This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on Web of Science (180)  • Contact me when this article is cited  Related Content  • Similar articles in JAMA  Topic Collections  • HIV/AIDS  • Infectious Diseases  • Alert me on articles by topic  Social Bookmarking   What's this?

100-Week Follow-up

Roy M. Gulick, MD, MPH; John W. Mellors, MD; Diane Havlir, MD; Joseph J. Eron, MD; Charles Gonzalez, MD; Deborah McMahon, MD; Leslie Jonas, BS; Anne Meibohm, PhD; Daniel Holder, PhD; William A. Schleif, MS; Jon H. Condra, PhD; Emilio A. Emini, PhD; Robin Isaacs, MD; Jeffrey A. Chodakewitz, MD; Douglas D. Richman, MD

JAMA. 1998;280:35-41.

Context.— Combination antiretroviral therapy can markedly suppress human immunodeficiency virus (HIV) replication but the duration of HIV suppression varies among patients.

Objective.— To compare the antiretroviral effect of a 3-drug regimen started simultaneously or sequentially in patients with HIV infection.

Design.— A multicenter, randomized, double-blind study, modified after at least 24 weeks of blinded therapy to provide open-label 3-drug therapy with follow-up through 100 weeks.

Setting.— Four clinical research units

Patients.— Ninety-seven patients with HIV infection who had taken zidovudine for at least 6 months with serum HIV RNA level of at least 20000 copies/mL and CD4 cell count of 0.05 to 0.40x10⁹/L.

Interventions.— Patients were initially randomized to receive 1 of 3 antiretroviral regimens: indinavir, 800 mg every 8 hours; zidovudine, 200 mg every 8 hours and lamivudine, 150 mg every 12 hours; or all 3 drugs. After at least 24 weeks of blinded therapy, all patients received open-label 3-drug therapy.

Main Outcome Measures.— Antiretroviral activity was assessed by changes in HIV RNA level and CD4 cell count from baseline. Data through 100 weeks were summarized.

Results.— Simultaneous initiation of indinavir, zidovudine, and lamivudine suppressed HIV RNA in 78% (25/32) of contributing patients to less than 500 copies/mL and increased CD4 cell count to a median of 0.209x10⁹/L above baseline at 100 weeks. When these 3 drugs were initiated sequentially, only 30% to 45% of contributing patients (10 of 33 in the zidovudine-lamivudine group and 13 of 29 in the indinavir group, respectively) had a sustained reduction in HIV RNA to less than 500 copies/mL, and median CD4 cell count increased to 0.101 to 0.163x10⁹/L above baseline at 100 weeks.

Conclusions.— A 3-drug combination of indinavir, zidovudine, and lamivudine started simultaneously has durable antiretroviral activity for at least 2 years. Sequential initiation of the same 3 drugs is much less effective.

From the Department of Medicine, New York University School of Medicine, New York (Drs Gulick and Gonzalez); Department of Medicine, University of Pittsburgh School of Medicine and Pittsburgh VA Medical Center, Pittsburgh, Pa (Drs Mellors and McMahon); Departments of Pathology and Medicine, University of California and San Diego VA Medical Center, San Diego (Drs Havlir and Richman); Department of Medicine, University of North Carolina, Chapel Hill (Dr Eron); and Merck Research Laboratories, West Point, Pa (Drs Meibohm, Holder, Condra, Emini, Isaacs, and Chodakewitz, Ms Jonas, and Mr Schleif).

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Triple Combination of Oseltamivir, Amantadine, and Ribavirin Displays Synergistic Activity against Multiple Influenza Virus Strains In Vitro
Nguyen et al.
Antimicrob. Agents Chemother. 2009;53:4115-4126.
ABSTRACT | FULL TEXT  

Combination Therapies against Chronic Myeloid Leukemia: Short-term versus Long-term Strategies
Komarova and Wodarz
Cancer Res. 2009;69:4904-4910.
ABSTRACT | FULL TEXT  

Cost-Effectiveness of HIV Screening in Patients Older than 55 Years of Age
Sanders et al.
ANN INTERN MED 2008;148:889-903.
ABSTRACT | FULL TEXT  

