Safety and Effectiveness of Short-Term Anti-HIV Drug Therapy for Recent HIV-1 Infection - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00414518

Purpose

The purpose of this study is to determine the safety and effectiveness of an anti-HIV drug regimen followed by treatment interruption in people recently infected with HIV. This study will also compare the effects of a treatment regimen including treatment interruption with a treatment plan based on clinical indicators.

Condition	Intervention
HIV Infections	Drug: Tenofovir disoproxil fumarate/Emtricitabine Drug: Lopinavir/Ritonavir

MedlinePlus related topics: AIDS AIDS Medicines

Drug Information available for: Ritonavir Lopinavir Tenofovir Tenofovir disoproxil Tenofovir Disoproxil Fumarate

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	An Open-Label Randomized Clinical Trial to Evaluate the Efficacy and Safety of Short Course Antiretroviral Therapy for Acute or Recent HIV-1 Infection in Zimbabwe and the United States

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Plasma HIV-1 viral load at Week 24 as compared between the two arms [ Time Frame: At Week 24 ] [ Designated as safety issue: No ]
Number of participants experiencing either an AIDS-defining event, a Grade 3 or 4 adverse event, or acute retroviral syndrome [ Time Frame: At Week 24 ] [ Designated as safety issue: Yes ]
Viral set point [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	36
Study Start Date:	January 2007
Estimated Study Completion Date:	February 2010
Estimated Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Oral TDF/FTC and LPV/RTV for 12 weeks followed by treatment interruption if CD4 count is 450 mm^3 or higher. When CD4 count is less than 350 mm^3 on two separate, consecutive measurements during treatment interruption, therapy will be resumed.	Drug: Tenofovir disoproxil fumarate/Emtricitabine 300 mg Tenofovir disoproxil fumarate/ 200 mg emtricitabine tablet taken orally once daily Drug: Lopinavir/Ritonavir Three 400 mg lopinavir/ 100 mg ritonavir soft gel capsules taken orally twice daily
2: Experimental ART will not be initiated until AIDS-defining illness occurs or if CD4 is confirmed at less than 350 mm^3 at two separate, consecutive measurements	Drug: Tenofovir disoproxil fumarate/Emtricitabine 300 mg Tenofovir disoproxil fumarate/ 200 mg emtricitabine tablet taken orally once daily Drug: Lopinavir/Ritonavir Three 400 mg lopinavir/ 100 mg ritonavir soft gel capsules taken orally twice daily

Detailed Description:

About 6 months after infection, HIV viral load reaches a temporarily stable level known as virus set point. Virus set point is different for each patient and can be a predictor for disease progression. Preliminary studies indicate that early, short-term antiretroviral therapy (ART) given to people newly infected with HIV may lead to lower virus set points and preserved CD4 counts. However, the length of short-term treatment needed to balance the possible adverse effects of ART with the achievement of lower virus set point is not yet known. By lowering the virus set point and maintaining CD4 counts, the need for long-term ART may be postponed. The purpose of this study is to determine the safety and efficacy of a short course of ART on producing a lower virus set point in adults recently infected with HIV.

This study will last at least 28 weeks. Participants will be randomly assigned to one of two arms. Arm A will receive ART for 12 weeks as emtricitabine/tenofovir disoproxil fumarate (TDF/FTC) daily and lopinavir/ritonavir (LPV/RTV) in tablet form twice daily. After 12 weeks, treatment will be interrupted unless the CD4 count is measured to be less than 350 cells/mm^3 on two consecutive occasions during treatment interruption. If that occurs therapy will be resumed. Participants in Arm B will receive no treatment until CD4 counts drop below 350 cells/mm^3, indicating ART is needed. Study visits will occur at study entry, at Weeks 2 and 4, and every 4 weeks thereafter. At each study visit, a physical exam, blood collection, and completion of an adherence questionnaire will occur. Participants are encouraged to enroll in a related substudy that will evaluate HIV viral load in genital secretions.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Acute or recent HIV-1 infection. More information about this criterion can be found in the protocol.
CD4 count 500 cells/mm3 or greater
No evidence of prior or current AIDS-defining illness
No signs or symptoms of HIV infection or AIDS-defining illness that, in the opinion of the investigator, requires ART
Willing to use acceptable forms of contraception

