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Interruptions of cART limits CD4 T-cell recovery and increases the risk for opportunistic complications and death

Kaufmann, Gilbert Ra; Elzi, Luigiaa; Weber, Rainerb; Furrer, Hansjakobc; Giulieri, Stefanod; Vernazza, Pietroe; Bernasconi, Enosf; Hirschel, Bernardg; Battegay, Manuelathe Swiss HIV Cohort Study

doi: 10.1097/QAD.0b013e3283430013
Clinical Science

Background: A major goal of antiretroviral therapy (ART) for HIV-1-infected persons is the recovery of CD4 T lymphocytes, resulting in thorough protection against opportunistic complications. Interruptions of ART are still frequent. The long-term effect on CD4 T-cell recovery and clinical events remains unknown.

Methods: Immunological and clinical endpoints were evaluated in 2491 participants of the Swiss HIV Cohort Study initiating ART during a mean follow-up of 7.1 years. Data were analysed in persons with treatment interruptions (n = 1271; group A), continuous ART, but intermittent HIV-1 RNA at least 1000 copies/ml (n = 469; group B) and continuous ART and HIV-1 RNA constantly less than 1000 copies/ml (n = 751; group C). Risk factors for low CD4 T-cell counts and clinical events were analysed using Cox proportional hazards models.

Results: In groups A–C, CD4 T lymphocytes increased to a median of 427, 525 and 645 cells/μl at 8 years. In group A, 63.0 and 37.2% reached above 350 and 500 CD4 T cells/μl, whereas in group B 76.3 and 55.8% and in group C 87.3 and 68.0% reached these thresholds (P < 0.001). CD4 T-cell recovery directly depended on the cumulative duration of treatment interruptions. In addition, participants of group A had more Centers for Disease Control and Prevention B/C events, resulting in an increased risk of death. Major risk factors for not reaching CD4 T cells above 500 cells/μl included lower baseline CD4 T-cell count, higher age and hepatitis C virus co-infection.

Conclusion: In persons receiving continuous ART larger CD4 T-cell recovery and a reduced risk for opportunistic complications and death was observed. CD4 T-cell recovery was smaller in persons with treatment interruptions more than 6 months.

aDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland

bDivision of Infectious Diseases and Hospital Epidemiology, University Hospital and University of Zurich, Zurich, Switzerland

cClinic for Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland

dDivision of Infectious Diseases, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

eDepartment of Internal Medicine, Cantonal Hospital St. Gallen, St Gallen, Switzerland

fDepartment of Internal Medicine, Regional Hospital, Lugano, Switzerland

gDivision of Infectious Diseases and Laboratory of Virology, University Hospital Geneva, Geneva, Switzerland.

Received 9 September, 2010

Revised 17 November, 2010

Accepted 22 November, 2010

Correspondence to Manuel Battegay, MD, Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland. Tel: +41 61 265 50 72; fax: +41 61 265 31 98; e-mail: mbattegay@uhbs.ch

© 2011 Lippincott Williams & Wilkins, Inc.