Page 28 - AIDSBK23C

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more easily transmitted heterosexually, particularly subtype AE which is more prevalent in Asia.
There is a greater tropism of the E subtype for Langerhans cells than subtype B, which is more
prevalent in the U.S. and Europe.[95,137]
Sexual contact with persons whose HIV viral load is greater increases the transmission
risk. Persons with HIV infection undergoing antiretroviral therapy that measurably lowers the
viral burden in blood will have a reduction in viral particles in genital fluids of men and women
that will render them less infective to others.[139,140] However, even with aggressive
antiretroviral therapy, HIV may be detectable at low levels in blood and genital fluid.[141]
The risk for HIV transmission from an HIV-infected person increases as that person's
immune status diminishes, as measured by a decrease in CD4 lymphocytes or an increase in
HIV-1 RNA in plasma, so that infectivity is greater in the later stages of AIDS; likewise, a
greater risk for transmission exists with the pronounced HIV viremia during primary HIV
infection. Transmission rarely occurs when the HIV-1 RNA level in serum is less than 1500
copies/mL.[142] 136 In one model of heterosexual HIV transmission, the likelihood increased
by 20% and that the annual risk of progression to an AIDS-defining illness or related death
increased by 25% with every 0.3 log10 increment in HIV-1 RNA. A 0.5 log10 increment in
HIV-1 RNA was associated with 40% greater risk of heterosexual transmission and 44%
increased risk of progression to AIDS or death. A 1.0 log10 increment in HIV-1 RNA was
associated with 100% greater risk of heterosexual transmission and 113% increased risk of
progression to AIDS or death.[143]
The presence of specific chemokine receptors plays a role in HIV transmission.
Chemokine receptors provide a pathway, separate from CD4 receptors, for entry of HIV into
cells. Mutations in the chemokine receptor genes appear to afford increased resistance to HIV
infection or progression of disease for hosts homozygous for this genetic trait. Approximately
11% of Caucasians and 2% of Blacks are homozygous for the CCR5-delta32 mutation.[137]
The presence of cervical ectopia, oral contraceptive use, or pregnancy or menstruation in
women, intact foreskin in men, and genital ulcer disease in either sex increases the risk for HIV
infection. The large numbers of Langerhans cells in foreskin and frenulum are poorly protected
by keratin.[144] 138 Thus, male circumcision affords some degree of protection, so that the
incidence of HIV infection is reduced 1.84-fold over uncircumcised men. Cervical ectopy, with
replacement of squamous by columnar epithelium, may increase the risk of HIV infection for
women 5-fold.[129,137,145] The greatest determinant of HIV in cervical and vaginal secretions
is the plasma level of HIV-1 RNA.[133] Increased detection of HIV can occur in women with
vitamin A deficiency and in women receiving high dose oral contraceptives or depot
contraceptives.[146]
There are multiple mechanisms by which the coexistence of other sexually transmissible
diseases (STDs) may increase the infectivity of HIV. Both Chlamydia trachomatis and
Treponema pallidum infection appear to increase HIV-1 replication. In men, urethritis with
infection by Neisseria gonorrhoeae and Trichomonas has been shown to increase the amount of
HIV-1 in semen. Likewise, in women cervicovaginal fluids contain more HIV-1, as well as CD4
cells when additional STDs are present.[137]
Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas, or diseases producing
genital ulcers such as herpes simplex virus, chancroid (Haemophilus ducreyi) or syphilis
(Treponema pallidum), all enhance infectivity by HIV. For example, HIV-1 virions can
consistently be detected in genital ulcers caused by herpes simplex virus-2.[147,148] Both
infectious HSV-2 and noninfectious particles induce Langerhans cell activation and decrease