HIV-Infected Men at Ongoing Risk for HCV Seroconversion, Study Finds

Norra MacReady

February 7, 2011 — Even with conscientious care and state-of-the-art medication, HIV-infected men are at risk for hepatitis C virus (HCV) seroconversion and should have access to ongoing HCV surveillance, the authors of a new study say. Their findings were published online January 31 and appear in the February print issue of Clinical Infectious Diseases.

HCV has become "a leading cause of non-AIDS related morbidity and mortality for HIV-infected persons in the highly active antiretroviral therapy (HAART) era," lead author Lynn E. Taylor, MD, from Brown University, Providence, Rhode Island, and coauthors write. They estimate that up to 30% of HIV-infected people in the United States are coinfected with HCV.

At this time, the US Public Health Service recommends testing for HCV when a patient is initially diagnosed with HIV infection, but not thereafter. However, reports are now surfacing of acute HCV outbreaks in Europe, Australia, New York, and California among HIV-infected men who have sex with other HIV-infected men and engage in potentially traumatic practices such as unprotected anal sex, use of sex toys, multiple partners, and manual insertion, which may involve some exchange of blood. Because HCV treatment is most effective during the acute stages of infection, "it is vital to diagnose incident HCV infection in HIV-infected persons," the authors say.

For a better idea of the risk for acute HCV infection among HIV-infected men, the researchers studied behavioral and demographic factors associated with HCV antibody seroconversion in men participating in the AIDS Clinical Trial Group (ACTG) Longitudinal Linked Randomized Trials (ALLRT) study. The ACTG was established in 1987 by the US Department of Health and Human Services, the National Institute of Allergy and Infectious Diseases, and the National Institutes of Health Division of AIDS, and is the largest HIV clinical trials organization in the world. ALLRT is a randomized cohort study of the long-term immunologic, virologic, pharmacologic, and clinical outcomes associated with the use of HAART by HIV-1-seropositive patients. It was started by ACTG in 2000.

Starting in 2002, patients participating in ALLRT have been tested for HCV on entry, with follow-up testing every 96 weeks beginning in 2006. Seventeen other ACTG-funded trials also test patients for HCV on entry and at various follow-up intervals, between 1996 and 2002. The authors determined the incidence of HCV infection from 1996 to 2008 among men participating in these studies. Of those 2848 patients, 2629 had at least 1 HCV antibody test result, with 264 (10%) of those individuals testing positive at baseline. Of the remaining 2365 patients, 1830 had at least 1 subsequent HCV antibody test and were included in this analysis. Their mean age at the time of the initial negative HCV antibody result was 42 years; other demographic information is shown in the table. The mean interval for HCV testing was 2.8 years for HCV seroconverters and 2.6 years for nonseroconverters.

Table

Characteristic   Percentage

Race
 * White 57%
 * Black 22%
 * Hispanic 18%
 * Asian/Pacific Islander 2%
 * Native American 1%

College-educated 70%

Using HAART 94%

Current or prior injection drug use at study entry 6%

HCV seroconversion occurred in 36 of the men studied (2%), for an overall incidence of .51 cases per 100 person-years. Twenty-five percent of the seroconverters reported a history of injection drug use compared with 5% of patients who remained seronegative (P < .001). However, the authors write, "compared with men with initial HCV antibody positivity, seroconverters were more likely to be white and less likely to be black and were more likely to have never injected drugs and to have attended college."

Patients who seroconverted also were more likely to have an HIV RNA level greater than 400 copies/mL compared with those who did not seroconvert. There is an association between less adherence to the HAART regimen and participation in risky sexual practices, and both of these may have figured in the higher seroconversion rate among patients with a higher viral load, the authors suggest. People in the acute stages of HCV infection are also less tolerant of HAART, which may have contributed to their poor compliance.

There were several study limitations. Only half of the participants underwent follow-up HCV testing at intervals shorter than 3 years, so the authors could not determine exactly when seroconversion occurred in these patients, making it impossible to report incidence trends over time. In addition, 23% of the participants did not undergo any follow-up HCV screening, which raises the possibility of selection bias. However, there was no difference in baseline data between those patients and the patients who did have follow-up testing, so "it is likely that the HCV seroconversions represent the true incidence among HIV-infected patients in care," the authors write.

These findings suggest that HIV-infected patients should undergo regular screening for HCV, the researchers conclude. Early detection "may permit more successful treatment and provide opportunity for intervention to mitigate disease spread among drug-using or sexual partners and education to limit liver damage."

This study was supported in part by the AIDS Clinical Trials Group funded by the National Institute of Allergy and Infectious Diseases; National Institute on Drug Abuse; Lifespan/Tufts/Brown Center for AIDS Research; Center for Drug Abuse and AIDS Research; and the National Institutes of Health. The Miriam Hospital is one of the Clinical 340 Research Sites under Harvard/Partners Clinical Trials Unit. Study authors report various financial relationships with Roche, Vertex, Genentech, BMS, Merck, SciClone, GlaxoSmithKline, Three Rivers, Johnson & Johnson, Regulus, and Tibotec.

Clin Infect Dis. Published online January 31, 2011.

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