The association between decidual vasculopathy and abnormal uterine artery Doppler measurement.

INTRODUCTION: Placental syndrome is an umbrella term encompassing the clinical phenotypes of preeclampsia and fetal growth restriction, and is associated with high maternal and neonatal morbidity. In women with placental syndrome, histologicl examination of the uteroplacental unit commonly demonstrates pathological lesions, such as decidual vasculopathy. Decidual vasculopathy are pathological changes in the spiral arteries, which are associated with adverse outcome in preeclampsia and long-term maternal cardiovascular health. The relation between placental syndrome phenotypes and placental pathology has been previously demonstrated; however, the role of uteroplacental Doppler measurements as a link between placental syndrome phenotypes and the underlying placental pathology is still unclear. We hypothesized that decidual vasculopathy is associated with abnormal uteroplacental Doppler profiles and ultrasound placental parameters, independent of clinical phenotype. MATERIAL AND METHODS: We performed a retrospective analysis of data from a prospective cohort of pregnancies with placental syndrome, as well as cases without hypertensive disease or fetal growth restriction. The study group was divided into women with decidual vasculopathy on histologic analysis of placental specimen and those without the lesions. Outcome parameters included maternal and fetal Dopplers, estimated fetal weight, placental weight and thickness, placental lacunae and abnormal placental calcification. RESULTS: Compared with the women without the lesions (n = 91), the group with decidual vasculopathy (n = 25) had a higher mean uterine artery pulsatility index (1.70 vs 0.81, p < 0.001) and uterine artery pulsatility index percentile (>p99 vs p67, p < 0.001). Decidual vasculopathy was associated with abnormal uterine artery Doppler profile (defined as pulsatility index p > 95 and/or bilateral notch) (82%) compared with women without the lesions (33%) (odds ratio [OR] 9.3, 95% CI 2.4-36.0), which remained significant after adjusting for possible confounding factors preeclampsia, tobacco use and gestational age at birth (OR 7.1, 95% CI 1.3-39.1). Decidual vasculopathy was not associated with fetal Doppler abnormalities or placental parameters and only modestly so with lower cerebroplacental ratio (p = 0.036). CONCLUSIONS: Histologic decidual vasculopathy is associated with abnormal uterine artery Doppler, independent of clinical phenotype during pregnancy.

Preconceptional evaluation of women with recurrent pregnancy loss: the additional value of assessing vascular and metabolic status.

BACKGROUND: A majority of recurrent pregnancy loss cases (RPL) remains unexplained. We hypothesized that complications in vascular and metabolic status may guide towards underlying problems that also predispose to RPL and that the number of pregnancy losses is related. METHODS: A retrospective study in 123 women with either a history of low-order RPL (2-3 pregnancy losses) or high-order RPL (≥ 4 pregnancy losses) and 20 women with a history of uncomplicated pregnancy (controls) was performed. Vascular status was assessed by measuring hemodynamic parameters, determining abnormal parameters and analyzing their contribution to the circulatory risk profile (CRP). In a similar way, metabolic status was assessed. Metabolic parameters were measured, used to determine abnormal parameters and analyzed for their contribution to the metabolic syndrome (MetS). RESULTS: No major differences were observed in vascular or metabolic parameters between women with RPL and controls. There was no relation with the number of pregnancy losses. However, when analyzing the presence of abnormal constituents, more than 80% of women with RPL had at least one abnormal constituent of the CRP. While only 27% had one or more abnormal constituent of the MetS. CONCLUSIONS: The presence of abnormal circulatory factors prior to pregnancy, and to lesser extent constituents of the metabolic syndrome, may predispose to RPL and offer new insights to its pathophysiology.

