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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00414518
• Other study ID #: 06-0757
• Secondary ID: P01AI055356
• Status: Completed
• Phase: N/A
• First received: December 19, 2006
• Last updated: January 16, 2013
• Start date: January 2007
• Est. completion date: February 2010

Study information

• Verified date: January 2013
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00525070
• NCT01030172

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: February 2010
• Est. primary completion date: February 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Communicable Diseases
• HIV Infections
• Infection

Intervention

Drug:
• Tenofovir disoproxil fumarate/Emtricitabine
300 mg Tenofovir disoproxil fumarate/ 200 mg emtricitabine tablet taken orally once daily
• Lopinavir/Ritonavir
Three 400 mg lopinavir/ 100 mg ritonavir soft gel capsules taken orally twice daily

Locations

Country	Name	City	State
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	University of Colorado Health Sciences Center	Denver	Colorado
Zimbabwe	University of Zimbabwe College of Health Sciences	Harare

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Zimbabwe, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

Gallant JE. Current status of antiretroviral treatment interruption and intermittent therapy strategies. MedGenMed. 2002 Sep 19;4(3):19. Review. — View Citation

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Plasma HIV-1 Viral Load (Copies/ml) at Week 24 as Compared Between the Two Arms		At Week 24	No
Primary	Number of Participants Experiencing Either an AIDS-defining Event, a Grade 3 or 4 Adverse Event, or Acute Retroviral Syndrome		At Week 24	Yes
Primary	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	No

External Links

•   Click here for more information about emtricitabine/tenofovir disoproxil fumarate
•   Click here for more information about lopinavir/ritonavir