Pregnancy outcomes in HIV-infected and uninfected women in rural and urban South Africa

OBJECTIVE: To describe pregnancy outcomes among clade C HIV-infected and uninfected women in South Africa. DESIGN: A longitudinal cohort study. METHODS: Pregnant women attending 9 rural/urban antenatal clinics were prospectively recruited and followed up. Women were seen at the clinic or at home after delivery on 4 occasions after enrollment: 2 times within the first 2 weeks of the newborn's life at home, and every 2 weeks thereafter until their first health clinic visit when the infant was 6 weeks old. RESULTS: A total of 3465 women were enrolled; 615 withdrew after delivery, moved away, or had a missing or indeterminate HIV status, leaving 2850 women (1449 HIV-infected women). Six women died after delivery and there were 17 spontaneous abortions and 104 stillbirths. An adverse pregnancy outcome was independently associated with HIV infection (adjusted odds ratio [AOR] = 1.63; P = 0.015), urban enrollment (AOR = 0.39; P = 0.020), and nonhospital delivery (AOR = 13.63; P < 0.001) as well as with a CD4 count <200 cells/mL among HIV-infected women (AOR = 1.86; P = 0.127). Among 2529 singleton liveborn babies, birth weight was inversely associated with maternal HIV (AOR = 1.45; P = 0.02) and maternal middle upper arm circumference (AOR = 0.93; P < 0.001). Early infant mortality was not significantly associated with maternal HIV (hazard ratio [HR] = 1.18; P = 0.52) but was with urban sites (HR = 0.34; P = 0.045). Low birth weight substantially increased mortality (AOR = 8.3; P < 0.001). HIV status of infants by 8 weeks of age (14.6%, 95% confidence interval: 12.5% to 17.0%) was inversely associated with maternal CD4 cell count and birth weight. CONCLUSIONS: HIV-infected women are at a significantly increased risk of adverse pregnancy outcomes. Low-birth-weight infants of HIV-infected and uninfected women are at substantially increased risk of dying.     

Selenium status, pregnancy outcomes, and mother-to-child transmission of HIV-1

BACKGROUND: Among HIV-infected pregnant women, low selenium status may increase risk of mother-to-child transmission (MTCT) of HIV and poor pregnancy outcomes (low birthweight, small for gestational age, preterm birth, and fetal death) through several mechanisms, such as by promoting maternal HIV disease progression, viral shedding in the genital tract, and development of mastitis. However, there is no direct epidemiologic evidence on these relations among HIV-infected pregnant women. OBJECTIVE: To investigate the association between selenium status during pregnancy and pregnancy outcomes, MTCT of HIV, and child mortality. DESIGN: Baseline plasma selenium measurements from HIV-positive pregnant women (n = 670) were obtained between 12-27 weeks of gestation and mother-child pairs were followed prospectively until 24 months after delivery. RESULTS: Low plasma selenium levels were associated with increased risks of fetal death, child death, and HIV transmission through the intrapartum route. Low selenium status was not associated with risks of low birthweight or preterm birth but was associated with an apparently lower risk of small for gestational age. CONCLUSION: Adequate selenium status may be beneficial for some but not all pregnancy outcomes. Further studies are needed to better understand the role of selenium status in pregnancy outcomes, HIV transmission, and child health.     

Mortality in HIV-infected and uninfected children of HIV-infected and uninfected mothers in rural Uganda

OBJECTIVE: To estimate 2-year mortality rates in HIV-1-infected and uninfected infants born to HIV and HIV mothers. METHODS: Data are from a prospective study in rural Rakai District, Uganda. Infant HIV status (determined by polymerase chain reaction) was evaluated at 1 to 6 weeks postpartum and during breast-feeding, and maternal HIV viral load and CD4 levels were measured at the postpartum visit. Multivariate Cox proportional hazards models and Kaplan-Meier survival analysis were used to assess survival of infants by maternal and infant HIV status and by quartiles of viral load. Log-rank tests were used to test the equality of survival functions. RESULTS: Of the 4604 pregnant women, 16.9% were HIV, and the proportion of children infected was 20.9%. Median survival of HIV-infected infants was 23 months. Two-year child mortality rates were 128 of 1000 children born to HIV mothers, 165.5 of 1000 uninfected children born to HIV mothers, and 540.1 of 1000 HIV-infected children (P < 0.0001). Compared with children of HIV mothers, the hazard of child mortality was 2.04 (P < 0.001) if the mother was HIV and 3.78 (P < 0.001) if the infant was also infected. In the adjusted model, the highest quartiles of log10 HIV viral load in infants and mothers were associated with significantly increased hazard of child mortality (hazard ratio [HR] = 8.54 and HR = 2.50, respectively). Maternal CD4 counts <200 cells/mL were also significant predictors of child mortality (HR = 2.61). A total of 67.6% of HIV-infected children with viral loads above the median died by the age of 2 years and are in need of early antiretroviral therapy (ART). CONCLUSIONS: More than half of HIV-infected infants died at less than 2 years of age. Therefore, ART may need to be initiated earlier in HIV-infected African children.     

