Longer prior exposure to zidovudine/lamivudine-containing combination antiretroviral therapy, age, and male gender are each associated with reduced subcutaneous adipose tissue

Whether zidovudine (AZT)-associated lipoatrophy occurrence differs by concomitant exposure to protease (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs) remains unclear. Baseline body composition data from a randomized trial in subjects stable on first-line AZT-based therapy were used to explore this issue.

CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE

Background Most adults infected with HIV achieve viral suppression within a year of starting combination antiretroviral therapy (cART). It is important to understand the risk of AIDS events or death for patients with a suppressed viral load. Methods and Findings Using data from the Collaboration of Observational HIV Epidemiological Research Europe (2010 merger), we assessed the risk of a new AIDS-defining event or death in successfully treated patients. We accumulated episodes of viral suppression for each patient while on cART, each episode beginning with the second of two consecutive plasma viral load measurements <50 copies/µl and ending with either a measurement >500 copies/µl, the first of two consecutive measurements between 50–500 copies/µl, cART interruption or administrative censoring. We used stratified multivariate Cox models to estimate the association between time updated CD4 cell count and a new AIDS event or death or death alone. 75,336 patients contributed 104,265 suppression episodes and were suppressed while on cART for a median 2.7 years. The mortality rate was 4.8 per 1,000 years of viral suppression. A higher CD4 cell count was always associated with a reduced risk of a new AIDS event or death; with a hazard ratio per 100 cells/µl (95% CI) of: 0.35 (0.30–0.40) for counts <200 cells/µl, 0.81 (0.71–0.92) for counts 200 to <350 cells/µl, 0.74 (0.66–0.83) for counts 350 to <500 cells/µl, and 0.96 (0.92–0.99) for counts ≥500 cells/µl. A higher CD4 cell count became even more beneficial over time for patients with CD4 cell counts <200 cells/µl. Conclusions Despite the low mortality rate, the risk of a new AIDS event or death follows a CD4 cell count gradient in patients with viral suppression. A higher CD4 cell count was associated with the greatest benefit for patients with a CD4 cell count <200 cells/µl but still some slight benefit for those with a CD4 cell count ≥500 cells/µl.

Impact of antiretroviral therapy on tuberculosis incidence among HIV-positive patients in high-income countries

The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We aim to estimate the effect of cART on tuberculosis incidence in HIV-positive individuals in high-income countries.

Renal function in patients with HIV starting therapy with tenofovir and either efavirenz, lopinavir or atazanavir

Tenofovir is associated with reduced renal function, but it is not clear whether there is a greater decline in renal function when tenofovir is co-administered with a boosted protease inhibitor rather than with a nonnucleoside reverse transcriptase inhibitor (NNRTI).

Metabolic syndrome and the risk of calcium stones

The metabolic syndrome (MS) is associated with increased prevalence of kidney stones, yet the specific stone type remains largely unknown. This study was conducted to assess whether risk factors associated with calcium nephrolithiasis increase with individual characteristics of the MS.

Unhealthy alcohol use, HIV infection and risk of liver fibrosis in drug users with hepatitis C

