A high prevalence of HCV is found among persons with blood exposures. HCV is transmitted by needle-stick exposures about 8 times more often than HIV, so individuals who acquire HIV through IVDU have a high risk of also acquiring HCV. Low socioeconomic status is also considered a risk factor. The risk of sexual transmission is controversial. Discussion below includes a study of the risk for sexual transmission among homosexual men. I've seen various studies report 5-15% incidence by sexual transmission. Whether exposure to blood is necessary for HCV transmission is controversial. HCV RNA has been detected in genital fluids, and HCV infection occurs more often in persons with high risk sexual practices. Individuals with multiple sex partners appear to be more at risk for HCV infection, while individuals in long-term monogomous relationships appear to remain uninfected. Mother to infant transmission can occur but it's uncommon. However, the risk appears to increase if the mother is HIV-infected. Partners of people with HCV should avoid sharing razors or tooth brushes.

M Bochet and C Katlama reported a follow-up on study exploring the impact of HAART protease inhibitor (PI) containing therapy on liver fibrosis. In the study group of 172 HCV/HIV co-infected individuals, HCV duration was 14 years, CD4 count was 327, HIV viral load (available in 122 patients) was 1230 copies/ml, 48 self-reported alcohol consumption >50 g/day. At the time of receiving a liver biopsy, 58 patients had received PI therapy for 14 months. FPR (fibrosis progression rate) was defined as the ratio between fibrosis progression and the amount of time having had HCV. Alcohol consumption was not different whether the person had received PI therapy or not.

Statistical analysis (logistic regression) found 3 independent risk factors for high fibrosis progression rate:

• CD4 count <200 (OR=15, p=0.006)
• no previous treatment with a PI (OR=22, p=0.01)
• alcohol consumption >50 g/day (OR=65, p=0.004)

The duration of PI therapy was higher in people with low FPR than in those with high FPR (13 vs 8 months, p=0.03), suggesting to me the longer and/or better HIV suppression one has may contribute to less HCV progression. I think it's possible that full HIV viral load suppression by any regimen, whether itís a PI, NNRTI, or triple NRTI combination, may also lead to the same results they saw in this study of PI regimens.

For more background details on th Bochet study, please read the summary study reported from its presentation at the Dallas AASLD meeting. Its available on the NATAP web site in the Conference Reports section (http://www.natap.org/nov/report_5_from_dallas_11499.html)

Treatment of HCV with Interferon+Ribivarin in HCV/HIV Co-Infection

D Dieterich, K Weisz, D Goldman and others reported a 12 month follow-up from their small study (mean age 40 yrs) of treating HCV/HIV co-infection with interferon 3 MIU 3X/week (n=10) or combination interferon+ribivarin (n=11). The IFN alone group crossed over after 3 months to IFN+RBV. 19/21 were receiving HAART with either AZT or d4T. Although they could observe the effect of the in vitro finding that RBV inhibits phosphorylation of AZT and d4T, they did not actually study the effect of phosphorylation by ribivarin on AZT and d4T. Median liver biopsy score was 1.9 for both groups. After 3 months, HCV-RNA (viral load) for individuals receiving IFN alone did not decrease, but their CD4s remained the same and HIV-RNA decreased from 1500 to <400 copies/ml. While at 3 months for those receiving IFN+RBV, their HCV-RNA decreased from 325,000 to 600 copies/ml (4/8 had undetectable HCV viral load). Their absolute CD4 counts declined from 544 to 237, and their median HIV viral load remained <400 copies/ml. It is thought that absolute count doesn't matter if CD4 percent remains the same and in this study the percent remained about the same. After a while on IFN+RBV therapy, the absolute count may rebound back to where it was prior to HBV+RBV therapy. After 3 months all patients receiving IFN alone added RBV.

