17-7.75), respectively. They were independently associated with increased risk of low birth weight (malaria: OR = 10.09, 95% CI: 6.50-15.65; HIV: OR = 3.16, 95% CI: 1.80-5.54) and very low birth weight (malaria: OR = 5.04, 95% CI: 1.00-25.43; HIV: OR = 10.74, 95% CI: 2.12-54.41), low Apgar score (malaria: OR = 4.45, 95% CI: 1.42-13.94; HIV: OR = 5.94, 95% CI: 1.66-21.30), and fetal growth restriction (malaria: OR = 3.98, 95% CI: 2.51-6.30; HIV: OR = 4.07, 95% CI: 2.40-6.92). Dual infection with malaria and HIV was associated with increased risk of maternal, perinatal, and early infant death. CONCLUSIONS: Women with single HIV or malaria infection have a significantly increased risk of adverse outcomes of pregnancy and childbirth. Dual infection has additional detrimental effects on maternal and infant survival in an area where HIV and malaria coexist.     

Independent effects of reported sexually transmitted infections and sexual behavior on HIV-1 prevalence among adult women, men, and teenagers in rural Uganda

OBJECTIVE: To assess whether sexually transmitted infections (STIs) and sexual behavior are independently associated with HIV-1 among adult women, men, and teenagers in rural Uganda. DESIGN: Cross-sectional survey. METHODS: All adults (13 years and older) residing in 18 communities were invited to participate. HIV status was determined from serum samples and data collected during confidential interview. Independent effects of risk factors for HIV were estimated using adjusted odds ratios (ORs) with 95% confidence intervals (CIs) from logistic regression. RESULTS: Women reporting genital ulcers in the last 12 months were over twice as likely to be HIV positive after adjustment for sociodemographic factors and number of lifetime sexual partners (OR, 2.5; 95% CI, 1.9-3.4). Equivalent associations were stronger for men (OR, 3.2; 95% CI, 2.2-4.7) but weaker for teenagers (OR, 2.0, 95% CI, 0.5-8.7). Number of lifetime sexual partners was associated ( p <.05) with HIV status for women, men, and teenagers independently of reported genital ulcers. Teenagers reporting casual partners were over four times ( p <.001), and men reporting condom use almost twice ( p <.001), as likely to be HIV positive. Neither history of genital discharge nor other measures of sexual behavior were independently related to HIV status. CONCLUSION: Reported STIs and sexual behavior are independently associated with HIV in rural Uganda. Community-based interventions to reduce HIV should target both and should include teenagers.     

Contraception use,family planning,and unprotected sex: few differences among HIV-infected and uninfected postpartum women in four US states

To describe pregnancy intentions and contraceptive use among a postpartum sample of women with and at risk for HIV infection, 258 HIV-seropositive and 228 HIV-seronegative women were recruited from prenatal clinics in 4 US states between June 1996-November 1998. Participants completed interviews at 24-40 weeks' gestation and at 6 months postpartum. At the 6-month interview, 78% of women reported vaginal sex, and 2% were pregnant. Among those not pregnant, 86% said that there was no likelihood of a pregnancy in the next 6 months. Condom use was reported by 68% of sexually active women; 65% of users reported consistent use. Those with HIV were more likely to report condom use, more likely to report condom use consistency, and less likely to report use of oral contraceptives than women without HIV (P < 0.05). In multivariate analysis, inconsistent condom use was associated with postpartum alcohol use (odds ratio [OR] 2.80; 95% CI = 1.34-5.84), with the respondent stating that a pregnancy would not be emotionally upsetting (OR 3.06; 95% CI = 1.41-6.59) and reporting an intention to terminate a pregnancy if one were to occur (OR 3.47; 95% CI = 1.58-7.60). HIV-seropositive women who had at least 1 child with HIV infection were less likely than seronegative women to report inconsistent condom use (OR 0.15; 95% CI = 0.03-0.76). Few differences were detected in reproductive behaviors as a function of HIV serostatus, although both cohorts engaged in unprotected sex. Counseling to decrease sexual risk behaviors should begin prior to or early in the postpartum period and include discussion of both reproductive and disease transmission issues.     