Spiral artery blood flow during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Downstream remodeling of the spiral arteries (SpA) decreases utero-placental resistance drastically, allowing sustained and increased blood flow to the placenta under all circumstances. We systematically evaluated available reports to visualize adaptation of spiral arteries throughout pregnancy by ultra-sonographic measurements and evaluated when this process is completed. METHODS: A systematic review and meta-analysis of spiral artery flow (pulsatility index (PI), resistance index (RI) and peak systolic velocity (PSV)) was performed. English written articles were obtained from Pubmed, EMBASE and Cochrane Library and included articles were assessed on quality and risk of bias. Weighted means of Doppler indices were calculated using a random-effects model. RESULTS: In healthy pregnancies, PI and RI decreased from 0.80 (95% CI: 0.70-0.89) and 0.50 (95% CI: 0.47-0.54) in the first trimester to 0.50 (95% CI: 0.45-0.55, p < 0.001) and 0.39 (95% CI: 0.37-0.42, p < 0.001) in the second trimester and to 0.49 (95% CI: 0.44-0.53, p = 0.752) and 0.36 (95% CI: 0.35-0.38, p = 0.037) in the third trimester, respectively. In parallel, PSV altered from 0.22 m/s (95% CI: 0.13-0.30 m/s) to 0.28 m/s (95% CI: 0.17-0.40 m/s, p = 0.377) and to 0.25 m/s (95% CI: 0.20-0.30 m/s, p = 0.560) in the three trimesters. In absence of second and third trimester Doppler data in complicated gestation, only a difference in PI was observed between complicated and healthy pregnancies during the first trimester (1.49 vs 0.80, p < 0.001). Although individual studies have identified differences in PI between SpA located in the central part of the placental bed versus those located at its periphery, this meta-analysis could not confirm this (p = 0.349). CONCLUSIONS: This review and meta-analysis concludes that an observed decrease of SpA PI and RI from the first towards the second trimester parallels the physiological trophoblast invasion converting SpA during early gestation, a process completed in the midst of the second trimester. Higher PI was found in SpA of complicated pregnancies compared to healthy pregnancies, possibly reflecting suboptimal utero-placental circulation. Longitudinal studies examining comprehensively the predictive value of spiral artery Doppler for complicated pregnancies are yet to be carried out.

Long-term Immune Response to Yellow Fever Vaccination in Human Immunodeficiency Virus (HIV)-Infected Individuals Depends on HIV RNA Suppression Status: Implications for Vaccination Schedule.

Background: In human immunodeficiency virus (HIV)-infected individuals, the immune response over time to yellow fever vaccination (YFV) and the necessity for booster vaccination are not well understood. Methods: We studied 247 participants of the Swiss HIV Cohort Study (SHCS) with a first YFV after HIV diagnosis and determined their immune responses at 1 year, 5 years, and 10 years postvaccination by yellow fever plaque reduction neutralization titers (PRNTs) in stored blood samples. A PRNT of 1:≥10 was regarded as reactive and protective. Predictors of vaccination response were analyzed with Poisson regression. Results: At vaccination, 82% of the vaccinees were taking combination antiretroviral therapy (cART), 83% had suppressed HIV RNA levels (<400 copies/mL), and their median CD4 T-cell count was 536 cells/µL. PRNT was reactive in 46% (95% confidence interval [CI], 38%-53%) before, 95% (95% CI, 91%-98%) within 1 year, 86% (95% CI, 79%-92%) at 5 years, and 75% (95% CI, 62%-85%) at 10 years postvaccination. In those with suppressed plasma HIV RNA at YFV, the proportion with reactive PRNTs remained high: 99% (95% CI, 95%-99.8%) within 1 year, 99% (95% CI, 92%-100%) at 5 years, and 100% (95% CI, 86%-100%) at 10 years. Conclusions: HIV-infected patients' long-term immune response up to 10 years to YFV is primarily dependent on the control of HIV replication at the time of vaccination. For those on successful cART, immune response up to 10 years is comparable to that of non-HIV-infected adults. We recommend a single YFV booster after 10 years for patients vaccinated on successful cART, whereas those vaccinated with uncontrolled HIV RNA may need an early booster.

Cumulative effect of maternal vascular malperfusion types in the placenta on adverse pregnancy outcomes.

