Skip to main content

Advertisement

SpringerLink
Log in

Impact of earlier HAART initiation on the immune status and clinical course of treated patients on the basis of cohort data of the German Competence Network for HIV/AIDS

  • Clinical and Epidemiological Study
  • Published:
Infection Aims and scope Submit manuscript

Abstract

Purpose

Hitherto, studies on highly active antiretroviral therapy (HAART) initiation have shown partly inconsistent results. Our study investigated the clinical course and course of immune status after HAART initiation at CD4-cell-count/μl of treated patients between 250 and 349 (group 1), compared to 350–449 (group 2), on the basis of the cohort of the Competence Network for HIV/AIDS (KompNet cohort).

Methods

Patients had to be HAART-naïve. Medication had to start at the earliest in 1996, being at least triple combination therapy. The primary endpoints of death, first AIDS-defining illness and first drop of CD4-cell-count/μl below 200 were evaluated as censored event times between the initiation of HAART (t 0) and the date of the first event/date of last observation. Probabilities of event-free intervals since t 0 were calculated by Kaplan–Meier estimation, compared by logrank tests. The results were adjusted for confounders using Cox regression. Additionally, incidences were estimated.

Results

A total of 822 patients met the inclusion criteria (group 1: 526, group 2: 296), covering 4,133 patient years (py) overall. In group 1, 0.64 death cases/100 py were found, with the corresponding vale being 0.17 in group 2. In group 1, 1.38 AIDS-defining events/100 py occurred, whereas it was 0.78 in group 2. In group 1, 2.64 events of first drop of CD4-cell-count/μl below 200 occurred per 100 py, compared to 0.77 in group 2. Kaplan–Meier estimations showed borderline significant differences regarding death (p = 0.063), no differences regarding first AIDS-defining illness (p = 0.148) and distinct differences regarding the first drop of CD4-cell-count/μl below 200 (p = 0.0004).

Conclusions

The results gave a strong hint for a therapy initiation at higher CD4-cell-count/μl regarding the outcome of death in treated patients. A distinct benefit was shown regarding the first decline of CD4-cell-count/μl below 200.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Notes

  1. Central clinical and therapy related data of patients regarding the time before enrolment into the cohort are documented retrospectively [3]. Due to the high proportion of data documented retrospectively before 2005, the calendar year of the start of HAART (<2005 vs. ≥2005) was considered as a confounder to adjust for potential influences of different modes of data documentation (retrospective vs. prospective).

  2. The percentage of quarters with a documented CD4-cell-count/μl measurement is lower for the subpopulation with an observation time ≥3 years than in all patients. For the analysis shown in Table 3, a fixed datum reference of 12 quarters was used as a basis for the analyses due to the observation period of at least 3 years. Because not every patient had a CD4-cell-count/μl measurement just in the 12 quarter, the named percentage is lower.

  3. It was not reasonable to calculate the incidences of death for this subpopulation due to the inclusion criteria of this group (observation period at least 3 years) and due to seven cases of death within the first 3 years.

References

  1. Emery S, Neuhaus JA, Phillips AN, et al. Major clinical outcomes in antiretroviral therapy (ART)-naive participants and in those not receiving ART at baseline in the SMART study. J Infect Dis. 2008;197:1133–44.

    Article  PubMed  Google Scholar 

  2. Strategies for Management of Antiretroviral Therapy (SMART) Study Group. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med. 2006;355:2283–96.

    Article  Google Scholar 

  3. Kitahata MM, Gange SJ, Abraham AG, et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med. 2009;360(18):1815–26.

    Article  PubMed  CAS  Google Scholar 

  4. Sterne JA, May M, Costagliola D, et al. Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet. 2009;373(9672):1352–63.

    Article  PubMed  Google Scholar 

  5. Ahdieh-Grant L, Yamashita TE, Phair JP, et al. When to initiate highly active antiretroviral therapy: a cohort approach. Am J Epidemiol. 2003;157:738–46.

