Effectiveness of Immediate and Deferred Antiretroviral Treatment in HIV-Infected Adults - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00821171

Purpose

The purpose of this study is to determine whether immediate initiation of antiretroviral treatment (ART) is superior to deferral of ART in HIV-infected adults.

Condition	Intervention	Phase
HIV Infections	Drug: Antiretroviral Treatment	Phase I

MedlinePlus related topics: AIDS

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Parallel Assignment, Safety/Efficacy Study
Official Title:	Strategic Timing of Antiretroviral Treatment (START)

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

AIDS or death from AIDS [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Non-AIDS or death not attributable to AIDS [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

All-cause mortality [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Non-AIDS [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
CVD (myocardial infarction, stroke, coronary revascularization) [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
ESRD (initiation of dialysis, renal transplantation) [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Decompensated liver disease [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Non-AIDS malignancy, excluding basal and squamous cell skin cancers [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Non-AIDS malignancy, including basal and squamous cell skin cancers [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
AIDS [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Bacterial pneumonia [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Adverse events [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Hospitalization [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Quality of life [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Health-care utilization and cost of care [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
HIV transmission risk behavior [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
HIV drug resistance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Pulmonary embolism or deep vein thrombosis [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
New-onset diabetes mellitus [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Coronary artery disease requiring drug treatment [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Congestive heart failure [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Peripheral arterial disease [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Change in estimated glomerular filtration rate (eGFR) and development of proteinuria [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Blood pressure and blood lipids [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Electrocardiogram (ECG) abnormalities [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Use of blood pressure- or lipid-lowering treatment or aspirin [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Change in neurocognitive function (in a subset of participants) [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:

4000

Arms	Assigned Interventions
A: Experimental ART regimen is initiated immediately after randomization	Drug: Antiretroviral Treatment Potent combination therapy will be prescribed for all participants by their physicians
B: Active Comparator ART regimen is deferred until the CD4 count is measured below 350 cells/mm^3	Drug: Antiretroviral Treatment Potent combination therapy will be prescribed for all participants by their physicians

Detailed Description:

Data from recent studies indicate that morbidity and mortality risk reduction with earlier use of ART may be greater than previously estimated. This randomized study will determine whether immediate initiation of ART is more effective than deferral of ART until the CD4 count declines below 350 cells/mm^3 in HIV-infected participants who are treatment naive with a CD4 count greater than 500 cells/mm^3.

This study will last approximately 6 years. Participants will be randomly stratified to one of two arms. Participants in Arm A will begin receiving ART immediately after randomization. Participants in Arm B will defer treatment until the CD4 count is measured below 350 cells/mm^3.

All participants taking ART in this study will be prescribed a potent combination therapy chosen by the participant and his or her physician. ART will not be provided by the study.

All participants will have scheduled visits at Months 1 and 4 after randomization and every 4 months thereafter. A targeted physical exam and blood and urine collection will occur at all visits. Behavioral and quality of life assessments will occur annually.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

HIV-infected
Kanofsky performance score of at least 80
Perceived life expectancy of at least 6 months
Two consecutive CD4 counts greater than 500 cells/mm^3 at least two weeks apart within 60 days prior to study entry
For women of child-bearing potential, willingness to use contraceptives as described in the product information of the ART they are prescribed

Exclusion Criteria:

Any previous use of ART or IL-2
Diagnosis of any clinical AIDS event prior to study entry, including esophageal candidiasis and chronic Herpes simplex infection
Presence of HIV progression such as oral thrush, unexplained weight loss, or unexplained fever
Cardiovascular event within 6 months prior to study entry. More information on this criterion can be found in the protocol.
Non-AIDS-defining cancer, excluding basal and squamous cell skin cancer, within 6 months prior to study entry
Dialysis within 6 months prior to study entry
History of decompensated liver disease
Current imprisonment or compulsory detention for treatment of a psychiatric or physical illness
Pregnant or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00821171

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Abdel Babiker, MD	Medical Research Council
Study Chair:	Sean Emery, PhD	University of New South Wales
Study Chair:	Fred Gordin, MD	George Washington University
Study Chair:	Jens Lundgren, MD	University of Copenhagen

More Information

Click here for the AIDSinfo Starting Anti-HIV Medications Fact Sheet This link exits the ClinicalTrials.gov site

Click here for the AIDSinfo Side Effects of Anti-HIV Medications Fact Sheet This link exits the ClinicalTrials.gov site

Publications:

Phillips AN, Gazzard BG, Clumeck N, Losso MH, Lundgren JD. When should antiretroviral therapy for HIV be started? BMJ. 2007 Jan 13;334(7584):76-8. Review. No abstract available.

Phillips AN, Lepri AC, Lampe F, Johnson M, Sabin CA. When should antiretroviral therapy be started for HIV infection? Interpreting the evidence from observational studies. AIDS. 2003 Sep 5;17(13):1863-9. Review. No abstract available.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	INSIGHT 001, START
Study First Received:	January 9, 2009
Last Updated:	January 9, 2009
ClinicalTrials.gov Identifier:	NCT00821171
Health Authority:	United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):

Treatment Naive

Study placed in the following topic categories:

Virus Diseases
Sexually Transmitted Diseases, Viral
HIV Infections
Sexually Transmitted Diseases

Acquired Immunodeficiency Syndrome
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

RNA Virus Infections
Slow Virus Diseases
Immune System Diseases
Lentivirus Infections
Infection

ClinicalTrials.gov processed this record on January 30, 2009