INTRODUCTION: Placental vascular disease, characterized by Maternal Vascular Malperfusion (MVM) lesions, is considered to be the underlying cause of pregnancy complications. Aim is to evaluate the relationship between the cumulative number of MVM lesion types, and adverse pregnancy- and neonatal outcomes. METHODS: This retrospective cohort study included 272 women with singleton gestations who gave birth at a Dutch tertiary hospital between 2017 and 2018 with available placental histopathology reports. Analyzed according to the Amsterdam Placental Workshop Group Consensus Statement, placentas were divided into groups based on the cumulative number of MVM lesions: no lesions (n = 124), 1-2 types (n = 124) and 3-5 types of lesions (n = 24). RESULTS: The proportion of placenta syndrome (PS) was highest (95.8%) in the 3-5 MVM lesions group (p < 0.001). The presence of MVM lesions was highly associated with PS during pregnancy (aOR 6.81, 95% CI 3.76-12.33). Furthermore, every additional type of MVM lesion corresponded with a threefold increased odds for the occurrence of PS (aOR 3.00, 95% CI 2.10-4.29). The group with 3-5 types of MVM lesions showed the highest incidence of adverse neonatal outcomes, lower mean birth weight, prolonged hospitalization, NICU admissions and neonatal deaths (aOR 6.47, 95% CI 0.33-127.68), corresponding with a fourfold increased odds for the occurrence of neonatal death for every additional MVM lesion (aOR 4.19, 95% CI 1.39-12.68). DISCUSSION: A higher number of MVM lesion types is strongly associated with an increased incidence of adverse pregnancy- and neonatal outcomes, indicating that guidelines should focus also on the amount of MVM lesion types for the monitoring/management of subsequent pregnancies.

Second-Trimester Constituents of the Metabolic Syndrome and Pregnancy Outcome: An Observational Cohort Study.

Background: Gestational diabetes mellitus (GDM) increases the risk of type 2 diabetes mellitus and cardiovascular disease (CVD) in women in later life. In the general population, metabolic syndrome (MetS) shows identical associations. The aim of this study was to evaluate the association between GDM, constituents of MetS and pregnancy outcomes. Methods: Of 2041 pregnant women undergoing an oral glucose tolerance test (OGTT) between 22 and 30 weeks of gestation, data were collected to evaluate the constituents of MetS. Odds ratios (ORs) were calculated to determine the associations between MetS and pregnancy outcomes. Results: GDM and obesity did not affect the risk of fetal growth abnormalities (SGA/LGA), preterm birth or preeclampsia (PE). Hypertension significantly increased the risk of SGA (OR­1.59), PE (OR­3.14), and preterm birth <37 weeks (OR­2.17) and <34 weeks (OR­2.96) and reduced the occurrence of LGA (OR­0.46). Dyslipidemia increased the risk of PE (OR­2.25), while proteinuria increased the risk of PE (OR­12.64) and preterm birth (OR­4.72). Having ≥2 constituents increased the risk of PE and preterm birth. Conclusions: Constituents of metabolic syndrome, rather than treating impaired glucose handling, increased the risk of preeclampsia, altered fetal growth and preterm birth. Obesity was not related to adverse outcomes.

Role of Beta Cell Function and Insulin Resistance in the Development of Gestational Diabetes Mellitus.

BACKGROUND: Gestational diabetes mellitus (GDM) is a pregnancy complication characterized by second trimester hyperglycemia. Untreated, GDM is related to an increased risk for adverse pregnancy outcomes. Both beta cell dysfunction and insulin resistance underlie impaired glucose tolerance. Understanding the dominant mechanism predisposing to GDM may be important to provide effective treatment in order to improve perinatal outcomes. We hypothesize that insulin resistance rather that beta cell dysfunction predisposes to GDM. METHODS: A 75g oral glucose tolerance test (OGTT) was performed on 2112 second-trimester pregnant women to determine the relationship between insulin resistance (HOMA-IR), beta cell function (HOMA-ß), and the prevalence of abnormal glucose handling. RESULTS: High insulin resistance raised the risk of GDM (relative risk (RR) 6.1, 95% confidence interval (CI) (4.4-8.5)), as did beta cell dysfunction (RR 3.8, 95% CI (2.7-5.4)). High insulin resistance, but not beta cell function, enhances the necessity for additional glucose lowering medication on top of a low carbohydrate diet in women diagnosed with GDM. CONCLUSIONS: Both high insulin resistance and beta cell dysfunction increase the risk of GDM. As increased insulin resistance, rather than beta cell function, is related to an insufficient response to a low carbohydrate diet, we speculate that insulin sensitizers rather than insulin therapy may be the most targeted therapeutic modality in diet-insensitive GDM.

