Visualization of HIV-1 interactions with penile and foreskin epithelia: clues for female-to-male HIV transmission

To gain insight into female-to-male HIV sexual transmission and how male circumcision protects against this mode of transmission, we visualized HIV-1 interactions with foreskin and penile tissues in ex vivo tissue culture and in vivo rhesus macaque models utilizing epifluorescent microscopy. 12 foreskin and 14 cadaveric penile specimens were cultured with R5-tropic photoactivatable (PA)-GFP HIV-1 for 4 or 24 hours. Tissue cryosections were immunofluorescently imaged for epithelial and immune cell markers. Images were analyzed for total virions, proportion of penetrators, depth of virion penetration, as well as immune cell counts and depths in the tissue. We visualized individual PA virions breaching penile epithelial surfaces in the explant and macaque model. Using kernel density estimated probabilities of localizing a virion or immune cell at certain tissue depths revealed that interactions between virions and cells were more likely to occur in the inner foreskin or glans penis (from local or cadaveric donors, respectively). Using statistical models to account for repeated measures and zero-inflated datasets, we found no difference in total virions visualized at 4 hours between inner and outer foreskins from local donors. At 24 hours, there were more virions in inner as compared to outer foreskin (0.0495 +/- 0.0154 and 0.0171 +/- 0.0038 virions/image, p = 0.001). In the cadaveric specimens, we observed more virions in inner foreskin (0.0507 +/- 0.0079 virions/image) than glans tissue (0.0167 +/- 0.0033 virions/image, p<0.001), but a greater proportion was seen penetrating uncircumcised glans tissue (0.0458 +/- 0.0188 vs. 0.0151 +/- 0.0100 virions/image, p = 0.099) and to significantly greater mean depths (29.162 +/- 3.908 vs. 12.466 +/- 2.985 μm). Our in vivo macaque model confirmed that virions can breach penile squamous epithelia in a living model. In summary, these results suggest that the inner foreskin and glans epithelia may be important sites for HIV transmission in uncircumcised men.

Gay men's estimates of the likelihood of HIV transmission in sexual behaviours

In 3 studies we recorded gay men's estimates of the likelihood that HIV would be transmitted in various sexual behaviours. In Study 1 (data collected 1993, n=92), the men were found to believe that transmissibility is very much greater than it actually is; that insertive unprotected anal intercourse (UAI) by an HIV-infected partner is made safer by withdrawal before ejaculation, and very much safer by withdrawal before either ejaculation or pre-ejaculation; that UAI is very much safer when an infected partner is receptive rather than insertive; that insertive oral sex by an infected partner is much less risky than even the safest variant of UAI; that HIV is less transmissible very early after infection than later on; and that risk accumulates over repeated acts of UAI less than it actually does. In Study 2 (data collected 1997/8, n=200), it was found that younger and older uninfected men generally gave similar estimates of transmissibility, but that infected men gave somewhat lower estimates than uninfected men; and that estimates were unaffected by asking the men to imagine that they themselves, rather than a hypothetical other gay man, were engaging in the behaviours. Comparison of the 1993 and 1997/8 results suggested that there had been some effect of an educational campaign warning of the dangers of withdrawal; however, there had been no effect either of a campaign warning of the dangers of receptive UAI by an infected partner, or of publicity given to the greater transmissibility of HIV shortly after infection. In Study 3 (data collected 1999, n=59), men induced into a positive mood were found to give lower estimates of transmissibility than either men induced into a neutral mood or men induced into a negative mood. It is argued that the results reveal the important contribution made to gay men's transmissibility estimates by cognitive strategies (such as the 'availability heuristic' and 'anchoring and adjustment') known to be general characteristics of human information-processing. Implications of the findings for AIDS education are discussed.