Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies

OBJECTIVE: To estimate the sex-specific effect of herpes simplex virus type 2 (HSV-2) on the acquisition of HIV infection. BACKGROUND: The increased number of longitudinal studies available since the last meta-analysis was published allows for the calculation of age- and sexual behaviour-adjusted relative risks (RR) separately for men and women. DESIGN: Systematic review and meta-analysis of longitudinal studies. METHODS: PubMed, Embase and relevant conference abstracts were systematically searched to identify longitudinal studies in which the relative timing of HSV-2 infection and HIV infection could be established. Where necessary, authors were contacted for separate estimates in men and women, adjusted for age and a measure of sexual behaviour. Summary adjusted RR were calculated using random-effects meta-analyses where appropriate. Studies on recent HSV-2 incidence as a risk factor for HIV acquisition were also collated. RESULTS: Of 19 eligible studies identified, 18 adjusted for age and at least one measure of sexual behaviour after author contact. Among these, HSV-2 seropositivity was a statistically significant risk factor for HIV acquisition in general population studies of men [summary adjusted RR, 2.7; 95% confidence interval (CI), 1.9-3.9] and women (RR, 3.1; 95% CI, 1.7-5.6), and among men who have sex with men (RR, 1.7; 95% CI, 1.2-2.4). The effect in high-risk women showed significant heterogeneity, with no overall evidence of an association. CONCLUSIONS: Prevalent HSV-2 infection is associated with a three-fold increased risk of HIV acquisition among both men and women in the general population, suggesting that, in areas of high HSV-2 prevalence, a high proportion of HIV is attributable to HSV-2.     

Use of intermittent preventive treatment for malaria in pregnancy in a rural area of western Kenya with high coverage of insecticide-treated bed nets

Kenya established intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) for malaria in pregnancy as national policy in 1998. We assessed the coverage of IPT among women who had recently delivered in a rural area of western Kenya with perennial malaria transmission and high coverage with insecticide treated nets (ITNs) through a cross-sectional, community-based survey in December 2002. Antenatal clinic (ANC) attendance was high (89.9% of the 635 participating women); 77.5% of attendees visited an ANC before the third trimester and 91.9% made more than one visit. Delivery of SP by the ANC was reported by 19.1% of all women but only 6.8% reported receiving more than one dose. Given the high rate of use of ANC services, if SP were given at each visit after the first trimester, the potential coverage of IPT (two doses of SP) would be 80.3% in this study population. ITNs were used by 82.4% of women during pregnancy, and almost all mothers (98.5%) who slept under an ITN shared the nets with their newborns after delivery. Women who thought malaria in pregnancy caused foetal problems were more likely to have used an ITN (adjusted odds ratio [AOR] 1.6, 95% confidence interval [CI] 1.0-2.4), and to have visited ANC more than once (AOR 2.4, 95% CI 1.2-4.7) compared to women who thought malaria in pregnancy was either not a problem or caused problems for the mother only. These findings illustrate the need for improved IPT coverage in this rural area. Identification and removal of the barriers to provision of IPT during ANC visits can help to increase coverage. In this area of Kenya, health messages stressing that foetal complications of malaria in pregnancy may occur in the absence of maternal illness may improve the demand for IPT.     

Prevalence of chronic hepatitis B and incidence of acute hepatitis B infection in human immunodeficiency virus-infected subjects

We determined incidence and risk factors for acute and chronic hepatitis B virus (HBV) infection and HBV vaccination rates among human immunodeficiency virus (HIV)-infected subjects from the Adult/Adolescent Spectrum of HIV Disease Project, during 1998-2001. Among 16,248 HIV-infected patients receiving care, the incidence of acute HBV was 12.2 cases/1000 person-years (316 cases), was higher among black subjects (rate ratio [RR], 1.4; 95% confidence interval [CI], 1.0-2.0), subjects with alcoholism (RR, 1.7; 95% CI, 1.2-2.3), subjects who had recently injected drugs (RR, 1.6; 95% CI, 1.1-2.4), and subjects with a history of AIDS-defining conditions (RR, 1.5; 95% CI, 1.2-1.9) and was lower in those taking either antiretroviral therapy (ART) with lamivudine (RR, 0.5; 95% CI, 0.4-0.6), ART without lamivudine (RR, 0.5; 95% CI, 0.3-0.7), or >/=1 dose of HBV vaccine (14% of subjects) (RR, 0.6; 95% CI, 0.4-0.9). Prevalence of chronic HBV was 7.6% among unvaccinated subjects. HBV rates in this population were much higher than those in the general population, and vaccination levels were low. HBV remains an important cause of comorbidity in HIV-infected persons, but ART and vaccination are associated with decreased disease.     