[HIV and AIDS: what's new in 2010?]. / VIH/SIDA: nombreuses nouveautés.

Antiretroviral therapy is now simpler than ever, with one tablet once daily being the gold standard for the development of new combinations. Indications for treatment initiation have now been extended before moderate immune suppression, taking in account not only the individual benefit, but also the public health aspect of preventing HIV transmission to a sexual partner. New preventing methods have been tested in 2010: microbicides as well as dual antiretroviral treatment in HIV-negative high risk population as a chemoprophylaxis have been published. If these last two tools offer some options for the future, their applicability at a large scale warrant further development.

Ultrasound evaluation of the placenta in healthy and placental syndrome pregnancies: A systematic review.

INTRODUCTION: An antepartum screening method to determine normal and abnormal placental function is desirable in the prevention of maternal and fetal pregnancy complications. Placental appearance can easily be obtained and evaluated using 2D ultrasonography, but surprisingly little is known about the change in placental appearance during gestation. Aim of this systematic review was to describe the antepartum placental appearance in placenta syndrome (PS) pregnancies, and to compare this to the appearance in healthy pregnancies. METHODS: A systematic review investigating placental thickness, -lakes and/or -calcifications by ultrasound examination in both uncomplicated (reference group) and PS pregnancies in relation to gestational age was performed. English literature was searched using PubMed (NCBI), EMBASE (Ovid) and the Cochrane Library, from database inception until September 2020. Data on placental thickness was presented as a continuous variable or as the proportion of abnormal placental thickness. Data on placental lakes and -calcifications was presented as prevalence (%). There was no restriction applied on the definition of placental lakes or -calcifications. Due to heterogeneity, pooling of the results was not performed. RESULTS: A total of 28 studies were included describing 1719 PS cases; consisting of 370 (21 %) cases with preeclampsia or pregnancy induced hypertension, 1341 (78 %) cases with fetal growth restriction (FGR) or small for gestational age (SGA), and 8 (1%) cases with combined clinical expressions. In addition, the reference group comprised 3315 pregnant women. Placental thickness showed an increase between the first and second trimester, which was higher in PS- compared to uncomplicated pregnancies. Placental lakes were frequently observed in FGR and SGA pregnancies, especially in the second trimester. Grade 3 calcifications were most prominent in the PS pregnancies, specifically in the late second and third trimester. Moreover, in the reference group, no grade 3 calcifications were reported before 35 weeks of gestation. CONCLUSION: Placental appearance in PS-pregnancies shows higher placental thickness and greater presence of placental lakes and -calcifications compared to uncomplicated pregnancies. Standardized definitions of (ab-)normal placental appearance and longitudinal research in both healthy and complicated pregnancies are needed to improve personalized obstetric care.

Preventing Recurrent Preeclampsia by Tailored Treatment of Nonphysiologic Hemodynamic Adjustments to Pregnancy.

[Figure: see text].

7T dynamic contrast-enhanced MRI for the detection of subtle blood-brain barrier leakage.

BACKGROUND AND PURPOSE: Dynamic contrast-enhanced MRI (DCE-MRI) can be employed to assess the blood-brain barrier (BBB) integrity. Detection of BBB leakage at lower field strengths (≤3T) is cumbersome as the signal is noisy, while leakage can be subtle. Utilizing the increased signal-to-noise ratio at higher field strengths, we explored the application of 7T DCE-MRI for assessing BBB leakage. METHODS: A dual-time resolution DCE-MRI method was implemented at 7T and a slow injection rate (0.3 ml/s) and low dose (3 mmol) served to obtain signal changes linearly related to the gadolinium concentration, that is, minimized for T2* degradation effects. With the Patlak graphical approach, the leakage rate (Ki ) and blood plasma volume fraction (vp ) were calculated. The method was evaluated in 10 controls, an ischemic stroke patient, and a patient with a transient ischemic attack. RESULTS: Ki and vp were significantly higher in gray matter compared to white matter of all participants. These Ki values were higher in both patients compared to the control subjects. Finally, for the lesion identified in the ischemic stroke patient, higher leakage values were observed compared to normal-appearing tissue. CONCLUSION: We demonstrate how a dual-time resolution DCE-MRI protocol at 7T, with administration of half the clinically used contrast agent dose, can be used for assessing subtle BBB leakage. Although the feasibility of DCE-MRI for assessing the BBB integrity at 3T is well known, we showed that a continuous sampling DCE-MRI method tailored for 7T is also capable of assessing leakage with a high sensitivity over a range of Ki values.