Exclusion Criteria:

Prior treatment with any antiretroviral drug for more than 7 days
Use of certain drugs within 21 days of study entry
Prior receipt of investigational anti-HIV-1 vaccine
Ongoing therapy with systemic corticosteroids, chemotherapeutic agents, nephrotoxic systemic agents, immunomodulatory treatments, or investigational agents
Known allergy/sensitivity to study drugs or their formulations
Current drug or alcohol use or abuse that, in the opinion of the investigator, may interfere with the study
Serious medical or psychiatric illness that may interfere with the study
Hepatitis B infected
Pregnancy or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00414518

Locations

United States, Colorado
University of Colorado Health Sciences Center	Recruiting
Denver, Colorado, United States, 80262
Contact: Thomas Campbell, MD Thomas.Campbell@uchsc.edu
United States, Georgia
AIDS Research Consortium of Atlanta	Recruiting
Atlanta, Georgia, United States, 30308
Contact: Janet Grace, CCRC 404-876-2317 janetg@aidsresearchatlanta.org
Principal Investigator: Melanie A. Thompson, MD
Zimbabwe
University of Zimbabwe College of Health Sciences	Not yet recruiting
Harare, Zimbabwe
Contact: Thomas Campbell, MD Thomas.Campbell@uchsc.edu

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Michelle A. Barron, MD	Division of Infectious Disease, University of Colorado Health Sciences Center
Study Chair:	Margaret Borok, MRCP	Department of Medicine, University of Zimbabwe

More Information

Click here for more information about emtricitabine/tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Click here for more information about lopinavir/ritonavir This link exits the ClinicalTrials.gov site

Publications:

Altfeld M, Rosenberg ES, Shankarappa R, Mukherjee JS, Hecht FM, Eldridge RL, Addo MM, Poon SH, Phillips MN, Robbins GK, Sax PE, Boswell S, Kahn JO, Brander C, Goulder PJ, Levy JA, Mullins JI, Walker BD. Cellular immune responses and viral diversity in individuals treated during acute and early HIV-1 infection. J Exp Med. 2001 Jan 15;193(2):169-80.

Fidler S, Oxenius A, Brady M, Clarke J, Cropley I, Babiker A, Zhang HT, Price D, Phillips R, Weber J. Virological and immunological effects of short-course antiretroviral therapy in primary HIV infection. AIDS. 2002 Oct 18;16(15):2049-54.

Coombs RW, Speck CE, Hughes JP, Lee W, Sampoleo R, Ross SO, Dragavon J, Peterson G, Hooton TM, Collier AC, Corey L, Koutsky L, Krieger JN. Association between culturable human immunodeficiency virus type 1 (HIV-1) in semen and HIV-1 RNA levels in semen and blood: evidence for compartmentalization of HIV-1 between semen and blood. J Infect Dis. 1998 Feb;177(2):320-30.

Gallant JE. Current status of antiretroviral treatment interruption and intermittent therapy strategies. MedGenMed. 2002 Sep 19;4(3):19. Review. No abstract available.

Gulick RM. Structured treatment interruption in patients infected with HIV: a new approach to therapy. Drugs. 2002;62(2):245-53. Review.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	AI55356, 5-P01-I055356-03
Study First Received:	December 19, 2006
Last Updated:	July 28, 2008
ClinicalTrials.gov Identifier:	NCT00414518
Health Authority:	United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Acute Infection
Early HIV Infection
Short-Term Antiretroviral Therapy

Treatment Interruption
ARV
ART

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
Lopinavir
Emtricitabine
Ritonavir
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Tenofovir
Retroviridae Infections
Immunologic Deficiency Syndromes
Tenofovir disoproxil

Additional relevant MeSH terms:

Anti-Infective Agents
Communicable Diseases
RNA Virus Infections
HIV Protease Inhibitors
Slow Virus Diseases
Anti-HIV Agents
Immune System Diseases
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors

Infection
Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Protease Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009