    Article  PubMed  Google Scholar 

  6. Anastos K, Barrón Y, Miotti P, et al. Risk of progression to AIDS and death in women infected with HIV-1 initiating highly active antiretroviral treatment at different stages of disease. Arch Intern Med. 2002;162:1973–80.

    Article  PubMed  Google Scholar 

  7. Hughes MD, Ribaudo HR. The search for data on when to start treatment for HIV infection. J Infect Dis. 2008;197:1084–6.

    Article  PubMed  Google Scholar 

  8. Opravil M, Ledergerber B, Furrer H, et al. Clinical efficacy of early initiation of HAART in patients with asymptomatic HIV infection and CD4 cell count >350 × 10(6)/l. AIDS. 2002;16:1371–81.

    Article  PubMed  CAS  Google Scholar 

  9. Palella FJ Jr, Deloria-Knoll M, Chmiel JS, et al. Survival benefit of initiating antiretroviral therapy in HIV-infected persons in different CD4+ cell strata. Ann Intern Med. 2003;138:620–6.

    PubMed  Google Scholar 

  10. Sterling TR, Chaisson RE, Moore RD. HIV-1 RNA, CD4 T-lymphocytes, and clinical response to highly active antiretroviral therapy. AIDS. 2001;15:2251–7.

    Article  PubMed  CAS  Google Scholar 

  11. Sterling TR, Chaisson RE, Moore RD. Initiation of highly active antiretroviral therapy at CD4+ T lymphocyte counts of >350 cells/mm3: disease progression, treatment durability, and drug toxicity. Clin Infect Dis. 2003;36:812–5.

    Article  PubMed  Google Scholar 

  12. Zolopa A, Andersen J, Powderly W, et al. Early antiretroviral therapy reduces AIDS progression/death in individuals with acute opportunistic infections: a multicenter randomized strategy trial. PLoS ONE. 2009;4(5):e5575.

    Article  PubMed  Google Scholar 

  13. Grant P, Zolopa A. Initiation of antiretroviral therapy in the hospitalized patient with an acute AIDS-related opportunistic infection and other conditions: no time to lose. Curr HIV/AIDS Rep. 2009;6(2):63–7.

    Article  PubMed  Google Scholar 

  14. Phillips AN, Gazzard B, Gilson R, et al. Rate of AIDS diseases or death in HIV-infected antiretroviral therapy-naive individuals with high CD4 cell count. AIDS. 2007;21(13):1717–21.

    Article  PubMed  Google Scholar 

  15. May MT, Sterne JA, Costagliola D, et al. HIV treatment response and prognosis in Europe and North America in the first decade of highly active antiretroviral therapy: a collaborative analysis. Lancet. 2006;368(9534):451–8.

    Article  PubMed  Google Scholar 

  16. Bonnet F, Thiébaut R, Chêne G, et al. Determinants of clinical progression in antiretroviral-naive HIV-infected patients starting highly active antiretroviral therapy. Aquitaine Cohort, France, 1996–2002. HIV Med. 2005;6(3):198–205.

    Article  PubMed  CAS  Google Scholar 

  17. Chêne G, Sterne JA, May M, et al. Prognostic importance of initial response in HIV-1 infected patients starting potent antiretroviral therapy: analysis of prospective studies. Lancet. 2003;362(9385):679–86.

    Article  PubMed  Google Scholar 

  18. Jacobson LP, Li R, Phair J, et al. Evaluation of the effectiveness of highly active antiretroviral therapy in persons with human immunodeficiency virus using biomarker-based equivalence of disease progression. Am J Epidemiol. 2002;155(8):760–70.

    Article  PubMed  CAS  Google Scholar 

  19. Thompson MA, Aberg JA, Cahn P, et al. Antiretroviral treatment of adult HIV infection: 2010 recommendations of the International AIDS Society USA—Panel. JAMA. 2010;304(3):321–33.

    Article  PubMed  CAS  Google Scholar 

  20. Clumeck N, Dedes N, Pozniak A, et al. Clinical management and treatment of HIV infected adults in Europe. EACS Guidelines Version 5.2. Available online at: http://www.europeanaidsclinicalsociety.org/guidelines.asp. Accessed 16 September 2010.

