Factors associated with viral load suppression in HIV-infected pregnant women in Rio de Janeiro, Brazil

Viral load (VL) near delivery is a determinant of mother-to-child transmission (MTCT) of HIV. To evaluate factors associated with an undetectable VL near delivery in HIV-infected pregnant women receiving highly active antiretroviral therapy (HAART) and non-HAART regimens, HIV-infected pregnant women with a detectable VL at entry and having used antiretrovirals for ≥4 weeks before delivery were selected. Multivariate analysis was employed using binary logistic unconditional models; the dependent variable was having a VL <400 copies/mL near delivery. VL suppression was achieved in 403/707 women (57%): 65.4% in the HAART group, but only 26% in the non-HAART group P = 0.001. Duration of HAART was correlated with VL suppression, with maximum benefit seen after ≥12 weeks of therapy (odds ratio [OR]: 2.51; 95% confidence interval [CI]: 1.72-3.65). CD4+ cell count near delivery (OR: 1.53; 95% CI: 1.06-2.20) and baseline VL (OR: 0.74; 95% CI: 0.58-0.94) were also independently associated with VL suppression. Overall MTCT rate was 1.6%. HAART for ≥12 weeks, baseline VL and CD4 cell count near delivery were independently associated with viral suppression near delivery.     

Invasive pneumococcal disease in a cohort of HIV-infected adults: incidence and risk factors, 1990-2003

OBJECTIVE: To investigate the association between the introduction of HAART and invasive pneumococcal disease (IPD) in HIV-infected patients. METHODS: Incidence of IPD was determined from 1990 to 2003 in a cohort of HIV-infected individuals and a nested case-control study assessed risk factors of IPD. RESULTS: There were 72 cases over 19,020 person-years of follow-up (overall IPD rate, 379/100,000 person-years). In the calendar periods 1990-1995, 1995-1998, and 1998-2003, the IPD incidence per 100,000 person-years was 279 [95% confidence interval (CI), 150-519], 377 (95% CI, 227-625) and 410 (95% CI, 308-545), respectively (P = 0.516). CD4 cell count < 200 cells/microl [odds ratio (OR), 3.0; 95% CI, 1.2-7.6), HIV RNA > 50,000 copies/ml (OR, 2.8; 95% CI, 1.2-6.5), hepatitis C (OR, 4.9; 95% CI, 1.7-14.9), serum albumin (OR, 0.1; 95% CI, 0.04-0.5), injection drug use in women (OR, 3.8; 95% CI, 1.6-8.8), and education beyond high school (OR, 0.2; 95% CI, 0.05-0.8) were significantly associated with IPD in multivariate analysis. No treatment factor, including HAART (OR, 0.7; 95% CI, 0.3-1.5) and pneumococcal vaccination (OR, 0.9; 95% CI, 0.5-1.6), was associated with IPD. CONCLUSIONS: IPD incidence did not change significantly during the widespread dissemination of HAART in this cohort. IPD risk was associated with several sociodemographic and clinical factors.     

Associations of Type 1 diabetes mellitus, maternal vascular disease and complications of pregnancy.

BACKGROUND: Maternal diabetes increases the risk of pre-eclampsia and abnormalities of fetal growth. We studied the additional impact of maternal vascular disease on these risks. METHODS: The first viable (> 23 weeks) pregnancies of 138 women with Type 1 diabetes mellitus (Type 1 DM), delivered between 1994 and 2003 at the Queen's Medical Centre, Nottingham, UK were studied. Women were divided into groups with and without vascular disease (retinopathy and/or nephropathy and/or pre-existing hypertension). Primary outcomes were pre-eclampsia and fetal customized birthweight percentile (cbp) (adjusted for maternal weight, height, parity, ethnicity, gestational age and gender). Secondary outcomes were perinatal outcome (miscarriage, intrauterine or neonatal death), preterm birth, birth asphyxia, neonatal hypoglycaemia and delivery mode. RESULTS: Women with vascular disease were more likely to develop pre-eclampsia (OR 3.5; CI 1.28-9.53) and deliver infants with lower cbp (median 89.0, range 0-100 vs. 98.0, range 0-100; P < or = 0.005). Infants were less likely to be macrosomic (OR 0.46; CI 0.224-0.928) but more likely to have intrauterine growth restriction (IUGR; OR 6.0; CI 1.54-23.33). Women with vascular disease had higher Caesarean section rates (90 vs. 56%, P < or = 0.001). CONCLUSIONS/INTERPRETATION: Women with Type 1 DM and vascular disease are at greater risk of pre-eclampsia and pathological fetal growth. This should influence counselling and merit increased pregnancy surveillance.     

