T Cell Activation in HIV‐Seropositive Ugandans: Differential Associations with Viral Load, CD4⁺T Cell Depletion, and Coinfection

Abstract

Immune activation is thought to play a major role in the pathogenesis of human immunodeficiency virus (HIV). This effect may be particularly relevant in Africa, where endemic coinfections may contribute to disease progression, perhaps as a consequence of enhanced immune activation. We investigated the expression of CD38 and human leukocyte antigen (HLA)-DR on T cells in 168 HIV-seropositive volunteers in Uganda. We observed higher levels of CD4(+) and CD8(+) T cell activation in Uganda, compared with those reported in previous studies from Western countries. Coexpression of CD38 and HLA-DR on both CD4(+) and CD8(+) T cell subsets was directly correlated with viral load and inversely correlated with CD4(+) T cell counts. In antiretroviral therapy (ART)-naive volunteers, viral load and CD4(+) T cell count had stronger associations with CD8(+) and CD4(+) T cell activation, respectively. Virus suppression by ART was associated with a reduction in T cell activation, with a stronger observed effect on reducing CD8(+) compared with CD4(+) T cell activation. The presence of coinfection was associated with increased CD4(+) T cell activation but, interestingly, not with increased CD8(+) T cell activation. Our results suggest that distinct mechanisms differentially drive activation in CD4(+) and CD8(+) T cell subsets, which may impact the clinical prognostic values of T cell activation in HIV infection.

CD4 T-cell Activation and Reduced Regulatory T-cell Populations are Associated with Early Development of Cataracts among HIV-infected Adults in Uganda

“…Indeed, our data is consistent with previous findings of expansion of Treg during HIV infection as shown by the significantly higher levels of Treg among HIV-positive without cataracts relative to HIV-negative without cataracts [16,17]. Despite persistent expansion of Treg among HAART-treated HIV-infected adults in this study, Treg populations were reduced to comparable levels among relatively younger-HIV-infectedadults-with-cataracts and elderly-HIV-negative-adults-with-cataracts.…”

HIV-Specific IL-10-Positive CD8+ T Cells Are Increased in Advanced Disease and Are Associated with Decreased HIV-Specific Cytolysis

“…Demographic information was obtained at the time of enrollment and blood draw. Clinical characteristics including the prevalence of coinfections in this population were previously described (24,25). Exclusion criteria included age Ͻ18 years, pregnancy, active tuberculosis, Schistosoma mansoni coinfection, or moribund status.…”

Alterations in T Cell Subsets in Human Immunodeficiency Virus–Infected Adults with Co-infections in Southern Mozambique

“…However, independently of HIV infection, it has been shown that persons from Africa have a higher proportion of activated circulating T cells and a more mature T cell phenotype than persons from Europe. [4][5][6] It is unknown what proportion of this higher activation is caused by co-infections (viral infections, tuberculosis, malaria) and what is caused by genetic differences. Because this excess activation may contribute to fuelling HIV pathogenesis, efforts to elucidate whether the control of co-infections can benefit the prognosis of persons infected with HIV is crucial.…”