11 Semen represents the main vector for HIV-1 transmission worldwide. It contains three major sources of infectious virus: free virions, infected leukocytes, Ipatasertib mw and spermatozoa-associated virions. It is difficult to separate the contribution of CF and CA HIV-1 to sexual transmission, as sexual exposure in humans includes both. The infectiousness of semen is influenced by several factors including stage of the disease and duration of infection in the male, with viral loads
peaking in the very early stages of infection or end-stage disease.12,13 Semen viral load typically peaks to about 4.5 ± 0.4 log10 copies/mL after initial infection and stabilizes after approximately 16 weeks of infection.13 Other factors such as coexisting herpes simplex virus
type 2 (HSV-2)14 also increase genital shedding and seminal viral load of HIV-1. Highly active antiretroviral therapy (HAART) serves to decrease viral load in the blood and to some extent in semen,15 but a non-detectable viral load in the serum does not guarantee that HIV-1 will be absent from the semen. This is in Selleckchem EGFR inhibitor part because of the anatomical sites, which are the source of seminal HIV-1. Anatomical features of the male reproductive tract and the limited access of the immune system to compartments containing germ cells suggest that HIV-1 in semen may originate from different compartments. Most CF HIV-1 in seminal plasma arises from sites distal to the vas deferens.16 Therefore, vasectomized men are still able to transmit HIV-1. HIV-1-infected leukocytes in semen do not parallel those found in serum and appear to arise from a genetically distinct compartment. Recent studies indicate that HIV-1 in men without urethritis or prostatitis comes
from sources in the male genital tract, which are distal to the prostate, further supporting a separate viral reservoir for seminal fluid and plasma HIV-1. Unprotected sexual intercourse between discordant couples is the most common route of HIV-1 transmission.3 Despite this, it PIK3C2G is known that the transmission of HIV-1 without other cofactors is poorly efficient. Several cofactors such as genital ulcer disease, BV,17 HSV-218 trichomoniasis9, and male circumcision19,20 have been shown to alter the efficiency of a productive HIV-1 infection. Other cofactors including race, age, menopausal status, parity, and environmental exposures such as hormones (e.g. contraceptive methods) and tobacco use likely affect the susceptibility of a host to HIV-1 infection, but less evidence exists regarding these variables. The fact that the risk of infection is low and highly variable suggests that several processes are involved in sexual transmission of the virus. At the biological level, enhancing and inhibitory factors are present in semen and female genital tract secretions.