Mode of delivery and postpartum morbidity among HIV-infected women: the women and infants transmission study

Cesarean delivery before onset of labor and rupture of membranes (i.e., scheduled cesarean delivery) is associated with a lower risk of vertical transmission of HIV. The following a priori hypotheses were tested: among HIV-infected women, scheduled cesarean delivery is associated with a higher risk of postpartum morbidity, longer hospitalization, and a higher risk of rehospitalization than spontaneous vaginal delivery. Postpartum morbidity occurred following 178 of 1,186 (15%) of deliveries during 1990 to 1998 in The Women and Infants Transmission Study. The most commonly reported postpartum morbidity events were: fever without infection, hemorrhage or severe anemia, endometritis, urinary tract infection, and cesarean wound complications. Several time trends were observed: the median duration of ruptured membranes decreased (p < .001), intrapartum antibiotic use increased (p < .001), the median antepartum plasma HIV RNA concentration decreased (p < .001), and the incidence of any postpartum morbidity decreased (p = .02). With spontaneous vaginal delivery as the reference category, both scheduled (odds ratio [OR] = 4.69; 95% confidence interval [95% CI], 2.03-10.84), and nonscheduled (OR, 2.50; 95% CI, 1.24-5.04) cesarean deliveries were associated with fever without infection; with urinary tract infection (OR, 3.79; 95% CI 1.04-13.85; OR, 3.86; 95% CI, 1.55-9.60, respectively), and with any postpartum morbidity (OR, 3.19; 95% CI 1.69-6.00; OR, 4.10; 95% CI, 2.71-6.19, respectively). Nonscheduled cesarean deliveries were more likely to be complicated by endometritis (OR, 6.98; 95% CI, 3.53-13.78). Adjusted ORs relating mode of delivery and each of the outcomes (fever without infection, urinary tract infection, endometritis, and any postpartum morbidity) were similar to unadjusted ORs. Results of this analysis indicate scheduled cesarean delivery is associated with an increased risk of any postpartum morbidity and, specifically, postpartum fever without infection. The potential for postpartum morbidity with scheduled cesarean delivery should be considered in light of possible adverse events associated with other interventions to decrease the risk of vertical transmission of HIV. Counseling of HIV-infected pregnant women regarding scheduled cesarean delivery as a possible intervention to decrease maternal-infant transmission of HIV should include discussion of these results, as well as new data as they become available, regarding the incidence and severity of postpartum morbidity events among HIV-infected women according to mode of delivery.     

Placental pathology in malaria: a histological, immunohistochemical, and quantitative study

To characterize the histological changes in malarial placentas and their relationship with parity and maternal and cord parasitemias, we conducted a histological study on 1,179 placentas from Ifakara, Tanzania, an area with intense and perennial malaria transmission. Immunohistochemical and quantitative studies for CD45, fibrin, and villous area were performed in 60 cases. Four hundred fifteen placentas (35.2%) showed parasites (active infections); in 303 of them, parasites co-existed with pigment covered by fibrin (chronic infections), and in 112 only parasites were detected (acute infections). Four hundred seventy-five cases (40.3%) showed hemozoin deposition without parasites (past infections). Of women with parasitized placentas, 46.3% did not show parasites in the peripheral blood. Basal membrane thickening (P = .002), fibrinoid necrosis (P = .004), and prominence of syncytial knots (P = .031) were associated with active malarial infection. No quantitative differences for perivillous fibrin deposition or villous area were found. The most significant association with active malarial infection was intervillous infiltration by mononuclear inflammatory cells (P < .001). Chronic infections were associated with the most severe changes, particularly intervillous mononuclear inflammation (OR, 28.7; 95% CI = 16.0 to 51.5, P< .001). Past infections showed only minimal differences with noninfected placentas. Primiparas showed chronic infections more frequently than multiparas (52% v 15%, P < .001). They also showed significantly higher placental parasitemias and intervillous inflammatory infiltrate. In conclusion, placental histology is more sensitive than peripheral blood examination in detecting malarial infection during pregnancy. Most malarial infections recover during pregnancy, leaving few residual changes in the placenta. Intervillous inflammation is the most frequent finding associated with malaria and is especially severe in primiparas, suggesting that mechanisms other than immunosuppression are responsible for the high susceptibility in this group.     

