Risk of antibody negative HCV infection in four US HIV cohorts: risk linked to IDU, elevated ALT and low CD4 count

Although HCV antibody screening is recommended in HIV management guidelines, false negative results can occur in both acute and chronic HCV infection. This has led to recommending wider use of HCV RNA screening in patients with HIV coinfection who have a negative antibody result.

Gabriel Chamie from University of California and colleagues reported an analysis in the February 2007 edition of Clinical Infectious Diseases, on the prevalence of HIV-positive patients who were HCV antibody-negative/PCR-positive, in four US cohorts.

The four cohorts (FRAM, Los Angeles, Iowa and REACH) included around 1800 patients, 37 of whom were Hcv antibodynegative/ PCR-positive, and reported a pooled seronegative prevalence of 3.2% (95%CI 2.2-4.3%] Prevalence in individual cohorts ranged from 1.3% (FRAM) to 4.6% (IOWA).

Standard variables in the multivariate analysis included age, ethnicity, sex, alcohol use, history of IDU, ALT, CD4 and viral load. In the combined data, three independently predictive factors of chronic seronegative HCV infection: history of IDU [OR 5.8 (2.7-12.8), p <0.0001], CD4 count <200 cells/mm3 [OR 2.3 (1.1 – 4.8), p= 0.025) and ALT [OR 2.0 per doubling (1.3-3.2), p=0.002], see Table 1. A similar pattern of OR were reported in each of the cohorts, looked at individually. For HCV antibody-negative patients, with a history of IDU and either raised AT or CD4 <200 cells/mm3 a pooled prevalence of 24% was reported for testing HCV RNA-positive.

Table 1: Factors associated with higher rate on antibody-negative HCV infection

Factor OR 95% CI p-value
History of IDU 5.8 2.7-12.8 <0.0001
CD4 count <200 cells/mm3 2.3 1.1-4.8 0.025
ALT level 2.0 (per doubling) 1.3-3.2 0.002

This is the largest study so far to look at prevalence of HCV antibody-negative/PCR-positive results in HIV-coinfection. Among US blood donors, the prevalence by comparison is estimated to be as low as 1 in 250,000, largely explained by acute HCV infection.

The researchers concluded that HCV PCR testing should be recommended in anitbody-negative, HIV-positive patients, especially those with a history of IDU and either a low CD4 count or a raised ALT.


This is an important study in that it highlights the issue of antibody negative chronic HCV infection in the context of HIV-co-infection.

The important message here is that in patients with ‘risk factors’ and persistent unexplained hepatic transaminase elevation an HCV-RNA by RT-PCR is mandatory in order to rule out chronic HCV infection.

The BHIVA guidelines on HIV/HCV co-infection (2004) suggest that consideration should be given to HCV RNA testing in patients with a negative HCV-antibody test and unexplained raised hepatic transaminases.


Chamie G, Bonacini M, Bangsberg DR, et al. Factors associated with seronegative chronic hepatitis C virus infection in HIV infection. Clin Infect Dis. 2007;44:577-583.

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