Study of bias in antenatal clinic HIV-1 surveillance data in a high contraceptive prevalence population in sub-Saharan Africa

OBJECTIVE: To describe patterns, sources and consequences of bias in antenatal clinic (ANC) HIV prevalence estimates in a high contraceptive prevalence population. BACKGROUND: HIV surveillance in Africa relies on data from pregnant women attending ANCs. HIV estimates from pregnant women understate female infection levels in low income, high fertility populations. Bias in high contraceptive use, delayed sexual debut populations remains undescribed. DESIGN AND METHOD: Comparison of parallel cross-sectional population and antenatal survey data from rural Zimbabwe, where 60% of women are recent contraceptive users. RESULTS: HIV prevalence in recently pregnant women (25.7%; n = 576) and all women (25.5%; n = 5138) is similar over the age-range 15-44 years. As in high fertility populations, HIV prevalence is higher in pregnant women at young ages and lower at older ages but the crossover point occurs later due to delayed sexual activity. HIV understatement at older ages due to HIV-associated infertility is mitigated by less HIV infection and less frequent ANC attendance in contraceptive users. The local ANC HIV prevalence estimate is lower [21.2%; n = 1215; risk ratio versus pregnant women in the general population, 0.8; 95% confidence interval (CI), 0.7-1.0], possibly because women from more remote areas are included. ANC estimates overstate the relative risk of HIV in more educated women (age-adjusted odds ratio, 1.1; 95% CI, 0.8-1.4 versus 0.7; 95% CI, 0.6-0.9). CONCLUSIONS: ANC estimates understate female HIV prevalence in this low fertility population but, here, the primary cause is not selection of pregnant women. ANC estimate adjustment procedures that control for contraceptive use and age at first sex are needed.     

Genetic diversity of HIV-1 in western Kenya: subtype-specific differences in mother-to-child transmission

BACKGROUND: Little is known about the impact of HIV-1 group M subtypes on mother-to-child transmission (MTCT) of HIV-1 in African settings where multiple HIV-1 group M subtypes are co-circulating. OBJECTIVE: To assess the role of subtype variation on MTCT. METHODS: HIV-1-infected women attending an antenatal clinic in western Kenya were enrolled for a prospective study (1996-2000) of MTCT. HIV-1 subtype analysis of p24gag and gp41env identified potential recombinants, and their role in MTCT was determined. RESULTS: Among 414 women for whom HIV-1 subtype and HIV transmission status were available, MTCT occurred in 80 (19.3%). MTCT rates were higher among women with subtype D compared with subtype A in either the gp41 region [31.6 versus 16.1%, relative risk (RR) 2.0, P=0.002] or p24 region (29.9 versus 18.0%, RR 1.7, P=0.02). Discordant subtype combinations were identified in 103 of the women (25.9%), and were associated with higher rates of MTCT (28.2 versus 17.0%, RR 1.7, P=0.01). In multivariate analysis, women with subtype combinations D/D, D/A, and A/D had an increased risk of MTCT (adjusted odds ratios 3.5, 2.5, 6.2; P=0.005, 0.05, and 0.0003, respectively) compared with A/A women after adjustment for maternal HIV viral load, placental malaria infection, episiotomy or perineal tear, and low birthweight. CONCLUSION: MTCT appears to be more common among mothers infected with subtype D compared with subtype A. Such differences in MTCT frequency may be caused by altered cellular tropism for placental cell types.     

