These data demonstrate that host genetic factors can influence the clinical manifestations of acute HIV-1 infection and provide a functional link between HLA-B57 and viral immune control.
Background
Since 2000, there has been a marked rise in acute hepatitis C virus (HCV) in HIV-positive men who have sex with men (MSM). We conducted an international phylogenetic study to investigate the existence of an HCV transmission network among MSM.
Methods
HIV-positive MSM diagnosed with recent HCV (n=226) in England (107), Netherlands (58), France (12), Germany (25) and Australia (24) between 2000 and 2006 were enrolled into a molecular phylogenetic study. Using real-time PCR, the NS5B region of the HCV genome (436 bp) was amplified, sequenced and compared with unrelated NS5B sequences.
Results
NS5B sequences were obtained from 200 (89%) cases. Circulating HCV genotypes were 1a (59%); 4d (23%), 3a (11%), 1b (5%), and 2b/c (3%). Phylogenetic analysis revealed 156 (78%) sequences that formed 11 clusters (bootstrap value >70%) containing between 4 and 37 individual sequences. Country mixing was associated with larger cluster size (17 vs 4.5 sequences; p=0.03). ‘Molecular clock’ analysis indicated that the majority (85%) of transmissions occurred since 1996.
Discussion
Phylogenetic analysis revealed a large international network of HCV transmission among HIV-positive MSM. The rapid spread of HCV among neighboring countries is supported by the large proportion (74%) of European MSM infected with an HCV strain co-circulating in multiple European countries; the low evolutionary distances among HCV isolates from different countries; and the trend toward increased country mixing with increasing cluster size. Temporally, this epidemic coincides with the introduction of highly active anti-retroviral therapy and associated increases in sexual risk behaviors. International collaborative public health efforts are needed to mitigate HCV transmission among this population.
Objective To determine the effectiveness of extracorporeal shock wave therapy compared with placebo in the treatment of chronic plantar fasciitis. Design Randomised, blinded, multicentre trial with parallel group design. Setting Nine hospitals and one outpatient clinic in Germany. Participants 272 patients with chronic plantar fasciitis recalcitrant to conservative therapy for at least six months: 135 patients were allocated extracorporeal shock wave therapy and 137 were allocated placebo. Main outcome measures Primary end point was the success rate 12 weeks after intervention based on the Roles and Maudsley score. Secondary end points encompassed subjective pain ratings and walking ability up to a year after the last intervention. Results The primary end point could be assessed in 94% (n=256) of patients. The success rate 12 weeks after intervention was 34% (n=43) in the extracorporeal shock wave therapy group and 30% (n=39) in the placebo group (95% confidence interval − 8.0% to 15.1%). No difference was found in the secondary end points. Few side effects were reported. Conclusions Extracorporeal shock wave therapy is ineffective in the treatment of chronic plantar fasciitis.
A study was performed in 10 European health care centers in which 914 patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) who had elevated serum alanine aminotransferase (ALT) levels underwent liver biopsy during the period of 1992 through 2002. Overall, the METAVIR liver fibrosis stage was F0 in 10% of patients, F1 in 33%, F2 in 22%, F3 in 22%, and F4 in 13%. Predictors of severe liver fibrosis (METAVIR stage, F3 or F4) in multivariate analysis were age of >35 years (odds ratio [OR], 2.95; 95% confidence interval [CI], 2.08-4.18), alcohol consumption of >50 g/day (OR, 1.61; 95% CI, 1.1-2.35), and CD4+ T cell count of <500 cells/mm3 (OR, 1.43; 95% CI, 1.03-1.98). Forty-six percent of patients aged >40 years had severe liver fibrosis, compared with 15% of subjects aged <30 years. The use of antiretroviral therapy was not associated with the severity of liver fibrosis. In summary, severe liver fibrosis is frequently found in HCV-HIV-coinfected patients with elevated serum ALT levels, and its severity increases significantly with age. The rate of complications due to end-stage liver disease will inevitably increase in this population, for whom anti-HCV therapy should be considered a priority.
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