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Association of Viral Load, CD4 Cell Count, and Treatment with Clinical Progression in HIV Patients with Very Low CD4 Cell Counts: The EuroSIDA Cohort V. MILLER*1, A. MOCROFT2, B. CLOTET3, B. LEDERGERBER4, O. KIRK5, A. D'ARMINIO MONFORTE6, and J. D. LUNDGREN5 for the EUROSIDA Cohort.
1JW Goethe Univ., Frankfurt, Germany; 2Royal Free Ctr. Univ. Hosp., London, UK; 3Hosp. Germans, Badalona, Spain; 4Univ. Hosp., Zurich, Switzerland; 5Hvidovre Hosp., Copenhagen, Denmark; and 6Hosp. L. Sacco, Milan, Italy A substantial number of patients experience virological failure and/or insufficient immune recovery while on potent combination treatment.
Objective: to assess the association between CD4 cell count, viral load and potent combination treatment with clinical progression in EuroSIDA patients with CD4 cell counts <50.
Study design: prospectively followed cohort including 52 centers in 17 European countries. Patients with a CD4 cell count <50 cells/µl with at least one viral load data point were identified and followed until diagnosis of or progression to a new AIDS defining event, death, or a rise of CD4 cells above 50 cells/µl. Potent combination treatment was defined as treatment including at least one PI.
Results: a total of 258 clinical events in 1170 patients yielded an overall incidence rate of 44.3 per 100 PYFU (95% CI 38.9-49.7). The incidence rate was significantly lower in the group of patients receiving PI (37.5 vs 68.4, p=.001). Overall, incidence rates increased with increasing viral load, with a rate ratio of 1.33 for patients with viral load 5000-100,000, and 2.49 for patients with a viral load 100,000 (p=.0001) compared to patients with a viral load of <5000 copies. Lower CD4 cell counts, increased viral load, reduced weight and reduced hemoglobin were all independently significantly associated with higher RH. Receiving a PI was associated with an independent RH of 0.57 (p=.0001). Similar results were obtained when defining potent combination therapy as those consisting of three or more drugs.
Conclusions: Patients with CD4 cell counts below 50 have a high risk of disease progression that remains significantly dependent on viral load and CD4 counts. However, patients receiving potent combination regimen had a 43% reduction in risk of progression, independent of surrogate marker status. This implies that patients with severe immunosuppression may benefit from treatment even though experiencing virologic failure. This potential benefit needs to be weighted against the risks associated with further viral evolution. Whether all types of potent combination regimen provide equal benefit remains to be determined.
Key Words: combination therapy, disease progression, protease inhibitors
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