Strategic Timing of Antiretroviral Treatment
- Conditions
- HIV Infection
- Interventions
- Drug: All licensed antiretroviral medications
- Registration Number
- NCT00867048
- Lead Sponsor
- University of Minnesota
- Brief Summary
Objectives:
* To find out if the chance of developing a serious illness or of getting AIDS is less if patients start taking HIV medicines at a time when their cluster-of-differentiation-4 (CD4)+ cell count is still fairly high, instead of waiting until the CD4+ count is at the level where there is good evidence for starting medicines.
* To learn more about how a strategy of starting HIV medicines early might affect other aspects of care, such as the chances of developing other illnesses or resistance to HIV medicines, the frequency of doctor visits, the cost of medical care, and general health and satisfaction.
- Detailed Description
Background:
* Most guidelines agree that if the number of your CD4+ cells (cells in your blood which help fight infection) drops below 350 cells/mm3, or if you have symptoms of AIDS, you should start taking HIV medicines. There are randomized trials that support this recommendation. (Randomized trials are usually considered the strongest form of evidence to support treatment decisions. Other studies, like observational studies, provide evidence too, but the evidence is often considered to be weaker than evidence from randomized trials. A randomized trial gives the most certain information about how well a treatment works because randomization makes sure each group is similar except for the treatment they receive.) Some experts believe that HIV treatment should be started even when the number of CD4+ cells is above 350 cells/mm3. For example, guidelines issued in the US in December 2009 include a new recommendation for starting HIV medicines if your CD4+ cell count is between 350 and 500 cells/mm3. However, this recommendation is based on information from observational studies, not randomized trials. We are doing this study to find out if the chances of getting a serious illness or of getting AIDS are less if people start taking HIV medicines at a time when their CD4+ cell counts are still fairly high, instead of waiting to take HIV medicines at a CD4+ count where there is good evidence for starting medicines.
Objectives:
* To find out if the chance of developing a serious illness or of getting AIDS is less if patients start taking HIV medicines at a time when their CD4+ cell count is still fairly high, instead of waiting until the CD4+ count is at the level where there is good evidence for starting medicines.
* To learn more about how a strategy of starting HIV medicines early might affect other aspects of care, such as the chances of developing other illnesses or resistance to HIV medicines, the frequency of doctor visits, the cost of medical care, and general health and satisfaction.
Eligibility:
* Patients 18 years of age and older who are infected with HIV, have CD4+ cell counts of greater than 500 cells/mm3, and who have never had antiretroviral therapy to treat HIV.
Design:
* Initial screening visits (2) to draw blood for CD4+ cell counts and provide a full medical history
* Patients will be randomly split into two groups:
Early: Patients will begin receiving HIV medications from the start of the study.
Deferred: Patients will begin to take HIV medications when the CD4 drops below 350 cells/mm3, or they develop AIDS or other symptoms of HIV infection.
* HIV medications for each patient will be determined by the study doctors.
* Evaluations during the treatment period:
* Physical examination, including vital signs and body weight checks, and pregnancy test for women who can become pregnant.
* Questions about daily life, including sexual behaviors.
* Blood and urine tests.
* Heart tests with electrocardiogram.
* Patients will return for evaluations at 1 and 4 months after randomization, and every 4 months thereafter for the duration of the study.
Substudies will take advantage of the START randomization to compare outcomes in people starting ART early vs. later.
The purpose of this randomized study is to determine whether immediate initiation of antiretroviral treatment (ART) is superior to deferral of ART until the CD4+ declines below 350 cells/mm(3) in terms of morbidity and mortality in HIV-1 (subsequently referred to as HIV) infected persons who are antiretroviral naive with a CD4+ count above 500 cells/mm(3).
The study will enroll an estimated 4,000 participants. Participants will be followed for at least 3 years after enrollment, to a common closing date.
Substudies will take advantage of the START randomization to compare outcomes in people starting ART early vs. later. These will measure outcomes that do not require the entire sample size of START to determine whether early ART is related to a difference in these outcomes over the course of the study.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 4688
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Early ART All licensed antiretroviral medications Initiate ART immediately following randomization Deferred ART All licensed antiretroviral medications Defer ART until the CD4+ count declines to \<350 cells/cu mm or AIDS develops
- Primary Outcome Measures
Name Time Method Composite Endpoint of AIDS, Serious Non-AIDS Diagnoses, and All-cause Mortality full follow-up, 9.3 years
- Secondary Outcome Measures
Name Time Method Death, All-cause Mortality full follow-up, 9.3 years Count of participants
Changes in Bone Mineral Density (in a Subset of Participants) Measure 1 4.5 years Mean percent change from baseline in bone mineral density at the spine. In the bone mineral density (BMD) substudy of START, participants underwent dual-enery x-ray absorptionmetry (DXA) to measure BMD at the spine and hip at baseline and annually. Analyses were by intention-to-treat principles.
