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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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