Aim To analyze alcohol use, clinical data and laboratory parameters that may affect FIB-4, an index for measuring liver fibrosis, in HCV-monoinfected and HCV/HIV-coinfected drug users. Patients and Methods Patients admitted for substance abuse treatment between 1994 and 2006 were studied. Socio-demographic data, alcohol and drug use characteristics and clinical variables were obtained through hospital records. Blood samples for biochemistry, liver function tests, CD4 cell count, and serology of HIV and HCV infection were collected at admission. Multivariate linear regression was used to analyze the predictors of FIB-4 increase. Results A total of 472 (83% M, 17% F) patients were eligible. The median age at admission was 31 years (Interquartile range (IQR) 27–35 years), and the median duration of drug use was 10 years (IQR 5.5–15 years). Unhealthy drinking (>50 grams/day) was reported in 32% of the patients. The FIB-4 scores were significantly greater in the HCV/HIV-coinfected patients (1.14, IQR 0.76–1.87) than in the HCV-monoinfected patients (0.75, IQR 0.56–1.11) (p<0.001). In the multivariate analysis, unhealthy drinking (p = 0.034), lower total cholesterol (p = 0.042), serum albumin (p<0.001), higher GGT (p<0.001) and a longer duration of addiction (p = 0.005) were independently associated with higher FIB-4 scores in the HCV-monoinfected drug users. The effect of unhealthy drinking on FIB-4 scores disappeared in the HCV/HIV-coinfected patients, whereas lower serum albumin (p<0.001), a lower CD4 cell count (p = 0.006), higher total bilirubin (p<0.001) and a longer drug addiction duration (p<0.001) were significantly associated with higher FIB-4 values. Conclusions Unhealthy alcohol use in the HCV-monoinfected patients and HIV-related immunodeficiency in the HCV/HIV-coinfected patients are important risk factors associated with liver fibrosis in the respective populations.

Should aortic arch replacement be performed during initial surgery for aortic root aneurysm in patients with Marfan syndrome?

OBJECTIVES: The aim of this study was to investigate whether total arch replacement (TAR) during initial surgery for root aneurysm should be routinely performed in patients with Marfan syndrome (MFS). METHODS: Retrospective analysis of 94 consecutive MFS patients fulfilling Ghent criteria who underwent 148 aortic surgeries and were followed at this institution during the past 16 years. RESULTS: The mean follow-up interval was 8.8 ± 7 years. Initial presentation was acute aortic dissection (AAD) in 35% of patients (76% Type A and 24% Type B) and aneurismal disease in 65%. TAR was performed in 8% of patients during initial surgery for AAD (otherwise a hemi-arch replacement was performed) and 1.6% in elective root repair. Secondary TAR had to be performed in only 3% of patients without, but in 33% following AAD (33% Type A and 33% Type B; P = 0.0001). Thirty-day, 6-month, 1-year and overall mortalities were 3.2, 5.3, 6.4 and 11.7%, respectively. Operative and 30-day mortalities in secondary aortic arch replacement were zero. Secondary TAR after AAD did not increase the need for the replacement of the entire thoracoabdominal aorta during follow-up compared with patients without secondary TAR (37 vs 40%, P = 1.0). CONCLUSIONS: MFS patients undergoing elective root repair have small risk of reinterventions on the aortic arch, and primary prophylactic replacement does not seem to be justified. In patients with AAD, the need for reinterventions is precipitated by the dissection itself and not by limiting the procedure to the hemi-arch replacement in the emergency setting. Limiting surgery to the aortic root, ascending aorta and proximal aortic arch is associated with low mortality in MFS patients presenting with AAD.

A novel SCN5A mutation, F1344S, identified in a patient with Brugada syndrome and fever-induced ventricular fibrillation

OBJECTIVE: Brugada syndrome (BS) is an inherited electrical cardiac disorder characterized by right bundle branch block pattern and ST segment elevation in leads V1 to V3 on surface electrocardiogram that can potentially lead to malignant ventricular tachycardia and sudden cardiac death. About 20% of patients have mutations in the only so far identified gene, SCN5A, which encodes the alpha-subunit of the human cardiac voltage-dependent sodium channel (hNa(v)1.5). Fever has been shown to unmask or trigger the BS phenotype, but the associated molecular and the biophysical mechanisms are still poorly understood. We report on the identification and biophysical characterization of a novel heterozygous missense mutation in SCN5A, F1344S, in a 42-year-old male patient showing the BS phenotype leading to ventricular fibrillation during fever. METHODS: The mutation was reproduced in vitro using site-directed mutagenesis and characterized using the patch clamp technique in the whole-cell configuration. RESULTS: The biophysical characterization of the channels carrying the F1344S mutation revealed a 10 mV mid-point shift of the G/V curve toward more positive voltages during activation. Raising the temperature to 40.5 degrees C further shifted the mid-point activation by 18 mV and significantly changed the slope factor in Na(v)1.5/F1344S mutant channels from -6.49 to -10.27 mV. CONCLUSIONS: Our findings indicate for the first time that the shift in activation and change in the slope factor at a higher temperature mimicking fever could reduce sodium currents' amplitude and trigger the manifestation of the BS phenotype.