Quality of Life- Mean Change From Baseline in a Visual Analog Scale (VAS) for Perceived Current Health 4.5 years Mean change from baseline of the VAS. This was a single data item where participants self-reported their perceived current state of health on a scale of 0-100 (0=worst possible and 100=best possible).
Large Artery Elasticity (in a Subset of Participants) 4.5 years Mean change from baseline in large arterial elasticity. In the Arterial Elasticity substudy of START, participants had non-invasive measurements of radial artery blood pressure waveforms recorded at baseline, study months 4, 8, and 12, and then annually. Small arterial elasticity (SAE) and large arterial elasticity (LAE) were derived from analysis of the diastolic pulse waveform. Analyses were by intention-to-treat principles.
AIDs or AIDs Related Death full follow-up, 9.3 years participant count
Transmission Risk Behavior Outcome 1 12 months Proportion of participants identifying as men who have sex with men (MSM) engaging in condomless sex with HIV serodifferent partners (CLS-D) at study month 12. Participant completed a self-reported questionnaire on transmission risk behavior during the "past two months" at the month 12 visit following randomization.
Changes in Bone Mineral Density (in a Subset of Participants) Measure 2 4.5 years Mean percent change from baseline in bone mineral density at the spine. In the bone mineral density (BMD) substudy of START, participants underwent dual-enery x-ray absorptionmetry (DXA) to measure BMD at the spine and hip at baseline and annually. Analyses were by intention-to-treat principles.
Change in Neurocognitive Function (in a Subset of Participants) 4.5 years Mean change from baseline of the QNPZ-8 score. In the Neurology substudy of START, participants were administered a neuropsychological test battery of 8 tests (grooved peg board, finger tapping, Color Trails 1 and 2, Semantic Verbal Fluency, WAIS III Digit Symbol, HVLT-R Learning, HVLT-R Delayed Recall). Test scores were standardized to z-scores using baseline values as reference such that baseline values had a mean of 0 and standard deviation of 1. Test scores were standardized to z-scores using baseline values as reference such that baseline values had a mean of 0 and standard deviation of 1. Z-scores \> 0 indicate improvement over baseline levels. The quantitative neuropsychological performance z-score (QNPZ-8) was the mean of the z-scores across the the 8 tests. Analyses were by intention-to-treat principles.
Transmission Risk Behavior Outcome 2 12 month visit Percentage of participants identifying as hetrosexual engaging in condomless sex with HIV serodifferent partners (CLS-D) at study month 12. Participant completed a self-reported questionnaire on transmission risk behavior during the "past two months" at the month 12 visit following randomization.
Small Artery Elasticity (in a Subset of Participants) 4.5 years Mean change from baseline in small arterial elasticity. In the Arterial Elasticity substudy of START, participants had non-invasive measurements of radial artery blood pressure waveforms recorded at baseline, study months 4, 8, and 12, and then annually. Small arterial elasticity (SAE) and large arterial elasticity (LAE) were derived from analysis of the diastolic pulse waveform. Analyses were by intention-to-treat principles.
Rate of Lung Function Decline (in a Subset of Participants) Among 4.5 years Rate of lung function decline (slope of forced expiratory volume (FEV1)) over follow-up among self-reported smokers at study entry. In the pulmonary substudy of START, participants had post-bronchodilator spirometry measures collected at baseline and annually. Analyses were by intention-to-treat principles.
Rate of Lung Function Decline (in a Subset of Participants) Among Non-smokers 4.5 years Rate of lung function decline (slope of forced expiratory volume (FEV1)) over follow-up among self-reported non-smokers at study entry. In the pulmonary substudy of START, participants had post-bronchodilator spirometry measures collected at baseline and annually. Analyses were by intention-to-treat principles.
Specific Non-AIDS Diagnoses full follow-up, 9.3 years
Related Research Topics
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Trial Locations
- Locations (218)
University of Southern California
🇺🇸Alhambra, California, United States
VA Greater Los Angeles Healthcare System
🇺🇸Los Angeles, California, United States
UCLA CARE-4-Families (LABAC CRS)
🇺🇸Los Angeles, California, United States
UCSD Mother-Child-Adolescent Program
🇺🇸San Diego, California, United States
Naval Medical Center San Diego
🇺🇸San Diego, California, United States
Denver Public Health
🇺🇸Denver, Colorado, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Georgetown University
🇺🇸Washington, District of Columbia, United States
George Washington Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
Washington DC VA Medical Center
🇺🇸Washington, District of Columbia, United States
Scroll for more (208 remaining)University of Southern California🇺🇸Alhambra, California, United States