Reduced mortality associated with breast-feeding-acquired HIV infection and breast-feeding among HIV-infected children in Zambia

OBJECTIVES: In developing countries, where mother-to-child transmission of HIV through breast-feeding is common, little is known about the impact of postpartum transmission on child survival. This study assessed whether children infected postpartum have longer survival from time of infection versus those infected during gestation or delivery. DESIGN: We used a prospective cohort study to analyze data from 213 HIV-infected children enrolled in a breast-feeding intervention trial in Lusaka, Zambia (2001 to 2004). METHODS: We compared mortality 1 year after HIV infection in children stratified by age of infection: 0 to 3 days (intrauterine [IU] group), 4 to 40 days (intrapartum/early postpartum [IP/EPP] group), and >40 days (postpartum [PP] group). RESULTS: A total of 61, 71, and 81 children were infected in the IU, IP/EPP, and PP groups, respectively. Children with intrauterine or intrapartum/early postpartum transmission had higher mortality over the first 12 months after infection than children with postpartum transmission (P = 0.001 and P = 0.006, respectively); no differences were detected between children with intrauterine and intrapartum/early postpartum transmission. Nearly 20% of the IU and IP/EPP groups died by 100 days after infection, whereas nearly 10% of the PP group had died by this time. After adjusting for birth weight, maternal CD4 cell count, breast-feeding, and maternal death, children infected postpartum had one quarter the mortality rate (hazard ratio [HR] = 0.27, 95% confidence interval [CI]: 0.15 to 0.50) of those infected in utero. Stopping breast-feeding increased mortality in infected children (HR = 3.1, 95% CI: 1.8 to 5.3). CONCLUSIONS: This study demonstrates a survival benefit among children infected postpartum versus children infected during pregnancy or delivery and a benefit to increased breast-feeding duration among infected children. Testing children for HIV early may provide a means to allow for earlier intervention.     

Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals

Mortality in HIV-infected patients has decreased dramatically since the introduction of highly active antiretroviral therapy (HAART). We analyzed progression to death in a population of 3678 antiretroviral treatment-naive patients from the ATHENA national observational cohort from 24 weeks after the start of HAART. Mortality was compared with that in the general population in the Netherlands matched by age and gender. Only log-transformed CD4 cell count (hazard ratio [HR] = 0.50, 95% confidence interval [CI]: 0.40 to 0.61 per unit increase) and plasma viral load (HR = 0.30, 95% CI: 0.15 to 0.60, HIV RNA level <100,000 vs. > or = 100,000 copies/mL) measured at 24 weeks and infection via intravenous drug use (IDU) (HR = 0.16, 95% CI: 0.10 to 0.26, non-IDU vs. IDU) were significantly associated with progression to death. For non-IDU patients with 600 x 10 CD4 cells/L and an HIV RNA level <100,000 copies/mL at 24 weeks, mortality was predicted to be 5.3 (95% CI: 3.5 to 8.4) and 10.4 (95% CI: 6.4 to 17.4) times higher than in the general population for 25-year-old men and women, respectively, and 1.15 (95% CI: 1.08 to 1.25) and 1.29 (95% CI: 1.16 to 1.50) times higher for 65-year-old men and women, respectively. Hence, mortality in HIV-infected patients with a good initial response to HAART is still higher than in the general population.     