Couples at risk: HIV-1 concordance and discordance among sexual partners receiving voluntary counseling and testing in Uganda

OBJECTIVE: To determine correlates of HIV-1 concordance for couples receiving voluntary HIV counseling and testing. DESIGN: Cross-sectional study of couples receiving voluntary HIV counseling and testing in Kampala, Uganda. METHODS: An interview and physical examination were conducted for 49 HIV-1-concordant (both partners infected with HIV) and 126 HIV-1-discordant (1 partner infected with HIV and 1 partner HIV negative) couples. Blood samples from all participants were tested for HIV-1 and syphilis serology. CD4 cell count and HIV load were characterized for all HIV-infected persons. Urine samples were tested for Neisseria gonorrhoeae and Chlamydia trachomatis using ligase chain reaction. Associations between couples' HIV status and key sociodemographic, behavioral, and biomedical factors were analyzed. RESULTS: Men in HIV-concordant couples were more likely than men in HIV-discordant couples to be living together with their sexual partner (odds ratio [OR], 11.3; 95% confidence interval [CI], 2.8-53.7; P=0.004), to be uncircumcised (OR, 4.5; 95% CI, 1.1-18.8; P=0.042), and to have higher HIV loads (OR for each log increase, 3.0; 95% CI, 2.0-4.7; P<0.001). Women in HIV-concordant couples were more likely than women in HIV-discordant couples to be living together with their sexual partner (OR, 19.0; 95% CI, 3.8-84.8), to have an uncircumcised male partner (OR, 6.5; 95% CI, 1.6-26.4), to have had a sexually transmitted disease in the 6 months before enrollment (OR, 1.9; 95% CI, 0.9-4.5), and to have higher HIV loads (OR for each log increase, 2.2; 95% CI, 1.5-3.2). CONCLUSIONS: Several behavioral and biologic risk factors were associated with HIV concordance for couples. Providing early sexually transmitted disease diagnosis and treatment, antiretroviral therapy, and specially designed counseling to HIV-discordant couples may help prevent HIV transmission in couples where being in a stable sexual relationship is a major risk factor for HIV infection.     

HIV infection in rural villages of Cameroon

OBJECTIVE: To evaluate HIV-1 antibody seroprevalence and risk factors for HIV seropositivity in rural areas of Cameroon. METHOD: The prevalences of HIV antibodies in 53 villages in rural Cameroon visited during May-October 2000 were determined with an HIV1/2 rapid assay, standard ELISA, and western blot. Demographic data and risk factors were elicited via face-to-face interviews with a structured questionnaire. RESULTS: HIV seroprevalence was 5.8% (243/4156, 95% confidence interval [CI] = 5.1-6.6) overall, 6.3% (151/2394, 95% CI = 5.4-7.4) among females and 5.2% (92/1762, 95% CI = 4.3-6.4) among males. HIV seroprevalence among persons aged 15 - 70 years did not differ significantly by province (5.6% in Center, 4.5% in East, 6.9% in South, and 5.8% in South-West) ( =.10). Analysis of age- and gender-standardized prevalence by village across provinces indicated a near-significant difference (nonparametric Wilcoxon signed rank test, =.06), with highest prevalence in South-West, followed by South, Center, and East. Multivariate analysis revealed that single women were significantly more likely to be HIV seropositive than were married or widowed women. Women with a history of sexual relations while traveling were at significantly increased risk of HIV seropositivity (OR adjusted for age and marital status = 2.4, 95% CI = 1.4-9.7). Among men, those who reported ever having a sexually transmitted disease were at significantly increased risk of HIV-seropositivity (OR adjusted for age = 1.8, 95% CI = 1.1-2.8). CONCLUSION: We have documented a wide range of HIV prevalences among rural villages of Cameroon. Age, marital status (in women) and sexual risk factors appear to be associated with HIV infection in this setting.     