[Swiss statements: a two-year follow-up]. / "Swiss statement": bilan deux ans apres.

An HIV-positive individual who has no other sexually transmitted infection and is on an effective antiretroviral therapy will not transmit the virus by sexual contact. This statement was issued by the Swiss National AIDS Commission in January 2008. It rapidly became known as the "Swiss Statement", and initially provoked a wave of international opposition, fueled by the fear that it would jeopardize current prevention strategies. Two years later, no negative consequences of the "Swiss Statement" has been observed. On the contrary, it has encouraged research to develop new prevention strategies focusing largely on the use of antiretroviral treatment.

The "sex gap" in COVID-19 trials: a scoping review.

BACKGROUND: Many studies investigate the role of pharmacological treatments on disease course in Corona Virus Disease 2019 (COVID-19). Sex disparities in genetics, immunological responses, and hormonal mechanisms may underlie the substantially higher fatality rates reported in male COVID-19 patients. To optimise care for COVID-19 patients, prophylactic and therapeutic studies should include sex-specific design and analyses. Therefore, in this scoping review, we investigated whether studies on pharmacological treatment in COVID-19 were performed based on a priori sex-specific design or post-hoc sex-specific analyses. METHODS: We systematically searched PubMed, EMBASE, UpToDate, clinical trial.org, and MedRxiv for studies on pharmacological treatment for COVID-19 until June 6th, 2020. We included case series, randomized controlled trials, and observational studies in humans (≥18 years) investigating antiviral, antimalarial, and immune system modulating drugs. Data were collected on 1) the proportion of included females, 2) whether sex stratification was performed (a priori by design or post-hoc), and 3) whether effect modification by sex was investigated. FINDINGS: 30 studies were eligible for inclusion, investigating remdesivir (n = 2), lopinavir/ritonavir (n = 5), favipiravir (n = 1), umifenovir (n = 1), hydroxychloroquine/chloroquine (n = 8), convalescent plasma (n = 6), interleukin-6 (IL-6) pathway inhibitors (n = 5), interleukin-1 (IL-1) pathway inhibitors (n = 1) and corticosteroids (n = 3). Only one study stratified its data based on sex in a post-hoc analysis, whereas none did a priori by design. None of the studies investigated effect modification by sex. A quarter of the studies included twice as many males as females. INTERPRETATION: Analyses assessing potential interference of sex with (side-)effects of pharmacological therapy for COVID-19 are rarely reported. Considering sex differences in case-fatality rates and genetic, immunological, and hormonal mechanisms, studies should include sex-specific analyses in their design to optimise COVID-19 care. FUNDING: None.

The role of compartment penetration in PI-monotherapy: the Atazanavir-Ritonavir Monomaintenance (ATARITMO) Trial.