Depressive symptoms increase risk of HIV disease progression and mortality among women in Tanzania

The effect of depression on HIV disease progression was examined among 996 HIV-positive Tanzanian women participating in a trial on micronutrients and pregnancy outcomes, vertical transmission, and disease progression. Depression and social support were measured 2 months after HIV screening and every 6 to 12 months thereafter. Depression measures from pregnancy and more than 12 months postpartum were included in this analysis. Participants' clinical condition and access to supportive individual or group counseling was assessed throughout the 6 to 8 years of follow-up. Cox proportional hazard models were used to estimate the time-varying effect of depression on progression to HIV clinical stage III/IV (World Health Organization) and all-cause mortality. Participation in group or individual counseling and baseline social support were also examined. More than half (57%) of the study sample had symptoms comparable with depression at least once during the follow-up period. Controlling for sociodemographic variables, psychosocial support, and clinical condition at enrollment, depression was associated with an increased risk of disease progression (HIV clinical stage III/IV [hazard ratio (HR) = 1.61, 95% confidence interval (CI): 1.28 to 2.03] and mortality [HR = 2.65, 95% CI: 1.89 to 3.71]). Depression is common among HIV-infected Tanzanian women and increases the risk of disease progression. Screening for depression and providing psychosocial interventions should be considered part of comprehensive HIV care.     

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.     

Determinants of HIV progression and assessment of the optimal time to initiate highly active antiretroviral therapy: PISCIS Cohort (Spain)

OBJECTIVE: We analyze the factors related to progression to AIDS or death in HIV-infected patients from the Proyecto para la Informatización del Seguimiento Clínico epidemiológico de los pacientes con Infección por VIH/SIDA (PISCIS) Cohort and we assess the optimal time to initiate highly active antiretroviral therapy (HAART) taking lead time into account. METHODS: We selected naive patients who were AIDS-free and initiated HAART after January 1998. Statistical analyses were performed using Cox proportional hazards models. Lead time was defined as the time it took the deferred group with an early disease stage to reach the later stage. The analysis accounting for lead time was performed using multiple imputation methods based on estimates from the pre-HAART period as described elsewhere. RESULTS: Multivariate analysis on 2035 patients (median follow-up = 34.3 months) showed significantly higher hazard ratios (HRs) for a CD4 count <200 cells/microL (HR = 3.79, 95% confidence interval [CI]: 2.18 to 6.57), HIV-1 RNA level >100,000 copies/mL (HR = 1.84, 95% CI: 1.26 to 2.69), and hepatitis C virus (HCV) coinfection (HR = 2.40, 95% CI: 1.65 to 3.49), whereas a lower risk was found for those who started HAART between January 2001 and June 2004 (HR = 0.55, 95% CI: 0.30 to 0.90). When lead time and unseen events were included, we found a higher risk of progression to AIDS among patients who deferred treatment when the CD4 count reached <200 cells/microL (HR = 2.97, 95% CI: 1.91 to 4.63) and 200 to 350 cells/microL (HR = 1.85, 95% CI: 1.03 to 3.33) compared with those who started treatment with CD4 counts from 200 to 350 cells/microL and >350 cells/microL, respectively. CONCLUSIONS: Advanced HIV disease, HCV coinfection, and early HAART period were determinants of AIDS progression or death. Lead-time analysis in asymptomatic HIV-infected patients suggests that the best time to start HAART is before the CD4 count falls to lower than 350 cells/microL.     

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.     

Morbidity among HIV-1-infected mothers in Kenya: prevalence and correlates of illness during 2-year postpartum follow-up

BACKGROUND: Much of the burden of morbidity affecting women of childbearing age in sub-Saharan Africa occurs in the context of HIV-1 infection. Understanding patterns of illness and determinants of disease in HIV-1-infected mothers may guide effective interventions to improve maternal health in this setting. METHODS: We describe the incidence and cofactors of comorbidities affecting peripartum and postpartum HIV-1-infected women in Kenya. Women were evaluated by clinical examination and standardized questionnaires during pregnancy and for up to 2 years after delivery. RESULTS: Five hundred thirty-five women were enrolled in the cohort (median CD4 count of 433 cells/mm) and accrued 7736 person-months of follow-up. During 1-year follow-up, the incidence of upper respiratory tract infections was 161 per 100 person-years, incidence of pneumonia was 33 per 100 person-years, incidence of tuberculosis (TB) was 11 per 100 person-years, and incidence of diarrhea was 63 per 100 person-years. Immunosuppression and HIV-1 RNA levels were predictive for pneumonia, oral thrush, and TB but not for diarrhea; CD4 counts <200 cells/mm(3) were associated with pneumonia (relative risk [RR] = 2.87, 95% confidence interval [CI]: 1.71 to 4.83), TB (RR = 7.14, 95% CI: 2.93 to 17.40) and thrush. The risk of diarrhea was significantly associated with crowding (RR = 1.86, 95% CI: 1.19 to 2.92) and breast-feeding (RR = 1.71, 95% CI: 1.19 to 2.44). Less than 10% of women reported hospitalization during 2-year follow-up; mortality risk in the cohort was 1.9% and 4.8% for 1 and 2 years, respectively. CONCLUSIONS: Mothers with HIV-1, although generally healthy, have substantial morbidity as a result of common infections, some of which are predicted by immune status or by socioeconomic factors. Enhanced attention to maternal health is increasingly important as HIV-1-infected mothers transition from programs targeting the prevention of mother-to-child transmission to HIV care clinics.     

