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Volume 339:1261-1268 October 29, 1998 Number 18 Next

	Full Text PDF Editorial by Cooper, D. A. Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

ABSTRACT

Background Combination antiretroviral therapy with indinavir, zidovudine, and lamivudine can suppress the level of human immunodeficiency virus (HIV) RNA in plasma below the threshold of detection for two years or more. We investigated whether a less intensive maintenance regimen could sustain viral suppression after an initial response to combination therapy.

Methods HIV-infected subjects who had CD4 cell counts greater than 200 per cubic millimeter, who had been treated with indinavir, lamivudine, and zidovudine, and who had less than 200 copies of HIV RNA per milliliter of plasma after 16, 20, and 24 weeks of induction therapy were randomly assigned to receive either continued triple-drug therapy (106 subjects), indinavir alone (103 subjects), or a combination of zidovudine and lamivudine (107 subjects). The primary end point was loss of viral suppression, which was defined as a plasma level of at least 200 copies of HIV RNA per milliliter on two consecutive measurements during maintenance therapy.

Results During maintenance treatment, 23 percent of the subjects receiving indinavir and 23 percent of those receiving zidovudine and lamivudine, but only 4 percent of those receiving all three drugs, had loss of viral suppression (P<0.001 for the comparison between triple-drug therapy and the other two maintenance regimens). Subjects with greater increases in CD4 cell counts during induction therapy, higher viral loads at base line (i.e., at the beginning of induction therapy), and slower rates of viral clearance were at greater risk for loss of viral suppression. The presence of zidovudine-resistance mutations in HIV RNA at base line was strongly predictive of the loss of viral suppression in subjects treated with zidovudine and lamivudine.

Conclusions The suppression of plasma HIV RNA after six months of treatment with indinavir, zidovudine, and lamivudine is better sustained by the continuation of these three drugs than by maintenance therapy with either indinavir alone or zidovudine and lamivudine.

Source Information

From the University of California, San Diego, and the San Diego Veterans Affairs Medical Center, San Diego, Calif. (D.V.H., D.D.R.); Harvard School of Public Health, Boston (I.C.M., R.L.B.); Harvard Medical School, Boston (M.S.H.); the University of Washington School of Medicine, Seattle (A.C.C.); Washington University, St. Louis (P.T.); the Division of AIDS, National Institute of Allergy and Infectious Diseases, Bethesda, Md. (J.P.A.I.); AIDS Clinical Trials Group Operations Center, Rockville, Md. (M.K.H.); Merck and Co., West Point, Pa. (R.L.); and Glaxo Wellcome, Research Triangle Park, N.C. (G.B.).

Address reprint requests to Dr. Havlir at the University of California, San Diego, 2760 Fifth Ave., Suite 300, San Diego, CA 92103.

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