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

NCT ID: NCT00414518

Last Updated: 2013-02-20

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2010-02-28

Brief Summary

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.

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.

Conditions

HIV Infections

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Tenofovir disoproxil fumarate/Emtricitabine

Intervention Type: DRUG

300 mg Tenofovir disoproxil fumarate/ 200 mg emtricitabine tablet taken orally once daily

Lopinavir/Ritonavir

Intervention Type: DRUG

Three 400 mg lopinavir/ 100 mg ritonavir soft gel capsules taken orally twice daily

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

Group Type: EXPERIMENTAL

Tenofovir disoproxil fumarate/Emtricitabine

Intervention Type: DRUG

300 mg Tenofovir disoproxil fumarate/ 200 mg emtricitabine tablet taken orally once daily

Lopinavir/Ritonavir

Intervention Type: DRUG

Three 400 mg lopinavir/ 100 mg ritonavir soft gel capsules taken orally twice daily

Interventions

Tenofovir disoproxil fumarate/Emtricitabine

300 mg Tenofovir disoproxil fumarate/ 200 mg emtricitabine tablet taken orally once daily

Intervention Type: DRUG

Lopinavir/Ritonavir

Three 400 mg lopinavir/ 100 mg ritonavir soft gel capsules taken orally twice daily

Intervention Type: DRUG

Other Intervention Names

TDF/FTC; LPV/RTV

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: collaborator

University of Colorado, Denver

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michelle A. Barron, MD

Role: STUDY_CHAIR

Division of Infectious Disease, University of Colorado Health Sciences Center

Margaret Borok, MRCP

Role: STUDY_CHAIR

Department of Medicine, University of Zimbabwe

Locations

University of Colorado Health Sciences Center

Denver, Colorado, United States

AIDS Research Consortium of Atlanta

Atlanta, Georgia, United States

University of Zimbabwe College of Health Sciences

Harare, , Zimbabwe

Countries

United States; Zimbabwe

References

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.

Reference Type: BACKGROUND

PMID: 11148221 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12370504 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9466517 (View on PubMed)

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

Reference Type: BACKGROUND

PMID: 12466762 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11817971 (View on PubMed)

Other Identifiers

P01AI055356

Identifier Type: NIH

Identifier Source: secondary_id

View Link

06-0757

Identifier Type: -

Identifier Source: org_study_id

NCT00525070

Identifier Type: -

Identifier Source: nct_alias

NCT01030172

Identifier Type: -

Identifier Source: nct_alias