  21. Lau B, Gange SJ, Kirk GD, et al. Evaluation of human immunodeficiency virus biomarkers: inferences from interval and clinical cohort studies. Epidemiology. 2009;20(5):664–72.

    Article  PubMed  Google Scholar 

  22. Jaén A, Esteve A, Miró JM, et al. Determinants of HIV progression and assessment of the optimal time to initiate highly active antiretroviral therapy: PISCIS Cohort (Spain). J Acquir Immune Defic Syndr. 2008;47(2):212–20.

    Article  PubMed  Google Scholar 

  23. Stöhr W, Dunn D, Porter K, et al. CD4 cell count and initiation of antiretroviral therapy: trends in seven UK centres, 1997–2003. HIV Med. 2007;8(3):135–41.

    Article  PubMed  Google Scholar 

  24. May M, Sterne JA, Sabin C, et al. Prognosis of HIV-1-infected patients up to 5 years after initiation of HAART: collaborative analysis of prospective studies. AIDS. 2007;21(9):1185–97.

    Article  PubMed  Google Scholar 

  25. Ho C, Lee S, Wong Kh, et al. Setting a minimum threshold CD4 count for initiation of highly active antiretroviral therapy in HIV-infected patients. HIV Med. 2007;8(3):181–5.

    Article  PubMed  Google Scholar 

  26. Lapadula G, Torti C, Maggiolo F, et al. Predictors of clinical progression among HIV-1-positive patients starting HAART with CD4+ T-cell counts > or = 200 cells/mm3. Antivir Ther. 2007;12(6):941–7.

    PubMed  CAS  Google Scholar 

  27. Locadia M, van Grieken RA, Prins JM, et al. Patients’ preferences regarding the timing of highly active antiretroviral therapy initiation for chronic asymptomatic HIV-1 infection. Antivir Ther. 2006;11(3):335–41.

    PubMed  Google Scholar 

  28. Fardet L, Mary-Krause M, Heard I, et al. Influence of gender and HIV transmission group on initial highly active antiretroviral therapy prescription and treatment response. HIV Med. 2006;7(8):520–9.

    Article  PubMed  CAS  Google Scholar 

  29. Ledergerber B, Lundgren JD, Walker AS, et al. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes. Lancet. 2004;364(9428):51–62.

    Article  PubMed  Google Scholar 

  30. Jansen K, Michalik C, Hahn M; Competence Network for HIV/AIDS, et al. The Patient Cohort of the German Competence Network For HIV/AIDS (KompNet): a profile. Eur J Med Res. 2009;14(10):323–31.

    PubMed  CAS  Google Scholar 

  31. Jansen K, Brockmeyer NH, Hahn M; Competence Network for HIV/AIDS, et al. Epidemiological composition, clinical and treatment characteristics of the patient cohort of the German Competence Network for HIV/AIDS. Eur J Med Res. 2009;14(10):415–25.

    PubMed  Google Scholar 

  32. Kalbfleisch JD, Prentice RL. The statistical analysis of failure time data. New York: Wiley; 1980. p. 21–38.

    Google Scholar 

  33. Kaplan JE, Hanson DL, Cohn DL, et al. When to begin highly active antiretroviral therapy? Evidence supporting initiation of therapy at CD4+ lymphocyte counts <350 cells/microL. Clin Infect Dis. 2003;37(7):951–8.

    Article  PubMed  Google Scholar 

  34. Palella F, Armon C, Buchacz K, et al. CD4 at HAART initiation predicts long-term CD4 responses and mortality from AIDS and non-AIDS causes in the HIV Outpatient Study (HOPS). In: Proceedings of the 17th Annual Canadian Conference on HIV/AIDS Research, Saskatoon, Canada, May 2010. San Francisco, CA: CROI; 2010. Abstract 983.

  35. Antiretroviral Therapy Cohort Collaboration. Causes of death in HIV-1-infected patients treated with antiretroviral therapy, 1996–2006: collaborative analysis of 13 HIV cohort studies. Clin Infect Dis. 2010;50(10):1387–96.