OBJECTIVES: To limit exposure to anti-HIV drugs and minimize risk of long-term side effects, studies have looked at the possibility of simplified maintenance strategies. Ritonavir-boosted protease-inhibitor (PI)-monotherapies are an attractive alternative, but limited compartmental penetration of PI remains a concern. DESIGN: Non-comparative 24-week pilot study. METHOD: Ritonavir-boosted atazanavir (ATV/r) monotherapy administered to fully suppressed patients (>3 month HIV RNA < 50 copies/ml). Plasma was obtained every 4 weeks and cerebrospinal fluid (CSF) and semen at W24. RESULTS: Two patients (7%) failed ATV/r monotherapy. One patient was subsequently identified as a protocol violator since he had a previous history of treatment failure under indinavir. The second patient deliberately decided to stop treatment after W20. Excluding failing patients, individual measurements of HIV RNA in patients having occasional viral 'blips' was found in five patients. At W24, 3/20 patients had elevated viral loads in CSF (HIV RNA > 100 copies/ml), and 2/15 in semen, despite viral suppression in plasma (< 50 copies/ml). Samples with elevated HIV RNA (> 500 copies/ml) in CSF were all wild type. The mean ATV drug concentration ratio (CSF/blood, n = 22) was 0.9%. Indicators of altered immune activation (CD8CD38 C-reactive protein) remained unchanged. CONCLUSION: This study supports previous results indicating the potential use of PI-based mono-maintenance therapies. However, our results in CSF cautions against the uncontrolled use of PI-based monotherapies.

Tenofovir-containing nucleoside/nucleotide-only antiretroviral maintenance therapy: decision making and virological outcome.

OBJECTIVE: To assess the virological outcome of patients with undetectable human immunodeficiency (HI) viremia switched to tenofovir (TDF)-containing nucleosideonly (NUKE-only) treatments and to investigate the factors influencing the physicians' decision for application of a nonestablished therapy. METHOD: Patients' characteristics and history were taken from the cohort database. To study the decision-making process, questionnaires were sent to all treating physicians. RESULTS: 49 patients were changed to TDF-containing NUKE-only treatment and 46 had a follow-up measurement of HI viremia. Virological failure occurred in 16 (35%) patients. Virological failure was associated with previous mono or dual therapy and with a regimen including didanosine or abacavir. No failure occurred in 15 patients without these predisposing factors. The main reasons for change to TDF-containing NUKE-only treatment were side effects and presumed favorable toxicity profile. The rationale behind this decision was mainly analogy to the zidovudine/lamivudine/abacavir maintenance therapy. CONCLUSION: TDF-containing NUKE-only treatment is associated with high early failure rates in patients with previous nucleoside reverse transcriptase inhibitor mono or dual therapy and in drug combinations containing didanosine or abacavir but not in patients without these predisposing factors. In HIV medicine, treatment strategies that are not evidence-based are followed by a minority of experienced physicians and are driven by patients' needs, mainly to minimize treatment side effects.

Plasma leptin levels in men are not related to the development of lipoatrophy during antiretroviral therapy.

OBJECTIVES: To assess the correlations between the hormone leptin and lipoatrophy in HIV-positive, treatment-naive patients on combination antiretroviral therapy (cART). DESIGN: Case-control study nested in a multicentre cohort of HIV-infected adults. Cases were patients that developed lipoatrophy and controls those who did not. PATIENTS AND METHODS: Clinical parameters and plasma leptin determinations were studied in 97 HIV-1-infected, treatment-naive Caucasian men (10 cases and 87 controls) on an unchanged and virologically successful drug regimen with a zidovudine/lamivudine backbone at baseline and after 2 years of cART. The association of plasma leptin levels and the development of lipoatrophy was investigated. RESULTS: Two years of cART was not associated with a change in plasma leptin levels. Plasma leptin levels remained sensible to changes in body mass index. There was no difference in leptin levels between patients who developed lipoatrophy and controls, neither before nor after cART. The only predictor of development of lipoatrophy was a higher age (P = 0.02). CONCLUSIONS: Leptin as measured in plasma is unlikely to play a major role in the genesis of lipoatrophy.

Long-term safety of discontinuation of secondary prophylaxis against Pneumocystis pneumonia: prospective multicentre study.

