Background We evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine prophylaxis for 28 weeks during breast-feeding to reduce postnatal transmission of human immunodeficiency virus type 1 (HIV-1) in Malawi. Methods We randomly assigned 2369 HIV-1–positive, breast-feeding mothers with a CD4+ lymphocyte count of at least 250 cells per cubic millimeter and their infants to receive a maternal antiretroviral regimen, infant nevirapine, or no extended postnatal antiretroviral regimen (control group). All mothers and infants received perinatal prophylaxis with single-dose nevirapine and 1 week of zidovudine plus lamivudine. We used the Kaplan–Meier method to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were HIV-1–negative 2 weeks after birth. Rates were compared with the use of the log-rank test. Results Among mother–infant pairs, 5.0% of infants were HIV-1–positive at 2 weeks of life. The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group (5.7%) than in either the maternal-regimen group (2.9%, P = 0.009) or the infant-regimen group (1.7%, P<0.001). The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0% in the control group, 4.1% in the maternal-regimen group (P = 0.02), and 2.6% in the infant-regimen group (P<0.001). The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen (6.2%) than among those in either the nevirapine group (2.6%) or the control group (2.3%). Among infants receiving nevirapine, 1.9% had a hypersensitivity reaction. Conclusions The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding. (ClinicalTrials.gov number, NCT00164736.)

Objectives-The primary objective of this study was to elucidate mechanisms underlying the link between vitamin D status and cardiovascular disease by exploring the relationship between 25-hydroxyvitamin D (25-OH D), an established marker of vitamin D status, and vascular function in healthy adults. Background-Mechanisms underlying vitamin D deficiency-mediated increased risk of cardiovascular disease remain unknown. Vitamin D influences endothelial and smooth muscle cell function, mediates inflammation, and modulates the renin-angiotensin-aldosterone axis. We investigated the relationship between vitamin D status and vascular function in humans, with the hypothesis that vitamin D insufficiency will be associated with increased arterial stiffness and abnormal vascular function. Methods-We measured serum 25-OH D in 554 subjects. Endothelial function was assessed as brachial artery flow-mediated dilation, and microvascular function was assessed as digital reactive hyperemia index. Carotid-femoral pulse wave velocity and radial tonometry-derived central augmentation index and subendocardial viability ratio were measured to assess arterial stiffness. Results-Mean 25-OH D was 31.8 ± 14 ng/ml. After adjustment for age, sex, race, body mass index, total cholesterol, low-density lipoprotein, triglycerides, C-reactive protein, and medication use, 25-OH D remained independently associated with flow-mediated vasodilation (β = 0.1, p = 0.03), reactive hyperemia index (β = 0.23, p < 0.001), pulse wave velocity (β = −0.09, p = 0.04), augmentation index (β = −0.11, p = 0.03), and subendocardial viability ratio (β = 0.18, p = 0.001). In 42 subjects with vitamin D insufficiency, normalization of 25-OH D at 6 months was associated with increases in reactive hyperemia index (0.38 ± 0.14, p = 0.009) and subendocardial viability ratio (7.7 ± 3.1, p = 0.04), and a decrease in mean arterial pressure (4.6 ± 2.3 mm Hg, p = 0.02).

