This spring, San Francisco became the first U.S. city to adopt a policy of offering antiretroviral treatment to everyone who tests HIV positive, regardless of CD4 cell count. The policy was developed by clinicians with the Positive Health Program at San Francisco General Hospital (SFGH) and also applies to other facilities run by the San Francisco Department of Public Health (SFDPH). But the ultimate decision about starting ART remains with individual patients and their physicians, said outgoing SFDPH director Mitch Katz, who emphasized, "we don't dictate medical practice by policy."
The policy change is supported by a growing body of evidence indicating that early antiretroviral treatment can help prevent a variety of non-AIDS complications -- including cardiovascular disease, neurocognitive impairment and the appearance of faster aging -- that occur before CD4 cell counts fall into the danger zone for opportunistic infections. (See "When to Start Treatment: A Changing Equation," BETA, Summer 2008, and "Inflammation, Immune Activation and HIV," BETA, Winter/Spring 2010.)
"We should perhaps think of AIDS as acquired inflammatory disease syndrome," said SFGH researcher Steven Deeks. "The old paradigm was that drugs are toxic so we should wait as long as possible. The new paradigm is that while today's drugs are not totally benign, they are less toxic than the virus."
DHHS treatment guidelines adopted in December 2009 recommend starting ART within the 350-500 cells/mm3 range, with 55% of the expert panel considering this a strong recommendation and 45% considering it moderate; above 500 cells/mm3, the panel was evenly divided, with half favoring treatment initiation and half deeming it optional.
While Katz and the SFGH doctors emphasized that the motivation behind the new policy is benefits for individual patients, another possible advantage of early treatment is reduced HIV incidence. ART can lower viral load to an undetectable level, which dramatically decreases the risk of passing on the virus.
Mathematical models have suggested that universal testing and early treatment could potentially halt the epidemic. Real-life studies have begun to provide evidence that expanded testing and treatment lowers "community viral load" and the number of new infections. At AIDS 2010 and in the August 14, 2010, issue of The Lancet, for example, Julio Montaner's team at the British Columbia Centre for Excellence in HIV/AIDS reported that increased treatment of injection drug users was associated with a recent drop in HIV incidence in British Columbia.
But this raises concerns about a potential conflict between individual and public health benefits. "Test-and-treat" skeptics fear that people could face mandatory testing and be pressured to start treatment -- with its attendant cost, inconvenience, unknown long-term toxicities and risk of drug resistance -- before they need it for their own health.
"It is unethical and irresponsible to coerce or encourage people who are not recommended for treatment under the guidelines to start therapy without fully informing them of the risks," wrote POZ magazine founder Sean Strub.
The San Francisco-based HIV/AIDS advocacy group Project Inform has endorsed a "testing and linkage to care plus" (TLC+) strategy, encouraging people to learn their status and enter care to address all their health and psychosocial needs, only then considering the benefits and drawbacks of ART.
The New York-based Treatment Action Group, in contrast, has declined to take a position on early ART, preferring to wait for data from controlled studies such as the START trial (see "Open Clinical Trials," in this issue). In this trial, HIV positive people with a CD4 count above 500 cells/mm3 will be randomly assigned to either initiate ART immediately or when their CD4 count falls to that level.
As reported at AIDS 2010 (abstract THLBB201), an analysis of more than 9,000 HIV positive people in the multinational CASCADE cohort found that participants who started ART with a CD4 count in the 350-500 cells/mm3 range had a significantly lower likelihood of progression to AIDS or death than people who deferred treatment. But starting treatment above 500 cells/mm3 did not reduce the risk any further.
While START looks for individual benefits of early therapy, NIAID has launched pilot programs in the Bronx and Washington, D.C., to see if a test-and-treat approach can reduce HIV rates on a community-wide basis.
On a global scale, UNAIDS included "treatment as prevention" as part of its Treatment 2.0 strategy, announced this summer in Vienna. This approach could potentially prevent up to one million new HIV infections per year if ART is made available to all who need it based on the latest WHO guidelines, tripling coverage from the current 5 million to 15 million people, the agency estimated.
Liz Highleyman (email@example.com) is a freelance medical writer based in San Francisco.