Infection with HIV occurs after the transfer of body fluids from an infected person to an uninfected one. The virus is carried in infected CD4+ T-cells, dendritic cells, macrophages and as a free virus in blood, semen and in vaginal fluid. It is commonly spread by homosexual or heterosexual intercourse, contaminated needles used for intravenous drug delivery and also from an infected mother to her baby during pregnancy, at birth or through breast milk (Janeway et al., 2005).
It has been suggested that up to 50% of new HIV infections are acquired from newly infected individuals, due to both the high level of plasma viral load during the early phase of disease and to virus-specific properties. Acute HIV infection, which causes very high plasma viral loads in the first few months, is an important driver of HIV epidemics (Celum et al., 2014; Girard et al., 2011).
Men who have sex with men (MSM) have a higher risk of infection because receptive anal intercourse has a relative risk of 1.43%, which is about 10 times higher that of receptive vaginal intercourse. Not all exposures to HIV, however, lead to infection and not all HIV infections lead to AIDS. Approximately a third of infants born to HIV infected mothers acquire infection while hetero-sexual transmission occurs approximately after between 1 out of 100 and 1 out of 1000 exposures, haemophiliacs exposed to infected blood products do not consistently get infected and some commercial sex workers and seronegative partners in serodiscordant couples appear to remain uninfected despite repeated extensive exposure to HIV (Girard et al., 2011).
2.2.1 Serodiscordancy
Emerging data indicate that a large proportion of new infections in Sub Saharan Africa occur in stable HIV discordant relationships and with increased testing of couples it has become apparent that a large proportion of couples affected by HIV are HIV serodiscordant (Achando et al., 2011; Bruyn et al., 2007). Demographic and health surveys (DHS) show that between 45% and 75% of married HIV positive individuals have HIV negative spouses. This affirms the importance of HIV prevention efforts for couples (Allen et al., 2008).
The current knowledge of HIV pathogenesis suggests that genetic variation can modulate the immune response and viral replication. Certain persons exhibit resistance to HIV infection despite multiple and repeated exposures to the virus. They are known as HIV exposed, but seronegative (HESN) individuals (Biasin et al., 2010). Approximately 15% of HIV exposed seronegative individuals repeatedly resist infection, a phenomenon that has been observed in all investigated HIV- exposed cohorts (Clerici et al., 2010). This group includes persons who have repeated unprotected sexual intercourse with a seropositive (SP) individual, such as HIV discordant couples, sex workers from areas of high HIV prevalence and men who have sex with men. This particular cohort of individuals represents an optimal chance to identify new therapeutic or vaccine targets (Estrada et al., 2013).
2.2.2 Causes of resistance to HIV amongst HESN individuals
The reasons for possible resistance to HIV infection in HESN subjects remain controversial and under investigation, although several nonmutually exclusive mechanisms have been proposed. First, there are known genetic factors at play such as the CCR5Δ32 mutation which occurs in a small proportion of humans that results in a CCR5 receptor unable to bind HIV and therefore prevention of infection in homozygous individuals. Second, there could be an antigen specific immune response generated upon HIV exposure that is sufficient to prevent infection. The first immunologic evidence of such HIV resistance was seen in the uninfected members of HIV serodiscordant partnerships, who specifically mounted CD8+ T cell responses to HIV envelope and core proteins. Similar HIV specific T cell responses have since been found in a variety of HESN populations, including sex workers and infants born to HIV-1-infected women (Baeten et al., 2013; Clerici et al., 2010).
Another mechanism proposed to account for HIV resistance in HESN is an overall CD4+ T cell quiescence, as defined by decreased expression of activation markers, cytokine secretion and gene expression profiling in HESN commercial sex workers. This reduced T cell activation has been proposed to be at least partially due to an increased percentage of regulatory T cells (Tregs). Tregs, a subset of CD4+ T cells, have demonstrated roles in regulating the immune system under homeostatic conditions as well as during infection. Tregs can suppress proliferation and function of several immune cell types, including Th1, Th2, and Th17 CD4+ T cells and CD8+ T cells. Moreover, they can modulate the migration of immune cells to the site of infection (Baeten et al., 2013).
Specifically, in a mouse model, it has been demonstrated that in the absence of Tregs the expression of CCL5/RANTES, a beta chemokine that binds to CCR5, was decreased in vaginal tissues following herpes simplex virus (HSV) infection, demonstrating that Tregs control the chemokine gradient in response to a viral exposure. The role of Tregs specifically in HIV infection remains unclear, though the recent finding of HIV-Gag-specific Tregs using class II tetramer staining suggests that they indeed participate in anti-HIV immunity. Given their role in suppressing immunity, they could be beneficial by dampening generalized immune activation, thereby reducing the pool of HIV-susceptible cells; alternately, they could be detrimental, by reducing the HIV-1-specific immune response. In support of the latter idea, in one study among HESN neonates, depletion of Tregs revealed strong HIV-specific CD4+ and CD8+ immune responses (Baeten et al., 2013).
This study’s aim was to determine the prevalence of HCV infection amongst serodiscordant couples in Thika, Kiambu County and to determine the correlation of CD4+ CD8+ count with HIV viral load in co- infected individuals, as given its contribution to the spread of the HIV/AIDS epidemic, it is imperative to better understand HIV discordancy and its correlates.