OBJECTIVES: To assess the long-term safety of discontinuation of secondary anti-Pneumocystis prophylaxis in HIV-infected adults treated with antiretroviral combination therapy and who have a sustained increase in CD4 cell counts. DESIGN: Prospective observational multicentre study. PATIENTS AND METHODS: The incidence of P. jirovecii pneumonia after discontinuation of secondary prophylaxis was studied in 78 HIV-infected patients on antiretroviral combination therapy after they experienced a sustained increase in CD4 cell counts to at least 200 x 10(6) cells/l and 14% of total lymphocytes measured twice at least 12 weeks apart. RESULTS: Secondary prophylaxis was discontinued at a median CD4 cell count of 380 x 10(6) cells/l. The median follow-up period after discontinuation of secondary prophylaxis was 40.2 months, yielding a total of 235 person-years of follow-up. No cases of recurrent P. jirovecii pneumonia occurred during this period. The incidence was thus 0 per 100 person-years with a 95% upper of confidence limit of 1.3 cases per 100 patient-years. CONCLUSIONS: Discontinuation of secondary prophylaxis against P. jirovecii pneumonia is safe even in the long term in patients who have a sustained immunologic response on antiretroviral combination therapy.

Tuberculosis risk varies with the duration of HIV infection: a prospective study of European drug users with known date of HIV seroconversion.

BACKGROUND: It is not known whether the risk of active tuberculosis disease varies with the length of time that individuals are infected with HIV. OBJECTIVE: To study how, independently of CD4 T cell count, the risk of tuberculosis varies with the duration of HIV infection. METHODS: Using Poisson regression analysis, the incidence of and risk factors for tuberculosis were studied in 683 injecting drug users (IDU) with a documented date of HIV seroconversion followed in seven cohorts in six European countries until 1998. RESULTS: Overall incidence was 11.5/1000 person-years. Adjusted for CD4 T cell count and geographic region, the risk ratio (RR) for tuberculosis (both pulmonary and extrapulmonary), compared with the first 3 years of HIV infection, was 2.8 for years 4 to 6 of HIV infection [95% confidence interval (CI), 1.3-6.3], 1.2 for year 7 to 9 (95% CI, 0.3-4.2) and 4.6 after 9 years (95% CI, 1.4-15.0). The adjusted RR for geographic region was 13.1 (95% CI, 4.3-40.0) for Amsterdam and 15.8 (95% CI, 4.8-52.0) for the Valencian region of Spain compared with all other sites combined. CONCLUSION: The risk of tuberculosis is increased relatively early in HIV infection (year 4 to 6) and also later (after year 9) with possibly a relatively silent period between. As expected, IDU in Southern Europe have a substantially higher risk of tuberculosis than IDU in Northern and Central Europe. Amsterdam forms an exception for Northern Europe, with very high incidence rates.

Low incidence of community-acquired pneumonia among human immunodeficiency virus-infected patients after interruption of Pneumocystis carinii pneumonia prophylaxis.

We compared the incidence of bacterial pneumonia among 336 patients who discontinued trimethoprim-sulfamethoxazole (TMP-SMX) as prophylaxis against Pneumocystis carinii pneumonia (PCP) with that among 75 patients who fulfilled the criteria for discontinuation but continued receiving prophylaxis. The difference in the overall incidence rates for the 2 groups (1.2 events per 100 person-years) was not statistically significant. Discontinuation of TMP-SMX prophylaxis against PCP is not associated with a significant increase in the incidence of bacterial pneumonia among patients with a sustained CD4 cell count increase to >200 cells/microL.

Pulmonary arterial hypertension related to HIV infection: improved hemodynamics and survival associated with antiretroviral therapy.

This study aimed to assess the long-term course of pulmonary arterial hypertension related to infection with human immunodeficiency virus (PAHRH) and the influence of antiretroviral therapy (ART) on its characteristics. We retrospectively analyzed all 47 patients in the Swiss HIV Cohort Study in whom PAHRH was diagnosed. Among 35 patients who underwent follow-up Doppler echocardiography, the right ventricular systolic pressure over right atrial pressure gradient increased by a median of 25 mm Hg in 9 patients who had not received ART, decreased by a median of 3 mm Hg in 12 patients who had received nucleoside analogs, and decreased by a median of 21 mm Hg in 14 patients who had received highly active ART (HAART) (P<.005). Among all 47 patients, median duration of survival after PAHRH diagnosis was 2.7 years. HAART significantly decreased mortality due to PAHRH as well as other causes. This study suggests a beneficial effect of combination ART in patients with PAHRH.