Acute partial Budd-Chiari syndrome and portal vein thrombosis in cytomegalovirus primary infection: a case report

BACKGROUND: Splanchnic vein thrombosis may complicate inherited thrombotic disorders. Acute cytomegalovirus infection is a rare cause of acquired venous thrombosis in the portal or mesenteric territory, but has never been described extending into a main hepatic vein. CASE PRESENTATION: A 36-year-old immunocompetent woman presented with acute primary cytomegalovirus infection in association with extensive thrombosis in the portal and splenic vein. In addition, a fresh thrombus was evident in the right hepatic vein. A thorough evaluation for a hypercoagulable state was negative. The clinical course, biological evolution, radiological and histological findings were consistent with cytomegalovirus hepatitis complicated by a partial acute Budd-Chiari syndrome and portal thrombosis. Therapeutic anticoagulation was associated with a slow clinical improvement and partial vascular recanalization. CONCLUSION: We described in details a new association between cytomegalovirus infection and acute venous thrombosis both in the portal vein and in the right hepatic vein, realizing a partial Budd-Chiari syndrome. One should be aware that this rare thrombotic event may be complicated by partial venous outflow block.

Stable virulence levels in the HIV epidemic of Switzerland over two decades

OBJECTIVE: To determine whether the virulence of HIV-1 has been changing since its introduction into Switzerland. DESIGN: A prospective cohort study of HIV-1 infected individuals with well-characterized pre-therapy disease history. METHODS: To minimize the effect of recently imported viruses and ethnicity-associated host factors, the analysis was restricted to the white, north-west-European majority population of the cohort. Virulence was characterized by the decline slope of the CD4 cell count (n = 817 patients), the decline slope of the CD4:CD8 ratio (n = 815 patients) and the viral setpoint (n = 549 patients) in untreated patients with sufficient data points. Linear regression models were used to detect correlations between the date of diagnosis (ranging between 1984 and 2003) and the virulence markers, controlling for gender, exposure category, age and CD4 cell count at entry. RESULTS: We found no correlation between any of the virulence markers and the date of diagnosis. Inspection of short-term trends confirmed that virulence has fluctuated around a stable level over time. CONCLUSIONS: The lack of long-term time trends in the virulence markers indicates that HIV-1 is not evolving towards increasing or decreasing virulence at a perceptible rate. Both highly virulent and attenuated strains have apparently been unable to spread at the population level. This result suggests that either the evolution of virulence may be slow or inhibited due to evolutionary constraints, or HIV-1 may have already evolved to optimal virulence in the human host.

Correlates of self-reported nonadherence to antiretroviral therapy in HIV-infected patients: the Swiss HIV Cohort Study

BACKGROUND: Adherence is one of the most crucial issues in the clinical management of HIV-infected patients receiving antiretroviral therapy (ART). METHODS: A 2-item adherence questionnaire was introduced into the Swiss HIV Cohort Study in July 2003. All 3607 eligible patients were on ART for > or =6 months and their current regimen for > or =1 month. Three definitions of nonadherence were considered: missing > or =1 dose, missing > or =2 doses, and taking <95% of doses in the past 4 weeks. RESULTS: Over 30% of patients reported missing > or =1 dose, 14.9% missed > or =2 doses, and 7.1% took <95% of doses in the previous 4 weeks. The rate of drug holidays was 5.8%. Whether using more or less conservative definitions of nonadherence, younger age, living alone, number of previous regimens, and boosted protease inhibitor regimens were independent factors associated with nonadherence. There was a significant association between optimal viral suppression and nonadherence as well as a significant linear trend in optimal viral suppression by missed doses. CONCLUSIONS: Younger age, lack of social support, and complexity of therapy are important factors that are related to nonadherence with ART. Investment in behavioral dimensions of HIV is crucial to improve adherence in ART recipients.

