Low-Level Exposure to HIV Induces Virus-Specific T Cell Responses and Immune Activation in Exposed HIV-Seronegative Individuals

Abstract

HIV-specific T cells response and T cell activation are frequently seen in exposed seronegative individuals (ESN). In this study, we report HIV-specific response and level of T cell activation in ESN partners of HIV-infected patients presenting low or undetectable levels of HIV-RNA. We evaluated 24 HIV-serodiscordant couples. ESN were classified into three categories of exposure to HIV (very low, low, and moderate-high), considering levels of HIV-RNA in their infected partner and frequency of sexual high-risk practices within the last 12 mo. HIV-specific T cell responses and activation levels in T cell subsets were evaluated by flow cytometry. We reported that 54% of ESN had detectable HIV-specific T cells response, being the highest prevalence seen in the low exposure group (64%). Several T cell subsets were significantly increased in ESN when compared with controls: CD4+CD38+ (p = 0.006), CD4+HLA-DR−CD38+ (p = 0.02), CD4+CD45RA+CD27+HLA-DR−CD38+ (p = 0.002), CD8+CD45RA+CD27+CD38−HLA-DR+ (p = 0.02), and CD8+CD45RA+CD27−CD38+HLA-DR+ (p = 0.03). Activation of CD8+ T cells was increased in ESN with detectable HIV T cell responses compared with ESN lacking these responses (p = 0.04). Taken together, these results suggest that persistent but low sexual HIV exposure is able to induce virus-specific T cells response and immune activation in a high proportion of ESN, suggesting that virus exposure may occur even in conditions of maximal viral suppression in the HIV-infected partner.

T Cell Distribution in Relation to HIV/HBV/HCV Coinfections and Intravenous Drug Use

“…More specifically, triple infected PWID had lower percentages of CD4 + cells and higher percentages of CD8 + cells and immune activation markers than HIV negative PWID groups, which was a finding similar to that for hetero-and homosexually infected HIV-positive individuals without known coinfections (21,25,35). Although we were unable to assess the distinct effects of HIV due to a lack of mono-infected subjects among the PWID, the changes in the T cell distribution among the Only values with significant differences between cell populations are presented.…”

“…To the best of our knowledge, this is the first study to demonstrate altered T cell subset distribution ( + T cell and macrophage shifts in response to opioid exposure (3,33) and in vitro studies have found opioids to have additional effects that lead to an increase in the expression of the HIV coreceptor CCR5 (19,24,32,33). The increased CD38 and or HLA-DR, together with the differences in the multiple cell populations of the PWID found in the present study, could be explained by various factors, such as the abiotic substances injected, to an individual's systemic circulation, an unproductive infection with HIV, or the two hepatitis viruses (4,21,25,26). Overall, the changes seen in the triple negative PWID may have been caused by opioids or viral exposure; nevertheless, the immune system is already altered as a consequence of IDU, even when individuals remain seronegative to HIV, HBV, and HCV.…”

Evidence for the innate immune response as a correlate of protection in human immunodeficiency virus (HIV)-1 highly exposed seronegative subjects (HESN)

“…Subsequent reports confirmed the presence of antigen-specific T cell responses to HIV-1 in HESN subjects while characterizing the functional and proliferative capacity of HIV-specific T cells in these subjects [7,[25][26][27]. Genetically, both major histocompatibility complex (MHC) class I [28] and human leucocyte antigen (HLA) class II [29] alleles have been associated with a reduced risk of infection with HIV-1.…”

AIDS Vaccines and Preexposure Prophylaxis: Is Synergy Possible?

“…A systematic review of these studies suggests that natural resistance to HIV infection in highly exposed individuals is mediated by multiple mechanisms, conferring on them an ''immunologic advantage'' that may be related to innate and/or adaptive immune systems. 66,67 Although offering only a partial explanation to the natural resistance to HIV infection, 68 observations in female sex workers in Nairobi with frequent HIV exposure, [69][70][71] in exposed uninfected infants with strong HIV-1-specific T cell responses, 72 and more recently in discordant couples 73 suggest that recurrent viral exposure may lead to priming of HIV-specific systemic and mucosal immune responses. These findings suggest that persons receiving PrEP who are exposed to HIV may generate HIV-specific T cell responses, potentially contributing to protection against the establishment of HIV infection.…”