Top

European Journal of Medical Research

Published in:

01-12-2009 | Research

Impaired CD4-cell immune reconstitution upon HIV therapy in patients with toxoplasmic encephalitis compared to patients with pneumocystis pneumonia as AIDS indicating disease

Authors: U Kastenbauer, E Wolf, C Kollan, O Hamouda, JR Bogner, The ClinSurv Study Group

Published in: European Journal of Medical Research | Issue 6/2009

Abstract

Objectives

There is only little data on immune reconstitution in antiretroviral naïve AIDS-patients with toxoplasmosis. The observation of several cases with reduced increase of CD4-cells upon start of antiretroviral treatment (ART) prompted us to investigate the topic using the ClinSurv cohort.

Methods

17 German HIV treatment centers contribute to ClinSurv, a multicentre observational cohort under the auspices of the Robert Koch Institute. We retrospectively selected all antiretroviral-naïve patients with toxoplasmic encephalitis (TE) and -as comparator group -with pneumocystosis (PCP) between January 1999 and December 2005.

Results

A total of 257 patients were included in the analysis, 61 with TE and 196 with PCP. Demographic baseline data showed differences with regard to gender, transmission group, and baseline CD4⁺ counts (60.9 vs. 44.7/μl, p = 0.022). After ART-initiation the increase in CD4⁺ lymphocytes was lower in the TE-versus the PCP-group in the first, second and fourth three-month-period (74.4 vs. 120.3/μl, p = 0.006; 96.6 vs. 136.2/μl, p = 0.021; 156.5 vs. 211.5/μl, p = 0.013). Viral load (VL) was higher in the PCP-group at baseline (4.46 log₁₀cop/ml vs. 5.00 log₁₀cop/ml, p = 0.008), while virological success of ART was equal.

Conclusions

Our data show for the first time that the average CD4⁺ T-cell increase of patients with toxoplasmosis is impaired compared to PCP-patients. Most clinicians would not be prepared to discontinue follow-up TE-therapy unless CD4⁺ counts of 200/μl are reached. Explanation for our finding might be the myelosuppressive side effect of pyrimethamine, possible interactions of toxoplasmosis therapy with ART, or an unknown direct biological influence of toxoplasmosis on immune restoration.

Abgrall S, Rabaud C, Costagliola D: Incidence and risk factors for toxoplasmic encephalitis in human immunodeficiency virus-infected patients before and during the highly active antiretroviral therapy era. Clin Infect Dis 2001,33(10):1747–55. 10.1086/322622PubMedCrossRef

San-Andres FJ, Rubio R, Castilla J, Pulido F, Palao G, de PI, et al.: Incidence of acquired immunodeficiency syndrome-associated opportunistic diseases and the effect of treatment on a cohort of 1115 patients infected with human immunodeficiency virus, 1989–1997. Clin Infect Dis 2003,36(9):1177–85. 10.1086/374358PubMedCrossRef

Brodt HR, Kamps BS, Gute P, Knupp B, Staszewski S, Helm EB: Changing incidence of AIDS-defining illnesses in the era of antiretroviral combination therapy. AIDS 1997,11(14):1731–8. 10.1097/00002030-199714000-00010PubMedCrossRef

Battegay M, Fluckiger U, Hirschel B, Furrer H: Late presentation of HIV-infected individuals. Antivir Ther 2007,12(6):841–51.PubMed

Keruly JC, Moore RD: Immune status at presentation to care did not improve among antiretroviral-naive persons from 1990 to 2006. Clin Infect Dis 2007,45(10):1369–74. 10.1086/522759PubMedCrossRef

Pulvirenti J, Herrera P, Venkataraman P, Ahmed N: Pneumocystis carinii pneumonia in HIV-infected patients in the HAART era. AIDS Patient Care STDS 2003,17(6):261–5. 10.1089/108729103322108139PubMedCrossRef

Benson CA, Kaplan JE, Masur H, Pau A, Holmes KK: Treating opportunistic infections among HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the Infectious Diseases Society of America. Webpage 2004 Available from: URL: http://aidsinfo.nih.gov/contentfiles/TreatmentofOI_AA.pdf

Clumeck N: Some aspects of the epidemiology of toxoplasmosis and pneumocystosis in AIDS in Europe. Eur J Clin Microbiol Infect Dis 1991,10(3):177–8. 10.1007/BF01964454PubMedCrossRef

Montoya JG, Liesenfeld O: Toxoplasmosis. Lancet 2004,363(9425):1965–76. 10.1016/S0140-6736(04)16412-XPubMedCrossRef

10.