Hepatitis C virus and non-Hodgkin's lymphoma: Findings from the Swiss HIV Cohort Study

Infections with hepatitis C virus (HCV) and, possibly, hepatitis B virus (HBV) are associated with an increased risk of non-Hodgkin's lymphoma (NHL) in the general population, but little information is available on the relationship between hepatitis viruses and NHL among people with HIV (PHIV). We conducted a matched case-control study nested in the Swiss HIV Cohort Study (SHCS). Two hundred and ninety-eight NHL cases and 889 control subjects were matched by SHCS centre, gender, age group, CD4+ count at enrollment, and length of follow-up. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were computed using logistic regression to evaluate the association between NHL and seropositivity for antibodies against HCV (anti-HCV) and hepatitis B core antigen (anti-HBc), and for hepatitis B surface antigen (HBsAg). Anti-HCV was not associated with increased NHL risk overall (OR = 1.05; 95% CI: 0.63-1.75), or in different strata of CD4+ count, age or gender. Only among men having sex with men was an association with anti-HCV found (OR = 2.37; 95% CI: 1.03-5.43). No relationships between NHL risk and anti-HBc or HBsAg emerged. Coinfection with HIV and HCV or HBV did not increase NHL risk compared to HIV alone in the SHCS.

Prospective genetic screening decreases the incidence of abacavir hypersensitivity reactions in the Western Australian HIV cohort study

Abacavir therapy is associated with significant drug hypersensitivity in approximately 8% of recipients, with retrospective studies indicating a strong genetic association with the HLA-B*5701 allele. In this prospective study, involving 260 abacavir-naive individuals (7.7% of whom were positive for HLA-B*5701), we confirm the usefulness of genetic risk stratification, with no cases of abacavir hypersensitivity among 148 HLA-B*5701-negative recipients.

Frequency of gynecologic follow-up and cervical cancer screening in the Swiss HIV cohort study

BACKGROUND: According to current recommendations, HIV-infected women should have at least 1 gynecologic examination per year. OBJECTIVES: To analyze factors associated with frequency of gynecologic follow-up and cervical cancer screening among HIV-infected women followed in the Swiss HIV Cohort Study (SHCS). METHODS: Half-yearly questionnaires between April 2001 and December 2004. At every follow-up visit, the women were asked if they had had a gynecologic examination and a cervical smear since their last visit. Longitudinal models were fitted with these variables as outcomes. RESULTS: A total of 2186 women were included in the analysis. Of the 1146 women with complete follow-up in the SHCS, 35.3% had a gynecologic examination in each time period, whereas 7.4% had never gone to a gynecologist. Factors associated with a poor gynecologic follow-up were older age, nonwhite ethnicity, less education, underweight, obesity, being sexually inactive, intravenous drug use, smoking, having a private infectious disease specialist as a care provider, HIV viral load <400 copies/mL, and no previous cervical dysplasia. No association was seen for living alone, CD4 cell count, and positive serology for syphilis. CONCLUSIONS: Gynecologic care among well-followed HIV-positive women is poor and needs to be improved.

Recurrent acute and chronic pancreatitis in two brothers with familial chylomicronemia syndrome

The chylomicronemia syndrome is well recognized as a rare etiologic factor of acute pancreatitis; however, whether hypertriglyceridemia can cause chronic pancreatitis (CP) remains unclear. We describe the long-time course of 2 brothers with the familial chylomicronemia syndrome caused by identical compound heterozygous mutations in the lipoprotein lipase (LPL) gene with markedly reduced LPL activity. Other etiologic factors were excluded, including mutations in the PRSS1, SPINK1, and CFTR gene. Although both brothers had recurrent acute pancreatitis and the same LPL genotype, CP became evident in only one patient. Progression to CP was associated with a more severe disease course. Thus, the chylomicronemia syndrome may cause CP in the absence of other known causative factors, and similar to alcoholic and hereditary CP, a more severe disease course is associated with disease progression.