Herpes zoster in women with and at risk for HIV: data from the Women's Interagency HIV Study

BACKGROUND: Herpes zoster occurs at all CD4 cell counts in HIV-infected adults. It was hypothesized that even in the era of highly active antiretroviral therapy (HAART), zoster risk is higher in HIV-infected than uninfected women. METHODS: Generalized estimating equations modeled self-reported occurrence of zoster between semiannual visits among 1832 HIV-infected and 489 HIV-uninfected women in the Women's Interagency HIV Study followed for up to 7.5 years. RESULTS: A total of 337 (18.4%) HIV-infected and 7 (1.4%) HIV-uninfected women reported zoster at some time during follow-up. Using HIV-infected women with CD4 >750 cells/microL as the reference category, the odds ratios for reporting zoster since the prior visit were: 1.43 (95% CI 0.86-2.37) for CD4 500-749 cells/microL, 2.07 (95% CI 1.27-3.38) for CD4 350-499 cells/microL, 2.72 (95% CI 1.66-4.46) for CD4 200-349 cells/microL, and 3.16 (95% CI 1.92-5.18) for CD4 <200 cells/microL, compared with 0.11 (95% CI 0.046-0.26) for HIV-uninfected women. In multivariate analyses using visits from all HIV-infected women and only those who initiated HAART, lower CD4 cell count was more strongly associated with zoster incidence than were other clinical indicators. CONCLUSIONS: Herpes zoster is associated with degree of immunosuppression in HIV-infected women, but even women with high CD4 counts are at greater risk of zoster than HIV-uninfected women.     

Anemia is an independent predictor of mortality and immunologic progression of disease among women with HIV in Tanzania

OBJECTIVES: To examine the association of anemia with mortality and disease progression among a cohort of women with HIV in Dar es Salaam, Tanzania. METHODS: Time to all-cause death, AIDS-related death, and a 50% decrease in CD4 cell count among 1078 HIV-positive pregnant women enrolled in a clinical trial of vitamin supplementation from 1995-2003. RESULTS: Adjusted models showed that anemia was associated with an increased risk of all-cause mortality (relative hazard [RH]: 2.06, 95% CI: 1.52 to 2.79 for moderate anemia and RH: 3.19, 95% CI: 2.23 to 4.56 for severe anemia) and AIDS-related mortality (RH: 2.21, 95% CI: 1.53 to 3.19 for moderate anemia and RH: 3.47, 95% CI: 2.25 to 5.33 for severe anemia), independent of CD4 cell count, World Health Organization clinical stage, age, pregnancy, vitamin supplementation, and body mass index. Anemia was also associated with a more rapid decline in CD4 counts, measured as time to a 50% drop in CD4 cell count from baseline. Erythrocyte characteristics suggestive of iron deficiency were also associated with all-cause and AIDS-related death and a 50% decline in CD4 cell count. CONCLUSIONS: Anemia is an independent predictor of mortality and disease progression in this cohort. Screening for anemia, coupled with prevention and treatment efforts, should be included in HIV care initiatives, particularly those that target women.     

