Combination Therapy with Efavirenz, Nelfinavir, and Nucleoside Reverse-Transcriptase Inhibitors in Children Infected with Human Immunodeficiency Virus Type 1
Stuart E. Starr, M.D., Courtney V. Fletcher, Pharm.D., Stephen A. Spector, M.D., Florence H. Yong, M.S., Terence Fenton, Ed.D., Richard C. Brundage, Pharm.D., Ph.D., Douglas Manion, M.D., Nancy M. Ruiz, M.D., Merril Gersten, M.D., Mark Becker, Pharm.D., James McNamara, M.D., Lynne M. Mofenson, M.D., for The Pediatric AIDS Clinical Trials Group 382 Team
Background Consistent long-term viral suppression has been difficultto achieve in children with human immunodeficiency virus type1 (HIV-1) infection. We tested the safety and antiviral efficacyof a novel combination consisting of efavirenz, nelfinavir,and one or more nucleoside reverse-transcriptase inhibitorsin 57 children previously treated with only nucleoside reverse-transcriptaseinhibitors.
Methods The children were monitored for 48 weeks after the initiationof therapy. We assessed plasma concentrations of efavirenz andnelfinavir, plasma HIV-1 RNA levels, and lymphocyte subpopulations.
Results At base line, the 57 HIV-1–infected children (agerange, 3.8 to 16.8 years) had a median of 699 CD4 cells percubic millimeter and 10,000 copies of HIV-1 RNA per milliliterof plasma. The most common treatment-related effects of at leastmoderate severity were rash (in 30 percent of children), diarrhea(in 18 percent), neutropenia (in 12 percent), and biochemicalabnormalities (in 12 percent). Serious side effects were uncommon.The mean values for the area under the curve for efavirenz andnelfinavir corresponded to expected values. In an intention-to-treatanalysis, 76 percent of children had plasma HIV-1 RNA levelsof less than 400 copies per milliliter after 48 weeks of therapyand 63 percent had levels of less than 50 copies per milliliter.A high plasma HIV-1 RNA level at base line significantly decreasedthe likelihood that plasma levels of HIV-1 RNA would becomeundetectable during treatment.
Conclusions In HIV-1–infected children who were previouslytreated with nucleoside reverse-transcriptase inhibitors, thecombination of efavirenz, nelfinavir, and nucleoside reverse-transcriptaseinhibitors was generally well tolerated and had a potent andsustained antiviral effect.
Source Information
From Children's Hospital of Philadelphia, Philadelphia (S.E.S.); the University of Minnesota, Minneapolis (C.V.F., R.C.B.); the University of California at San Diego, San Diego (S.A.S.); Harvard School of Public Health, Boston (F.H.Y.); Frontier Science and Technology Research Foundation, Brookline, Mass. (T.F.); Dupont Pharmaceuticals Company, Wilmington, Del. (D.M., N.M.R.); Agouron Pharmaceuticals, La Jolla, Calif. (M.G., M.B.); the National Institute of Allergy and Infectious Diseases, Rockville, Md. (J.M.); and the National Institute of Child Health and Human Development, Rockville, Md. (L.M.M.). Other authors were Lynette Purdue, Pharm.D., National Institute of Allergy and Infectious Diseases, Rockville, Md.; Suzanne Siminski, M.S., and Bobbie Graham, B.S., Frontier Science and Technology Research Foundation, Amherst, N.Y.; David M. Kornhauser, M.D., and William Fiske, Ph.D., Dupont Pharmaceuticals Company, Wilmington, Del.; Carol Vincent, C.R.N.P., Children's Hospital of Philadelphia, Philadelphia; Harold W. Lischner, M.D., St. Christopher's Hospital for Children, Philadelphia; Wayne M. Dankner, M.D., University of California at San Diego, San Diego; and Patricia M. Flynn, M.D., St. Jude Hospital for Children, Memphis, Tenn.Presented in part at the 38th Interscience Conference on Antimicrobial Agents and Chemotherapy, San Diego, Calif., September 24–27, 1998.
Address reprint requests to Dr. Starr at the Division of Immunologic and Infectious Diseases, Children's Hospital of Philadelphia, 34th St. and Civic Center Blvd., Philadelphia, PA 19104, or at starr{at}email.chop.edu.
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