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High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort.

Abstract

BACKGROUND

Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated.

METHODS

T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34 ], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30].

RESULTS

Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022].

CONCLUSION

T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART.

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  • Authors+Show Affiliations

    ,

    Department of Medicine, Makerere University School of Medicine, Kampala, Uganda. drdamalie@yahoo.com

    , , , , , , ,

    Source

    BMC infectious diseases 11: 2011 Feb 08 pg 43

    MeSH

    Adult
    Anti-HIV Agents
    Antiretroviral Therapy, Highly Active
    Cohort Studies
    Female
    HIV Infections
    Humans
    Lymphocyte Activation
    Lymphocyte Depletion
    Male
    Prospective Studies
    RNA, Viral
    T-Lymphocytes
    Viral Load

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    21299909

    Citation

    Nakanjako, Damalie, et al. "High T-cell Immune Activation and Immune Exhaustion Among Individuals With Suboptimal CD4 Recovery After 4 Years of Antiretroviral Therapy in an African Cohort." BMC Infectious Diseases, vol. 11, 2011, p. 43.
    Nakanjako D, Ssewanyana I, Mayanja-Kizza H, et al. High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort. BMC Infect Dis. 2011;11:43.
    Nakanjako, D., Ssewanyana, I., Mayanja-Kizza, H., Kiragga, A., Colebunders, R., Manabe, Y. C., ... Cao, H. (2011). High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort. BMC Infectious Diseases, 11, p. 43. doi:10.1186/1471-2334-11-43.
    Nakanjako D, et al. High T-cell Immune Activation and Immune Exhaustion Among Individuals With Suboptimal CD4 Recovery After 4 Years of Antiretroviral Therapy in an African Cohort. BMC Infect Dis. 2011 Feb 8;11:43. PubMed PMID: 21299909.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - High T-cell immune activation and immune exhaustion among individuals with suboptimal CD4 recovery after 4 years of antiretroviral therapy in an African cohort. AU - Nakanjako,Damalie, AU - Ssewanyana,Isaac, AU - Mayanja-Kizza,Harriet, AU - Kiragga,Agnes, AU - Colebunders,Robert, AU - Manabe,Yukari C, AU - Nabatanzi,Rose, AU - Kamya,Moses R, AU - Cao,Huyen, Y1 - 2011/02/08/ PY - 2010/09/09/received PY - 2011/02/08/accepted PY - 2011/2/9/entrez PY - 2011/2/9/pubmed PY - 2011/6/8/medline SP - 43 EP - 43 JF - BMC infectious diseases JO - BMC Infect. Dis. VL - 11 N2 - BACKGROUND: Antiretroviral therapy (ART) partially corrects immune dysfunction associated with HIV infection. The levels of T-cell immune activation and exhaustion after long-term, suppressive ART and their correlation with CD4 T-cell count reconstitution among ART-treated patients in African cohorts have not been extensively evaluated. METHODS: T-cell activation (CD38+HLA-DR+) and immune exhaustion (PD-1+) were measured in a prospective cohort of patients initiated on ART; 128 patient samples were evaluated and subcategorized by CD4 reconstitution after long-term suppressive treatment: Suboptimal [median CD4 count increase 129 (-43-199) cells/μl], N = 34 ], optimal [282 (200-415) cells/μl, N = 64] and super-optimal [528 (416-878) cells/μl, N = 30]. RESULTS: Both CD4+ and CD8 T-cell activation was significantly higher among suboptimal CD4 T-cell responders compared to super-optimal responders. In a multivariate model, CD4+CD38+HLADR+ T-cells were associated with suboptimal CD4 reconstitution [AOR, 5.7 (95% CI, 1.4-23, P = 0.014)]. T-cell exhaustion (CD4+PD1+ and CD8+PD1+) was higher among suboptimal relative to optimal (P < 0.001) and super-optimal responders (P < 0.001). T-cell exhaustion was significantly associated with suboptimal responders [AOR, 1.5 (95%CI, 1.1-2.1), P = 0.022]. CONCLUSION: T-cell activation and exhaustion persist among HIV-infected patients despite long-term, sustained HIV-RNA viral suppression. These immune abnormalities were associated with suboptimal CD4 reconstitution and their regulation may modify immune recovery among suboptimal responders to ART. SN - 1471-2334 UR - https://www.unboundmedicine.com/medline/citation/21299909/High_T_cell_immune_activation_and_immune_exhaustion_among_individuals_with_suboptimal_CD4_recovery_after_4_years_of_antiretroviral_therapy_in_an_African_cohort_ L2 - https://bmcinfectdis.biomedcentral.com/articles/10.1186/1471-2334-11-43 DB - PRIME DP - Unbound Medicine ER -