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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Tenofovir disoproxil fumarate/Emtricitabine; Drug: Lopinavir/Ritonavir

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 cluster of differentiation 4 (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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Denver, Colorado, United States, 80262
      • University of Colorado Health Sciences Center
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • AIDS Research Consortium of Atlanta
• Zimbabwe
  • Harare, Zimbabwe
    • University of Zimbabwe College of Health Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment interruption; Oral Tenofovir disoproxil fumarate/Emtricitabine and Lopinavir/Ritonavir 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; Other Names: TDF/FTC; Drug: Lopinavir/Ritonavir; Three 400 mg lopinavir/ 100 mg ritonavir soft gel capsules taken orally twice daily; Other Names: LPV/RTV
Experimental: CD4 T cell guided therapy; Anti Retroviral Therapy initiated when AIDS-defining illness occurs or if CD4 count 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; Other Names: TDF/FTC; Drug: Lopinavir/Ritonavir; Three 400 mg lopinavir/ 100 mg ritonavir soft gel capsules taken orally twice daily; Other Names: LPV/RTV

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma HIV-1 Viral Load (Copies/ml) at Week 24 as Compared Between the Two Arms		At Week 24
Number of Participants Experiencing Either an AIDS-defining Event, a Grade 3 or 4 Adverse Event, or Acute Retroviral Syndrome		At Week 24
Viral Set Point	set point is reached after the immune system has developed HIV antibodies and begins to attempt to fight the virus	Throughout study

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• 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

Publications and helpful links

General Publications

• 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. doi: 10.1097/00002030-200210180-00010.
• 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. doi: 10.1084/jem.193.2.169.
• 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. doi: 10.1086/514213.
• Gallant JE. Current status of antiretroviral treatment interruption and intermittent therapy strategies. MedGenMed. 2002 Sep 19;4(3):19. No abstract available.
• Gulick RM. Structured treatment interruption in patients infected with HIV: a new approach to therapy. Drugs. 2002;62(2):245-53. doi: 10.2165/00003495-200262020-00001.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Actual): February 1, 2010
• Study Completion (Actual): February 1, 2010

Study Registration Dates

• First Submitted: December 19, 2006
• First Submitted That Met QC Criteria: December 19, 2006
• First Posted (Estimate): December 21, 2006

Study Record Updates

• Last Update Posted (Estimate): February 20, 2013
• Last Update Submitted That Met QC Criteria: January 16, 2013
• Last Verified: January 1, 2013

More Information

Terms related to this study

• Keywords: Acute Infection; ART; Treatment Interruption; Early HIV Infection; Short-Term Antiretroviral Therapy; Antiretroviral Drug (ARV)
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; HIV Infections; Infections; Communicable Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Tenofovir; Emtricitabine; Ritonavir; Lopinavir
• Other Study ID Numbers: 06-0757; P01AI055356 (U.S. NIH Grant/Contract)