    Article  Google Scholar 

  36. HIV-CAUSAL Collaboration. The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals. AIDS. 2010;24(1):123–37.

    Article  Google Scholar 

Download references

Acknowledgments

Firstly, we thank all of the patients participating in our cohort for providing their data and biomaterials to the study. We are grateful for all the work and dedication of the documentation officers and of the heads of our documenting sites. We thank the Ruhr University Bochum for the financial and structural encouragement. We thank the Federal Ministry of Education and Research especially for its ongoing financial and ideal support since 2002 (grant no. BMBF-01 KI 0501). The following documenting sites currently contribute data to the basis module of the KompNet cohort: Gemeinschaftspraxis Driesener Straße, Berlin; Gemeinschaftspraxis Mehringdamm, Berlin; Gemeinschaftspraxis Turmstraße, Berlin; Gemeinschaftspraxis Fuggerstraße, Berlin; Praxiszentrum Kaiserdamm, Berlin; Universitätsklinikum Benjamin Franklin, Charité, Berlin; Dermatologische Klinik, Ruhr Universität, Bochum; Klinikum, Dortmund; Universitätsklinikum, Düsseldorf; Medizinische Klinik 3, Universitätsklinikum, Erlangen; Klinik für Dermatologie, Universität Essen; HIVCENTER, Universitätsklinikum, Frankfurt; Ifi-Institut, Hamburg; Infektionsmedizinisches Centrum Hamburg (ICH), Hamburg; Medizinische Hochschule, Hannover; Praxis Georgstraße, Hannover; Gemeinschaftspraxis, Kriegsstraße, Karlsruhe; Städtisches Krankenhaus Kemperhof, Koblenz; Praxis Hohenstaufenring, Köln; Gemeinschaftspraxis Isartorplatz, München; MVZ Karlsplatz, HIV Research and Clinical Centre, München; Praxisgemeinschaft Franz Joseph-Straße, München; Klinikum, Osnabrück; Gemeinschaftspraxis Ulmer/Frietsch/Müller, Stuttgart.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Ifi-Institute, Hamburg, Germany

    A. Plettenberg & T. Lorenzen

  2. Competence Network for HIV/AIDS, Bochum, Germany

    N. H. Brockmeyer & K. Jansen

  3. Clinic for Dermatology, Venerology and Allergology, St. Josef-Hospital, Ruhr University, Bochum, Germany

    N. H. Brockmeyer

  4. mediStatistica, Neuenrade, Germany

    B. Haastert

  5. Clinical Trial Centre, University Cologne, Cologne, Germany

    C. Michalik

  6. Clinical Centre, Driesener Straße, Berlin, Germany

    S. Dupke

  7. Infektionsmedizinisches Centrum Hamburg (ICH), Hamburg, Germany

    K. Schewe

  8. Clinical Centre Fuggerstraße, Berlin, Germany

    M. Rausch

  9. City Clinic, Dortmund, Germany

    M. Hower

  10. Clinical Centre Ulmer/Frietsch/Mueller, Stuttgart, Germany

    A. Ulmer

  11. MVZ Karlsplatz, HIV Research and Clinical Centre, Munich, Germany

    E. Wolf

  12. University Clinic, Dusseldorf, Germany

    G. Arendt

Authors
  1. A. Plettenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. N. H. Brockmeyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. B. Haastert
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Michalik
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Dupke
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. Schewe
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. M. Rausch
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Hower
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. A. Ulmer
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. E. Wolf
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. T. Lorenzen
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. G. Arendt
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. K. Jansen
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

the Competence Network for HIV/AIDS

Corresponding author

Correspondence to K. Jansen.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Plettenberg, A., Brockmeyer, N.H., Haastert, B. et al. Impact of earlier HAART initiation on the immune status and clinical course of treated patients on the basis of cohort data of the German Competence Network for HIV/AIDS. Infection 39, 3–12 (2011). https://doi.org/10.1007/s15010-010-0070-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s15010-010-0070-8

Keywords

Search

Navigation