Health care costs associated with clinic visits for prevention of mother-to-child transmission of HIV in Dar es Salaam,Tanzania

Early and appropriate antenatal care (ANC) is key for the effectiveness of prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV). We evaluated the importance of ANC visits and related service costs for women receiving option B⁺ to prevent mother-to-child transmission (MTCT) of HIV in Tanzania.A cost analysis from a health care sector perspective was conducted using routine data of 2224 pregnant women newly diagnosed with HIV who gave birth between August 2014 and May 2016 in Dar es Salaam, Tanzania. We evaluated risk of infant HIV infection at 12 weeks postnatally in relation to ANC visits (<4 vs ≥4 visits). Costs for service utilisation were estimated through empirical observations and the World Health Organisation Global Price Reporting Mechanism.Mean gestational age at first ANC visit was 22 (±7) weeks. The average number of ANC/prevention of MTCT visits among the 2224 pregnant women in our sample was 3.6 (95% confidence interval [CI] 3.6–3.7), and 57.3% made ≥4 visits. At 12 weeks postnatally, 2.7% (95% CI 2.2–3.6) of HIV exposed infants had been infected. The risk of MTCT decreased with the number of ANC visits: 4.8% (95% CI 3.6–6.4) if the mother had <4 visits, and 1.0% (95% CI 0.5–1.7) at ≥4. The adjusted MTCT rates decreased by 51% (odds ratio 0.49, 95% CI 0.31–0.77) for each additional ANC visit made. The potential cost-saving was 2.2 US$ per woman at ≥4 visits (84.8 US$) compared to <4 visits (87.0 US$), mainly due to less defaulter tracing.Most pregnant women living with HIV in Dar es Salaam initiated ANC late and >40% failed to adhere to the recommended minimum of 4 visits. Improved ANC attendance would likely lead to fewer HIV-infected infants and reduce both short and long-term health care costs due to less spending on defaulter tracing and future treatment costs for the children.     

The effect of dual infection with HIV and malaria on pregnancy outcome in western Kenya

OBJECTIVE: To determine the effect of dual infection with HIV and malaria on birth outcomes and maternal anaemia among women delivering at a large public hospital in Kisumu, western Kenya. SUBJECTS AND METHODS: Data on obstetric and neonatal characteristics, maternal and placental parasitaemia, and postpartum haemoglobin levels were collected from women enrolled in a cohort study of the interaction between malaria and HIV during pregnancy. RESULTS: Between 1996 and 1999, data were available from 2466 singleton deliveries. The maternal HIV seroprevalence was 24.3%, and at delivery 22.0% of the women had evidence of malaria. Low birthweight, preterm delivery (PTD), intrauterine growth retardation (IUGR) and maternal anaemia (haemoglobin < 8 g/dl) occurred in 4.6, 6.7, 9.8 and 13.8% of deliveries, respectively. Maternal HIV, in the absence of malaria, was associated with a 99 g (95% CI 52-145) reduction in mean birthweight among all gravidae. Malaria was associated with both IUGR and PTD, resulting in a reduction in mean birthweight of 145 g (95% CI 82-209) among HIV-seronegative and 206 g (95% CI 115-298) among HIV-seropositive primigravidae, but not among multigravidae. Both HIV and malaria were significant risk factors for postpartum maternal anaemia, and HIV-seropositive women with malaria were twice as likely to have anaemia than HIV-seronegative women with or without malaria. CONCLUSION: Women with dual infection are at particular risk of adverse birth outcomes. In areas with a moderate or high prevalence of HIV and malaria, all pregnant women should be the focus of malaria and anaemia control efforts to improve birth outcomes.     

Risk factors for osteonecrosis in HIV-infected patients: impact of treatment with combination antiretroviral therapy

BACKGROUND: Osteonecrosis was increasingly associated with HIV infection in the 1990s. It is unclear whether its risk increases with the duration of HIV infection, the duration of combination antiretroviral therapy (cART) or both. OBJECTIVE: To analyse factors associated with the rate of symptomatic osteonecrosis, particularly the relative impacts of the duration of HIV infection and the duration of cART, using the French Hospital Database on HIV, which comprises a large number of subjects with substantial follow-up. METHODS: Poisson regression model was used to identify factors associated with the rate of osteonecrosis among patients enrolled in 1996-2002. RESULTS: The study involved 56,393 subjects with a total follow-up of 229,031 person-years. Symptomatic osteonecrosis was diagnosed in 104 subjects with an incidence rate of 4.5/10,000 person-years. Multivariate analysis identified three factors associated with the rate of osteonecrosis: prior AIDS-defining illnesses [adjusted relative rate (RR), 3.1; 95% confidence interval (CI), 2.0-4.9], the CD4 cell nadir [RR, 1.6 (95% CI, 0.9-2.9) for CD4 cell count 50-199 cells/microl; RR, 1.8 (95% CI, 1.0-3.3) for CD4 cell count < 50 cells/microl; both relative to CD4 cell count > or = 200 cells/microl] and exposure to cART. Compared with unexposed patients, the RR of osteonecrosis ranged from 2.6 (95% CI, 1.2-5.9) in patients treated with cART for < 12 months to 5.1 (95% CI, 2.1-12.6) in patients treated for > or = 60 months. CONCLUSIONS: Osteonecrosis appears to be a complication of both HIV infection and cART.     

