nosuppression, whereas PCR should be performed for subjects with a reactive HTLV EIA which is not further confirmed by WB.As with other retroviruses, the diagnosis of human T-cell lymphotropic virus type 1 (HTLV-1) or type 2 infections is generally made using serological assays that assess the presence of specific HTLV-1/2 antibodies. The recommended algorithm advises to first perform a screening enzyme immunoassay (EIA) to detect both viruses followed by Western blot (WB) testing of reactive samples to confirm infection and discriminate between HTLV-1 and HTLV-2. This approach is often accompanied by a high proportion of indeterminate WB results when low-risk populations, such as blood donors (1, 10), are tested, although subsequent PCR analyses discharge the presence of HTLV-1/2 infection in almost all cases. In contrast, in high-risk populations, such as intravenous drug users (IDU), indeterminate HTLV WB patterns or even nonreactive EIA results may be seen in persons with true HTLV-2 infection (6, 11). Since IDU are often coinfected with human immunodeficiency virus type 1 (HIV-1), it has been suggested that immunosuppression could explain the inability to mount and/or maintain an appropriate level of HTLV-2 antibodies, particularly in advanced stages of HIV disease (6). A similar poor antibody response has been described for hepatitis C virus in HIV-positive individuals, causing "occult" infections (2). Herein, we assess the impact of HIV-related immunosuppression on the performance of current serological tests used for HTLV-2 diagnosis.A large group of former IDU known to be HIV positive and on regular follow-up at our institution was analyzed. We have previously reported a high prevalence of HLTV-2 infection in this population (8). A total of 175 IDU had severe immunosuppression, with a CD4 cell count below 200 cells/l. They were matched by age, gender, and place of residence with 175 HIV-positive IDU with a preserved immune status and CD4 cell counts above 500 cells/l. Serum specimens were tested for antibodies to HTLV-1/2 using a commercial EIA (Murex HTLV IϩII; Abbott, Barcelona, Spain). Samples with repeated EIA reactivity were tested using a commercial WB (Bioblot HTLV; Genelabs, Singapore). These WB strips contain HTLV-1 viral lysate and three recombinant envelope proteins: the transmembranous HTLV gp21 (rgp21), the surface gp46 from HTLV-2 (rgp46-II), and the surface gp46 from HTLV-1 (rgp46-I). The HTLV European Research Network criteria (5) were used for interpreting WB patterns. Briefly, HTLV-2 positivity was considered when reactivity to at least two recombinant envelope bands (rgp21 and rgp46-II) and the gag band p24 was seen. HTLV-2 infection was considered negative when no bands appeared in the WB. Other WB patterns were interpreted as HTLV indeterminate.A specific HTLV-1/2 PCR was performed in all subjects with CD4 counts below 200 cells/l, as previously described elsewhere (9). Briefly, the HTLV-1/2 PCR was performed using nested primers (12P1, SK111, 12P5, 1P1, and 2P3) directed against th...