Sexual Transmission of HIV: Amplification and Inhibition

Myron S. Cohen, MD.

Professor of Medicine, Microbiology and Immunology, University of North Carolina at Chapel Hill (USA)

The probability of the sexual transmission of HIV has been directly correlated with the concentration of virus in blood, which acts as a surrogate for HIV in the genital secretions.  However, HIV concentrations in the blood and genital secretions are increased in patients with acute and late stage HIV disease, some subjects with malaria, helminthic infections and tuberculosis, and perhaps most importantly  “classical” sexually transmitted diseases, including both ulcers and discharges.  HIV infected men with trichomonas and/or gonococcal urethritis demonstrate greater than 8-fold increased excretion of HIV in semen, which is reduced with antibiotic therapy, although much more slowly than the elimination of the STD pathogen.  Patients with acute HIV infection demonstrate high blood and genital tract viral burden for 21 days after infection.  In a recent study in Malawi (Pilcher et al. AIDS, in press), a substantial number of men (11.5%) who presented with genital ulcer were found to have asymptomatic acute HIV infection, suggesting the concomitant acquisition of two pathogens or a strong influence of a recurrent ulcer.  Clade may also influence transmission:  R5 (NSI) variants are recovered in subjects with acute and early HIV, suggesting their preferential sexual transmission.  The viral swarm recovered from blood from patients in Malawi with advanced clade C HIV infection retains a homogenous R5 phenotype, so a larger number of organisms are available for transmission. Antiviral therapy can be used to prevent HIV transmission as therapy directed at index patients, pre-exposure prophylaxis, or post-exposure prophylaxis.  The penetration of many antiviral agents into the genital tract explains the ability of such drugs to greatly reduce the concentration of HIV in semen and female genital secretions.  While the ability of ART to reduce sexual transmission of HIV has not been demonstrated, several lines of evidence support this idea: i) ART prevents vertical transmission of HIV; ii) in a retrospective study, zidovudine reduced  transmission of HIV in serodiscordant couples; iii) in recent studies conducted in Taiwan and San Francisco widespread usage of ARTreduced the anticipated spread of HIV; iv) some (but not all) mathematical modeling studies suggest that ART will reduce transmission of HIV.  A randomized controlled in serodiscordant sexual partners (NIH HPTN052) has been designed to address this question directly.  HPTN052 will enroll 1750 serodiscordant couples into a trial that allows randomization of HIV infected subjects with CD4 greater than 250 to early or delayed ART, with uniform use of couples counseling.  Prevention of acquisition of HIV in the uninfected subject is the primary endpoint of the study.  It seems likely that use of ART will become an increasingly important part of HIV prevention strategy.