Survival in HIV-infected patients is associated with hepatitis C virus infection and injecting drug use since the use of highly active antiretroviral therapy in the Lyon observational database

Highly active antiretroviral therapy (HAART) has reduced the incidence of death in HIV-infected patients but various rates of survival have been reported due to the infection with hepatitis C virus (HCV) and the use of injecting drugs (IDU). A survival analysis was performed to estimate and compare the death rates in HIV-positive patients infected by IDU and/or positive for HCV antibodies in the pre-HAART and HAART periods in Lyon (France) between 1992 and 2002. Patients were stratified into four groups (G): HCV-/IDU-(G1), HCV+/IDU-(G2), HCV+/IDU-(G3), HCV+/IDU+ (G4) and adjusted death rates in the pre-HAART era (< 1996) and the HAART era (> or = 1996) were compared. The aHR of progression to death was 1.05 (95% CI 0.75-1.47, P = 0.75) for G2, 1.09 (95% CI 0.54-2.22, P = 0.81) for G3 and 0.90 (95% CI 0.65-1.24, P =0.51) for G4 compared with G1 in the pre-HAART era. The aHR of progression to death was 0.76 (95% CI 0.28-2.08, P = 0.59) for G2, 1.23 (95% CI 0.17-8.86, P = 0.84) for G3 and 2.90 (95% CI 1.62-5.20, P < 0.001) for G4, compared with G1 in the HAART era. HAART management of HCV+/IDU+ patients needs to be optimized for them to achieve a similar benefit as observed among other individuals.     

Ten-year predicted coronary heart disease risk in HIV-infected men and women.

BACKGROUND: Highly active antiretroviral therapy (HAART), in addition to traditional vascular risk factors, may affect coronary heart disease (CHD) risk in individuals with human immunodeficiency virus (HIV) infection. METHODS: Among HIV-infected (931 men and 1455 women) and HIV-uninfected (1099 men and 576 women) adults, the predicted risk of CHD was estimated on the basis of age, sex, lipid and blood pressure levels, the presence of diabetes, and smoking status. RESULTS: Among HIV-infected men, 2% had moderate predicted risk of CHD (10-year CHD risk, 15%-25%), and 17% had high predicted risk (10-year CHD risk of > or = 25% or diabetes). Among HIV-infected women, 2% had moderate predicted CHD risk, and 12% had high predicted CHD risk. Compared with users of protease inhibitor-based HAART, the adjusted odds ratio (OR) for moderate-to-high risk of CHD was significantly lower among HAART-naive individuals (OR, 0.57; 95% confidence interval [CI], 0.36-0.89). Users of HAART that was not protease inhibitor based (OR, 0.74; 95% CI, 0.53-1.01) and former HAART users (OR, 0.68; 95% CI, 0.46-1.03) were also less likely than users of protease inhibitor-based HAART to have moderate-to-high CHD risk, although 95% CIs overlapped the null. Low income was associated with increased likelihood of moderate-to-high CHD risk (for annual income < $10,000 vs. > $40,000: OR, 2.32; 95% CI, 1.51-3.56 ). Elevated body mass index (calculated as weight in kilograms divided by the square of height in meters) predicted increased likelihood of moderate-to-high CHD risk (for BMI of 18.5-24.9 vs. BMI of 25-30: OR, 1.41 [95% CI, 1.03-1.93]; for BMI of 18.5-24.9 vs. BMI > or = 30: OR, 1.79 [95% CI, 1.25-2.56]). CONCLUSIONS: Among HIV-infected adults, in addition to antiretroviral drug exposures, being overweight and having a low income level were associated with increased predicted CHD risk. This suggests a need to target HIV-infected men and women with these characteristics for vascular risk factor screening.     

