What prevents a HIV positive mother from infecting her unborn baby? What prevents a highly exposed person from contracting HIV virus? What is the cause of discordance in HIV virus in couples and why are discordances in HIV infection between married couples on the rise?

The generally held perception has been that all individuals are equally susceptible to HIV virus, and once infected remain infected for life. However, there appears to be heterogeneity in susceptibility to HIV-1 virus, which may be occasioned by specific protective immunity possibly related to host genetics or barriers to transmission of HIV-1 virus variable in individuals.

The first indirect evidence of heterogeneity in infection with HIV was deduced from the declining incidence of infections within a cohort of highly exposed commercial sex workers in Nairobi by Keith Fowke et al in 1996.  The rate of seroconversion was observed to significantly decline despite continued exposure to HIV-1 infected partners in the commercial sex work. The investigators gave three possible reasons to account for the persistent lack of seroconversion in this group of women. An earlier study in Kenya had demonstrated that acquisition of sexually transmitted infections in both males and females was related to the study participant's engagement in commercial sex work (Moses S, et al, 1994). Naturally, since most transmissions of HIV-1 infection have been accounted for by heterosexual transmission in Africa, investigation in the incidence of new HIV-1 infections in a group of commercial sex workers was and still is a powerful tool in studying susceptibility patterns and possibility of resistance to infection.

The first possible explanation may drawn from the difference in the sexual behaviors of the women such as condom usage or numbers of sexual partners or the lower exposure to factor know to increase susceptibility to HIV infection oral contraception and sexually transmitted infections. The differences brought about by condom usage, or number of regular sexual partners did not the explain the effect of the cumulative exposure (weighted against the years of prostitution). Although sexually transmitted infections had been demonstrated by then to be risk factors for HIV-1 transmission, again the cumulative exposure (weighted against duration of prostitution) was observed to be independent to the decrease in risk to infection with HIV.

The second explanation alluded to the possible failure of the three HIV tests techniques used to screen the women to detect the HIV virus or HIV-1 antibodies. The possibility of cryptic infection with HIV which would have remained undetectable was also ruled out due to and earlier observation by that HIV is active during the latent phase of the infection in the lymph nodes or lymphoid organs (Pantaleo G. et al., 1993). The possibility of the women being able to control the virus replication for as the duration of study (3years) was ruled out. Whereas those that seroconverted progressed rapidly to AIDS as at the time of these findings the usage of antiretrovirals was limited.

 The third possibility was that the seronegative women were in fact resistant to infection with HIV-1 virus was the most logical conclusion. This conclusion was the birth of the HIV resistance hypothesis that triggered immunological, epidemiological and genetical studies to aiming to find the immune correlates that would then be tested for vaccines or efficient microbicidial agents that would be used to prevent HIV infection or ameliorate the deleterious effects on the already infected.

 This indirect evidence of existence of natural resistance to HIV-1 infection, invigorated research on the immune systems, genes and behaviours of in the seronegative women. This initial discovery was made through mathematical models; the investigators sought immunological genetical or molecular evidences that would give a direct relationship to some immune of non-immune correlates that provide protection to infection. Vairous studies have since then demonstrated specific anti-HIV immune responses and genes whose presence or absence has related to reduced infection with HIV-1 virus.

HIV-1 virus primarily infects a white blood cells bearing the CD4 receptor and either CCR5 or CXCR4 chemokine receptors. Thus only the cells bearing the two types of receptors i.e. the CD4 receptor and CCR5/CXCR4 receptors can be entered by the HIV virus.  The cells bearing these receptors have so far been demonstrated in blood, brain tissues, mucosal surfaces, lymphoid organs, bone marrow among others.