Polymorphisms in methionine synthase reductase and betaine-homocysteine S-methyltransferase genes: risk of placental abruption

OBJECTIVES: Methionine synthase reductase (MTRR) and betaine-homocysteine S-methyltransferase (BHMT) are two enzymes that regulate homocysteine metabolism. Elevated homocysteine (hyperhomocysteinemia) is associated with adverse pregnancy outcomes and vascular disease. We assessed whether polymorphisms in MTRR (66A-->G; I22M) and BHMT (742G-->A; R239Q) were associated with abruption. We further evaluated whether homocysteine levels differed between cases and controls for MTRR and BHMT genotypes. METHODS: Data were derived from the New Jersey Placental Abruption Study (NJ-PAS)-an ongoing, multicenter, case-control study since August 2002. Women with a clinical diagnosis of abruption were recruited as incident cases (n=196), and controls (n=191) were matched to cases based on maternal race/ethnicity and parity. Total plasma homocysteine concentrations were evaluated in a subset of 136 cases and 136 controls. DNA was genotyped for the MTRR and BHMT polymorphisms. RESULTS: Frequencies of the minor allele of MTRR were 40.8% and 42.2% in cases and controls, respectively (adjusted OR 0.79, 95% CI 0.45, 1.40). The corresponding rates for BHMT were 33.9% and 31.7%, respectively (adjusted OR 1.93, 95% CI 0.99, 4.09). Distributions for the homozygous mutant form of MTRR were similar between cases and controls (OR 1.18, 95% CI 0.62, 2.24). The rate of homozygous mutant BHMT genotype was 2.8-fold (OR 2.82, 95% CI 1.84, 4.97) higher in cases than controls. Stratification of analyses based on maternal race did not reveal any patterns in association. CONCLUSIONS: In this population, there was an association between the homozygous mutant form of BHMT (742G-->A) polymorphism and increased risk for placental abruption.     

Incidence of HIV infection in stable sexual partnerships: a retrospective cohort study of 1802 couples in Mwanza Region,Tanzania

OBJECTIVE: To describe the dynamics of HIV transmission in stable sexual partnerships in rural Tanzania. DESIGN: Retrospective cohort study nested within community-randomized trial to investigate the impact of a sexually transmitted disease treatment program. METHODS: A cohort of 1802 couples was followed up for 2 years, with the HIV status of each couple assessed at baseline and follow-up. RESULTS: At baseline, 96.7% of couples were concordant-negative, 0.9% were concordant-positive, 1.2% were discordant with the male partner being HIV-positive, and 1.2% were discordant with the female partner being HIV-positive. Individuals living with an HIV-positive partner were more likely to be HIV-positive at baseline (women: odds ratio [OR] = 75.7, 95% confidence interval [CI]: 33.4-172; men: OR = 62.4, CI: 28.5-137). Seroincidence rates in discordant couples were 10 per 100 person-years (py) and 5 per 100 py for women and men, respectively (rate ratio [RR] = 2.0, CI: 0.28-22.1). In concordant-negative couples, seroincidence rates were 0.17 per 100 py in women and 0.45 per 100 py in men (RR = 0.38, CI: 0.12-1.04). Individuals living in discordant couples were at a greatly increased risk of infection compared with individuals in concordant-negative couples (RR = 57.9, CI: 12.0-244 for women; RR = 11.0, CI: 1.2-47.5 for men). CONCLUSION: Men were more likely than women to introduce HIV infection in concordant-negative partnerships. In discordant couples, incidence in HIV-negative women was twice as high as in men. HIV-negative individuals in discordant partnerships are at high risk of infection, and preventive interventions targeted at such individuals are urgently needed.     