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.     

Pregnancy outcomes among patients with sickle cell disease at Korle-Bu Teaching Hospital, Accra, Ghana: retrospective cohort study

Pregnancy in sickle cell disease (SCD) patients is associated with increased risk of maternal and fetal mortality. This study determines pregnancy outcomes among women with SCD delivering at Korle-Bu Teaching Hospital, Accra, Ghana. Nine hundred sixty (960) medical records of pregnant women (131 HbSS, 112 HbSC, and 717 comparison group) from 2007 to 2008 were reviewed. The HbSS women were at increased risk of eclampsia (adjusted odds ratio [AOR] = 10.56, 95% confidence interval [CI] = 3.60-30.96, P < 0.001), intrauterine growth restriction (AOR = 4.00, 95% CI = 1.38-11.64, P = 0.011), and placenta previa (AOR = 22.03, 95% CI = 9.87-49.14, P < 0.001) compared with the comparison group. The HbSC women had increased risk for intrauterine fetal death (AOR = 3.38, 95% CI = 1.15-9.96, P = 0.027) and decreased risk of delivering low birth weight babies (AOR = 0.21, 95% CI = 0.06-0.73, P = 0.014). Women with SCD in Ghana are at a greater risk of morbidity and mortality in pregnancy compared with women without hemoglobinopathies. Improved maternal and fetal outcomes in Ghanaian women with SCD can be achieved through effective intervention by health care providers with thorough knowledge about predisposing factors toward adverse outcomes.     

Acute renal failure in hospitalized patients with HIV: risk factors and impact on in-hospital mortality

BACKGROUND: Kidney disease is an increasingly important complication of HIV. OBJECTIVES: To examine the incidence and predictors of acute renal failure before and after the introduction of HAART, and the impact of acute renal failure on in-hospital mortality in the post-HAART era. METHODS: Adults hospitalized in acute care hospitals in New York State during 1995 (pre-HAART) or 2003 (post-HAART) were identified from the state Planning and Research Cooperative System database. HIV status was defined by primary or secondary diagnosis code. The impact of HIV and HAART on the incidence of acute renal failure and mortality, and the impact of acute renal failure on mortality, was assessed using chi analysis and multivariate regression. RESULTS: There were 52,580 HIV-infected patients discharged from hospital in 1995 and 25,114 in 2003. Compared with uninfected patients, HIV-infected patients had an increased incidence of acute renal failure in both the pre-HAART [adjusted odds ratio (OR), 4.62; 95% confidence interval (CI), 4.30-4.95] and post-HAART eras (adjusted OR, 2.82; 95% CI, 2.66-2.99). In the post-HAART cohort, acute renal failure was associated with traditional predictors such as age, diabetes mellitus, and chronic kidney disease, as well as acute or chronic liver failure or hepatitis coinfection (P < 0.001 for all comparisons). Acute renal failure was associated with mortality among HIV-infected patients in the post-HAART era (OR, 5.83; 95% CI, 5.11-6.65). CONCLUSIONS: Acute renal failure remains common among hospitalized patients with HIV and is associated with chronic kidney disease, liver disease, and increased mortality.     

