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Joint effects of HIV-1 RNA levels and CD4 lymphocyte cells on the risk of specific opportunistic infections

Williams, Paige L.a; Currier, Judith S.b; Swindells, Susanc

Concise Communication

Objectives: To evaluate the predictive value of baseline plasma HIV-1 RNA levels and CD4 lymphocyte counts and early changes in these markers after initiating antiretroviral therapy on the risk of development of specific opportunistic infections (OIs).

Design: Patient data from four antiretroviral therapy studies were combined for a retrospective analysis. The analysis included 842 participants from the virology substudies of these trials who had baseline measurements for both HIV-1 RNA levels and CD4 cell counts.

Methods: Cox proportional hazards models were used to assess the joint effects of baseline CD4 cell count and HIV-1 RNA level and early treatment-associated changes in these values on the risk of development of Pneumocystis carinii pneumonia (PCP), cytomegalovirus (CMV), or Mycobacterium avium complex (MAC). The effects of potential confounders such as prior prophylaxis and previous OIs were also addressed.

Results: Baseline CD4 cell counts and HIV-1 RNA measurements showed significant associations with the risk of PCP, CMV, and MAC. Patients with higher levels of HIV-1 RNA were estimated to have three to six times the risk of these OIs than those with lower levels. Reductions in viral load were linked to significantly reduced risks of PCP, CMV, and MAC. Early decreases in RNA were generally more predictive of risk than were early increases in CD4 cell counts.

Conclusions: Baseline viral load and reductions in viral load during therapy appeared to influence the risk of these OIs independently of the CD4 cell count. Future guidelines for the initiation of prophylaxis for these OIs may be improved by incorporating information on viral load.

From the aDepartment of Biostatistics, Harvard School of Public Health, Boston, MA, USA; bUniversity of Southern California, Los Angeles, CA, USA; and cUniversity of Nebraska Medical Center, Omaha, NE, USA.

Sponsorship: This work was supported by the Statistical and Data Analysis Center of the AIDS Clinical Trial Group under NIAID contract U01-AI38855 (P.L.W.), from University of Southern California grant U01-AI2767311 (J.S.C.) and from University of Nebraska Medical Center Grant 2U01-AI27661-11 (S.S.).

Note: Presented in part at the Fourth Conference on Retroviruses and Opportunistic Infections, Washington, DC, January 1997 [abstract 359].

Requests for reprints to: Paige L. Williams, PhD, Department of Biostatistics, Harvard School of Public Health, 655 Huntington Avenue, Boston, MA 02115, USA. Tel: +1 (617) 432-3872; fax: +1 (617) 432-2832; e-mail:

Received: 22 January 1999; revised: 4 March 1999; accepted: 10 March 1999.

© 1999 Lippincott Williams & Wilkins, Inc.