| Abstract |
Chronic HCV (CHCV) is a leading cause of morbidity and mortality for HIV+ persons in the HAART era. With aggressive disease progression, low potential for spontaneous viral clearance and ineffective therapy in the setting of HIV coinfection, the NIH 2007 Plan for HIV-Related Research requests new approaches to HCV prevention and treatment. Preliminary data reveal that treatment of acute HCV (AHCV) among HIV+ persons results in Sustained Virologic Response rates up to 91%, dramatically higher than CHCV rates. Diagnosis is rarely made because most people are asymptomatic and HCV has been thought to precede HIV infection in most cases. Recent reports demonstrate an alarming rise in AHCV among HIV+ MSM in association with traumatic sexual practices and STIs in the absence of IDU, suggesting that sexual transmission is promoted via bleeding with sex, HIV and mucosal lesions. AHCV is increasingly reported in HIV+ injection/non-injection drug users. Case numbers are small, identified serendipitously or retrospectively, though early diagnosis may permit viral eradication, halt progression to CHCV, reduce adverse effects and costs with shorter therapy and allow interventions that may reduce transmission of both viruses. AHCV screening among HIV+ populations has not been investigated. We will develop, implement and evaluate a screening strategy among at-risk patients in an HIV clinic, hypothesizing that AHCV is more frequent than previously thought in the setting of high-risk sexual behavior among MSM, underappreciated in drug users and identifiable with routine, low-cost blood tests. Aims are to examine feasibility of screening based on risk factors and ALT and to estimate AHCV incidence in this pilot study. For identified cases, acquisition risks will be described to refine risk surveys for an NIH application. 100 HIV+ subjects with drug and/or sexual risk factors without CHCV/AHCV will be enrolled in a yearlong study to detect HCV in the acute state. At months 0, 3, 6 and 9 blood will be drawn for ALT and a second specimen drawn and held. ALT rise will trigger HCV RNA nucleic acid testing: for normal baseline, if follow-up ALT becomes abnormal or increases by >= 20 IU/mL; for abnormal baseline, if follow-up ALT is >= 1.5 times baseline. Baseline STI testing and a Behavioral Risk Questionnaire will be performed and repeated if HCV RNA or STI signs/symptoms are detected. Feasibility will be assessed using 3 outcomes: percent of study visits attended by the 100 subjects, percent of subjects dropping out prior to study's end, and by estimating the cost of the additional laboratory tests needed to discover cases. The rate of new cases will be calculated as the ratio of the number of cases divided by the total time in study for all participants. Findings will be used to support extramural funding for a multi-center study to determine precise modes of transmission and predictors of AHCV, epidemiology, incidence and biology and to develop and test broader screening strategies leading to prevention and treatment efforts. Dr. Taylor initiated and directs Miriam's Coinfection Clinic and studies approaches to HCV treatment and prevention for HIV+ populations.
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