The Korean journal of internal medicine

The Korean Association of Internal Medicine (대한내과학회)
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The CD4 slope can be a predictor of immunologic recovery in advanced HIV patients: a case-control study

  • Kim, Kye-Hyung (Division of Infectious Diseases, Department of Internal Medicine, Pusan National University Hospital) ;
  • Yi, Jongyoun (Biomedical Research Institute, Pusan National University Hospital) ;
  • Lee, Sun Hee (Division of Infectious Diseases, Department of Internal Medicine, Pusan National University Hospital)
  • Received : 2015.02.05
  • Accepted : 2015.03.31
  • Published : 2015.09.01
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Abstract

Background/Aims: Advanced human immunodef iciency virus (HIV) infection, despite sustained viral suppression by highly active antiretroviral therapy (HAART), is a risk factor for poor immunologic recovery. However, some patients with advanced infection do show immunologic recovery. In this study, predictive factors of immunologic recovery were analyzed in advanced HIV patients showing sustained viral suppression. Methods: A case-control study was conducted in HIV-infected adult patients with HIV-1 RNA < 50 copies/mL maintained for 4 years or longer and who were receiving HAART. Advanced HIV infection was defined as a baseline CD4 T cell count < $200/mm^3$. Immunologic responders were defined as patients showing immunologic recovery (CD4 T cell counts ${\geq}500/mm^3$ at 4 years with HAART). To analyze the CD4 T cell kinetics, the CD4 slope (monthly changes in the CD4 T cell count) was estimated for each patient using a linear regression between the CD4 T cell count and the time since HAART initiation. Results: Of 102 eligible patients, 73 had advanced HIV, and 33 (45.2%) showed immunologic recovery. The median CD4 slopes ($cells/mm^3$ per month) during 0 to 6 and 0 to 12 months of HAART in the 73 advanced patients were significantly higher in responders than in non-responders (0 to 6 months, 38.6 vs. 22.8; 0 to 12 months, 24.5 vs. 13.5). Multivariate analyses showed opportunistic infections at the start of HAART (adjusted odds ratio [OR], 0.28) and a CD4 slope ${\geq}20$ during 0 to 12 months of HAART (adjusted OR, 10.10) were independently associated with immunologic recovery. Conclusions: The CD4 slope can be an early predictor of long-term immunologic recovery in advanced HIV patients.

