Semen is the body fluid most commonly associated with sexual transmission o
f human immunodeficiency virus type-1 (HIV-1). Because the male genitourina
ry tract is distinct immunologically from blood, compartment-dependent fact
ors may determine HIV-1 shedding in semen. To identify these factors, the a
uthors obtained 411 semen and blood specimens from 149 men seen up to three
times. Seminal plasma was assayed for HIV-1 RNA and semen was cocultured f
or HIV-1 and cytomegalovirus (CMV), which may up-regulate HIV-1 replication
. The best multivariate model for predicting a positive semen HIV-1 cocultu
re included two local urogenital factors, increased seminal polymorphonucle
ar cell count (odds ratio (OR) = 12.6 for each log(10) increase/mL, 95% con
fidence interval (CI) 12.2, 134.5) and a positive CMV coculture (OR = 3.0,
95% CI 1.2, 7.7). The best multivariate model for predicting semen HIV-1 RN
A included two systemic host factors, CD4+ cell counts <200/mu liter (OR =
3.0, 95 percent CI 1.3, 6.9) and nucleoside antiretroviral therapy (monothe
rapy: OR = 0.5, 95% CI 0.3, 1.0; combination therapy: OR = 0.4, 95% CI 0.2,
0.9), and a positive CMV coculture (OR = 1.7, 95% CI 1.0, 3.0). Thus, both
systemic and local genitourinary tract factors influence the risk of semen
HIV-1 shedding. These findings suggest that measures of systemic virus bur
den alone may not predict semen infectivity reliably.