Activation of CD8 T Cells Predicts Progression of HIV Infection in Women Coinfected with Hepatitis C Virus

Abstract

Background Because activation of T cells is associated with human immunodeficiency virus (HIV) pathogenesis, CD4 and CD8 activation levels in patients coinfected with HIV and hepatitis C virus (HCV) may explain conflicting reports regarding effects of HCV on HIV disease progression. Methods Kaplan-Meier and multivariate Cox regression models were used to study the risk of incident clinical AIDS and AIDS-related deaths among 813 HCV-negative women with HIV infection, 87 HCV-positive nonviremic women with HIV coinfection, and 407 HCV-positive viremic women with HIV coinfection (median follow-up time, 5.2 years). For 592 women, the percentages of activated CD4 and CD8 T cells expressing HLA-DR (DR) and/or CD38 were evaluated. Results HCV-positive viremic women had a statistically significantly higher percentage of activated CD8 T cells (P < .001) and a statistically significantly higher incidence of AIDS compared with HCV-negative women (P < .001 [log-rank test]). The AIDS risk was greater among HCV-positive viremic women in the highest tertile compared with the lowest tertile (>43% vs <26%) of CD8+CD38+DR+ T cells (hazard ratio, 2.94 [95% confidence interval, 1.50–5.77]; P =.001). This difference was not observed in the HCV-negative women (hazard ratio, 1.87 [95% confidence interval, 0.80–4.35]; P =.16). In contrast, CD4 activation predicted AIDS in both groups similarly. Increased percentages of CD8+CD38−DR+, CD4+CD38−DR−, and CD8+CD38−DR− T cells were associated with a >60% decreased risk of AIDS for HCV-positive viremic women and HCV-negative women. Conclusion HCV-positive viremic women with HIV coinfection who have high levels of T cell activation may have increased risk of AIDS. Earlier treatment of HIV and HCV infection may be beneficial.

Inhibitory effects of chloroquine on the activation of plasmacytoid dendritic cells in SIVmac239-infected Chinese rhesus macaques

“…It even correlates with CD4 1 T cell counts better than HIV RNA levels and could be used as an effective clinical prognostic indicator. 6 However, the molecular contributors to this immune activation in HIV/SIV infection remain unclear.…”

“…1 Recently, it has been accepted that in addition to the direct infection of CD4 1 T lymphocytes by HIV virions, chronic immune activation in HIV-infected human and simian immunodeficiency virus (SIV)-infected non-natural hosts, such as rhesus macaques and cynomolgus macaques, may greatly contribute to the pathogenesis of AIDS. [2][3][4][5][6][7] Accumulated evidence suggests that large amounts of type I interferons (IFNs) produced by activated plasmacytoid dendritic cells (pDCs) might play a critical role in this chronic immune activation during HIV-1 infection. Clinical strategies aimed at inhibiting pDC activation could effectively counter disease progression in HIV patients.…”

Immune activation during acute HIV infection and the impact of early antiretroviral therapy

“…coinfections [20], damage to gut integrity, leakage of gut microbial products [21], damage to the lymphoid tissues, and loss of T regulatory (Treg) cells [22][23][24]. Several studies have shown a clear relationship between markers of immune activation and viral replication; however, it is currently unclear whether immune activation during ART drives viral persistence or whether viral persistence drives immune activation or both, as reviewed in [25].…”

Natural history of liver disease and effect of hepatitis C virus on HIV disease progression

“…A meta-analysis of eight trials showed that the mean increase in the CD4 cell count in coinfected patients was 33 cells/mm 3 less than that for HIV-infected patients without HCV infection [72], and these results have been confirmed in a more recent meta-analysis in which also an increase in AIDS events was seen in coinfected patients [73]. A chronic HCV coinfection contributes to systemic inflammation and immune activation in coinfected individuals which may in return lead to progression of their HIV disease [74]. HCV may therefore contribute to 'accelerated aging' which now has increasingly been described in HIV-infected individuals [75].…”