Micronutrient levels and HIV disease status in HIV-infected patients on highly active antiretroviral therapy in the Nutrition for Healthy Living cohort

BACKGROUND: Low serum micronutrient levels were common before widespread use of highly active antiretroviral therapy (HAART) and were associated with adverse outcomes. Few data are available on micronutrient levels in subjects taking HAART. OBJECTIVE: To determine the prevalence of low serum retinol, alpha-tocopherol, zinc, and selenium in HIV-infected subjects taking HAART and to assess the association of micronutrient levels with HIV disease status. DESIGN: Cross-sectional. SETTING: Nutrition for Healthy Living (NFHL) study. PARTICIPANTS: HIV-infected subjects on HAART. METHODS: Retinol, alpha-tocopherol, zinc, and selenium were determined in frozen serum samples from 171 men and 117 women. Low serum levels were defined as retinol <30 microg/dL, selenium <85 microg/L, alpha-tocopherol <500 microg/dL, and zinc <670 microg/L. Association of micronutrient quartiles with CD4 cell count, CD4 count <200 cells/mm, HIV viral load (VL), and undetectable VL was assessed using adjusted multivariate regression. RESULTS: Five percent of men and 14% of women had low retinol, 8% of men and 3% of women had low selenium, and 7% of men and no women had low alpha-tocopherol. Forty percent of men and 36% of women had low zinc, however. Subjects in the upper quartiles of zinc had lower log VL levels than those in the lowest quartile (significant for women). Subjects in the upper quartiles of selenium also tended to have lower VL levels compared with those in the lowest quartile. Surprisingly, women in the upper quartiles of retinol had higher log VLs than those in the lowest quartile. There was no significant association of any micronutrient with CD4 cell count or likelihood of CD4 count <200 cells/mm. The level of CD4 cell count influenced the association of retinol with log VL in men, however. In men with CD4 counts >350 cells/mm, those with higher retinol had higher log VLs compared with the lowest quartile, whereas in men with CD4 counts <350, those with higher retinol levels had lower log VLs compared with the lowest quartile. CONCLUSIONS: Low retinol, alpha-tocopherol, and selenium are uncommon in HIV-infected subjects on HAART. Zinc deficiency remains common, however. Decreased retinol levels in women and in men with CD4 counts >350 cells/mm and increased zinc and selenium levels in both genders may be associated with improved virologic control.     

Efavirenz in human breast milk, mothers', and newborns' plasma

BACKGROUND AND METHODS: Highly active antiretroviral therapy with efavirenz (EFV) has been prescribed to HIV-positive pregnant women in Rwanda (HIV status 1 and CD4 cell count > 350 cells/mm) during the last trimester of pregnancy and for 6 months after delivery. The EFV concentrations in maternal plasma, breast milk and in newborns' plasma of 13 women and their children between 6 weeks and 6 months post partum are reported. RESULTS: Results show a mean EFV plasma concentration of 6.55 mg/L in maternal plasma, 3.51 mg/L in skim milk, and 0.85 mg/L in infant plasma. Significant linear correlations between maternal plasma and skim milk (r = 0.8666, P < 0.0001) and between skim milk and infant plasma (r = 0.6646, P < 0.02) were found, but no significant correlation was observed between maternal and infant plasma concentrations (P > 0.05). CONCLUSIONS: After 6 months of breast-feeding, no child out of the 13 had been infected with HIV and all had good psychomotor and growth development. Our results suggest that EFV may be an alternative to nevirapine (NVP) during the third trimester of pregnancy and during the breast-feeding period. Further studies on larger groups of newborns will be necessary to get a better understanding of possible prophylactic protection of the newborns by highly active antiretroviral therapy with EFV given to the mothers.     

Impact of highly active antiretroviral therapy on anemia and relationship between anemia and survival in a large cohort of HIV-infected women: Women's Interagency HIV Study