Age differences in sexual partners and risk of HIV-1 infection in rural Uganda

OBJECTIVES: To assess whether differences in age between sexual partners affect the risk of HIV infection in female adolescents and young adults. METHODS: A total of 6177 ever sexually active women aged 15 to 29 years completed a sociodemographic and sexual behavior questionnaire and provided a blood sample for HIV-1 serology. The age difference between partners was categorized as men 0 to 4 years older (referent group), 5 to 9 years older and 10 or more years older. HIV prevalence and incidence were assessed, and adjusted RR was estimated by multivariate regression. RESULTS: Prevalent HIV-1 infection in female participants increased with older male sexual partners. Among women aged 15 to 19 years, the adjusted risk of HIV infection doubled (RR = 2.04; 95% CI: 1.29-3.22) among those reporting male partners 10 or more years older compared with those with male partners 0 to 4 years older; among women 20 to 24 years of age, the RR was 1.24 (95% CI: 0.96-1.60). The attributable fraction (exposed) of prevalent HIV infection in women aged 15 to 24 years associated with partners 10 or more years older was 9.7% (95% CI: 5.2-14.0). HIV incidence did not increase with differences in age of partners. CONCLUSION: The age difference between young women and their male partners is a significant HIV risk factor, suggesting that high HIV prevalence in younger women is caused, in part, by transmission from older male partners.     

Risk factors for human herpesvirus 8 seropositivity in the AIDS Cancer Cohort Study.

BACKGROUND: Cigarette smoking has been associated with a decreased risk for AIDS-related and classical KS, but whether it is associated with decreased risk of human herpesvirus 8 (HHV-8) infection is unknown. STUDY DESIGN: We evaluated factors associated with HHV-8 seropositivity in 2795 participants (132 with KS) in the National Cancer Institute AIDS Cancer Cohort, including 1621 men who have sex with men (MSM), 660 heterosexual men and 514 women. Odds ratios (OR) and 95% confidence intervals were estimated using logistic regression models. RESULTS: Among non-KS subjects, HHV-8 seropositivity was 6%, 13% and 29% among women, heterosexual men and MSM, respectively. HHV-8 seropositivity was decreased in heavier (> or =1/2 pack/day) compared to lighter smokers among women (5% versus 8%; adjusted OR (aOR) 0.4; 95% CI 0.2-0.8) and MSM (27% versus 32%; aOR 0.7; 95% CI 0.6-1.0), but not among heterosexual men (12% versus 16%; aOR 0.7; 95% CI 0.4-1.2). HHV-8 seroprevalence was increased in heavier (> or =1 drink/day) compared to lighter consumers of alcohol among women (16% versus 4%; adjusted OR 5.2; 95% CI 2.3-12), but not among MSM (33% versus 28%; aOR 1.2; 95% CI 0.9-1.6) or heterosexual men (13% versus 13%; aOR 1.1; 95% CI 0.6-2.0). In analyses adjusted for smoking and drinking, HHV-8 seropositivity was positively associated with chlamydia infection (OR=4.3; 95% CI 1.2-13) and with marital status among women p(heterogeneity)=0.03, and with hepatitis (OR=1.6; 95% CI 1.2-2.1), gonorrhea (OR=1.5; 95% CI 1.1-1.9), genital warts (OR=1.5; 95% CI 1.1-2.0) and nitrate inhalant use (OR=1.7; 95% CI 1.3-2.3) among MSM. CONCLUSIONS: Inverse association of HHV-8 seropositivity with cigarette smoking may indicate protective effect of tobacco smoke on HHV-8 infection, whereas positive associations with alcohol may reflect either behavioral factors or biological effects modulating susceptibility. Smoking and drinking may influence KS risk, at least in part, by altering the natural history of HHV-8 infection.