Forty-three MSM with acute HCV infection were identified. These patients constitute part of an emerging outbreak of HCV in HIV-positive men presenting to St Mary's Hospital, London. The risk factors for infection were intravenous, intramuscular, intranasal and intrarectal drug use (80%) and recent unprotected anal intercourse (94%). Fifty-three percent of patients were receiving treatment HAART at the time of infection. The median time from the last negative to the first positive RT–PCR was 96 days (IQR 70–119 days).
The median HCV viral load was 1 836 595 IU/ml. A variety of HCV genotypes were identified. Genotype 1a was the most prevalent (75%), genotype 4d occurred in 17.5% and genotypes 1b and 3a in 2.5%, respectively. One patient was coinfected with genotypes 1a and 4d.
The median CD4 cell count at the time of HCVacquisition was 570 cells/μl (). Patients who cleared infection spontaneously had a higher median CD4 cell count of 830 cells/μl than those who progressed to chronic infection (median CD4 cell count of 540 cells/μl; P=0.09). The median nadir CD4 cell count was 325 cells/μl. Those patients who spontaneously cleared infection also had a higher nadir CD4 cell count (median 440 cells/μl versus median 320 cells/μl; P=0.07). No correlation between CD4 cell count at the time of HCV diagnosis and seroconversion time was found (P=0.96). However, a weak negative association between nadir CD4 cell count and seroconversion time was observed (P=0.09).
The sensitivity of HCV PCR, antibody and alanine transaminase (ALT) was assessed at 1–3 monthly time-points. The median ALT at baseline was 65 IU/ml (normal <40 IU/ml). Elevated ALT levels were present in 76% of patients at baseline and 74% at 3 months. Most patients (88%) had an elevated ALTat either baseline or 3 months postinfection. An elevated ALT level was significantly more sensitive than antibody testing (P
=0.017). When a lower normal value of less than 30 IU/ml was used (recently proposed as normal in men [9
]), the sensitivity of ALT testing increased to 79% at baseline and 82% at 3 months. As many as 93% of patients had an ALT level higher than 30 IU/ml at either baseline or 3 months postinfection. The ALT levels at baseline and at 3 months postinfection were not significantly different in patents who cleared infection spontaneously from those who progressed to chronicity (P
=0.66 and 0.92, respectively).
On first amplification of HCV, only 25% of patients were serologically positive. Antibody detection rose from 63% by 3 months to 87% at 6 months, 90% at 9 months and 95% by 12 months ().
The median time from HCV RNA detection by PCR to the development of anti-HCV antibodies was estimated to be 91 days (range 0–1206 days). An analysis of seroconversion time in a subset of patients where the last negative and first positive RT–PCR were less than 30 days apart (n=8) revealed a median seroconversion time of 158 days (range 47–209 days). Two patients (4.7%) developed anti-HCV antibodies more than 1 year after the initial infection, one of whom did not become antibody positive until after 3 years. Seroconversion in one of these patients was associated with a superinfection with genotype 1a virus on a background of genotype 4 infection.
Seroconversion time in ‘spontaneous clearers’ and ‘progressors’ was not significantly different (P=0.88). However, seroconversion time was significantly longer in patients with a low HCV viral load (P=0.04) or low ALT (P=0.0005) at the time of the first positive PCR. A low ALT level at 3 months into HCV infection was also weakly associated with prolonged seroconversion time (P=0.08).
The early development of anti-HCV antibodies did not correlate with patient age (P=0.78), HCV genotype (P=0.51) or HIV viral load (P=0.22).