Israelski DM, Chmiel JS, Poggensee L, Phair JP, Remington JS: Prevalence of Toxoplasma infection in a cohort of homosexual men at risk of AIDS and toxoplasmic encephalitis. J Acquir Immune Defic Syndr 1993,6(4):414–8.PubMed

11.

Ancelle-Park R: Expanded European AIDS case definition. Lancet 1993,341(8842):441.PubMedCrossRef

12.

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.

13.

Nath A, Sinai AP: Cerebral Toxoplasmosis. Curr Treat Options Neurol 2003,5(1):3–12. 10.1007/s11940-003-0018-8PubMedCrossRef

14.

Masters PA, O'Bryan TA, Zurlo J, Miller DQ, Joshi N: Trimethoprim-sulfamethoxazole revisited. Arch Intern Med 2003,163(4):402–10. 10.1001/archinte.163.4.402PubMedCrossRef

15.

Freund YR, Dabbs J, Creek MR, Phillips SJ, Tyson CA, MacGregor JT: Synergistic bone marrow toxicity of pyrimethamine and zidovudine in murine in vivo and in vitro models: mechanism of toxicity. Toxicol Appl Pharmacol 2002,181(1):16–26. 10.1006/taap.2002.9397PubMedCrossRef

16.

Kirk O, Reiss P, Uberti-Foppa C, Bickel M, Gerstoft J, Pradier C, et al.: Safe interruption of maintenance therapy against previous infection with four common HIV-associated opportunistic pathogens during potent antiretroviral therapy. Ann Intern Med 2002,137(4):239–50.PubMedCrossRef

17.

D'Egidio GE, Kravcik S, Cooper CL, Cameron DW, Fergusson DA, Angel JB: Pneumocystis jiroveci pneumonia prophylaxis is not required with a CD4⁺ T-cell count < 200 cells/microl when viral replication is suppressed. AIDS 2007,21(13):1711–5. 10.1097/QAD.0b013e32826fb6fcPubMedCrossRef

18.

Linares GG, Gismondi S, Codesido NO, Moreno SN, Docampo R, Rodriguez JB: Fluorine-containing aryloxyethyl thiocyanate derivatives are potent inhibitors of Trypanosoma cruzi and Toxoplasma gondii proliferation. Bioorg Med Chem Lett 2007,17(18):5068–71. 10.1016/j.bmcl.2007.07.012PubMedCentralPubMedCrossRef

19.

el Kouni MH: Adenosine metabolism in Toxoplasma gondii: potential targets for chemotherapy. Curr Pharm Des 2007,13(6):581–97. 10.2174/138161207780162836PubMedCrossRef

20.

Shubar HM, Mayer JP, Hopfenmuller W, Liesenfeld O: A new combined flow-cytometry-based assay reveals excellent activity against Toxoplasma gondii and low toxicity of new bisphosphonates in vitro and in vivo. J Antimicrob Chemother 2008,61(5):1110–9. 10.1093/jac/dkn047PubMedCrossRef

21.

Moreno SN, Li ZH: Anti-infectives targeting the isoprenoid pathway of Toxoplasma gondii. Expert Opin Ther Targets 2008,12(3):253–63. 10.1517/14728222.12.3.253PubMedCrossRef

22.

Durier C, Capitant C, Lascaux AS, Goujard C, Oksenhendler E, Poizot-Martin I, et al.: Long-term effects of intermittent interleukin-2 therapy in chronic HIV-infected patients (ANRS 048–079 Trials). AIDS 2007,21(14):1887–97. 10.1097/QAD.0b013e3282703825PubMedCrossRef

23.

