Background: An isolated, positive test for IgG anti-HBc may represent either: 1) resolved HBV infection with loss of HBsAb; 2) occult chronic HBV infection with undetectable HBsAg; or 3) a false positive result. In healthy blood donors, 2%–5% have isolated anti-HBc. We studied the frequency of and factors associated with isolated anti-HBc in an U.S. HIV⁺ cohort.

Methods: We screened 651 subjects for HBsAg and HBsAb in 3 HIV clinics. Subjects who were negative for HBsAg and HBsAb underwent testing for anti-HBc.

Results: From a total of 387 persons (59%) who were negative for both HBsAg and HBsAb, 147 underwent further testing for anti-HBc. Of these 147 subjects, 62 (42%) were positive for anti-HBc. Seventy-nine percent (79%) of subjects with isolated anti-HBc were HCV seropositive, whereas only 12% of individuals who were negative for HBsAg, HbsAb, and anti-HBc were HCV seropositive (see table). Individuals co-infected with HIV and HCV were more likely to have isolated anti-HBc than subjects with HIV alone (83% vs 15%, crude OR = 28.3, p < 0.0001). Isolated anti-HBc was also more frequent in subjects who had a history of injection drug use (IDU) than in those who did not (88% vs 20%). In a multivariate model, isolated anti-HBc was highly associated with HCV seropositivity (adjusted OR = 10.4, p = 0.0074) and with blood-borne route of transmission (including IDU) (AOR = 6.8, p = 0.028). Isolated anti-HBc was not associated with age, nadir or current CD4 count, or an undetectable HIV RNA. Subjects who are negative for HBsAg and HbsAb, but positive for anti-HBc, do not have lower nadir CD4 counts than subjects who are negative for HBsAg but positive for HBsAb and anti-HBc.

 

	HbsAg/ HbsAb/ anti-HBc		P value
	Neg/Neg/Neg	Neg/Neg/Pos
N	85 (58%)	62 (42%)
HCV Ab+	10 (12%)	49 (79%)	< 0.0001
Mean CD4 ct	376 ± 251	412 ± 277	NS
Mean CD4 nadir	281 ± 229	324 ± 256	NS

 

Conclusions: In an U.S. HIV⁺ cohort, isolated anti-HBc is associated with HCV seropositivity and bloodborne route of transmission. Individuals with HIV/HCV co-infection, who do not have serologic evidence for HBV when screened with HBsAg and HbsAb, will be positive for anti-HBc in over 3/4 of cases. A screening strategy in HIV⁺ patients that tests only for HBsAb and HBsAg will miss a large number with isolated anti-HBc. Studies of HBV DNA and the effect of immunization in HIV⁺ subjects who have isolated anti-HBc may allow further understanding of whether they are protected from HBV infection.