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Effective Detection of Acute Hepatitis C Infection Using RNA Screening and Antibody Testing in Young Injectors in San Francisco: The UFO Study
Kimberly Page-Shafer*1, P Lum1, J Hahn1, J Evans1, S Cooper2, L Tobler3, W Andrews4, B Phelps4, and M Busch3
1Univ of California, San Francisco, US; 2California Pacific Med Ctr, San Francisco, US; 3Blood Systems Res Inst, San Francisco, CA, US; and 4Chiron Corp, Emeryville, CA, US
Background: Acute hepatitis C virus (HCV) occurs mostly
among active at-risk injecting drug users (IDU). This acute period may have
important implications for the HCV epidemic, including high-risk behavior and
high infectivity possibly leading to increased secondary transmission to
uninfected partners. We demonstrate the utility of
identifying acute HCV using anti-HCV and sensitive RNA testing.
Methods: We enrolled 321 young IDU between 1999-2001 and
2003-2004 and followed them prospectively (quarterly) to detect acute and
incident HCV infection. Serum and plasma samples, respectively, were
systematically tested for anti-HCV using 2 enzyme immunoassays (EIA-2 and EIA-3), confirmed using HCV
RIBA™-3.0 Test System, and for HCV RNA
using transcription-mediated amplification testing with the Procleix
HIV-1/HCV Assay. HCV viremia and ALT were assessed
retrospectively from frozen sera. After detection of HCV infection,
participants were asked to return monthly.
Results: We detected 93 new HCV infections over 353
person-years of observation; Observed HCV incidence was 26% (95%CI 21% to 32%).
In addition, 23 anti-HCV/HCV RNA+ were identified at
baseline, but were not followed. Including these, HCV incidence is estimated at
32% (95%CI, 27% to 38%) (based on a 50.9 day window
period). Median age was 22, median years injecting was 3 years, 62% were male, 80% Caucasian. Of 93 infections 34 (37%) were
detected in the acute window (anti-HCV/HCV RNA+); 59
(63%) were detected using anti-HCV. Using the between-visit midpoint as a time
of infection, median time to detection of HCV RNA was 57.8 days (95%CI 46 to
110), 60.5 days (95%CI 43 to 121) to detection of anti-HCV using EIA 3.0, and
80.5 days using EIA 2.0 (95%CI 49 to 150). Abnormal alanine
aminotransferases (ALT) was detected in 28 of 71
(39%) TMA reactives. Unusual
profiles, including intermittent low-level HCV RNA for months preceding
seroconversion were also detected by the high-sensitivity RNA screening.
Conclusions: IDU
are known to be at high risk for HCV, and despite risk reduction counseling,
incidence is high, >25%. Over a third of new infections were detected prior
to seroconversion by RNA screening in antibody negatives. EIA 3.0 anti-HCV
testing detected HCV 20 days earlier than EIA 2.0. Immunology and clinical
studies of HCV will be benefit from earlier detection and confirmation of HCV
infection using these methods.
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