Highly Active Antiretroviral Therapy Decreases Mortality and Morbidity in Patients with Advanced HIV Disease

Highly Active Antiretroviral Therapy Decreases Mortality and Morbidity in Patients with Advanced HIV Disease

Edward L. Murphy, MD, MPH;
Ann C. Collier, MD;
Leslie A. Kalish, ScD;
Susan F. Assmann, PhD;
Michael F. Para, MD;
Timothy P. Flanigan, MD;
Princy N. Kumar, MD;
Letty Mintz, ANP;
Frances R. Wallach, MD;
George J. Nemo, PhD; and
for the Viral Activation Transfusion Study Investigators*

From University of California, San Francisco, San Francisco, California; University of Washington, Seattle, Washington; New England Research Institutes, Watertown, Massachusetts; Ohio State University, Columbus, Ohio; Miriam Hospital, Brown University, Providence, Rhode Island; Georgetown University, Washington, D.C.; Mount Sinai Medical Center, New York, New York; and National Heart, Lung, and Blood Institute, Bethesda, Maryland.

Abstract

Background: Mortality and morbidity related to AIDS have decreased among HIV-infected patients taking highly active anti-retroviral therapy (HAART), but previous studies may have been confounded by other changes in treatment.

Objective: To assess the benefit of HAART in patients with advanced AIDS and anemia.

Design: Prospective, multicenter cohort study.

Setting: The Viral Activation Transfusion Study (VATS), with enrollment from August 1995 through July 1998 and follow-up through June 1999.

Patients: 528 HIV-infected patients with cytomegalovirus (CMV) seropositivity or disease who were receiving a first red blood cell transfusion for anemia.

Measurements: In a person-year analysis of follow-up before and after initiation of HAART, Poisson regression was used to calculate crude rate ratios and rate ratios adjusted for CD4 count, HIV RNA level, calendar period, time on study, sex, ethnicity, and injection drug use.

Results: At baseline, patients had a median CD4⁺ lymphocyte count of 0.015 × 10⁹ cell/L, median plasma HIV RNA level of 4.8 log₁₀ copies/mL, and median hemoglobin concentration of 73 g/L. Use of HAART increased from 1% of active patients in January 1996 to 79% of active patients in January 1999. The crude death rate was 0.24 event/person-year among patients taking HAART and 0.88 event/person-year among those not taking HAART (rate ratio, 0.26; adjusted rate ratio, 0.38; P < 0.001 for both comparisons). Rates of non-CMV disease were 0.15 event/person-year after HAART and 0.45 event/person-year before HAART (crude rate ratio, 0.34 [P < 0.001]; adjusted rate ratio, 0.66 [P < 0.05]). Rates of CMV disease were 0.10 event/person-year after HAART and 0.25 before HAART (crude rate ratio, 0.42 [P < 0.01]; adjusted rate ratio, 1.01 [P > 0.2]). Results were similar in patients with baseline CD4⁺ lymphocyte counts less than 0.010 × 10⁹ cells/L.

Conclusions: The data support an independent reduction in mortality and opportunistic events attributable to HAART, even in patients with very advanced HIV disease. However, patients with CMV infection or disease may not have a reduction in new CMV events due to HAART.

*For a list of the Viral Activation Transfusion Study Investigators, see Appendix.

Article and Author Information

Acknowledgments: The authors thank the patients and the transfusion service and hospital nursing personnel.
Grant Support: By National Heart, Lung, and Blood Institute contract N01-HB-57121.
Requests for Single Reprints: Edward L. Murphy, MD, MPH, Department of Laboratory Medicine, University of California, San Francisco, Box 0884, San Francisco, CA 94143-0884; e-mail, murphy{at}itsa.ucsf.edu.
Current Author Addresses: Dr. Murphy: Department of Laboratory Medicine, University of California, San Francisco, Box 0884, San Francisco, CA 94143-0884
Dr. Collier: University of Washington, Box 359929, 325 9th Avenue, Seattle, WA 98104.
Dr. Kalish and Assmann: New England Research Institute, 9 Galen Street, Watertown, MA 02472.
Dr. Para: Ohio State University, 456 West 10th Avenue, Columbus, OH 43210.
Dr. Flanigan: Brown University Medical School, Miriam Hospital, 164 Summit Avenue, Providence, RI 02906-2853.
Dr. Kumar: Georgetown University Medical Center, 3800 Reservoir Road, Washington, DC 20007.
Ms. Mintz and Dr. Wallach: Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029.
Dr. Nemo: National Heart, Lung, and Blood Institute, 6701 Rockledge Drive, Bethesda, MD 20892.
Author Contributions: Conception and design: E.L. Murphy, A.C. Collier, L.A. Kalish, S.F. Assmann, M.F. Para, T.P. Flanigan, P.N. Kumar.
Analysis and interpretation of the data: E.L. Murphy, A.C. Collier, L.A. Kalish, S.F. Assmann, P.N. Kumar.
Drafting of the article: E.L. Murphy, S.F. Assmann, P.N. Kumar.
Critical revision of the article for important intellectual content: E.L. Murphy, A.C. Collier, L.A. Kalish, S.F. Assmann, M.F. Para, T.P. Flanigan, P.N. Kumar.
Final approval of the article: E.L. Murphy, A.C. Collier, L.A. Kalish, S.F. Assmann, M.F. Para, T.P. Flanigan, P.N. Kumar, G.J. Nemo.
Provision of study materials or patients: A.C. Collier, M.F. Para, P.N. Kumar, L. Mintz, F.R. Wallach.
Statistical expertise: L.A. Kalish, S.F. Assmann.
Obtaining of funding: A.C. Collier, L.A. Kalish, G.J. Nemo.
Administrative, technical, or logistic support: A.C. Collier, F.R. Wallach, G.J. Nemo.
Collection and assembly of data: E.L. Murphy, A.C. Collier, T.P. Flanigan, P.N. Kumar, L. Mintz.