Seminal Shedding of CMV and HIV Transmission among Men Who Have Sex with Men

Abstract

As in many urban areas in the United States, the largest burden of the HIV epidemic in San Diego is borne by men who have sex with men (MSM). Using data from well-characterized HIV transmitting and non-transmitting partner pairs of MSM in San Diego, we calculated the population attributable risk (PAR) of HIV transmissions for different co-infections common among MSM in this area. We found that over a third of HIV transmissions could be potentially attributed to genital shedding of cytomegalovirus (CMV) (111 transmission events), compared to 21% potentially attributed to bacterial sexually transmitted infections (STI) (62 events) and 17% to herpes simplex virus type-2 (HSV-2) (51 events). Although our study cannot infer causality between the described associations and is limited in sample size, these results suggest that interventions aimed at reducing CMV shedding might be an attractive HIV prevention strategy in populations with high prevalence of CMV co-infection.

Natural Inhibitor of Human Cytomegalovirus in Human Seminal Plasma

“…Infection of the controls was set to 100% and samples were normalized accordingly. *, P Ͻ 0.01; **, P Ͻ 0.001; ***, P Ͻ 0.0001. higher HCMV loads, which are often found in HIV patients (32,39,40), could still result in transmission. In addition, our data suggest that virus particles are not irreversibly inactivated by human semen and dilution of the body fluid after ejaculation might allow infection of target cells.…”

Partners in Crime: The Role of CMV in Immune Dysregulation and Clinical Outcome During HIV Infection

“…When an infected person has a compromised immune system, shedding of CMV increases dramatically. For example, in Southern California, almost half of HIV-infected men who have sex with men asymptomatically shed CMV in their genital tract, regardless of CD4+ T cell count or use of ART [12–14]. Less is known about the frequency of CMV shedding in the genital tract of HIV-infected women.…”

“…Several mechanisms could play a role including the following: (i) direct interaction between CMV-encoded regulatory proteins and the HIV long terminal repeat (LTR) region resulting in transactivation of viral gene expression [70, 71], (ii) enhanced HIV replication stimulated through a release of CMV-induced inflammatory cytokines and chemokines [72], (iii) upregulation of CCR5 expression in central memory T cells, which has been recently described in cord blood mononuclear cells exposed in vitro [73] and might be mediated by enhanced (CMV-induced) interferon production [74], and (iv) clonal expansion of HIV-infected T cells through CMV-induced inflammatory cytokines and chemokines [75]. This relationship between CMV and HIV has been widely documented in the genital tract, where presence of detectable CMV DNA has been repeatedly associated with increased genital shedding of HIV RNA [12, 13, 76–79] and with increased HIV transmission [11, 14, 76]. Additionally, presence of detectable CMV DNA was also associated with increased levels of HIV DNA in peripheral blood cells in both treated and untreated HIV infected individuals [20, 21, 75].…”

Ongoing burden of disease and mortality from HIV/CMV coinfection in Africa in the antiretroviral therapy era

“…In the Western world, the rate of CMV seropositivity is much higher among adults with risk factors for acquisition of HIV infection, for example MSM (Gianella et al, 2015 ), than in the general population. Likewise, in a West African cohort, increased CMV seropositivity has also been demonstrated in HIV-positive individuals compared to HIV-uninfected controls (Compston et al, 2009 ).…”