At 12 months, the median HCV viral load was undetectable for the group receiving IFN+RBV from the beginning. Their CD4 count was 311, and HIV viral load was <400 in 4/4 patients (I said the study was small). After irritability, the main adverse event was anemia. It occurred more often in the RBV+IFN group (5/11) than for those receiving IFN alone (1/10). But apparently, the anemia can be successfully treated with erythropoietin (r-HuEPO). All patients with Hgb (hemoglobin) <10g/dL were treated with 40,000 units of recombinant human erythropoietin for at least 3 months. After about 4 weeks Hgb increased to 12.7 g/dL in 4/5 patients in the IFN+RBV group and after 8 weeks in the remaining patient. 1 patient discontinued the study due to intractable anemia. The 1 patient in the IFN alone group responded to erythropoietin after 8 weeks of treatment. Since 19/21 patients were taking AZT or d4T and all in the RBV+IFN group reduced HCV viral load from a median 325,000 copies/ml at baseline to undetectable, this suggests that the potential interaction previously seen in vitro between RBV and d4T and AZT may not be a problem.

M Perez-Olmeda reporting for a Spanish research group also reported on a small study (n=18; mean age 33) of IFN+RBV in HCV/HIV co-infected individuals. They had previously been treated with IFN monotherapy for 1 year without achieving a sustained virologic response (6 non-responders and 11 relapsers. All but 1 person were IVDUs. The mean Knodell index was 9.11. All had CD4s >200 and 11 were receiving ART for their HIV. Patients received IFN 3 MIU 3X/week plus ribivarin 1000/1200 mg/day for 6 months. 6/11 patients (54%) who completed the 6 months therapy had virologic response (undetectable HCV-RNA). They also had abiochemical response which means normalized AST and ALT. 7 patients (38%) did not complete the 6 month course of treatment. Loss of follow-up occurred for 4, and suicidal ideation, deficient compliance, and anemia were reported as causes of treatment withdrawal in the other cases. The authors reported that HIV viral load and CD4 counts remained unchanged in all patients during RBV+IFN therapy. As expected, relapsers responded better than previous non-responders (5/6 vs 1/6; p<0.05). A sustained response (6 months after stopping therapy) was seen in 5 patients. The one relapser had genotype 1. Those having genotype 3 in this study tended to respond much better than those infected with genotype 1 or 4.

Craib and others from British Columbia, Vancouver reported on this study to determine HCV prevalence and identify risk factors in a group of sexually active homosexual men followed over time. A random sample of 232 men were selected from 1000 men. Of these 112 were HIV negative and 120 were HIV positive. The most recent serum collected from each person was tested for HCV antibody. Of the 232 men, 20 (8.6%) were HCV+. HCV prevalence was significantly higher (6-fold) among HIV+ than HIV- men (17/120 -14%- vs 3/112 -2.7%). HCV+ men had more sexual partners in the past year (>= 20 partners: 80% vs 40%), and in their lifetime (>=100 partners: 90% vs 61%). They also had greater incidence of receptive fisting (30% vs12%; p=0.40), insertive fisting (55% vs 25%; p=0.004), more often reported receptive oral-anal contact (100% vs 85%; p=0.067), more often reported injection drug use (21% vs 2%; p<0.001), cocaine use (50% vs 24%; p=0.013), MDA use (70% vs 36%; p=0.003), and amphetamine use (30% vs 13%; p=0.056).

Multivariate analysis showed injection drug use (p=0.024), being HIV+ (p=0.056), low education level (p=0.031) and insertive fisting (p=0.032) to be independent risk factors for being HCV+.

Low CD4 Count (<200) Correlates with HCV Progression. J Tor for a German nd Spanish research group compared HCV/HIV co-infected cases (n=105), to a group with only HCV (n=57). All received biopsies, and co-infected individuals had Knodell index of 5.44, while those with HCV alone had 4.77 (p=0.115). Although ALT, AST, CD4s, and HIV & HCV viral loads were not related to hepatic inflammation at the time of biopsy, ALT & AST, and a previous CD4 count <200 were correlated with the degree of hepatic fibrosis.

Mark Kaplan and others from the North Shore Hospital in Manhasset, Long Island reported on a study comparing HIV-infected persons with CCR5 deletion heterozygotes (n=16) to people without the deletion (n=55). Those with the deletion had lower HCV viral load (mean 296,000 copies/ml vs 701,000 copies/ml), and those with the deletion were more likely to clear HCV completely (6/19 37% vs 9/57 15%). HIV viral load was lower in the those with the deletion but it wasn't statistically significant. Since there was no HIV-negative control group the results could be affected by the role of CCR5 deletion in HIV.