Goldberg GL, Zakrzewski JL, Perales MA, van den Brink MR: Clinical strategies to enhance T cell reconstitution. Semin Immunol 2007, 19: 289–96. 10.1016/j.smim.2007.08.001PubMedCentralPubMedCrossRef

24.

Moore DM, Hogg RS, Yip B, Wood E, Tyndall M, Braitstein P, et al.: Discordant immunologic and virologic responses to highly active antiretroviral therapy are associated with increased mortality and poor adherence to therapy. J Acquir Immune Defic Syndr 2005,40(3):288–93. 10.1097/01.qai.0000182847.38098.d1PubMedCrossRef

25.

Hafner R, Inderlied CB, Peterson DM, Wright DJ, Standiford HC, Drusano G, et al.: Correlation of quantitative bone marrow and blood cultures in AIDS patients with disseminated Mycobacterium avium complex infection. J Infect Dis 1999,180(2):438–47. 10.1086/314865PubMedCrossRef

26.

Lazaro E, Coureau G, Guedj J, Blanco P, Pellegrin I, Commenges D, et al.: Change in T-lymphocyte count after initiation of highly active antiretroviral therapy in HIV-infected patients with history of Mycobacterium avium complex infection. Antivir Ther 2006,11(3):343–50.PubMedCentralPubMed

27.

Kremer L, Estaquier J, Wolowczuk I, Biet F, Ameisen JC, Locht C: Ineffective cellular immune response associated with T-cell apoptosis in susceptible Mycobacterium bovis BCG-infected mice. Infect Immun 2000,68(7):4264–73. 10.1128/IAI.68.7.4264-4273.2000PubMedCentralPubMedCrossRef

28.

Petakov M, Stojanovic N, Jovcic G, Bugarski D, Todorovic V, Djurkovic-Djakovic O: Hematopoiesis during acute Toxoplasma gondii infection in mice. Haematologia (Budap) 2002,32(4):439–55.

29.

Andrieu JM, Lu W, Levy R: Sustained increases in CD4 cell counts in asymptomatic human immunodeficiency virus type 1-seropositive patients treated with prednisolone for 1 year. J Infect Dis 1995,171(3):523–30. 10.1093/infdis/171.3.523PubMedCrossRef

30.

Ulmer A, Muller M, Bertisch-Mollenhoff B, Frietsch B: Low dose prednisolone reduces CD4⁺ Tcelllossintherapy-naive HIV-patients without antiretroviral therapy. Eur J Med Res 2005,10(3):105–9.PubMed

31.

Manzardo C, Zaccarelli M, Aguero F, Antinori A, Miro JM: Optimal timing and best antiretroviral regimen in treatment-naive HIV-infected individuals with advanced disease. J Acquir Immune Defic Syndr 2007,46(Suppl 1):S9–18. S9–18 10.1097/01.qai.0000286599.38431.efPubMedCrossRef

Title: Impaired CD4-cell immune reconstitution upon HIV therapy in patients with toxoplasmic encephalitis compared to patients with pneumocystis pneumonia as AIDS indicating disease
Authors: U Kastenbauer
E Wolf
C Kollan
O Hamouda
JR Bogner
The ClinSurv Study Group
Publication date: 01-12-2009
Publisher: BioMed Central
Published in: European Journal of Medical Research / Issue 6/2009
Electronic ISSN: 2047-783X
DOI: https://doi.org/10.1186/2047-783X-14-6-244

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Impaired CD4-cell immune reconstitution upon HIV therapy in patients with toxoplasmic encephalitis compared to patients with pneumocystis pneumonia as AIDS indicating disease

Abstract

Objectives

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 6/2009

Short-term outcome after posterior versus lateral surgical approach for total hip arthroplasty - a randomized clinical trial*

BCL2-938C > A and CALCA-1786T > C polymorphisms in aseptic loosened total hip arthroplasty

Dysplasia epiphysealis hemimelica of the distal ulna: a case report and review of the literature

Chest wall and intrathoracic desmoid tumors: surgical experience and review of the literature

Natural history, clinical pattern, and surgical considerations of pneumatosis intestinalis

Acoustic monitoring (RFM) of total hip arthroplasty results of a cadaver study