Keywords

References

  1. Joint United Nations Programme on HIV/AIDS (UNAIDS). The Gap Report. Geneva: Joint United Nations Programme on HIV/AIDS, 2014.
  2. Corbeau P, Reynes J. Immune reconstitution under antiretroviral therapy: the new challenge in HIV-1 infection. Blood 2011;117:5582-5590. https://doi.org/10.1182/blood-2010-12-322453
  3. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents [Internet]. Rockville (MD): AIDSinfo, 2015 [cited 2015 Jul 6]. Available from: http://aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf.
  4. Broder S. The development of antiretroviral therapy and its impact on the HIV-1/AIDS pandemic. Antiviral Res 2010;85:1-18. https://doi.org/10.1016/j.antiviral.2009.10.002
  5. Chun TW, Stuyver L, Mizell SB, et al. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc Natl Acad Sci U S A 1997;94:13193-13197. https://doi.org/10.1073/pnas.94.24.13193
  6. Chun TW, Engel D, Berrey MM, Shea T, Corey L, Fauci AS. Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection. Proc Natl Acad Sci U S A 1998;95:8869-8873. https://doi.org/10.1073/pnas.95.15.8869
  7. Guihot A, Tubiana R, Breton G, et al. Immune and virological benefits of 10 years of permanent viral control with antiretroviral therapy. AIDS 2010;24:614-617. https://doi.org/10.1097/QAD.0b013e32833556f3
  8. Autran B, Carcelaint G, Li TS, et al. Restoration of the immune system with anti-retroviral therapy. Immunol Lett 1999;66:207-211. https://doi.org/10.1016/S0165-2478(98)00159-X
  9. Guihot A, Bourgarit A, Carcelain G, Autran B. Immune reconstitution after a decade of combined antiretroviral therapies for human immunodeficiency virus. Trends Immunol 2011;32:131-137. https://doi.org/10.1016/j.it.2010.12.002
  10. Kaufmann GR, Perrin L, Pantaleo G, et al. CD4 T-lymphocyte recovery in individuals with advanced HIV-1 infection receiving potent antiretroviral therapy for 4 years: the Swiss HIV Cohort Study. Arch Intern Med 2003;163:2187-2195. https://doi.org/10.1001/archinte.163.18.2187
  11. Tsukamoto H, Clise-Dwyer K, Huston GE, et al. Age-associated increase in lifespan of naive CD4 T cells contributes to T-cell homeostasis but facilitates development of functional defects. Proc Natl Acad Sci U S A 2009;106:18333-18338. https://doi.org/10.1073/pnas.0910139106
  12. Viard JP, Mocroft A, Chiesi A, et al. Influence of age on CD4 cell recovery in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy: evidence from the EuroSIDA study. J Infect Dis 2001;183:1290-1294. https://doi.org/10.1086/319678
  13. Egger M, May M, Chene G, et al. Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet 2002;360:119-129. https://doi.org/10.1016/S0140-6736(02)09411-4
  14. Nicastri E, Chiesi A, Angeletti C, et al. Clinical outcome after 4 years follow-up of HIV-seropositive subjects with incomplete virologic or immunologic response to HAART. J Med Virol 2005;76:153-160. https://doi.org/10.1002/jmv.20352
  15. Lawn SD, Myer L, Bekker LG, Wood R. CD4 cell count recovery among HIV-infected patients with very advanced immunodeficiency commencing antiretroviral treatment in sub-Saharan Africa. BMC Infect Dis 2006;6:59. https://doi.org/10.1186/1471-2334-6-59
  16. Rajasuriar R, Gouillou M, Spelman T, et al. Clinical predictors of immune reconstitution following combination antiretroviral therapy in patients from the Australian HIV Observational Database. PLoS One 2011;6:e20713. https://doi.org/10.1371/journal.pone.0020713
  17. Havlir DV, Bassett R, Levitan D, et al. Prevalence and predictive value of intermittent viremia with combination hiv therapy. JAMA 2001;286:171-179. https://doi.org/10.1001/jama.286.2.171
  18. Kelley CF, Kitchen CM, Hunt PW, et al. Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis 2009;48:787-794. https://doi.org/10.1086/597093
  19. 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 1992;41(RR-17):1-19.
  20. Kaufmann GR, Furrer H, Ledergerber B, et al. Characteristics, determinants, and clinical relevance of CD4 T cell recovery to <500 cells/microL in HIV type 1-infected individuals receiving potent antiretroviral therapy. Clin Infect Dis 2005;41:361-372. https://doi.org/10.1086/431484
  21. Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents [Internet]. Rockville (MD): AIDSinfo, 2015 [cited 2015 Jul 6]. Available from: http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf.
  22. Morris L, Martin DJ, Bredell H, et al. Human immunodeficiency virus-1 RNA levels and CD4 lymphocyte counts, during treatment for active tuberculosis, in South African patients. J Infect Dis 2003;187:1967-1971. https://doi.org/10.1086/375346
  23. Autran B, Carcelain G, Li TS, et al. Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 1997;277:112-116. https://doi.org/10.1126/science.277.5322.112
  24. Carcelain G, Debre P, Autran B. Reconstitution of CD4+ T lymphocytes in HIV-infected individuals following antiretroviral therapy. Curr Opin Immunol 2001;13:483-488. https://doi.org/10.1016/S0952-7915(00)00245-4
  25. Pido-Lopez J, Imami N, Aspinall R. Both age and gender affect thymic output: more recent thymic migrants in females than males as they age. Clin Exp Immunol 2001;125:409-413. https://doi.org/10.1046/j.1365-2249.2001.01640.x
  26. Hoffmann CJ, Schomaker M, Fox MP, et al. CD4 count slope and mortality in HIV-infected patients on antiretroviral therapy: multicohort analysis from South Africa. J Acquir Immune Defic Syndr 2013;63:34-41. https://doi.org/10.1097/QAI.0b013e318287c1fe
  27. Kaufmann GR, Bloch M, Finlayson R, Zaunders J, Smith D, Cooper DA. The extent of HIV-1-related immunodeficiency and age predict the long-term CD4 T lymphocyte response to potent antiretroviral therapy. AIDS 2002;16:359-367. https://doi.org/10.1097/00002030-200202150-00007

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