Clinical trial NCT00050284: Discontinuation of Antiretroviral Therapy in Patients With Asymptomatic HIV Infection
Official title: Predictors of Immunologic and Clinical Progression in Subjects With CD4+ Cell Counts Greater Than 350 Cells/mm3 Who Discontinue Antiretroviral Therapy
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Keywords: Treatment Experienced
Disease Progression
Anti-HIV Agents
Treatment Interruption
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2002-12-04
Enrollment: 158
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE

Brief summary: The purpose of this study is to determine whether patients who have asymptomatic HIV infection can discontinue antiretroviral therapy (ART) without adverse clinical, virologic, or immunologic consequences. This study will also assess the virologic, immunologic, and clinical outcomes in any patients who restart ART.

Detailed description: Patients who can discontinue ART without a significant loss of virologic or immunologic control and without an increase in clinical events may be spared the expense and adverse effects of treatment. However, the consequences of treatment discontinuation in patients with asymptomatic HIV infections are not well understood. This study will follow the clinical and immunologic progression of HIV infection in patients who have low HIV viral load and preserved CD4+ cell counts at the time ART is stopped.

Patients will fast for at least 8 hours prior to the first study visit. At this visit, blood will be drawn and body measurements will be taken. Patients will then discontinue their ART. Patients taking nonnucleoside reverse transcriptase inhibitors (NNRTIs) will stop taking NNRTIs 48 hours before withdrawing their other ART drugs. Study visits will occur every 4 to 8 weeks for the first year, then every 12 weeks for the second year. Blood will be taken at most visits, and patients will be asked to fast for at least 8 hours prior to Week 12 and 24 visits and again every 6 months. Patients who reinitiate ART for any reason will be registered to Step 2 and followed for 24 weeks.

Eligibility criteria: Inclusion Criteria:

* HIV infection
* ART with 2 or more drugs for 6 or more months
* CD4+ cell count(s) \> 350 cells/mm3 immediately prior to initiation of first ART
* CD4+ cell count \> 350 cells/mm3 within 45 days prior to study entry
* Plasma viral load \< 55,000 copies/ml within 45 days prior to study entry
* Willingness to discontinue ART at study entry
* Negative serum or urine pregnancy test within 14 days prior to study entry

Exclusion Criteria:

* Pregnancy or breast-feeding
* Systemic cancer chemotherapy, systemic investigational agents, or immunomodulators within 30 days prior to study entry
* Drug or alcohol use or dependence that would interfere with adherence to study requirements
* Illness requiring systemic treatment and/or hospitalization until the patient either completes therapy or has been clinically stable on therapy for at least 30 days prior to study entry
* Chronic medical condition that would have a negative impact on the participation of the patient or would be expected to result in significant use of the medical care system
* History of an HIV-related illness or complication in CDC categories B and C
* Nonadherence to ART
* Active infection with hepatitis B and currently taking adefovir at doses \> 10 mg or 3TC and/or TDF

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Univ of Southern California
state: California
city: San Diego
country: United States
facility: Univ of California, San Diego Antiviral Research Ctr
state: California
city: San Francisco
country: United States
facility: Univ of California San Francisco
state: California
city: Stanford
country: United States
facility: San Mateo County AIDS Program
state: California
city: Stanford
country: United States
facility: Santa Clara Valley Med Ctr
state: California
city: Stanford
country: United States
facility: Stanford Univ
state: California
city: Stanford
country: United States
facility: Willow Clinic
state: California
city: Torrance
country: United States
facility: Harbor General/UCLA
state: California
city: Washington
country: United States
facility: Georgetown Univ Med Ctr
state: District of Columbia
city: Honolulu
country: United States
facility: Univ of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Northwestern Univ
state: Illinois
city: Chicago
country: United States
facility: Cook County Hosp Core Ctr
state: Illinois
city: Chicago
country: United States
facility: Rush-Presbyterian / St.Lukes (Chicago)
state: Illinois
city: Indianapolis
country: United States
facility: Indiana Univ Hosp
state: Indiana
city: Indianapolis
country: United States
facility: Methodist Hosp of Indiana
state: Indiana
city: Indianapolis
country: United States
facility: Wishard Hosp
state: Indiana
city: Minneapolis
country: United States
facility: Univ of Minnesota
state: Minnesota
city: St. Louis
country: United States
facility: St. Louis Connect Care
state: Missouri
city: St. Louis
country: United States
facility: Washington Univ (St. Louis)
state: Missouri
city: New York
country: United States
facility: Beth Israel Med Ctr
state: New York
city: New York
country: United States
facility: NYU/Bellevue
state: New York
city: New York
country: United States
facility: Chelsea Clinic
state: New York
city: New York
country: United States
facility: The Cornell Clinical Trials Unit
state: New York
city: Chapel Hill
country: United States
facility: Univ of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Cincinnati
country: United States
facility: Univ of Cincinnati
state: Ohio
city: Norristown
country: United States
facility: Presbyterian Med Ctr- Univ of PA
state: Pennsylvania
city: Philadelphia
country: United States
facility: Univ of Pennsylvania, Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Univ of Pittsburgh
state: Pennsylvania
city: Providence
country: United States
facility: Rhode Island Hosp
state: Rhode Island
city: Providence
country: United States
facility: Stanley Street Treatment and Resource
state: Rhode Island
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Nashville
country: United States
facility: Comprehensive Care Clinic
state: Tennessee
city: Dallas
country: United States
facility: Univ of Texas, Southwestern Medical Ctr
state: Texas
Study officials:
affiliation: University of Texas Southwestern Medical Center
name: Daniel J. Skiest, M. D.
role: STUDY_CHAIR
References:
citation: Le Moing V, Chene G, Leport C, Lewden C, Duran S, Garre M, Masquelier B, Dupon M, Raffi F; Antiproteases Cohorte (APROCO) Study Group. Impact of discontinuation of initial protease inhibitor therapy on further virological response in a cohort of human immunodeficiency virus-infected patients. Clin Infect Dis. 2002 Jan 15;34(2):239-47. doi: 10.1086/324354. Epub 2001 Dec 4.
citation: Mocroft A, Youle M, Moore A, Sabin CA, Madge S, Lepri AC, Tyrer M, Chaloner C, Wilson D, Loveday C, Johnson MA, Phillips AN. Reasons for modification and discontinuation of antiretrovirals: results from a single treatment centre. AIDS. 2001 Jan 26;15(2):185-94. doi: 10.1097/00002030-200101260-00007.
citation: Deeks SG, Wrin T, Liegler T, Hoh R, Hayden M, Barbour JD, Hellmann NS, Petropoulos CJ, McCune JM, Hellerstein MK, Grant RM. Virologic and immunologic consequences of discontinuing combination antiretroviral-drug therapy in HIV-infected patients with detectable viremia. N Engl J Med. 2001 Feb 15;344(7):472-80. doi: 10.1056/NEJM200102153440702.
citation: Daar ES, Bai J, Hausner MA, Majchrowicz M, Tamaddon M, Giorgi JV. Acute HIV syndrome after discontinuation of antiretroviral therapy in a patient treated before seroconversion. Ann Intern Med. 1998 May 15;128(10):827-9. doi: 10.7326/0003-4819-128-10-199805150-00005. No abstract available.
citation: Robertson KR, Su Z, Margolis DM, Krambrink A, Havlir DV, Evans S, Skiest DJ; A5170 Study Team. Neurocognitive effects of treatment interruption in stable HIV-positive patients in an observational cohort. Neurology. 2010 Apr 20;74(16):1260-6. doi: 10.1212/WNL.0b013e3181d9ed09. Epub 2010 Mar 17.