Abstract
Background. We sought to determine the safety of treatment interruption (TI) and to identify parameters that would define patients with human immunodeficiency virus (HIV) for whom TI is safer. Methods. AIDS Clinical Trials Group 5170 was a multicenter, 96-week-long, prospective study of HIV-infected patients receiving antiretroviral therapy (ART) who had CD4+ cell counts >350 cells/mm3 and who underwent TI. Results. A total of 167 patients were enrolled. The median nadir in CD4+ cell count was 436 cells/mm3. The initial decrease (i.e., during the first 8 weeks) in CD4+ cell count after ART interruption was 20 cells/mm 3/week; the subsequent decrease was 2.0 cells/mm3/week until week 96. Both the CD4+ cell count before enrollment and the increase in CD4+ cell count during ART predicted early decrease; later decrease was predicted by the level of interleukin-7 at enrollment. A Centers for Disease Control and Prevention (CDC) diagnosis of a category B or C event was made for 2 and 2 patients, respectively (all had CD4+ cell counts >350 cells/mm3). At week 96, 17 patients had CD4 + cell counts ≤250 cells/mm3, and 46 patients had resumed ART; 5 patients died (unrelated to HIV or acquired immunodeficiency syndrome). In a multivariate analysis, a higher nadir in CD4+ cell count (>400 cells/mm3), a lower HIV load (<50 copies/mL) at the time of TI, and an HIV load ≤22,000 copies/mL before ART predicted a longer time to the primary end point (CDC category B or C event, death, CD4+ cell count ≤250 cells/mm3, or resumption of ART). Conclusion. Disease progression after TI was low in this cohort. A higher nadir in CD4 + cell count, a lower HIV load before ART, and an HIV load ≤50 copies/mL at the time of TI predicted a longer time to the primary end point.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1426-1436 |
| Number of pages | 11 |
| Journal | Journal of Infectious Diseases |
| Volume | 195 |
| Issue number | 10 |
| DOIs | |
| State | Published - May 15 2007 |
Bibliographical note
Funding Information:AIDS Clinical Trials Group 5170 thanks Dr. Ronald Bosch (Harvard School of Public Health) for his assistance with statistical methods; David Rusin (Frontier Science & Technology Research Foundation Inc.) for his assistance with data retrieval; and Dr. Elizabeth Adams (Division of AIDS) for oversight of safety issues.
Funding Information:
The members of the AIDS Clinical Trials Group are Daniel J. Skiest and Tianna Petersen (University of Texas Southwestern Medical Center at Dallas [group A3751]) (supported by AIDS Clinical Trials Unit [ACTU] grant 3 U01 AI046376-05); Deborah McMahon and Nancy Mantz (University of Pittsburgh [group A1001]); Diane Havlir and Michele Downing (San Francisco General Hospital [group A0801]); Beverly Sha (Rush University Medical Center) and Jessica Shore (Rush University Medical Center and Northwestern University; Northwestern AIDS Clinical Trials Unit [groups A2701, A2702, and A2705]) (supported by ACTU grant AI 25915); Sylvia Stoudt and Debbie Slamowitz (Stanford University [group A0501]) (supported by ACTU grant 5UO1 AI027666); Linda Meixner and Susan Cahill (University of California, San Diego [group A0701]) (supported by ACTU grant AI27670); Peter Frame and Michelle Saemann (University of Cincinnati [group A2401]) (supported by ACTG grant AI-25897); Alexandra Nesbitt and Joseph J. Eron Jr. (University of North Carolina [UNC] at Chapel Hill [group A3201]) (supported by ACTU grant AI25868, General Clinical Research Center [GCRC] grant RR00046, and UNC Center for AIDS Research [CFAR] grant AI50410); Timothy Wilkin and Todd Stroberg (Cornell Clinical Trials Unit [groups A7803 and A7804]) (supported by Columbia-Cornell ACTU grant AI46386 and Weill Medical College GCRC grant M01 RR00047); Charles Gonzalez and Margarita Vasquez (New York University/New York City HHC at Bellevue Hospital Center [group A0401]) (supported by ACTU grant AI27665 and GCRC grant M01 RR00096); Ann C. Collier and Shelia Duna-way (University of Washington, Seattle [group A1401]) (supported by ACTU grant AI 27664); Karen T. Tashima and Pamela Poethke (The Miriam Hospital [group A2951]) (supported by Miriam Hospital ACTU grant AI46381); Ian Frank and Joyce Okawa (University of Pennsylvania, Philadelphia [group A6201]) (supported by ACTU grant U01-AI 032783-13 and CFAR grant 5-P30-AI-045008-07); Eric S. Daar and Sadia Shaik (Harbor–University of California, Los Angeles, Medical Center [grant A0603]) (supported by ACTU grant AI27660); Donna Mildvan and Ronald D’Amico (Beth Israel Medical Center [group A2851]) (supported by Beth Israel ACTU grant AI46370); William A. O’Brien and Gerianne Casey (University of Texas Medical Branch at Galveston [group A6301]) (supported by ACTU grant PHS 5U01AI032782); Connie A. Funk and Luis M. Mendez (University of Southern California [USC] [group A1201]) (supported by ACTU grant AI27673); Kim-berly Gray and Ge-Youl Kim (Washington University, St. Louis [grant A2101]) (supported by ACTU grant A125903); Jane Reid and Carol Greisberger (University of Rochester [A1101]) (supported by ACTU grant AI27658 and GCRC grant 5-M01 RR00044); Winston Cavert and Christine Fietzer (University of Minnesota [group A1501]) (supported by ACTU grant AI27661); Nathan Thielman and Lee McClurkin (Duke University Medical Center [group A1601]) (supported by ACTU grant 5U01-AI-39156-09); and Deborah K. O’Connor and Mitchell Goldman (Indiana University [group A2601]) (supported by ACTU grant AI25859).
Funding Information:
Financial support: AIDS Clinical Trials Group (National Institute of Allergy and Infectious Diseases grant AI38858 and Statistical Data Analysis Center grant AI38855; General Clinical Research Center units (National Center for Research Resources grant). a Members of AIDS Clinical Trials Group 5170 are listed after the text.
