Fifth International Congress Drug Therapy in HIV Infection 22-26 October, 2000 Glasgow, UK

INFECTIVITY AND SEXUAL TRANSMISSION

P.L. Vernazza
Cantonal Hospital, St. Gallen, Switzerland

Int Cong Drug Therapy HIV 2000 Oct 22-26;5:Abstract No. PL6.2
AIDS 2000, Oct 22-26;14(Suppl. 4);S6

The risk of sexual transmission of HIV depends on the infectivity of the infected individual, the susceptibility of the non-infected partner and the nature of the sexual contact between the two. The infectivity of the index case is most likely a result of the viral shedding in the genital fluids. Epidemiological and biological evidence support the notion that the strongest factor influencing both genital viral shedding as well as the risk of transmission in partner studies is the level of systemic viral replication, or plasma HIV-RNA load. Of note, inflammatory processes that increase the viral load in the genital tract, such as gonorrhoea, genital ulcers and other STDs increase the risk of sexual transmission not only by increasing the inoculum size but probably also by creating a cytokine micro-environment that enhances transmission.

Animal studies have elegantly shown that the simian counterpart of HIV, SIV very rapidly reaches the dendritic cells in the vaginal epithelia and is subsequently transported to the regional lymph node where systemic replication by CD4+ cells is initiated. Despite the limited knowledge on the mechanisms of female to male transmission, it is likely that similar events take place.

Once the virus has reached the recipient, the events leading to the establishment of infection with overt seroconversion are highly dependent on the susceptibility to infection of the recipient. Animal models as well as studies in highly exposed uninfected individuals support the existence of a protective immunity in some exposed partners. From analogy with the LCMV model and limited evidence from the HIV field we hypothesize that the degree of the exposure to HIV (i.e. the inoculum size during sexual contact) predicts the outcome. With increasing inoculum size, outcome might vary from noevent to the establishment of a (protective?) cell-mediated immune-response (CMI) and to overt seroconversion with long-term non-progression up to infection with rapid progressive disease.

The establishment of a (partially) protective immune response after limited exposure to the virus would explain the discrepancies of the estimates for the risk of transmission obtained in partner studies and in studies with commercial sex workers (CSW). While estimates of the per-contact risk from longitudinal partner studies are quite low (approx. 0.3%) the respective figures from studies of single contacts with CSW are in the range of 3–8%. Mathematical models undermine the relatively high risk of transmission during the first few sexual contacts of an HIV-discordant couple and lower risk afterwards.

Antiretroviral therapy significantly reduces the genital shedding of HIV, i.e. the viral inoculum. There is limited information about this effect of therapy on HIV incidence but intuitively, any reduction of the inoculum size must result in lower risk of transmission, as has been demonstrated for the case of vertical transmission. On the basis of the hypothesis mentioned above, one might also speculate that reduction of the inoculum size could also shift the whole spectrum of events towards a lower level, thus leading to fewer cases with high viral load as well as high infectiousness.

Presenting author: P.L. Vernazza

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2000-10-22
PL6-2

Originally published in AIDS Volume 14, Supplement 4 and hosted with permission of the publisher Lippincott Williams & Wilkins, 250 Waterloo Road, London, SE1 8RD, UK. Tel: +44 (0)20 7981 0700 Fax: +44 (0) 7981 0701

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