Pregnancy and HIV disease progression during the era of highly active antiretroviral therapy

BACKGROUND: Before the availability of highly active antiretroviral therapy (HAART), there was no clear effect of pregnancy on human immunodeficiency virus (HIV) disease progression. This has not been assessed during the HAART era. METHODS: We conducted an observational cohort study among HIV-infected women with >or=1 outpatient clinic visit between January 1997 and December 2004. HIV disease progression was defined as the occurrence of an AIDS-defining event or death. RESULTS: Of 759 women who met the inclusion criteria, 139 (18%) had had >1 pregnancy, and 540 (71%) had received HAART. There was no difference in HAART duration by pregnancy status. Eleven pregnant (8%) and 149 nonpregnant (24%) women progressed to AIDS or death. After controlling for age, baseline CD4(+) lymphocyte count, baseline HIV-1 RNA level, and durable virologic suppression in a Cox proportional hazards model that included propensity score for pregnancy, pregnancy was associated with a decreased risk of disease progression (hazard ratio [HR], 0.40 [95% confidence interval {CI}, 0.20-0.79]; P=.009]). In a matched-pair analysis of 81 pregnant women matched to 81 nonpregnant women according to age, baseline CD4(+) lymphocyte count, receipt of HAART, and date of cohort entry, pregnant women had a lower risk of disease progression both before (HR, 0.10 [95% CI, 0.01-0.89]; P=.04) and after (HR, 0.44 [95% CI, 0.19-1.00]; P=.05) the pregnancy event. CONCLUSION: Pregnancy was associated with a lower risk of HIV disease progression in this HAART-era study. This finding could be the result of the healthier immune status of women who become pregnant or could possibly be related to a beneficial interaction between pregnancy and HAART.     

Epidemiology of bloodstream infections and predictive factors of mortality among HIV-infected adult patients in Thailand in the era of highly active antiretroviral therapy

Few studies have described the pattern of bloodstream infections (BSI) among HIV-infected patients in the highly active antiretroviral therapy (HAART) era, particularly in resource-limited settings. A retrospective cohort study was conducted among 140 HIV-infected patients who had a positive blood culture from 2004-2008. Of the 140 patients, 91 (65%) were male with a mean (SD) age of 38 (9.1) years and a median (IQR) CD4 cell count of 32 (9-112) cells/mm(3). Community-acquired infection was detected in 89% of patients. The blood cultures contained Gram-negative bacteria, 40%; fungi, 24%; Mycobacterium spp., 20%; and Gram-positive bacteria, 16%. Common causative pathogens were Cryptococcus neoformans, 21%; Salmonella spp., 15%; and Mycobacterium tuberculosis, 12%. Common focal sites of infection were the central nervous system, 24%; respiratory tract, 20%; and gastrointestinal tract, 18%. CD4 cell count (OR, 0.61 per 50 cells/mm(3) increment; 95% CI, 0.39-0.96; P = 0.031) was the only factor associated with mycobacterial or fungal BSI. The crude mortality was 21%. HAART (OR, 0.23; 95% CI, 0.01-0.77; P = 0.017), focal infection (OR, 0.31; 95% CI, 0.10-0.97; P = 0.044), and complication (e.g., shock) (OR, 9.26; 95% CI, 3.25-26.42; P < 0.001) were the predictive factors of mortality. In conclusion, opportunistic infections are still the leading causes of BSI among HIV-infected patients in the HAART era.     

Antiretroviral therapy and premature delivery in diagnosed HIV-infected women in the United Kingdom and Ireland

OBJECTIVE: To explore the association between antiretroviral therapy in pregnancy and premature delivery, birthweight, stillbirth and neonatal mortality, in pregnancies in HIV-infected women delivering between 1990 and 2005. DESIGN: Pregnancies in women with diagnosed HIV infection in the UK and Ireland are notified to the National Study of HIV in Pregnancy and Childhood (NSHPC) through a well-established surveillance scheme. RESULTS: The prematurity rate (< 37 weeks gestation) was higher in women on highly active antiretroviral therapy (HAART) (14.1%, 476/3384) than in women on mono/dual therapy (10.1%, 107/1061), even after adjusting for ethnicity, maternal age, clinical status and injecting drug use as the source of HIV acquisition [adjusted odds ratio (AOR) = 1.51, 95% confidence interval (CI), 1.19-1.93; P = 0.001]. Delivery at < 35 weeks was even more strongly associated with HAART (AOR = 2.34; 95% CI, 1.64-3.37; P < 0.001). The effect was the same whether or not HAART included a protease inhibitor. In comparison with exposure to mono/dual therapy, exposure to HAART was associated with lower birthweight standardized for gestational age (P < 0.001), and an increased risk of stillbirth (AOR = 2.27; 95% CI, 0.96-5.41; P = 0.063). CONCLUSIONS: These findings, based on comprehensive population surveillance, demonstrate an increased risk of prematurity associated with HAART, and a possible association with other perinatal outcomes, including stillbirth and birthweight. Although the beneficial effects of antiretroviral therapy on mother-to-child transmission are indisputable, monitoring antiretroviral therapy in pregnancy remains a priority.     

