Quantifying the strength and durability of induced immunity to HIV infection in women engaging in unprotected sexual contacts with infected men

• Published in: Mathematical and computer modelling Vol. 36; no. 11; pp. 1435 - 1458
• Main Authors: Kramer, I., Shearer, G.M.
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.12.2002
• Subjects: AIDS; Cellular immunity; HIV infection; Induced immunity; Innate immunity; Mucosal barriers; Seroprevalence; Induced immunity; Mucosal barriers; Innate immunity; AIDS; Cellular immunity; HIV infection; Seroprevalence
• ISSN: 0895-7177; 1872-9479
• DOI: 10.1016/S0895-7177(02)00299-6

Evidence is accumulating that exposure to human immunodeficiency virus (HIV) can lead to an increased resistance or immunity to subsequent infection. A multirisk model that permits either induced immunity or infection to develop after heterosexual inoculation with HIV is shown to be compatible with a wide spectrum of disparate male-to-female transmission data. When the model is applied to time- dependent, HIV-seroprevalence data, the probability that an unexposed woman would remain unexposed after an unprotected contact with an infected man was estimated to be greater than 0.95 on the average. Thus, it would require at least 14 unprotected sexual contacts with HIV-infected men for 50% of an unexposed cohort of women to become exposed to the virus. This suggests that there is a low probability that HIV virions will be found to have penetrated the mucosal barriers of the reproductive tract after a contact. The model also predicts, that the average woman whose mucosal barriers have been breached by HIV has a significant probability of developing immunity to the virus rather than infection. Modelling data for a cohort of unexposed Nairobi women leads to the prediction that the probability of acquiring induced immunity per contact is about 60% of the probability of acquiring the disease per contact. The modelling results also predict that those who had developed resistance to HIV run the small, but significant risk of becoming infected nonetheless by continuing high-risk behavior. For the common contact rate of ten per month, the modelling predicts that the HIV-transmission risk per contact for unexposed women in the Nairobi cohort is 1 178 while the transmission risk for the cohort's immunized women is 1 1548 . These numbers suggest that HIV infection is difficult to transmit through heterosexual intercourse on the average and that male-to-female HIV-transmission risk per contact for African women lies between 1 178 and 1 1548 . Direct confirmation of the predictions in the last paragraph has been subsequently observed in two completely independent studies. The Nairobi research team recently reported that a notable number of Nairobi prostitutes previously identified to be members of the HIV-resistant group became infected nonetheless. Second, in a study of 174 sexually monogamous, discordant couples in Rakai, Uganda reporting contacts rates of nine to ten per month, the male-to-female HIV-transmission risk per contact was found to be 1 769 by direct measurement, a value that falls between the above limits of 1 178 and 1 1548 predicted by the modelling. Thus, a second major prediction of this paper has been directly confirmed, and induced immunity to HIV is limited and not absolutely protective. Circumstantial evidence suggests that the induced immunity to HIV predicted by the model could be generated and/or initiated by nonspecific innate immune responses, specific immunological responses, including IgA-mediated mucosal immunity and cytotoxic T lymphocytes (CTL) immunity, or some combination of the above. It is suggested here, that a decrease in the ability of HIV virions to penetrate the protective mucus layer of the reproductive tract may be a prerequisite, cofactor, or the principle cause of the induced immunity or resistance demonstrated to exist in this paper. The value of the probability that induced immunity to HIV will develop after a contact is shown to be a sensitive function of the woman's human leucocyte antigen (HLA) supertype profile.