Clinical trial NCT00414518: Safety and Effectiveness of Short-Term Anti-HIV Drug Therapy for Recent HIV-1 Infection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: HIV Infections
Keywords: Acute Infection
Early HIV Infection
Short-Term Antiretroviral Therapy
Treatment Interruption
Antiretroviral Drug (ARV)
ART
Lead sponsor: University of Colorado, Denver
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2006-12-21
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Plasma HIV-1 Viral Load (Copies/ml) at Week 24 as Compared Between the Two Arms
timeFrame: At Week 24
measure: Number of Participants Experiencing Either an AIDS-defining Event, a Grade 3 or 4 Adverse Event, or Acute Retroviral Syndrome
timeFrame: At Week 24
measure: Viral Set Point
timeFrame: Throughout study
Secondary outcomes:
Other outcomes:
Locations:
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Harare
country: Zimbabwe
facility: University of Zimbabwe College of Health Sciences
Study officials:
affiliation: Division of Infectious Disease, University of Colorado Health Sciences Center
name: Michelle A. Barron, MD
role: STUDY_CHAIR
affiliation: Department of Medicine, University of Zimbabwe
name: Margaret Borok, MRCP
role: STUDY_CHAIR
References:
citation: 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.
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. doi: 10.1097/00002030-200210180-00010.
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. doi: 10.1086/514213.
citation: Gallant JE. Current status of antiretroviral treatment interruption and intermittent therapy strategies. MedGenMed. 2002 Sep 19;4(3):19. No abstract available.
citation: 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.