icon-folder.gif   Conference Reports for NATAP  
  12th Conference on Retroviruses and Opportunistic Infections (CROI)
Feb 22-25, 2005
Boston, MA
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Sexual HCV Transmission Reported Among MSM
  Reported by Jules Levin
"Homosexually Transmitted HCV Acute Infection Related to a Clustered Genotyope 4 HCV in HIV-1 Infected Men and Inefficacy of early Antiviral Therapy"
Marie-Laure Chaix reported at the 12th CROI reported on sexual transmission of HCV among men who have sex with men in Paris, France. HCV sexual transmission remains controversial. Recent studies suggested an increased frequency of HCV infections among homosexual HIV-1 infected men (Ghosen et al 2004, Brown et al 2004, Rauch et al 2004, Gotz et al 2004, Rauch 2005 #943).
We report a retrospective analysis of 12 cases of HCV acute infections in HIV-1 infected men in the recent period of time (2001-2004). These men were diagnosed with acute HCV, defined by both seroconversion of antiHCv antibodies and detection of serum HCV RNA in previously anti-HCV & HCV RNA-negative patients. We studied the response to early therapy with interferon. We investigated the phylogenetic lineage of the HCV strains. 12 HIV-1 infected patients, all homosexual men (median 40 years) were followed in 3 hospital centers in Paris; ALT/AST: 7.5/7.9 x UNL). Median seropositivity for HIV was 9 years. 9 of the 12 were on HAART. Median CD4 count was 625; mean HIV VL was 3.1 log copies/ml. 2 were symptomatic (jaundice) and 10 were asymptomatic and tested after sexual exposure or during routine follow-up of HIV-infection.
Detection of anti-HCV antibodies was done with a third generation ELISA test. HCV RNA was detected & quantified by PCR. Viral strains were genotyped using a line probe assay (LIPA). Clinical , biochemical, & virologic evaluations were done every 3 months. Among the 12 HCV strains, using LIPA they found 10 patients had genotype 4, 1 genotype 1a, and 1 genotype 3a.
The study authors reported that homosexual exposure was the only significant risk factor reported in this population. (Edit note from Jules Levin: the presence of HIV or an STD can increase the risk for HCV sexual transmission, so this may have been a factor). Phylogenetic analysis revealed that all 10 genotype 4 viruses were from subtype 4d. The 10 genotype 4d viruses formed a monophylogenetic group and clustered separately from other local sequences of HCV genotype 4d with a bootstrap value of 90%, suggesting a common source of infection.
2 patients refused treatment. 10 patients agreed to be treated & the median time between diagnosis & treatment was 50±22 days. Patients were treated with various different mostly standard interferon regimens (1 patient recd peginterferon), and only 2 patients received ribavirin. 4 patients discontinued treatment before week 12 because of side effects. None of the patients showed a sustained response to treatment defined as undetectable. 9 patients were non-responders (positive HCV RNA during and after treatment). 1 patient was a relapser (negative HCV RNA during treatment & positive HCV RNA after treatment). This is a different experience from other researchers who have reported a high sustained viral response rate when treating acute HCV. The authors suggested the poor response may in part be due to patients having genotypes 1 & 4, which are not very responsive to therapy. Recent results suggest that treatment of acute HCV in HIV+ patients with 6 months of Peg-IFN associated with ribavirin led to a high rate of sustained virologic response (Dominguez et al, Amsterdam, 2004, Vogel CROI 2005 #922, see below).
The authors concluded that these results demonstrate a risk for sexual transmission of HCV in HIV-infected men who have sex with men; a cluster of HCV genotype 4d suggesting a common source of infection over a 4 years period of time; and the breakdown in prevention counseling; and an inefficiency of early treatment with standard interferon of acute HCV in HIV-infected patients to prevent chronic evolution of HCV. HIV-infected patients should be regularly followed for liver enzymes and anti-HCV antibodies to early diagnose HCV infections.
In poster 922, Martin Vogel (Bonn Univ, Germany) reported results from treatment of acute HCV-infection in HIV-positive patients. This was a multicenter, prospective, non-randomized clinical trial. Main inclusion criteria were HIV+ patients with a CD4 count >300 and an acute HCV-infection defined by the simultaneous presence of 2 of the following 3 criteria within 4 months prior to diagnosis: known or suspected exposure to HCV, documented seroconversion to positivity for antibodies against HCV, or a serum ALT level of more than 350 IU/L with documented normal levels the year before infection. Patients were treated with pegylated interferon over 24 weeks; addition of ribavirin was recommended in case of HCV-genotype 1 or 4.
For these 17 patients, median age was 36 years. Atbaseline median ALT was 248 IU/L, median HCV RNA was 534 to 568 IU/mL, and median CD4 count was 426. Patients carried genotype 1 (n=10), 2 (n=2), 3 (n=3), or 4 (n=2). Of the treated patients, 82% (14/17) showed a negative HCV RNA at the end of treatment. Of the 14 responders, 9 had a normalized ALT at the end of treatment, while 5 of the responders and all 3 non-responders showed persistent low-level ALT elevations (<1.5 upper limit of normal). HCV RNA <600 IU/mL at 4 or 8 weeks was predictive for a virologic end of treatment response in 100% of responders; conversely, detectable HCV RNA (>600 IU/mL) at week 4 or 8 was predictive for a virologic non-response up to week 24 in all 3 non-responders.
The authors concluded that early interferon therapy of acute HCV-infection appears to achieve high virologic response rates in patients with HIV co-infection. Week 4 HCV RNA appears to be predictive for virologic end-of-treatment response in acute HCV infection.