Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposures

Some individuals remain uninfected with human immunodeficiency virus type- 1 (HIV-1) despite multiple high-risk sexual exposures. We studied a cohort of 25 subjects with histories of multiple high-risk sexual exposures to HIV-1 and found that their CD8⁺ lymphocytes had greater anti-HIV-1 activity than did CD8⁺ lymphocytes from nonexposed controls. Further studies indicated that their purified CD4⁺ lymphocytes were less susceptible to infection with multiple primary isolates of HIV-1 than were CD4⁺ lymphocytes from the nonexposed controls. This relative resistance to HIV-1 infection did not extend to T-cell line-adapted strains, was restricted by the envelope glycoprotein, was not explained by the cell surface density of CD4 molecules, but was associated with the aCtivity of the C-C chemokines RANTES, MIP-1α, and MIP-1β. This relative resistance of CD4⁺ lymphocytes may contribute to protection from HIV-1 in multiply exposed persons.