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−1, and MIP−1. This relative resistance of CD4⁺; lymphocytes may contribute to protection from HIV−1 in multiply exposed persons.

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