Background:  A limited number of seronegative HIV individuals with AIDS have been reported in the literature. In contrast, hepatitis C virus (HCV) -seronegativity does not seem to be rare in HIV patients. It is unclear whether seronegativity for any of these infections may occur as a result of loss of pre-existing antibodies (seroreversion) or to primary lack of antibody production. Herein, we report HIV and HCV antibody responses in a large series of HIV patients with profound immunosuppression.

Methods:  From 2001 to 2006, all patients diagnosed with HIV-1 infection (enzyme-linked immunoassay [EIA] reactive and positive Western blot) who presented with CD4 counts <50 cells/μL at our institution were identified. Sera were screened by 2 different EIA, a third generation and a second-generation EIA. The latter assay has been proven to be particularly useful to detect HIV-1 seroreversion. In subjects with CD4 counts <10 cells/μL, an HIV-1 Western blot assay was additionally performed. All HIV patients with a history of intravenous drug use were screened for HCV antibodies using a commercial EIA. A sensitive HCV-RNA polymerase chain reaction (PCR) assay was performed HCV-seronegative subjects.

Results:  Of 417 subjects fulfilling the requested criteria, 331 had samples available. For this group, the median CD4 count was 23 cells/μL (IQR 10 to 39); median plasma HIV RNA was 5 log copies/mL (IQR 4.3 to 5.5). All were reactive for HIV using both EIA. Low-level optical density values using the second-generation EIA (which could be associated with seroreversion) were not observed. All 86 subjects with CD4 counts <10 cells/μL had a positive Western blot pattern (reactivity to at least 2 env bands), although a few had weak or lack of reactivity to gag or pol products. Over time, 20 subjects maintained severe immunodeficiency for long periods (median of 13.3 months; IQR 6.9 to 26.5), but did not show changes in EIA reactivities for HIV. Of the 255 injection drug users (IDU) who were screened for HCV antibodies, only 17 (6.7%) were seronegative. However, 6 of them were serum HCVRNA⁺. Interestingly, all showed low-level HCV RNA (<10⁶ IU/mL) and 4 of them could be genotyped (3 HCV-1 and 1 HCV-4).

Conclusions:  Complete HIV seroreversion in subjects with profound immunosuppression seems to be a very rare event. Seronegativity in HIV infection may be more the result from lack of antibody formation. In contrast, HCV seronegativity is relatively common in immunosuppressed HIV patients and might result from low HCV replication or impaired antibody production.