BACKGROUND: Anemia is common in HIV-infected individuals and may be associated with decreased survival. OBJECTIVE: To ascertain the impact of highly active antiretroviral therapy (HAART) on anemia and the relationship between anemia and overall survival in HIV-infected women. METHODS: A prospective multicenter study of HIV-1 infection in women. Visits occurred every 6 months, including a standardized history, physical examination, and comprehensive laboratory evaluation. The setting was a university-affiliated clinic at 6 sites in the United States. Participants were 2056 HIV-infected women from the Women's Interagency HIV Study (WIHS). The outcome measure was anemia, defined as hemoglobin (Hb) <12 g/dL. Survival analysis was based on overall mortality during the follow-up period. RESULTS: Among HIV-infected women who were not anemic at baseline, 47% became anemic by 3.5 years of follow-up. On multivariate analysis, the use of HAART was associated with resolution of anemia even when used for only 6 months (odds ratio [OR] = 1.45; P < 0.05). In the multivariate model, a CD4 cell count <200 cells/microL (OR = 0.56; P < 0.001); HIV-1 RNA level > or =50,000 copies/mL (OR = 0.65; P < 0.001), and mean corpuscular volume (MCV) value <80 fL (OR = 0.40; P < 0.001) were also associated with an inability to correct anemia. Similarly, use of HAART for 12 months or more was associated with a protective effect against development of anemia (OR = 0.71; P < 0.001). Among HIV-infected women, anemia was independently associated with decreased survival (hazard ratio [HR] = 2.58; P < 0.001). Other factors associated with decreased survival included a CD4 cell count <200 cells/microL (HR = 5.83; P < 0.001), HIV-1 RNA level > or = 50,000 copies/mL (HR = 2.12; P < 0.001), and clinical diagnosis of AIDS (HR = 2.83; P < 0.001). CONCLUSIONS: Anemia is an independent risk factor for decreased survival among HIV-infected women. HAART therapy for as little as 6 months is associated with resolution of anemia.     

Transmission of HIV-1 through breastfeeding among women in Dar es Salaam,Tanzania

BACKGROUND: Transmission of HIV-1 through breastfeeding is a major problem, although its timing is not well characterized. METHODS: The authors examined the timing and correlates of HIV-1 transmission through breastfeeding among 1078 HIV-infected pregnant women from Dar es Salaam, Tanzania enrolled in a trial to examine the effect of vitamin A and other vitamin supplements on mother-to-child transmission of HIV-1 and other health outcomes. Cumulative incidence was measured among children of women not randomized to vitamin A (n = 312), given the higher risk of infection observed among those in the vitamin A arm. For analyses of correlates, data from all children not infected by age 6 weeks were used (p = 659). RESULTS: Mean duration of breastfeeding was 20.3 months (SD = 4.4 months; median = 20.5 months). Thirty-seven infections were observed during 4372 child-months of follow-up evaluation, or 10.2 cases per 100 child-years. Infection risk by age 4 months was 3.8% (95% confidence interval [CI], 1.6%-6.1%) and increased to 17.9% (95% CI, 11.2%-24.5%) by age 24 months. In a multivariate proportional hazards model, high maternal viral load (p =.0001), low CD4 cell count (p =.004), and high maternal erythrocyte sedimentation rate (ESR; p=.004) were significant predictors of transmission of HIV-1 through breastfeeding. Mothers who had breast lesions during pregnancy were 2.00 times more likely to transmit the virus during breastfeeding than mothers without these lesions (95% CI, 1.29-3.08; p=.002). CONCLUSIONS: The rate of breastfeeding transmission of HIV-1 is high, and early weaning is likely to be associated with reduced transmission. Antiretroviral drugs given to HIV-infected mothers are likely to reduce the risk of breastfeeding transmission. In their absence, interventions that enhance immune reconstitution, such as micronutrient supplements, may be beneficial against transmission. Methods to prevent and treat nipple cracks and mastitis may also be important.     

Impact of neighborhood-level socioeconomic status on HIV disease progression in a universal health care setting

OBJECTIVES: The objectives of this study were to examine neighborhood measures of socioeconomic status and their effect on the risk of mortality among HIV-positive persons accessing and not accessing treatment, the effects of late access to treatment by CD4 cell count, and survival among those who accessed treatment. METHODS: We limited our analysis to the era of highly active antiretroviral therapy (HAART). We used individual-level patient and clinical characteristics and neighborhood-level socioeconomic data to address our objectives. The Pearson chi2 and Wilcoxon sign rank tests were used to compare mortality among HIV-positive persons accessing and not accessing treatment, logistic regression models were used to compare persons who accessed treatment with low CD4 cell counts (<50 cells/mm(3)) with those who accessed treatment earlier (CD4 count > or =50 cells/mm(3)), and Weibull survival models were used to compare mortality among those who accessed treatment. RESULTS: Forty percent of people who died from HIV/AIDS-related causes never accessed treatment. Among those who accessed treatment, 16% did so when their CD4 counts were <50 cells/mm(3). Unemployment was associated with delayed access to treatment (odds ratio = 1.41, 95% confidence interval [CI]: 1.14 to 1.74). Postsecondary education (hazard ratio [HR] = 0.80, 95% CI: 0.71 to 0.91) and percent of residents below the poverty line (HR = 1.07, 95% CI: 1.01 to 1.13) were associated with mortality. CONCLUSIONS: In a setting where treatment for HIV is free of charge, a significant number of HIV-positive persons did not access HAART. Low socioeconomic status was associated with this delay and with increased mortality among persons receiving HAART. Social and health policy initiatives, beyond free and universal health care, are required to optimize access to HAART.     