The Cost-Effectiveness of Counseling Strategies to Improve Adherence to Highly Active Antiretroviral Therapy among Men Who Have Sex with Men
Zaric et al.
Med Decis Making 2008;28:359-376.
ABSTRACT  

Biological characterization of human immunodeficiency virus type 1 subtype C protease carrying indinavir drug-resistance mutations.
Gonzalez et al.
J. Gen. Virol. 2006;87:1303-1309.
ABSTRACT | FULL TEXT  

Covalent stabilization of coiled coils of the HIV gp41 N region yields extremely potent and broad inhibitors of viral infection
Bianchi et al.
Proc. Natl. Acad. Sci. USA 2005;102:12903-12908.
ABSTRACT | FULL TEXT  

Contradicted and Initially Stronger Effects in Highly Cited Clinical Research
Ioannidis
JAMA 2005;294:218-228.
ABSTRACT | FULL TEXT  

Cost-Effectiveness of Screening for HIV in the Era of Highly Active Antiretroviral Therapy
Sanders et al.
NEJM 2005;352:570-585.
ABSTRACT | FULL TEXT  

Incorporating Pharmakon: HIV, Medicine, and Body Shape Change
Persson
Body Society 2004;10:45-67.
ABSTRACT  

Pharmacokinetics of Indinavir Combined with Low-Dose Ritonavir in Human Immunodeficiency Virus Type 1-Infected Children
Bergshoeff et al.
Antimicrob. Agents Chemother. 2004;48:1904-1907.
ABSTRACT | FULL TEXT  

Pharmacokinetic-Pharmacodynamic Analysis of Lopinavir-Ritonavir in Combination with Efavirenz and Two Nucleoside Reverse Transcriptase Inhibitors in Extensively Pretreated Human Immunodeficiency Virus-Infected Patients
Hsu et al.
Antimicrob. Agents Chemother. 2003;47:350-359.
ABSTRACT | FULL TEXT  

Treatment for Hepatitis C Virus in Human Immunodeficiency Virus-Infected Patients: Clinical Benefits and Cost-effectiveness
Kuehne et al.
Arch Intern Med 2002;162:2545-2556.
ABSTRACT | FULL TEXT  

Efficacy of Zidovudine Compared to Stavudine, Both in Combination with Lamivudine and Indinavir, in Human Immunodeficiency Virus-Infected Nucleoside-Experienced Patients with No Prior Exposure to Lamivudine, Stavudine, or Protease Inhibitors (Novavir Trial)
Joly et al.
Antimicrob. Agents Chemother. 2002;46:1906-1913.
ABSTRACT | FULL TEXT  

Longitudinal Use of a Line Probe Assay for Human Immunodeficiency Virus Type 1 Protease Predicts Phenotypic Resistance and Clinical Progression in Patients Failing Highly Active Antiretroviral Therapy
Servais et al.
Antimicrob. Agents Chemother. 2002;46:1928-1933.
ABSTRACT | FULL TEXT  

Cost-Effectiveness of Earlier Initiation of Antiretroviral Therapy for Uninsured HIV-Infected Adults
Schackman et al.
AJPH 2001;91:1456-1463.
ABSTRACT | FULL TEXT  

Use of Genotypic Resistance Testing To Guide HIV Therapy: Clinical Impact and Cost-Effectiveness
Weinstein et al.
ANN INTERN MED 2001;134:440-450.
ABSTRACT | FULL TEXT  

The Cost Effectiveness of Combination Antiretroviral Therapy for HIV Disease
Freedberg et al.
NEJM 2001;344:824-831.
ABSTRACT | FULL TEXT  

Abacavir-Lamivudine-Zidovudine vs Indinavir-Lamivudine-Zidovudine in Antiretroviral-Naive HIV-Infected Adults: A Randomized Equivalence Trial
Staszewski et al.
JAMA 2001;285:1155-1163.
ABSTRACT | FULL TEXT  

Variant Human Immunodeficiency Virus Type 1 Proteases and Response to Combination Therapy Including a Protease Inhibitor
Servais et al.
Antimicrob. Agents Chemother. 2001;45:893-900.
ABSTRACT | FULL TEXT  

Pharmacological Basis for Concentration-Controlled Therapy with Zidovudine, Lamivudine, and Indinavir
Kakuda et al.
Antimicrob. Agents Chemother. 2001;45:236-242.
ABSTRACT | FULL TEXT  

