Strategic Timing of Antiretroviral Treatment (START)

• Composite endpoint of AIDS, serious non-AIDS diagnoses, and all-cause mortality [ Time Frame: 4.5 years ] [ Designated as safety issue: Yes ]
  

• Components of the composite primary outcome measure [ Time Frame: 4.5 years ] [ Designated as safety issue: Yes ]
  
• Specific non-AIDS diagnoses [ Time Frame: 4.5 years ] [ Designated as safety issue: Yes ]
  
• Adverse events [ Time Frame: 4.5 years ] [ Designated as safety issue: Yes ]
  
• Hospitalization, health-care utilization, quality of life [ Time Frame: 4.5 years ] [ Designated as safety issue: No ]
  
• HIV drug resistance and transmission risk behavior [ Time Frame: 4.5 years ] [ Designated as safety issue: Yes ]
  
• Change in neurocognitive function (in a subset of participants) [ Time Frame: 4.5 years ] [ Designated as safety issue: No ]
  
• Obtain a whole blood sample from which DNA will be extracted to study validated genetic variants that determine the risk of the various primary and secondary outcomes assessed in START (in a subset of participants) [ Time Frame: Blood taken at study entry and stored in a central repository indefinitely ] [ Designated as safety issue: No ]
  
• Evaluate understanding of study information and satisfaction with the consent process among START participants, after receiving information from either a standard or a concise consent form (at a subset of sites) [ Time Frame: Before randomization into START ] [ Designated as safety issue: No ]
  
• Large and small artery elasticity (in a subset of participants) [ Time Frame: 4.5 years ] [ Designated as safety issue: No ]
  
• Rate of lung function decline (in a subset of participants) [ Time Frame: 4.5 years ] [ Designated as safety issue: No ]
  
• Changes in bone mineral density (in a subset of participants) [ Time Frame: 4.5 years ] [ Designated as safety issue: No ]
  

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.