Impact of GB virus type C infection on mother-to-child HIV transmission in the Women and Infants Transmission Study Cohort

BACKGROUND: GB virus type C (GBV-C) viraemia is associated with a beneficial outcome in HIV-infected individuals in several though not all studies. GBV-C viraemia was examined in a matched case-control study of 133 HIV-infected pregnant women who transmitted HIV to their infants ('cases') and 266 non-transmitting controls. METHODS: HIV-infected children and controls were pair-matched for high-risk delivery, race and year of delivery. GBV-C status was determined in maternal plasma samples obtained at or within 3 months of delivery. RESULTS: Pregnant women with GBV-C viraemia (11% of those studied) had lower HIV RNA levels (P=0.01) and higher CD4 percentages (P=0.0006) [corrected] than women without GBV-C. A trend towards decreased mother-to-child transmission in the multivariate analysis was observed among GBV-C viraemic women delivering after highly active antiretroviral therapy (HAART) became available [odds ratio (OR) 0.30, 95% confidence interval (CI) 0.08-1.05; P=0.06], but not in women delivering prior to the widespread use of HAART. CONCLUSIONS: GBV-C viraemia was associated with a beneficial effect on CD4 percentage and HIV RNA level in these pregnant women, and was also associated with a trend towards reduced risk of mother-to-child HIV transmission among women after HAART became available. Further studies with larger or multiple cohorts are necessary to assess possible benefits in this population.     

Initiating highly active antiretroviral therapy in sub-Saharan Africa: an assessment of the revised World Health Organization scaling-up guidelines

OBJECTIVES: To assess the utility of the 2003 revised World Health Organization (WHO) criteria [initiating highly active antiretroviral therapy (HAART) in stage IV, in stage III plus CD4 cell count < 350 x 10(6) cells/l, or in stage I or II plus CD4 cell count < 200 x 10 cells/l] relative to other scenarios of HAART initiation. METHODS: Progression to AIDS and death in 292 patients taking HAART and 974 not taking HAART in a South African institution in 1992-2001, stratifying patients by baseline CD4 cell count and WHO stage. RESULTS: HAART was associated with decreased AIDS [adjusted rate ratio [ARR], 0.16; 95% confidence interval (CI), 0.08-0.31) and death (ARR, 0.10; 95% CI, 0.06-0.18). Benefit of HAART was significant across all WHO stages plus CD4 cell counts. The greatest number of deaths averted was in stages IV [74.0/100 patient-years (PY); 95% CI, 50.2-84.5) and III (32.8/100 PY; 95% CI, 22.4-40.9). AIDS cases averted in stage III (22.0/100 PY; 95% CI, 6.1-26.9) were higher than in stage I and II with CD4 cell count < 200 x 10(6) cells/l (8.9/100 PY 95% CI, 5.6-13.3). Treatment initiation for symptomatic disease resulted in greater benefits than using any CD4 cell thresholds. Application of WHO criteria increased the treatment-eligible proportion from 44.5% to 56.7% (P < 0.05) but did not prevent more death (P > 0.05) than treating symptomatic disease. CONCLUSION: Implementation of the revised WHO guidelines in sub-Saharan Africa may result in a significantly increased number of individuals eligible for treatment but would not be as effective a strategy for preventing death as treating symptomatic disease.     

