Tags

Type your tag names separated by a space and hit enter

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; 11:43BI

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.

Authors+Show Affiliations

Department of Medicine, Makerere University School of Medicine, Kampala, Uganda. drdamalie@yahoo.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

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 -