Early pregnancy levels of pregnancy-associated plasma protein a and the risk of intrauterine growth restriction, premature birth, preeclampsia, and stillbirth

The risk of adverse perinatal outcome among 8839 women recruited to a multicenter, prospective cohort study was related to maternal circulating concentrations of trophoblast-derived proteins at 8-14 wk gestation. Women with a pregnancy-associated plasma protein A (PAPP-A) in the lowest fifth percentile at 8-14 wk gestation had an increased risk of intrauterine growth restriction [adjusted odds ratio, 2.9; 95% confidence interval (CI), 2.0-4.1], extremely premature delivery (adjusted odds ratio, 2.9; 95% CI, 1.6-5.5), moderately premature delivery (adjusted odds ratio, 2.4; 95% CI, 1.7-3.5), preeclampsia (adjusted odds ratio, 2.3; 95% CI, 1.6-3.3), and stillbirth (adjusted odds ratio, 3.6; 95% CI, 1.2-11.0). The strengths of the associations were similar when the test was performed before 13 wk gestation or between 13 and 14 wk gestation. In contrast, levels of free beta-human CG, another circulating protein synthesized by the syncytiotrophoblast, were not predictive of later outcome in multivariate analysis. PAPP-A has been identified as a protease specific for IGF binding proteins. We conclude that control of the IGF system in the first and early second trimester trophoblast may have a key role in determining subsequent pregnancy outcome.     

Impact of hepatitis C infection on long-term mortality of injecting drug users from 1990 to 2002: differences before and after HAART

OBJECTIVE: To assess the impact of HIV and hepatitis C virus (HCV) infection on long-term mortality in injecting drug users (IDU). DESIGN: Community-based prospective cohort study. METHODS: Mortality data from follow-up in clinical sites and the Mortality Registry by December 2002 were collected for 3247 IDU who attended three centres for voluntary counselling and testing for HIV/AIDS, HCV and hepatitis B virus (HBV) in 1990-1996. Mortality rates by Poisson regression were adjusting for age, sex, duration of drug use, education, HBV and calendar period (1990-1997 and 1998-2002). RESULTS: Overall, 11.2% were HIV/HCV negative, 43.7% positive only for HCV and 45.1% positive for both. During 26 772 person-years of follow-up, 585 deaths were detected (2.19/100 person-years). Before 1997, HIV/HCV-positive subjects had a five-fold increase in risk of death [relative risk (RR), 5.4; 95% confidence interval (CI), 2.5-11.4] compared with those negative for both; after 1997, a three-fold increase was observed (RR, 2.7; 95% CI, 1.7-4.2). Being HCV positive/HIV negative was not associated with an increase in the risk of death either before (RR, 1.3; 95% CI, 0.6-2.9) or after (RR, 1.2; 95% CI, 0.8-1.9) 1997 compared with HCV/HIV negative. While increases in mortality were seen in those HCV/HIV negative (RR, 1.6; 95% CI, 0.7-3.7) and those only positive for HCV (RR, 1.5; 95% CI, 1.0-2.1), a 20% reduction among coinfected IDUs was observed after 1997 (interaction P = 0.033). CONCLUSIONS: HCV/HIV coinfection has had a large impact on mortality in IDU. After 1997, mortality increased in HIV negative/HCV positive subjects and decreased in HIV positive/HCV positive.     

