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The Swiss HIV Cohort Study

Bruno Ledergerber, PhD; Matthias Egger, MD; Véronique Erard, MD; Rainer Weber, MD; Bernard Hirschel, MD; Hansjakob Furrer, MD; Manuel Battegay, MD; Pietro Vernazza, MD; Enos Bernasconi, MD; Milos Opravil, MD; Daniel Kaufmann, MD; Philippe Sudre, MD, PhD; Patrick Francioli, MD; Amalio Telenti, MD; for the Swiss HIV Cohort Study

JAMA. 1999;282:2220-2226.

Context  Acquired immunodeficiency syndrome–related opportunistic illnesses (OIs) continue to occur after initiation of potent antiretroviral therapy in patients with human immunodeficiency virus (HIV) infection. Risk factors for clinical progression to OIs during potent therapy are not well defined.

Objective  To examine the incidence of and risk factors for OIs among patients treated with potent antiretroviral therapy in a population-based study.

Design  The Swiss HIV Cohort Study, a prospective cohort study of adult HIV-infected persons.

Setting  Seven study centers throughout Switzerland.

Patients  A total of 2410 cohort study participants with a potential follow-up of at least 15 months after starting potent therapy between September 1995 and December 1997.

Main Outcome Measures  Disease-specific incidence of OIs during the 6 months preceding potent antiretroviral therapy and at 3 intervals after initiating therapy; risk factors for development of OIs during therapy.

Results  Of the 2410 participants, 143 developed 186 OIs after initiation of potent antiretroviral therapy. Incidence of any OI decreased from 15.1 per 100 person-years in the 6 months before therapy to 7.7 in the first 3 months after starting treatment, 2.6 in the following 6 months, and 2.2 per 100 person-years between 9 and 15 months. Reductions in incidence ranged from 38% per month for Kaposi sarcoma (P<.001) to 5% per month for non-Hodgkin lymphoma (P = .31). Baseline CD4 cell count continued to predict the risk of disease progression after initiating potent therapy. Compared with CD4 cell counts above 200x10⁶/L, the hazard ratio for developing OIs was 2.5 (95% confidence interval [CI], 1.4-4.5) for counts between 51 and 200x10⁶/L and 5.8 (95% CI, 3.2-10.5) for counts below 51x10⁶/L at baseline. Independent of baseline CD4 cell count, a rise in CD4 cell count by 50x10⁶/L or more and undetectable HIV-1 RNA in plasma (<400 copies/mL) by 6 months reduced risk of subsequent events, with hazard ratios of 0.32 (95% CI, 0.20-0.52) and 0.39 (0.24-0.65), respectively.

Conclusions  Our data indicate that the risk of developing an OI for a person receiving potent antiretroviral therapy is highest during the initial months of therapy. Baseline CD4 cell count and immunologic and virologic response to treatment were strong predictors of disease progression in patients receiving potent therapy. Individuals with CD4 cell counts of 50x10⁶/L or below may need close clinical surveillance after initiation of potent therapy.

Author Affiliations: Division of Infectious Diseases and Hospital Epidemiology, University Hospital, Zurich, Switzerland (Drs Ledergerber, Weber, and Opravil); Medical Research Council Health Services Research Collaboration, Department of Social Medicine, University of Bristol, Bristol, England (Dr Egger); Division of Infectious Diseases, University Hospital, Lausanne, Switzerland (Drs Erard, Kaufmann, Sudre, Francioli, and Telenti); Division of Infectious Diseases, University Hospital, Geneva, Switzerland (Dr Hirschel); University Medical Policlinic, Inselspital, Bern, Switzerland (Dr Furrer); University Medical Policlinic, Cantonal Hospital, Basel, Switzerland (Dr Battegay); Internal Medicine Clinic A, Cantonal Hospital, St Gall, Switzerland (Dr Vernazza); Infectious Diseases Ambulatorium, Regional Hospital, Lugano, Switzerland (Dr Bernasconi).

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