P regnancy-induced hypertension (PIH) or pregnancyaggravated hypertension (PAH) occurs in B7% of pregnant women, but whether medical treatment for mildto-moderate gestational hypertension is necessary is controversial. Knowledge of the long-term effects of prenatal exposure to antihypertensive medications is necessary so that risks to the infant can be weighed against benefits to the mother. This historical cohort study examined the functional development of children whose mothers were treated with labetalol or methyldopa or received no antihypertensive medication (bed rest only) for mildto-moderate gestational hypertension.The children studied were born at 12 Dutch hospitals (7 teaching hospitals, 5 general hospitals) whose mothers agreed to participate in the study. The mothers of these children had received prenatally either labetalol or methyldopa, or were treated only with bed rest for gestational hypertension. Functional development was measured at ages 4 to 10 year using standard tests that assessed IQ, concentration, memory, motor development, and behavior. Linear regression and the Pearson w 2 tests were used to compare the 3 groups.A total of 4000 hospital records were reviewed, from which data on 355 mother-child pairs were extracted; 99 were treated with labetalol, 101 with methyldopa, and 155 with bed rest. Of these 355 women, 275 agreed to allow their children to participate. Ultimately, 203 children met eligibility criteria, and 202 underwent testing. Pregnancy characteristics were determined from the patients' hospital records. Compared with the medication groups, the bedrest only patients had a later onset of hypertension, more often had PIH rather than PAH, and were less likely to receive any other drugs for their disorder. Nearly 20% of women in the labetalol and methyldopa groups received phenobarbital during the pregnancy. Infants in the bed-rest group were less likely than those in the medication groups to be born very preterm, but were more likely to be small for gestational age. The groups did not differ significantly for modes of delivery and the presence of other pregnancy complications. Treatment in the methyldopa group began earlier in the pregnancy compared to women in the labetalol group, and women receiving methyldopa more frequently received other medical treatments for PIH/PAH.There was a trend towards better gross motor development for children in the labetalol and bed-rest groups compared to youngsters in the methyldopa group, but this was not statistically significant. More children in the labetalol group had attention deficit hyperactivity disorder compared to children whose mothers received methyldopa or were only on bed rest during the pregnancy. Children in the methyldopa group were more likely to have sleeping problems as reported by their parents than children in the labetalol or bed-rest groups. Other aspects of functional development were not found to differ among the three groups.In this historical cohort study, prenatal exposure to labetalol was associated with an inc...

BackgroundCompared with whites, black Americans suffer from a disproportionate burden of cardiovascular disease (CVD). We hypothesized that racial differences in the prevalence of CVD could be attributed, in part, to impaired vascular function in blacks after adjustment for differences in risk factor burden.Methods and ResultsWe assessed vascular function in 385 black and 470 white subjects (mean age, 48±11 years; 45% male). Using digital pulse amplitude tonometry (EndoPAT) we estimated the reactive hyperemia index (RHI), a measure of microvascular endothelial function, and peripheral augmentation index (PAT‐AIx). Central augmentation index (C‐AIx) and pulse‐wave velocity (PWV) were measured as indices of wave reflections and arterial stiffness, respectively, using applanation tonometry (Sphygmocor). Compared with whites, blacks had lower RHI (2.1±0.6 versus 2.3±0.6, P<0.001), greater arterial wave reflections assessed as both PAT‐AIx (20.4±21.5 versus 17.0±22.4, P=0.01) and CAIx (20.8±12.3 versus 17.5±13.3, P=0.001), and greater arterial stiffness, measured as PWV (7.4±1.6 versus 7.1±1.6 m/s, P=0.001). After adjustment for traditional CVD risk factors, black race remained a significant predictor of lower RHI and higher PAT‐AIx and CAIx (all P<0.001) in all subjects and of higher PWV in men (P=0.01). Furthermore, these associations persisted in a subgroup analysis of “healthy” individuals free of CVD risk factors.ConclusionBlack race is associated with impaired microvascular vasodilatory function, and greater large arterial wave reflections and stiffness. Because impairment in these vascular indices may be associated with worse long‐term outcomes, they may represent underlying mechanisms for the increased CVD risk in blacks.

In order to evaluate strategies to reduce HIV transmission through breast milk and optimize both maternal and infant health among HIV-infected women and their infants, we designed and implemented a large, randomized clinical trial in Lilongwe, Malawi. The development of protocols for large, randomized clinical trials is a complicated and lengthy process often requiring alterations to the original research design. Many factors lead to delays and changes, including study site-specific priorities, new scientific information becoming available, the involvement of national and international human subject committees and monitoring boards, and alterations in medical practice and guidance at local, national, and international levels. When planning and implementing a clinical study in a resource-limited setting, additional factors must be taken into account, including local customs and program needs, language and socio-cultural barriers, high background rates of malnutrition and endemic diseases, extreme poverty, lack of personnel, and limited infrastructure. Investigators must be prepared to modify the protocol as necessary in order to ensure participant safety and successful implementation of study procedures. This paper describes the process of designing, implementing, and subsequently modifying the Breastfeeding, Antiretrovirals, and Nutrition, (BAN) study, a large, ongoing, randomized breastfeeding intervention trial of HIVinfected women and their infants conducted at a single site in Lilongwe, Malawi. We highlight some of the successes, challenges, and lessons learned at different stages during the conduct of the trial.