Voluntary HIV counseling and testing acceptance, sexual risk behavior and HIV incidence in Rakai, Uganda

OBJECTIVE: To assess the acceptance of voluntary HIV counseling and testing (VCT) and the effects of VCT on sexual risk behavior and HIV acquisition in Rakai, Uganda. METHODS: In a rural cohort, 10 694 consenting adults were interviewed, provided blood for HIV testing and were offered free VCT by community resident counselors. The proportions receiving VCT and the adjusted risk ratio (adj. RR) of VCT acceptance were estimated by log binomial regression. Risk behaviors and HIV incidence per 100 person-years (PY) in HIV-negative acceptors and non-acceptors of VCT were assessed prospectively. RESULTS: Although 93% initially requested HIV results, 62.2% subsequently accepted VCT. VCT acceptance was lower among persons with no prior VCT [Adj. RR = 0.88; 95% confidence interval (CI), 0.85-0.90], individuals with primary education (adj. RR = 0.94; 95% CI, 0.90-0.99) or higher (adj. RR = 0.91; 95% CI, 0.87-0.97), individuals who were HIV-positive (adj. RR = 0.72; 95% CI, 0.68-0.76), and persons reporting condom use in the past 6 months (inconsistent users, adj. RR = 0.95; 95% CI, 0.90-0.99; consistent users, adj. RR = 0.88; 95% CI, 0.82-0.95). VCT acceptance was higher among the currently married (adj. RR = 1.14; 95% CI, 1.08-1.20) and previously married (adj. RR = 1.11; 95% CI, 1.04-1.18). Receipt of results was not significantly associated with age, gender, and self-perception of HIV risk. There were no significant differences in sexual risk behaviors, or in HIV incidence between acceptors (1.6/100 PY) and non-acceptors (1.4/100 PY) of VCT. CONCLUSION: In this rural cohort where VCT services are free and accessible, there is self-selection of individuals accepting VCT, and no impact of VCT on subsequent risk behaviors or HIV incidence.     

Predictors of mortality from type 2 diabetes mellitus in Canterbury, New Zealand; a ten-year cohort study

The aim was to establish mortality rates in a cohort of subjects with type 2 diabetes mellitus over 10 years in Canterbury, New Zealand (NZ) and to determine baseline prognostic factors. Subjects (447) with type 2 diabetes (208 male, 239 female; age range 30-82 years, median 62 years; of predominantly European origin) were characterised in a clinic survey in 1989. Individual status (dead or alive) at June 1 1999 (10 year follow-up) was ascertained. Mortality rates were compared with the general NZ population and the relative risk (RR) of baseline prognostic factors evaluated with Cox's proportional hazards model. At 10 years, 232 subjects were confirmed as alive and 187 as dead - only 28 were untraceable. Ten year survival was 55% (95% CI: 50-60) for the cohort, compared with 70% (95% CI: 65-75) at 6 years. Factors assessed at baseline (1989), that were independently prognostic of total mortality, included age (RR 2.0, 95% CI: 1.6-2.5), pre-existing coronary artery disease (CAD; RR 1.7, 95% CI: 1.2-2.4) and albuminuria (RR 1.58, 95% CI: 1.1-2.3). Glycated haemoglobin was not a significant predictor of total mortality, although was a predictor of CAD mortality in those subjects free of CAD in 1989 (RR 1.6, 95% CI: 1.1-2.3). In the latter subset, independent prognostic factors for CAD mortality also included age (RR 2.5, 95% CI: 1.7-3.8), hypertension (RR 1.9, 95% CI: 1.0-3.7), peripheral vascular disease (RR 2.4, 95% CI: 1.3-4.5) and smoking (RR 2.6, 95% CI: 1.2-5.8). Increased mortality in type 2 diabetic subjects is therefore attributable to multiple risk factors. Improved outcomes will depend on interventions targeted at glycaemic and all other remediable factors.     

Factors Associated With Isolated Right Heart Failure in Women: A Pilot Study From Western Kenya

