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Long-term complications in patients with poor immunological recovery despite virological successful HAART in Dutch ATHENA cohort

van Lelyveld, Steven F.L.a; Gras, Luukb; Kesselring, Anoukb; Zhang, Shuangjieb; De Wolf, Frankb; Wensing, Annemarie M.J.c; Hoepelman, Andy I.M.a; on behalf of the ATHENA national observational cohort study

doi: 10.1097/QAD.0b013e32834f32f8
Clinical Science

Objective: We investigated the risk of AIDS and serious non-AIDS-defining diseases (non-ADDs) according to the degree of immunological recovery after 2 years of virological successful antiretroviral therapy (HAART).

Design: Retrospective observational cohort study including HIV-infected patients treated with HAART resulting in viral suppression (<500 copies/ml).

Methods: Patients were grouped according to their CD4 cell count after 2 years of HAART: CD4 cell count less than 200 cells/μl (group A), 200–350 cells/μl (group B), 351–500 cells/μl (group C) or more than 500 cells/μl (group D). Analysis was done to assess predictors for poor immunological recovery and the occurrence of a composite endpoint [death, AIDS, malignancies, liver cirrhosis and cardiovascular events (CVEs)], non-ADDs, CVEs and non-AIDS-defining malignancies (non-ADMs).

Results: Three thousand and sixty-eight patients were included. Older age, lower CD4 cell nadir and lower plasma HIV-RNA at the start of HAART were independent predictors for a poor immunological recovery. The composite endpoint, non-ADDs and CVE were observed most frequently in group A (overall log rank, P < 0.0001, P = 0.002 and P = 0.01). In adjusted analyses, age was a strong independent predictor for all endpoints. Compared with group A, patients in group D had a lower risk for the composite endpoint [hazard ratio 0.54 (95% confidence interval [CI] 0.33–0.87]; patients in group B had a lower risk for CVEs [hazard ratio 0.34 (95% CI 0.14–0.86)].

Conclusion: Poor immunological recovery despite virological successful HAART is associated with a higher risk for overall morbidity and mortality and CVEs in particular. This study underlines the importance of starting HAART at higher CD4 cell counts, particularly in older patients.

aDepartment of Internal Medicine & Infectious Diseases, University Medical Center Utrecht, Utrecht

bStichting HIV Monitoring, Amsterdam

cDepartment of Virology, Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.

Correspondence to Steven F.L. van Lelyveld, Department of Internal Medicine & Infectious Diseases, Huispostnummer F.02.126, Postbus 85500, 3508 GA Utrecht, The Netherlands. Tel: +31 88 7556228; e-mail:

Received 7 September, 2011

Revised 11 November, 2011

Accepted 14 November, 2011

© 2012 Lippincott Williams & Wilkins, Inc.