Acute hepatitis C infection is recognized in HIV-infected men who have sex with men (MSM), but the risk in HIV-negative MSM remains unclear. We evaluated a population of MSM with acute hepatitis C. From January 2010 to May 2014, all cases of HCV antibody positive HIV-negative MSM were identified. European AIDS Network criteria were applied to determine acute infection, and 44 individuals fulfilled the criteria for acute hepatitis C. Ten were RNA negative at baseline and classed as prior spontaneous clearance. 15 (34.1%) had a previously negative HCV antibody within 1 year. 11 (25.0%) had significant elevation in ALT levels, and 18 (40.9%) were clinically diagnosed from risk exposure and history. Median age was 37 years (range 24-75). 41 (93.2%) individuals reported unprotected anal sex, 36 with (87.8%) both insertive and receptive intercourse, 4 (9.8%) with receptive intercourse, 1 (2.4%) with insertive intercourse, and no data were recorded for 3 (7.3%) patients. Individuals had an average of 7.3 reported (median 2, range 1-100) partners. 12 (27.3%) engaged in group sex, 11 (25.0%) practised fisting, 11 (25.0%) admitted using drugs during sexual activity, 16 (36.4%) reported nasal, and 9 (20.5%) reported injection drug use. 14 (31.8)% had unprotected sex whilst under the influence of recreational drugs. 29 individuals were aware of a partner's status. 2 (4.5%) individuals had sexual contact with a known HCV monoinfected partner, 13 (29.5%) with a HIV monoinfected partner and 6 (13.6%) with a HCV/HIV coinfected partner. 9 (20.5%) reported a partner/partners with no known infection. No data were available in 14 (31.8%) individuals. 13 (29.5%) individuals had a coexisting STI at the time of acute HCV diagnosis. 8 (18.2%) received HIV postexposure prophylaxis (PEP) within the 6 months prior to the HCV diagnosis (2 were participants in a HIV pre-exposure prophylaxis trial). 15 (34.1%) individuals achieved spontaneous clearance of HCV, and 11 patients received HCV treatment. Similar to the ongoing epidemic of acute HCV infection in HIV+ MSM, HIV-negative MSM remain at risk.
Pegylated interferon-a (PEG-IFN-a) forms an integral part of the current treatment for hepatitis C virus (HCV) infection. PEG-IFN-a suppresses HCV production by augmenting the innate antiviral immune response. Recent studies have reported the induction of hepcidin, the iron regulatory hormone, by IFN-a in vitro. As hepcidin plays an important role in innate immunity, we hypothesized that this finding may be of clinical relevance to HCV and investigated the changes in iron homeostasis during the first 24 hours of treatment. Blood samples were obtained from HCV patients immediately prior to and 6, 12, and 24 hours following the first dose of PEG-IFN-a/ribavirin (RBV). Samples were analyzed for hepcidin, cytokine, iron levels, and HCV viral load, and hepcidin messenger RNA (mRNA) expression was quantified in peripheral blood mononuclear cells. Hepcidin induction by IFN-a was further analyzed in cell culture. In HCV patients a single dose of PEG-IFN-a/RBV resulted in a significant increase in serum hepcidin, peaking at 12 hours, coinciding with a 50% reduction in serum iron and transferrin saturation over the 24-hour period. Patients with a !2 log decline in HCV viral load over the first 24 hours had significantly lower SI and TS levels at 12 and 24 hours. Moreover, 24-hour SI levels were an independent predictor of the immediate HCV viral decline, an indicator of ultimate treatment outcome. In cell culture, a direct induction of hepcidin by IFN-a was seen, controlled by the STAT3 transcription factor. Conclusion: Hepcidin induction occurs following the initiation of PEG-IFN-a treatment for HCV, and is mediated by way of STAT3 signaling. The subsequent hypoferremia was greatest in those with the most significant decline in viral load, identifying systemic iron withdrawal as a marker of immediate interferon-a efficacy in HCV patients. (HEPATOLOGY 2012;56:492-500)
Screening and treatment of sexually transmissible infections, including HIV, are free in the UK nations; pre-exposure prophylaxis (PrEP) became free in England in October 2017 through the PrEP Impact trial. Doctor-led PrEP clinics started at 56 Dean Street in September 2015, with the drug purchased privately at full price. The service was expanded to other staff to support initiation and monitoring of increasing numbers of attendees purchasing PrEP from online pharmacies. Nonetheless, when the clinic was given a target of 1700 for the PrEP Impact trial, it was clear this could not be achieved in a timely manner through 56 Dean Street alone. To prepare for the trial, all staff with HIV testing competencies were trained in good clinical practice and trial-specific procedures, and a patient group directive was approved to facilitate nurse prescribing and dispensing. Electronic pro formas to capture eligibility for starting or continuing PrEP were adapted for the Dean Street Express clinic, with some information collected directly from service users using touch screens. These interventions, together with an update to the 2016 information leaflet developed by the community, enabled enrolment and follow-up of 1700 participants in 4 months. PrEP advice and monitoring were easily accommodated in the 56 Dean Street sexual health service, but did require additional training and approval for nurse prescribing and dispensing drug in order to achieve the target, which still fell short of the demand.
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