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Objective:To investigate the clinical and immunologic effects, and pattern of mortality associated with HIV-2 infection.Setting:A rural community in Guinea-Bissau.Methods:Serologic screening of 2774 subjects aged>14 years followed by studies of the prevalence of clinical and immunologic abnormalities among 133 subjects with HIV-2 infection and 160 seronegative controls, and surveillance of mortality among all subjects who were screened during a mean of 2 years of follow-up.Results:Generalized lymphadenopathy was the only clinical abnormality significantly associated with HIV-2 infection. Infection was associated with lower CD4 counts and higher β2-microglobulin and neopterin levels. During follow-up, 5.5% of infected subjects died compared with 1.8% of the seronegatives (rate ratio adjusted for age and sex, 3.5; 95% confidence interval ((Cl), 1.8–6.7). Proportional hazard regression analysis showed that the rate ratio varied with age (P= 0.003) and there was some evidence that the excess of mortality in infected subjects was, in absolute terms, least in the oldest subjects (trend test; P=0.08).Conclusions:The findings support previous suggestions that HIV-2 is less pathogenic than HIV-1; the data also suggest that mortality associated with infection may be lower in older subjects.