Top HIV/AIDS-Related Clinical Developments of 2010
December 8, 2010
A review of:
Cohen MS. HIV treatment as prevention: to be or not to be? [abstract]. J Acquir Immune Defic Syndr [serial online]. October 1, 2010;55(2):137-138. Available at: http://journals.lww.com/jaids/Citation/2010/10010/HIV_Treatment_as_Prevention__To_be_or_not_to_be_.1.aspx.
The "seek, test and treat" (TnT) model aims to reduce the spread of HIV by identifying those who are unaware they are HIV infected and offering them HIV treatment to reduce their infectiousness. The approach received considerable attention last year, and continues to go strong as 2010 comes to a close. Although it is a theoretical approach rather than a proven method to reduce new infections, TnT is nonetheless already accepted by some as tried-and-true. True, it may be. Tried? Not really.
Only now are efforts to implement TnT strategies underway and the immediate impact being examined. Pilot projects in Washington, D.C., and the Bronx in New York City have been put in place to increase HIV testing of the populace. Regarding the former, a presentation at the 17th Conference on Retroviruses and Opportunistic Infections in February 2010 reported a dramatic increase -- numbering in the tens of thousands -- in the number of Washingtonians tested, as well as a 17% jump in HIV diagnoses from 2006 to 2009. Importantly, CD4+ cell counts of those found to be HIV infected also rose to more than 300 cells/mm3, demonstrating the ability of expanded HIV screening to find people earlier in the course of their disease.
However, determining whether early testing and more aggressive treatment of HIV lead to fewer infections is a difficult thing to measure. It is notoriously challenging to capture true HIV incidence data; studies that look at new diagnoses within a given community usually just reflect transmissions that occurred years ago, rather than the leading edge of the epidemic.
While the potential benefits of TnT -- early case finding and the administration of behavioral and medical interventions to reduce infectiousness -- are highly compelling, the absence of a demonstrated impact on HIV transmission and the practical challenges for scale-up of TnT have led to concerns and calls for caution.
In the "concerns" column is the prospect of TnT causing an increase in antiretroviral resistance. Broader application of antiretroviral therapy -- which would include those who may adhere as poorly to HIV therapy as they do to condoms -- can potentially lead to cultivation and then transmission of resistant virus, this argument warns. It's unclear whether this would be offset by a reduction in viral load and less overall transmission. There is also a separate issue of cost, which may not be trivial even if the approach is cost-effective overall.
Caution is urged by others who point to an under-appreciation of the limits of TnT. There is a differential concentration of antiretrovirals into the genital tract, which means there is a potential disconnect between HIV viral load in the blood plasma and HIV viral load in genital secretions. Further, even when antiretrovirals are present in these compartments, HIV may not be reliably suppressed. Therefore, in some people, on some regimens, there may remain sufficient virus in the semen or cervico-vaginal fluid to permit HIV transmission.
As is made clear from reports of transmission of HIV by individuals who are being treated with potent antiretrovirals, HIV therapy does not render all people incapable of passing along their virus. In a real-world application, 84 HIV transmission events were noted among a group of 1,927 couples in China who were followed from 2006 through 2008, and these transmission events were equally distributed among patients who were receiving and those who were not receiving HIV therapy. Problems with adherence to medications, incidence of other sexually transmitted diseases or HIV infection from another partner may explain these infections, but such explanations are a part of life. They may reflect the limits of what TnT can accomplish outside of the clean inputs of computer models.
Lastly, there are some data suggesting that a disproportionate amount of HIV transmission comes from those with acute or early infection. TnT does not reach these newly infected patients, who may well be considered hyper-infectious.
The Bottom Line
The enthusiastic embrace of TnT, fanned by modeling studies that help us to envision a world without AIDS, is understandable. But as the gleam of the idea of TnT begins to pass, it is wise to consider the practical aspects of the strategy. Those of us who believe data and experience support earlier use of antiretrovirals can also push for increased attention to the development of evidence-based and scalable interventions to support medication adherence and deal with factors that threaten suppression of viremia, including substance abuse and mental illness.
A wise man (OK, Dr. Myron Cohen, the guy who signs my paychecks) once said, "We cannot treat our way out of the HIV epidemic." Dr. Cohen is right, but the question is: Can we use HIV therapy, despite its limitations, thoughtfully to prevent thousands of infections? Let's find out.
The results of the 2010 mid-term elections in the U.S. will have an effect on issues you care about, regardless of whether you are red or blue, triumphant or disheartened. The 2011 Congress will likely determine what stays and what goes from the President's health care overhaul, which will have ramifications for health care coverage and clinician reimbursement.
Perhaps even more important is how the elections played at the local level: Many state legislatures and governorships moved to the right, and it is these policy-makers who may have the greatest impact on how clinical care will be delivered to persons living with HIV.
Predicting what will happen in health care policy over the next year is for fools and pundits. Regardless, the elections, like all elections of late, were important. Thus, although I list it last, it is hardly the least important clinical development of the year.
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