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Dr. Yasuhiro Yamamaura
Title: Role of Two Seminal HIV-1 Compartment in Heterosexual Transmission


Infection of Human Immunodeficiency Virus Type 1 (mV-l) is a serious global health problem. Over 75% of all HIV -1 infections are associated with heterosexual transmission (HST), and 45% of all mV-l infections occur in women. Highly active antiretroviral therapies (HAART) have markedly reduced the incidence of acquired immunodeficiency syndromes (AIDS) and HIV-l infected persons may now be expected to live nearly normal life spans. However, incidence of new HIV-l infection continues to increase particularly among women of ethnic minorities. Today, one in three new cases of HIV-l infection in the USA occurs in a female, often through HST from HAART-experienced males. However, the exact mechanisms by which HIV-l HST occurs are not clearly understood. There is an increasing awareness that HIV -1 infection becomes highly compartmentalized in the body. HIV-l in genital secretions is one such compartment. [Hypothesis-I] Genital cell-free (cf) and cell-associated (ca) mV-l in therapy naive HST donors and recipients are primarily R5 and X4, respectively. However, the history of HAART alters the properties of the virus surviving in semen, which is then transmitted to vaginal compartments. [Hypothesis-2] mV-l in the semen is the direct male to female HST mediator. [Hypothesis-3] HST involves as a rule both cf and ca mV-l in semen. Since HST more often occurs from male to female, the present study will therefore focus on the role of seminal HIV-l in HST and will also determine how HAART experience of HST donor males influences the HST mechanisms. Our data and those by others have clearly shown that cf and ca HIV-l in semen are genetically distinct from each other. The present study will therefore attempt to determine which (cf or ca) seminal HIV-l compartment is a more likely source of HST. We will further determine how HAART/ART perturbation of seminal HIV-l compartments alters the risk of HST. The specific aims of the present study are to: (1) Characterize the role of seminal ca and cf HIV-l compartments in HST from therapy naive donor males. (2) Characterize the role of seminal ca and cf mV-l compartments in 30 HST pairs involving HAART experienced donor males. And also to (3) determine the differential responses of ca and cf seminal resident mV-l to the standard-of-practice (SPO) ART/HAART that patients receive and implications on their HST capacity.

 


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