Infant CD4 C868T polymorphism is associated with increased human immunodeficiency virus (HIV-1) acquisition

The C868T single nucleotide polymorphism (SNP) in the CD4 receptor encodes an amino acid change that could alter its structure and influence human immunodeficiency virus (HIV‐1) infection risk. HIV‐1‐infected pregnant women in Nairobi were followed with their infants for 1 year postpartum. Among 131 infants, those with the 868T allele were more likely than wild‐type infants to acquire HIV‐1 overall [hazard ratio (HR) = 1·92, 95% confidence interval (CI) 1·05, 3·50, P = 0·03; adjusted HR = 2·03, 95% CI 1·03, 3·98, P = 0·04], after adjusting for maternal viral load. This SNP (an allele frequency of ～15% in our cohort) was associated with increased susceptibility to mother‐to‐child HIV‐1 transmission, consistent with a previous study on this polymorphism among Nairobi sex workers.     

Survival in children with perinatal HIV infection and very low CD4 lymphocyte counts

OBJECTIVES: To evaluate clinical conditions associated with mortality in HIV-infected children with CD4+ counts <100 cells/microl. METHODS: The Pediatric Spectrum of HIV Disease Project is a longitudinal medical record review study with eight study sites in the United States, which have been enrolling children since 1989. Survival time from baseline very low CD4 count (<100 cells/microl) to death was estimated using the Kaplan-Meier method. Cox proportional hazards models were used to evaluate the effect of clinical variables on mortality. RESULTS: Of 522 children (>/=1 year of age) with serial CD4+ T-lymphocyte measurements, the median age at the first very low CD4 count was 4.8 years. The estimated median survival following the first very low CD4 count was 36 months. The following factors present at the first very low CD4 count were independently associated with a higher risk of death: younger age, weight-for-age >2 standard deviations below the mean, and previously diagnosed AIDS. The subsequent development of cytomegalovirus (CMV)-associated disease, Mycobacterium avium intracellulare (MAI) infection, wasting syndrome, or esophageal candidiasis was also independently associated with a higher risk of death. CONCLUSION: Survival in HIV-infected children with very low CD4 counts before introduction of highly active antiretroviral therapy was highly variable. Poor nutritional status and the development of CMV disease or MAI infection were associated with the shortest survival times.     

Elevated iron status strongly predicts mortality in West African adults with HIV infection

OBJECTIVE: To comprehensively assess iron status and determine whether elevated iron status, like anemia, predicts mortality. METHODS: We followed 1362 Gambian adults (53% female) in an HIV-seroprevalent clinic-based cohort over 11.5 years to ascertain all-cause mortality. Baseline iron status (iron, soluble transferrin receptor [sTfR], transferrin, ferritin, transferrin saturation, log [transferrin receptor: ferritin]), age, gender, ethnicity, hemoglobin, body mass index, HIV type, absolute CD4 count, malaria status, and [alpha]-(1)-antichymotrypsin were measured. RESULTS: The mortality rate was 25.9/100 person-years. Elevated iron universally predicted greater mortality compared to normal iron status for all iron status indices, with the exception of sTfR in unadjusted models. In fully adjusted models, transferrin (elevated vs. normal, hazard ratio [HR]: 1.77; 95% confidence interval [CI]: 1.30 to 2.42; P < 0.001), ferritin (elevated vs. normal, HR: 1.40; 95% CI: 1.07 to 1.83; P = 0.014), and the combined iron status index (highly elevated vs. normal, HR: 2.20; 95% CI: 1.16 to 4.18; P = 0.016) remained significant predictors. As expected, hemoglobin (Hb) concentration and absolute CD4 counts were each inversely associated with mortality. CONCLUSIONS: Elevated iron status predicts mortality in HIV infection, even after adjustment for immunosuppression and other confounders. This finding has implications in the clinical monitoring of disease progression and for iron-supplementation practices in areas of high HIV prevalence.