Simultaneous Quantitation of Intracellular Zidovudine and Lamivudine Triphosphates in Human Immunodeficiency Virus-Infected Individuals
Rodriguez et al.
Antimicrob. Agents Chemother. 2000;44:3097-3100.
ABSTRACT | FULL TEXT  

Use of Saliva Specimens for Monitoring Indinavir Therapy in Human Immunodeficiency Virus-Infected Patients
Wintergerst et al.
Antimicrob. Agents Chemother. 2000;44:2572-2574.
ABSTRACT | FULL TEXT  

Wild-Type and YMDD Mutant Murine Leukemia Virus Reverse Transcriptases Are Resistant to 2',3'-Dideoxy-3'-Thiacytidine
Halvas et al.
J. Virol. 2000;74:6669-6674.
ABSTRACT | FULL TEXT  

3-Year Suppression of HIV Viremia with Indinavir, Zidovudine, and Lamivudine
Gulick et al.
ANN INTERN MED 2000;133:35-39.
ABSTRACT | FULL TEXT  

Anti-Human Immunodeficiency Virus Type 1 (HIV-1) CD8+ T-Lymphocyte Reactivity during Combination Antiretroviral Therapy in HIV-1-Infected Patients with Advanced Immunodeficiency
Rinaldo et al.
J. Virol. 2000;74:4127-4138.
ABSTRACT | FULL TEXT  

Effect of Antiretroviral Therapy on Viral Load, CD4 Cell Count, and Progression to Acquired Immunodeficiency Syndrome in a Community Human Immunodeficiency Virus-Infected Cohort
Erb et al.
Arch Intern Med 2000;160:1134-1140.
ABSTRACT | FULL TEXT  

CD8+ T-Cell Gamma Interferon Production Specific for Human Immunodeficiency Virus Type 1 (HIV-1) in HIV-1-Infected Subjects
Huang et al.
CVI 2000;7:279-287.
ABSTRACT | FULL TEXT  

Antiretroviral Therapy in Adults: Updated Recommendations of the International AIDS Society-USA Panel
Carpenter et al.
JAMA 2000;283:381-390.
ABSTRACT | FULL TEXT  

Evolution of Envelope Sequences of Human Immunodeficiency Virus Type 1 in Cellular Reservoirs in the Setting of Potent Antiviral Therapy
Gunthard et al.
J. Virol. 1999;73:9404-9412.
ABSTRACT | FULL TEXT  

Human Immunodeficiency Virus 1 Protease Inhibitors in Clinical Practice: Predictors of Virological Outcome
Valdez et al.
Arch Intern Med 1999;159:1771-1776.
ABSTRACT | FULL TEXT  

Sarcoid-like Pulmonary Disorder in Human Immunodeficiency Virus-infected Patients Receiving Antiretroviral Therapy
NACCACHE et al.
Am. J. Respir. Crit. Care Med. 1999;159:2009-2013.
ABSTRACT | FULL TEXT  

The Clinical Effectiveness and Cost-effectiveness of Screening for Anal Squamous Intraepithelial Lesions in Homosexual and Bisexual HIV-Positive Men
Goldie et al.
JAMA 1999;281:1822-1829.
ABSTRACT | FULL TEXT  

Induction/Maintenance Treatment Regimens for HIV
Montaner
JAMA 1999;281:1680-1682.
FULL TEXT  

The Costs, Clinical Benefits, and Cost-Effectiveness of Screening for Cervical Cancer in HIV-Infected Women
Goldie et al.
ANN INTERN MED 1999;130:97-107.
ABSTRACT | FULL TEXT  

Therapeutic Strategies for HIV Infection -- Time to Think Hard
Cooper and Emery
NEJM 1998;339:1319-1321.
FULL TEXT  

Simultaneous Triple-Drug Therapy for HIV Superior to Sequentially Added Antiretrovirals
JWatch Infect. Diseases 1998;1998:8-8.
FULL TEXT  

Treating AIDS in 1998
JWatch General 1998;1998:1-1.
FULL TEXT  

HIV/AIDS in 1998--Gaining the Upper Hand?
Cohen and Fauci
JAMA 1998;280:87-88.
FULL TEXT