Central African Republic (CAR) has a high prevalence rate of HIV-1 infection estimated at 18% among pregnant women . The primary route of transmission is heterosexual. High rates of infection in HIV-1-infected individuals in Africa have been suggested to be related to immune hyperactivation driven by environmental factors, including high exposure to infectious agents and poor hygienic conditions . Indeed, higher levels of CD4 and CD8 T cell activation have been reported in HIV-1 infected Africans in comparison with European populations . In particular, HLA-DR expression on CD4 T cells was correlated with CD4 T cell count, viral load and coinfections . Successful antiretroviral therapy was reported to decrease the levels of T cell activation markers, with a stronger effect on CD8 than on CD4 T cell activation [4, 5]. A pattern of immune activation, including an increase of activated T cell subsets and of the HIV-1 CCR5 co-receptor expression, has been reported not only in HIV-infected but also in HIV-uninfected African populations [6–9]. Interestingly, peripheral blood mononuclear cells (PBMC) from individuals with a chronic immune activation exhibited higher susceptibility to HIV-1 infection in vitro .
In spite of the spreading of HIV-epidemic in CAR, a consistent proportion of Central Africans who have been persistently exposed for several years to infection through unprotected sexual relationships with HIV-1 infected partners remained seronegative (Bégaud E. et al., unpublished data). Most studies on correlates of protection against HIV-1 infection in seronegative exposed individuals in other African countries were conducted on cohorts of commercial sex workers (CSW) whereas only a few studies concerned seronegative partners in serodiscordants couples [11–18]. In these studies, HIV-1-specific helper and cytotoxic T cell responses have been detected in a significant proportion of exposed seronegative individuals [19–23]. HIV-1-specific mucosal IgA were also detected in persistently negative Kenyan CSW and were shown to be capable of in vitro neutralization of HIV-1 [24, 25]. The question of whether these specific immune responses exert a protective role or they reflect exposure to HIV-1 is, however, still debated [26–28]. Other immunological or genetic factors potentially related to the resistance have also been addressed in exposed seronegative African individuals but no clear protective mechanisms emerged from these studies [12, 13, 29–31]. Genetic polymorphism in the CCR5 gene, such as the CCR5-Δ32 mutation, which was associated to the resistance to HIV-1 infection in Caucasian populations, has not been found in Africans .
We studied a group of exposed seronegative partners of HIV-1 infected individuals in Bangui with a long history of leading a common life and practicing unprotected sexual relations. Considering the background of immune activation reported in African populations, we asked whether differences in the levels of CD4 T cell activation and in the capacity to replicate HIV-1 in vitro could be related to the apparent resistance to infection in this group. From the studies conducted, we found lower levels of CD4 T cell activation and reduced in vitro susceptibility to HIV-1 infection in exposed seronegative individuals than in low-risk Central African blood donors.