Eric A. Engels, MD, MPH; Philip S. Rosenberg, PhD; Thomas R. O'Brien, MD, MPH; James J. Goedert, MD; for the Multicenter Hemophilia Cohort Study
For members of the Multicenter Hemophilia Cohort Study, see Appendix.
Acknowledgments: The authors thank the patients in the Multicenter Hemophilia Cohort Study for their time and efforts in supporting this research. They also thank David Waters, PhD, and Wendell J. Miley (Scientific Applications International Corp., Frederick Cancer Research and Development Center, Frederick, Maryland) for measuring viral load; Myhanh Dotrang (Computer Sciences Corp., Rockville, Maryland) for preparing the database used for this analysis; and Barbara L. Kroner, PhD, and Virginia Lamprecht (Research Triangle Institute, Rockville, Maryland) for study management.
Grant Support: In part by National Cancer Institute contract N01-CP-33002 with Research Triangle Institute, Rockville, Maryland.
Requests for Reprints: Eric A. Engels, MD, MPH, Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS 8005, Rockville, MD 20822; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Engels, O'Brien, and Goedert: Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, EPS 8005, Rockville, MD 20822.
Dr. Rosenberg: Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Boulevard, Rockville, MD 20822.
For patients infected with HIV, plasma HIV viral load in early disease predicts long-term prognosis. However, the implications of viral load measurements late in HIV disease are uncertain.
To evaluate the relation between plasma HIV viral load and subsequent risk for disease progression in patients with late-stage HIV disease.
Retrospective cohort study.
16 treatment centers for patients with hemophilia.
389 patients with hemophilia and late-stage HIV disease (CD4 count < 200 cells/mm3).
Plasma HIV viral load was measured at baseline. Patients were followed for AIDS-related illnesses (primary outcome) and, specifically, Pneumocystis carinii pneumonia (secondary outcome).
HIV viral load strongly predicted AIDS-related illness. For patients with viral loads less than 4.00 log10 copies/mL, the 1-year actuarial risk was 0% and the 5-year risk was 25%. For patients with viral loads of at least 6.00 log10 copies/mL, the 1-year actuarial risk was 42% and the 5-year risk was 78%. A linear relation existed between viral load and risk for AIDS-related illness (hazard ratio, 2.37 per log10 copies/mL; P < 0.001). In addition, viral load most strongly predicted risk for illness immediately after viral load testing; this predictive relation attenuated over time (P = 0.002). These findings changed little after adjustment for CD4 cell counts that were updated during follow-up. In the first year after viral load was measured, it predicted occurrence of P. carinii pneumonia (hazard ratio, 4.69 per log10 copies/mL; P < 0.001).
In patients with hemophilia and late-stage HIV disease, viral load predicts disease progression independently of CD4 cell counts. Because viral load most strongly predicts progression immediately after load is measured, it seems to reflect the current level of immunosuppression.
Table 1. Baseline Characteristics
KaplanMeier curves showing time to AIDS-related illness for strata defined by baseline HIV viral load.
Hazard ratios for AIDS-related illness (unadjusted), corresponding to a 1-logincrease in baseline viral load, presented separately for each 6-month interval of follow-up.P
Table 2. Proportional Hazards Models for Time to AIDS-Related Illness
KaplanMeier curves showing time to development of AIDS-related illness for strata defined by baseline CD4 cell count.
Hazard ratios for AIDS-related illness (unadjusted), corresponding to a decrease of 50 cells/mm a3 in baseline CD4 count, presented separately for each 6-month interval of follow-up.P
Kaplan-Meier curves showing time to development of AIDS-related illness for patients with baseline CD4 counts less than 50 cells/mm3.
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Engels EA, Rosenberg PS, O'Brien TR, Goedert JJ, for the Multicenter Hemophilia Cohort Study. Plasma HIV Viral Load in Patients with Hemophilia and Late-Stage HIV Disease: A Measure of Current Immune Suppression. Ann Intern Med. 1999;131:256–264. doi: 10.7326/0003-4819-131-4-199908170-00004
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Published: Ann Intern Med. 1999;131(4):256-264.
HIV, Infectious Disease.
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