Twin pregnancy as a risk factor for mother-to-child transmission of HIV-1: trends over 20 years

OBJECTIVE: We investigated whether twin pregnancies were at increased risk of mother-to-child HIV-1 transmission (MTCT), in comparison with singletons. METHODS: Among HIV-1 infected women enrolled in the French Perinatal HIV Cohort (n = 9262), we studied the association between twin deliveries and MTCT rate according to three time periods (pre-1994, 1994-1996, 1997-2004) and the effect of birth order. The mother was considered to have transmitted if at least one of the twins was infected. Univariate and multivariate analyses of risk factors for MTCT were performed for deliveries in the periods up to 1996. RESULTS: Overall, 2.1% (192/9262) of all the deliveries were twins. The rate of prematurity was greater in twins than in singletons (54% and 13%, respectively). Up to 1996 the rate of MTCT of HIV-1 was 28.3% (15/53) in twin pregnancies, versus 13.5% (414/3077) in singletons [odds ratio (OR), 2.5; 95% confidence interval (CI), 1.4-4.7; P = 0.002; adjusted OR, 2.3: 95% CI, 1.1-2.3; P = 0.03). In the period from 1997 to 2003, MTCT was low and did not differ between twins (1.0%) and singletons (1.8%; P = 1.0). Overall, the transmission rate for the first-born child was threefold that for the second-born child (14/164, 8.5% versus 4/164, 2.4%; P = 0.008). CONCLUSION: Twin pregnancies were at increased risk of transmission, but in the era of HAART this risk was reduced for twins, as well as singletons. Management of multiple pregnancies should take into account the risks of premature rupture of the membranes and preterm delivery.     

Regional differences in the prevalence of pre-eclampsia in relation to the risk factors for coronary artery disease in women in Finland.

AIMS: The aim of this study was to examine the prevalence of pre-eclampsia in Southern, Eastern, and Northern Finland, and the relationship between history of pre-eclampsia and maternal coronary artery disease (CAD) risk factors. METHODS AND RESULTS: Women aged 25-64 years, who participated in a cross-sectional population survey and had been pregnant (n=3650), were studied. The proportion of women who had ever had pre-eclampsia was lower in Southern (7.9%) compared with Northern Finland (13.9%) (P=0.001), but did not differ from Eastern Finland (11.1%). In the logistic regression model, the age-adjusted prevalence of pre-eclampsia was 1.92-fold in Northern (95% CI: 1.46-2.53, P<0.001) and 1.47-fold in Eastern Finland (95% CI: 1.11-1.96, P=0.008) compared with Southern Finland. The odds ratios (ORs) were 1.70 (95% CI: 1.21-2.38, P=0.002) and 1.16 (95% CI: 0.82-1.64, P=0.40), respectively, when adjusted for age at first birth, current age, parity, body mass index (BMI), increased blood cholesterol, hypertension, diabetes/impaired glucose tolerance, CAD, and mother's myocardial infarction. History of pre-eclampsia was associated with increased blood cholesterol, higher current BMI and blood pressure, and higher current prevalence of hypertension, diabetes/impaired glucose tolerance. CONCLUSIONS: Pre-eclampsia is most prevalent in the Northern part of Finland and could only be partly explained by higher prevalence of CAD risk factors.     

Infection with HIV as a risk factor for adverse obstetrical outcome

We carried out a case-control study to investigate the role of sexually transmitted diseases (STDs), including infection with HIV, as risk factors for adverse outcome of pregnancy. Overall, 1507 women were enrolled within 24 h of delivery. Cases (n = 796) were mothers of low-birthweight infants (less than 2500 g) or of stillborns. Low-birthweight infants were divided into preterms (n = 373) and neonates small for gestational age (n = 234). Stillborns were separated into intrauterine fetal deaths (n = 120), and intrapartum fetal deaths (n = 69). Controls were selected from mothers delivering a live baby of greater than or equal to 2500 g (n = 711). The maternal HIV seroprevalence in the control group was 3.1%. Prematurity was associated with maternal HIV antibody [8.6% seropositive; adjusted odds ratio (OR) 2.1; 95% confidence interval (CI) 1.1-4.0], as was being born small for gestational age (7.7% seropositive; adjusted OR 2.3; 95% CI 1.2-4.2). In mothers who delivered a stillborn baby, both intrauterine fetal death (11.7% seropositive; adjusted OR 2.7; 95% CI 1.3-5.5) and intrapartum fetal death (11.6% seropositive; adjusted OR 2.9; 95% CI 1.3-6.5) were independently associated with HIV seropositivity in the mother. Maternal syphilis was confirmed as an important risk factor for intrauterine fetal death (14.3% positive; adjusted OR 4.8; 95% CI 2.4-9.5). No significant association was found between other STDs, including gonococcal and chlamydial infection, and adverse obstetrical outcome. These results suggest an association between maternal HIV infection and adverse obstetrical outcome, defined as low birthweight and stillbirth.     

