Origins of HIV-infected leukocytes and virions in semen

Although semen is the principal vector of human immunodeficiency virus (HIV) dissemination worldwide, the origin of the infected leukocytes and free viral particles in this body fluid remain elusive. Here we review the accumulated evidence of the genital origin of HIV in semen from therapy naive individuals and men receiving suppressive highly active antiretroviral therapy (HAART), summarize the data on the detection and localization of HIV/SIV within the male genital tract, discuss the potential involvement of each genital tissue as a source of infected cells and virions in semen in the absence and presence of HAART, and suggest further studies. Deciphering the exact sources of HIV in semen will be crucial to improving HIV transmission prevention strategies.