The Prognostic Importance of Changes in CD4⁺ Cell Count and HIV-1 RNA Level in Women after Initiating Highly Active Antiretroviral Therapy

17 February 2004 | Volume 140 Issue 4 | Pages 256-264

Background: The prognostic value of CD4⁺ cell counts and HIV-1 RNA levels attained after the initiation of highly active antiretroviral therapy (HAART) compared with before the initiation of HAART has not been well defined.

Objective: To determine the prognostic value for clinical outcomes of CD4⁺ cell counts and HIV-1 RNA levels attained after initiating therapy.

Design: Prospective cohort study.

Setting: Women's Interagency HIV Study.

Patients: 1132 participants in the Women's Interagency HIV Study.

Measurements: HIV-1 RNA level, CD4⁺ cell counts, AIDS-defining illness, and death.

Results: In multivariate analyses with a median follow-up of 3.9 years, women with CD4⁺ cell counts of less than 0.200 x 10⁹ cells/L compared with women with CD4⁺ cell counts of greater than 0.350 x 10⁹ cells/L after HAART initiation had a relative hazard of death from all causes of 2.66 (95% CI, 1.42 to 4.99) and a relative hazard of death from AIDS of 47.61 (CI, 5.69 to 398.40). The relative hazard of all-cause death was 3.44 (CI, 1.67 to 7.09) in women with RNA levels of more than 10 000 copies/mL compared with women with attained RNA levels of less than 80 copies/mL. The relative hazard of AIDS-related or all-cause death did not increase for women with post-HAART CD4⁺ cell counts between 0.200 and 0.350 x 10⁹ cells/L compared with women with CD4⁺ cell counts of greater than 0.350 x 10⁹ cells/L. Also, the relative hazard did not increase in women with post-HAART HIV-1 RNA levels between 80 and 10 000 copies/mL compared with women with post-HAART HIV-1 RNA levels of less than 80 copies/mL. Of the laboratory markers, only the post-HAART CD4⁺ cell count and HIV-1 RNA level were predictive of new AIDS-defining illness.

Conclusion: Post-HAART laboratory markers predicted death and new AIDS-defining illness. Pre-HAART CD4⁺ cell count and HIV-1 RNA level were not predictive of clinical outcomes if adjusted for values attained after HAART initiation, suggesting that even advanced immune suppression can be overcome with HAART that results in CD4⁺ cell counts of greater than 0.200 x 10⁹ cells/L and RNA levels of less than 10 000 copies/mL.

Editors' Notes Context Clinicians have been uncertain about whether they should use pretreatment or post-treatment laboratory markers to predict outcomes for patients receiving highly active antiretroviral therapy (HAART). Contribution The authors used predictive models to simultaneously test the ability of pre- and post-treatment CD4+ cell counts and HIV-1 RNA levels to predict new AIDS-defining illness or death. Post-treatment CD4+ cell count and HIV-1 RNA levels predicted new AIDS-defining illness or death, but pretreatment levels did not. Implication Patients with a good CD4+ cell count and HIV-1 RNA response to HAART have a favorable prognosis despite poor pretreatment values of these markers. –The Editors

 

Author and Article Information

From Montefiore Medical Center and Lincoln Medical and Mental Health Center, Bronx, New York; Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland; Cook County Hospital, Chicago, Illinois; University of California, San Francisco, San Francisco, California; Health Science Center at Brooklyn, Brooklyn, New York; University of Southern California, Los Angeles, California; and Georgetown University Medical Center, Washington, DC.

Grant Support: The WIHS is funded by the National Institute of Allergy and Infectious Diseases with supplemental funding from the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute of Dental Research (grants U01-AI-35004, U01-AI-31834, U01-AI-34994, U01-AI-34989, U01-AI-34993, and U01-AI-42590). Funding was also provided by the National Institute of Child Health and Human Development (grant U01-HD-32632) and the National Center for Research Resources (grants M01-RR-00071, M01-RR-00079, and M01-RR00083).

Potential Financial Conflicts of Interest: None disclosed.

Requests for Single Reprints: Kathryn Anastos, MD, Women's Interagency HIV Study, 3311 Bainbridge Avenue, Second Floor, Bronx, NY 10467; e-mail, kanastos{at}verizon.net.

Current Author Addresses: Dr. Anastos: WIHS, Montefiore Medical Center, 3311 Bainbridge Avenue, Bronx, NY 10467.

Ms. Barrón: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public of Health, 615 North Wolfe Street/Room E7012, Baltimore, MD 21205.

Dr. Cohen: Core Center, Cook County Bureau of Health Services, 2020 W. Harrison, Chicago, IL 60612.

Dr. Greenblatt: Infectious Diseases Division, Box 1352, University of California, San Francisco, San Francisco, CA 94143-1352.

Dr. Minkoff: Maimonides Medical Center, 967 48th Street, Brooklyn, NY 11219.

Dr. Levine: Division of Hematology, USC/Norris Cancer Hospital, 1441 Eastlake Avenue, Room 3468, Los Angeles, CA 90033.

Dr. Young: Georgetown University Medical Center, 110 Kober-Cogan Building, 3800 Reservoir Road, NW, Washington, DC 20007.

Dr. Gange: Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320-1799.

Author Contributions: Conception and design: K. Anastos, M.H. Cohen, R.M. Greenblatt, A. Levine, S.J. Gange.

Analysis and interpretation of the data: K. Anastos, Y. Barrón, M.H. Cohen, S.J. Gange.

Drafting of the article: K. Anastos, Y. Barrón, R.M. Greenblatt, A. Levine, S.J. Gange.

Critical revision of the article for important intellectual content: K. Anastos, Y. Barrón, M.H. Cohen, R.M. Greenblatt, H. Minkoff, A. Levine, M. Young, S.J. Gange.

Final approval of the article: K. Anastos, Y. Barrón, M.H. Cohen, R.M. Greenblatt, H. Minkoff, A. Levine, M. Young, S.J. Gange.

Provision of the study materials or patients: K. Anastos, M.H. Cohen, R.M. Greenblatt, H. Minkoff, A. Levine, M. Young.

Statistical expertise: Y. Barrón, S.J. Gange.

Obtaining of funding: K. Anastos, M.H. Cohen, R.M. Greenblatt, H. Minkoff, A. Levine, M. Young, S.J. Gange.

Administrative, technical, or logistic support: K. Anastos.

Collection and assembly of the data: K. Anastos, M.H. Cohen, R.M. Greenblatt, S.J. Gange.