Improved survival with highly active antiretroviral therapy in HIV-infected patients with severe Pneumocystis carinii pneumonia

BACKGROUND: Although the incidence of pneumonia (PCP) has declined, mortality of patients who require intensive care for this disease remains high. Highly active antiretroviral therapy (HAART) might alter the course of PCP either via effects on the immune system or through anti- actions; however, HAART has not been studied in patients acutely ill with PCP. OBJECTIVE: To assess the effects of HAART on outcome of patients admitted to the intensive care unit (ICU) with PCP. DESIGN AND SETTING: Retrospective cohort study carried out at a University-affiliated county hospital. PARTICIPANTS: Fifty-eight HIV-infected adults with PCP admitted to an ICU from 1996 to 2001. MEASUREMENTS: A standardized chart review was performed to collect information on demographic variables, hospital course, and use of antiretroviral therapy. Outcome measured was death while in the ICU or hospital. RESULTS: A total of 20.7% of patients were either receiving HAART or were started on therapy while hospitalized. Mortality in this group was 25%, whereas mortality in those not receiving therapy was 63% (P = 0.03). Multiple logistic regression analyses adjusting for potential confounders showed that HAART started either before or during hospitalization was associated with a lower mortality [odds ratio (OR), 0.14; 95% confidence interval (95% CI), 0.02-0.84; = 0.03). The need for mechanical ventilation and/or development of a pneumothorax (OR, 20.9; 95% CI, 1.9-227.2; = 0.01) and delayed ICU admission (OR, 9.7; 95% CI, 2.2-42.1; = 0.002) were associated with increased mortality. CONCLUSIONS: Use of HAART is an independent predictor of decreased mortality in severe PCP and may represent a potential therapy to improve outcome in this disease.     

Long-term survival of HIV-infected patients treated with highly active antiretroviral therapy in Serbia and Montenegro

BACKGROUND: Highly active antiretroviral therapy (HAART) has dramatically changed the prognosis of HIV disease, even in terminally ill patients. Although these patients may survive many years after the diagnosis of AIDS if treated with HAART, some still die during treatment. METHODS: A retrospective study in a cohort of 481 HIV-infected patients treated with HAART between January 1998 and December 2005 was conducted to compare subgroups of long-term survivors (LTSs) and patients who died during treatment. RESULTS: A total of 48 patients survived for more than 72 months (mean 83.8+/-standard deviation 5.6 months). Thirty patients died during treatment (mean 35.3+/-25.0 months), of whom nine died from non-AIDS-related causes, 18 died from AIDS-related causes, and three died as a result of HAART toxicity. Although LTSs were significantly (P=0.015) younger at HAART initiation, age below 40 years was not a predictor of long-term survival. The subgroups did not differ in the proportion of clinical AIDS cases at HAART initiation, in the prevalence of hepatitic C virus (HCV) coinfection, or in pretreatment and end-of-follow-up CD4 cell counts. In contrast, the viral load achieved during treatment was lower in the survivors (P=0.03), as was the prevalence of hepatitis B virus (HBV) coinfection (P=0.03). Usage of either protease inhibitor (PI)-containing regimens [odds ratio (OR) 9.0, 95% confidence interval (CI) 2.2-35.98, P<0.001] or all three drug classes simultaneously (OR 7.4, 95% CI 2.2-25.1, P<0.001) was associated with long-term survival. Drug holidays incorporated in structured treatment interruption (STI) were also associated with a good prognosis (OR 14.9, 95% CI 2.9-75.6, P<0.001). CONCLUSIONS: Long-term survival was associated with PI-based HAART regimens and lower viraemia, but not with the immunological status either at baseline or at the end of follow up. STI when CD4 counts reach 350 cells/microL, along with undetectable viraemia, was a strong predictor of long-term survival.     