BackgroundSmall observational studies have found that isolated right heart failure (IRHF) is prevalent among women of sub-Saharan Africa. Further, several risk factors for the development of IRHF have been identified. However, no similar studies have been conducted in Kenya.ObjectiveWe hypothesized that specific environmental exposures and comorbidities were associated with IRHF in women of western Kenya.MethodsWe conducted a case-control study at a referral hospital in western Kenya. Cases were defined as women at least 35 years old with IRHF. Control subjects were similarly aged volunteers without IRHF. Exclusion criteria in both groups included history of tobacco use, tuberculosis, or thromboembolic disease. Participants underwent echocardiography, spirometry, 6-min walk test, rest/exercise oximetry, respiratory health interviews, and human immunodeficiency virus (HIV) testing. Home visits were performed to evaluate kitchen ventilation, fuel use, and cook smoke exposure time, all surrogate measures of indoor air pollution (IAP). A total of 31 cases and 65 control subjects were enrolled. Surrogate measures of indoor air pollution were not associated with IRHF. However, lower forced expiratory volume at 1 s percent predicted (adjusted odds ratio [AOR]: 2.02, 95% confidence interval [CI]: 1.27 to 3.20; p = 0.004), HIV positivity (AOR: 40.4, 95% CI: 3.7 to 441; p < 0.01), and self-report of exposure to occupational dust (AOR: 3.9, 95% CI: 1.14 to 14.2; p = 0.04) were associated with IRHF. In an analysis of subgroups of participants with and without these factors, lower kitchen ventilation was significantly associated with IRHF among participants without airflow limitation (AOR: 2.63 per 0.10 unit lower ventilation, 95% CI: 1.06 to 6.49; p = 0.04), without HIV (AOR: 2.55, 95% CI: 1.21 to 5.37; p = 0.02), and without occupational dust exposure (AOR: 2.37, 95% CI: 1.01 to 5.56; p = 0.05).ConclusionsIn this pilot study among women of western Kenya, lower kitchen ventilation, airflow limitation, HIV, and occupational dust exposure were associated with IRHF, overall or in participant subgroups. Direct or indirect causality requires further study.     

Hypertension as a risk factor for cardiovascular morbidity and mortality in an elderly German population; the prospective STEPHY II study. Starnberg Study on Epidemiology of Parkinsonism and Hypertension in the Elderly.

AIM: To prospectively study the relationship between blood pressure levels and subsequent cardiovascular morbidity and mortality in a population aged 65 years and older. METHODS: Participants of the 1992 baseline survey of the population-based Starnberg Study on Epidemiology of Parkinsonism and Hypertension in the Elderly (STEPHY, 394 men and 588 women above age 65) were followed up for 3 years. Total mortality was assessed by official death data. Cardiovascular morbidity, that is, the occurrence of non-fatal events (new cases of acute myocardial infarction, angina pectoris, stroke, and heart failure) could be assessed in 681 of the 863 survivors by a second interview and analysis of general practitioners' records. The mortality and morbidity risks were compared for hypertensives (baseline blood pressure > or = 160/95 mmHg or antihypertensive treatment) and non-hypertensives. RESULTS: During follow-up a total of 55 men and 64 women died resulting in a 2.7-year cumulative mortality in this population of 12%. Mortality was higher in men (14%) than in women (11%). Hypertensives had no increased risk of death compared to non-hypertensives (adjusted relative risk (RR)=0. 92; 95% CI: 0.48-1.76 for men and RR=1.36; 95% CI 0.67-2.78 for women). This was confirmed in age-stratified analyses. However, among survivors hypertension was associated with a significantly higher occurrence of non-fatal cardiovascular events. After controlling for potentially confounding baseline conditions, the relative risk for any event (RR=1.44; 95% CI: 1.04-2.0) and, in particular, of acute myocardial infarction (RR=5.5; 95% CI: 1.6-18. 7) was raised among hypertensives. Higher rates for angina pectoris (RR=1.4; 95% CI: 0.9-2.4) and heart failure (RR 1.7; 95% CI: 0.9-2. 9) were of borderline significance. Positive risk associations were confined to the age group 65 to 75 years and not detected at higher ages. CONCLUSION: This study demonstrates for a Central European population older than 65 years the impact of hypertension as a risk factor for cardiovascular and cerebrovascular morbidity. To address the issue that risk of death showed no significant relationship to blood pressure, a longer follow-up period might be necessary.     

Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study

BACKGROUND: An increasing proportion of deaths among human immunodeficiency virus (HIV)-infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases. METHODS: We investigated the frequency of and risk factors associated with liver-related deaths in the Data Collection on Adverse Events of Anti-HIV Drugs study, which prospectively evaluated 76 893 person-years of follow-up in 23 441 HIV-infected persons. Multivariable Poisson regression analyses identified factors associated with liver-related, AIDS-related, and other causes of death. RESULTS: There were 1246 deaths (5.3%; 1.6 per 100 person-years); 14.5% were from liver-related causes. Of these, 16.9% had active hepatitis B virus (HBV), 66.1% had hepatitis C virus (HCV), and 7.1% had dual viral hepatitis co-infections. Predictors of liver-related deaths were latest CD4 cell count (adjusted relative rate [RR], 16.1; 95% confidence interval [CI], 8.1-31.7 for <50 vs > or =500/microL), age (RR, 1.3; 95% CI, 1.2-1.4 per 5 years older), intravenous drug use (RR, 2.0; 95% CI, 1.2-3.4), HCV infection (RR, 6.7; 95% CI, 4.0-11.2), and active HBV infection (RR, 3.7; 95% CI, 2.4-5.9). Univariable analyses showed no relationship between cumulative years patients were receiving cART and liver-related death (RR, 1.00; 95% CI, 0.93-1.07). Adjustment for the most recent CD4 cell count and patient characteristics resulted in an increased risk of liver-related mortality per year of mono or dual antiretroviral therapy before cART (RR, 1.09; 95% CI, 1.02-1.16; P = .008) and per year of cART (RR, 1.11; 95% CI, 1.02-1.21; P = .02). CONCLUSIONS: Liver-related death was the most frequent cause of non-AIDS-related death. We found a strong association between immunodeficiency and risk of liver-related death. Longer follow-up is required to investigate whether clinically significant treatment-associated liver-related mortality will develop.     

Anemia in human immunodeficiency virus-infected and uninfected women in Rwanda

To determine the prevalence and risk factors of anemia among human immunodeficiency virus (HIV)-infected women in Rwanda and the influence of highly active antiretroviral therapy (HAART) on anemia, we analyzed 200 HIV-positive women and 50 HIV-negative women in a cross-sectional study. Clinical examinations and iron and vitamin B(12) assays were performed, and complete blood counts, serum folic acid levels, and CD4 cell count determined. The prevalence of anemia was significantly higher among HIV-positive women (29%) than among HIV-negative women (8%) (P < 0.001). Risk factors for anemia were lower body mass index (odds ratio [OR] = 3.4, 95% confidence interval [CI] = 2.4-4.1), zidovudine use (OR = 1.14, 95% CI = 1.01-1.29), lack of HAART (OR = 1.44, 95% CI = 1.21-1.67), oral candidiasis (OR = 1.4, 95% CI = 1.2-1.6), pulmonary tuberculosis (OR = 1.8, 95% CI = 1.7-2.2), cryptococcal meningitis (OR = 1.6, 95% CI = 1.21-1.8), Pneumocystis jiroveci pneumonia (OR = 1.41, 95% CI = 1.20-1.65) and CD4 lymphocyte count < 200 cells/μL (OR = 2.41, 95% CI = 2.01-3.07). The mean ± SD hemoglobin level of 10.9 ± 1.6 g/dL at HAART initiation significantly increased to 12.3 ± 1.5 g/dL in 8 months (P < 0.001). Anemia increases with HIV stage, and HAART is associated with a significant improvement in hemoglobin levels.     

Prevalence and clinical determinants of mitral, tricuspid, and aortic regurgitation (the Framingham Heart Study)

Little information is available on the prevalence and determinants of valvular regurgitation in the general population. This study sought to assess the prevalence and clinical determinants of mitral (MR), tricuspid (TR), and aortic (AR) regurgitation in a population-based cohort. Color Doppler echocardiography was performed in 1,696 men and 1,893 women (aged 54 +/- 10 years) attending a routine examination at the Framingham Study. After excluding technically poor echocardiograms, MR, TR, and AR were qualitatively graded from trace to severe. Multiple logistic regression analysis was used to examine the association of clinical variables with MR and TR (more than or equal to mild severity) and AR (more than or equal to trace severity). MR and TR of more than or equal to mild severity was seen in 19.0% and 14.8% of men and 19.1% and 18.4% of women, respectively, and AR of more than or equal to trace severity in 13.0% of men and 8.5% of women. The clinical determinants of MR were age (odds ratio [OR] 1.3/9.9 years, 95% confidence interval [CI] 1.2 to 1.5), hypertension (OR 1.6; 95% CI 1.2 to 2.0), and body mass index (OR 0.8/4.3 kg/m2; 95% CI 0.7 to 0.9). The determinants of TR were age (OR 1.5/9.9 years; 95% CI 1.3 to 1.7), body mass index (OR 0.7/4.3 kg/m2; 95% CI 0.6 to 0.8), and female gender (OR 1.2; 95% CI 1.0 to 1.6). The determinants of AR were age (OR 2.3/9.9 years; 95% CI 2.0 to 2.7) and male gender (OR 1.6; 95% CI 1.2 to 2.1). A substantial proportion of healthy men and women had detectable valvular regurgitation by color Doppler echocardiography. These data provide population-based estimates for comparison with patients taking anorectic drugs.     

