To investigate the influence of HLA specificities on the rate of progression and outcome of human immunodeficiency virus (
HIV) infection, we performed (a) a case-control study in 1989-1990 of HIV-seropositive individuals stratified by both risk behavior and ethnic background, (b) a longitudinal cohort study of HIV-infected male homosexuals enrolled in 1981-1982, and (c) an analysis of individuals with a diffuse infiltrative CD8
lymphocytosis syndrome. In the case-control study, there was a significantly higher frequency of
HLA-B35 among intravenous drug users, but not homosexuals, who developed illnesses meeting the case definition for
AIDS compared with asymptomatic HIV-positive controls, regardless of ethnic status. In the longitudinal study, HLA-B35-positive homosexuals had a significantly increased rate of progression to
AIDS and decreased survival over a 7-year period compared with those without this specificity. Finally, there was a significantly decreased frequency of
HLA-B35 in individuals with the diffuse infiltrative
lymphocytosis syndrome, a clinically and genetically distinctive disorder occurring in
HIV infection in which a low rate of progression to
opportunistic infections was found. The high rate of salivary and lacrimal gland
lymphoma in this group suggests that there is dissociation between the presence of
HLA-B35 and the development of particular
AIDS-defining conditions. We conclude that
HLA-B35 is a risk factor for more rapid progression to
AIDS, particularly
opportunistic infections and
Kaposi's sarcoma, operating in groups with high rates of newly acquired
HIV infections such as New York City male homosexuals in 1981-1982, and intravenous drug users in 1989-1990.(ABSTRACT TRUNCATED AT 250 WORDS)