Higher rates of post-partum complications in HIV-infected than in uninfected women irrespective of mode of delivery

OBJECTIVE: To inform the debate on the use of elective caesarean section (CS) delivery in HIV-infected women, we investigated the occurrence of clinical events in the immediate post-partum period in women delivering in 13 European centres. DESIGN: Two separate matched case-control studies (vaginal and elective CS deliveries) among infected women (cases) and uninfected controls delivering between 1992 and 2002. METHODS: The prevalence of minor and major post-partum complications was assessed overall for infected and uninfected women; within mode of delivery group (vaginal/CS) the complication rates of infected cases were compared with uninfected controls in a matched analysis. RESULTS: Overall complication rates were 29.2% (119 of 408) for HIV-infected women, 19.4% (79 of 408) for uninfected women, 42.7% (135 of 316) for CS deliveries and 12.6% (63 of 500) for vaginal deliveries. There were no major complications in women delivering vaginally; but, compared with controls, HIV-infected cases were at increased risk of puerperal fever [odds ratio (OR), 4.5; 95% confidence interval (CI), 1.55-13.07), especially after medio-lateral episiotomy. In the CS group, there were six major complications (five among cases, one control) (OR, 5.1; 95% CI, 0.58-45) and cases had an increased risk of minor complications (OR, 1.51; 95% CI, 1.22-2.41) compared with controls, mainly anaemia not requiring blood transfusion. CONCLUSION: HIV-infected pregnant women are at increased risk of post-partum complications regardless of mode of delivery, but modification of clinical practice, particularly use of prophylactic antibiotics, would reduce this risk. Infected women should be informed about risks of vertical transmission and post-partum complications, and be involved in mode of delivery decisions.     

Patterns of the hazard of death after AIDS through the evolution of antiretroviral therapy: 1984-2004

OBJECTIVE: To characterize changing survival patterns after development of clinical AIDS from 1984 to 2004, when different antiretroviral therapies were being introduced. DESIGN: Cohort of homosexual men since 1984 and cohort of women since 1994. METHODS: A total of 1504 men and 461 women were followed for all-cause mortality after an incident AIDS diagnosis. Relative hazards of death and relative times to death were determined in five therapy eras: no/monotherapy (July 1984-December 1989), monotherapy/combination therapy (January 1990-December 1994), HAART introduction (January 1995-June 1998), short-term stable HAART use (July 1998-June 2001), and moderate-term stable HAART use (July 2001-December 2003). RESULTS: A total of 1057 (54%) study participants died. The time at which 25% of individuals died after an AIDS diagnosis increased significantly from 0.56 years [95% confidence interval (CI), 0.50-0.64] in the no/monotherapy era to 0.74 (95% CI, 0.67-0.82), 1.78 (95% CI, 1.29-2.44), 4.22 (95% CI, 2.94-6.05) and 5.08 years (95% CI, 2.39-10.79) in the four subsequent therapy eras, respectively. Inferences on the beneficial effects of HAART were confirmed after adjustment by age, sex, type of AIDS diagnosis and CD4 cell count at diagnosis. The pattern of the hazard of death after AIDS changed from increasing in the pre-HAART era to being lower and non-increasing in the eras of HAART. CONCLUSIONS: The sustained beneficial effect of HAART, even in individuals with clinical AIDS and extensive treatment histories, attenuates concerns about emergence of resistance but augurs that a substantial number of HIV-infected individuals may require care for very long periods.