Malaria and anaemia among pregnant women at first antenatal clinic visit in Kisumu, western Kenya

Objective To determine the prevalence of malaria and anaemia among urban and peri‐urban women attending their first antenatal clinic (ANC) in an area of perennial malaria transmission. Methods Between November 2003 and May 2004 we screened first ANC attenders for malaria and anaemia in a large urban hospital in Kisumu (western Kenya) and interviewed them to obtain demographic and medical information. Results Among the 685 study participants, prevalence of malaria parasitaemia was 18.0%, prevalence of any anaemia (haemoglobin < 11 g/dl) was 69.1% and prevalence of moderate anaemia was (haemoglobin < 8 g/dl) 11.8%. Sixteen women were hospitalized during pregnancy, eight because of malaria. In multivariate analysis, young age, living in a house with mud walls, a visit to rural area, peri‐urban residence, second trimester of pregnancy and Luo ethnicity were significant risk factors for malaria parasitaemia. Malaria was an important risk factor for any and moderate anaemia; use of an insecticide‐treated net (ITN) was a protective factor for any anaemia. Married women with a higher level of education, better‐quality housing and full‐time employment were more likely to use an ITN. Conclusion Malaria and anaemia are established problems by the time of the first ANC visit. Mechanisms to deliver ITNs to women of child‐bearing age before they become pregnant need to be explored. Early ANC visits are warranted in order for women to benefit from policies aimed at reducing the burden of malaria and anaemia.     

Differential of HIV prevalence in women and men who attended sexually transmitted disease clinics at HIV sentinel surveillance sites in Kenya, 1990-2001

Several studies in sub-Saharan Africa have reported that HIV prevalence in young women is higher than in young men. We used data from Kenya HIV sentinel surveillance conducted from 1990 to 2001 among sexually transmitted disease (STD) patients (15-49 years old) to investigate consistency of gender differentials over time and their risk factors. Of the 15,889 STD patients, the HIV prevalence ranged from 16.0% in 1990 to 41.8% in 1997. The odds ratios (ORs) of HIV infection for women compared to men decreased by age; women 15-24 years were nearly twice as likely as men of the same ages to be HIV infected (OR 1.7 [1.5-2.0]), but risk in those >44 years was almost equal (OR 0.8 [95% CI 0.7-1.2]). The odds of HIV infection for women compared to men were twice in unmarried patients (OR 2.1 [95% CI 1.8-2.3]). This association persisted after controlling for age groups or marital status, residence, level of education, and presence of STD syndromes. This pattern had been consistent over 12 years. Adolescent women with symptoms of STDs should be a focus for the HIV/STD intervention programmes because of their high risk for HIV.     

Increased risk of high-grade cervical squamous intraepithelial lesions and invasive cervical cancer among African women with human immunodeficiency virus type 1 and 2 infections

To assess the risk of prevalent high-grade cervical squamous intraepithelial lesions (HSILs) or invasive cervical cancer (ICC) associated with human immunodeficiency virus (HIV) type 1, HIV-2, and human papillomavirus (HPV) infections, HIV load, and CD4 cell count, we studied 4119 women attending an outpatient clinic in Senegal. HIV infection was associated with increased rates of cervical infection with high-risk HPVs. Among women infected with high-risk HPVs, those with HIV-1 (odds ratio [OR], 2.2; 95% confidence interval [CI], 1.0-4.8), HIV-2 (OR, 6.0; 95% CI, 2.1-17.1), or dual HIV infection (OR, 8.0; 95% CI, 2.0-31.5) were more likely to have HSILs or ICC diagnosed than were HIV-negative women; this association was not observed among women not infected with high-risk HPVs. Among women with HIV, higher HIV plasma RNA loads and lower CD4 cell counts were associated with high-risk HPV infection and degree of cervical abnormality. Furthermore, HIV-2-positive women were more likely to have HSILs (OR, 3.3; 95% CI, 0.9-12.4) or ICC (OR, 7.9; 95% CI, 1.1-57) than were HIV-1-positive women.