Monday, April 2, 2012

Treatment as Prevention: an interview with Dr. Anthony Fauci

In August of 2011, Cohen et al. published an article in the New England Journal of Medicine entitled "Prevention of HIV-1 Infection with Early Antiretroviral Therapy" that changed the way we think about HIV prevention.  This groundbreaking study was later heralded by the American Association for the Advancement of Science as the 'Scientific Breakthrough of the Year'.  I had the opportunity to sit down with Dr. Anthony Fauci, a leading expert in HIV research and advocacy to discuss, among other things, the potential impact of this emerging concept of 'Treatment as Prevention' in HIV care.



When we put a patient on the appropriate anti-TB medication for 6 months the patient is cured of TB and, thus, no longer infects other people with this devastating disease.  There is both a individual and community benefit.  This is true of nearly all communicable diseases.  Treat, cure, and by extension, prevent transmission.  Do this well and you are on your way to eliminate that disease.   

We know that we cannot yet feasible cure HIV/AIDS.  As such, the HIV care community has traditionally had a divided effort in fighting this epidemic: those focused on improving individual patient care through the development of highly efficacious treatment protocols and others focused large-scale campaigns aimed at prevention of transmission.  

When a person is diagnosed with HIV, they are not automatically put on antiretrovirals (ARVs).  The HIV virus has a complex relationship with an individual's immune system; some become dramatically immunocompromised quite rapidly, others can live for many years before the virus begins to have an impact on their ability to fight off infections.  When a person with HIV is placed on ARVs is dependent upon their CD4 cell count.  Traditionally patients are placed on ARVs when their CD4 count falls below 200-250 cells/mm^3.  Why?  There appears to be little benefit in terms of prevention of opportunistic infections to the patient to begin ARVs prior to this threshold.  As such, there is a balance to be struck between the risk of taking these caustic drugs to the benefit of improving health outcomes of these individual patients if placed on drug sooner.  

HIV Monthly Summary Sheets: Busia District Hospital, Kenya
In the 1990s, the greatest advancement of HIV care was that of the prevention of mother-to-child transmission of HIV (PMTCT).  That is, putting HIV+ pregnant women on a particular regime of ARVs prevents the transmission of the virus to the fetus.  ARVs dramatically reduce the circulating viral load, thus virtually eliminating the chance that developing fetus will become infected trans-placentally.  Make sense.  

This recent study takes the concept of PMTCT and applies it to heterosexual transmission, the most common route of infection world-wide.  It asks the question: if we lower the threshold of when we start a patient on ARVs, thereby reducing the viral load, will this prevent the transmission of the viral to a non-infected partner?  The answer to this question, as this $72 million dollar study reveals, is unequivocally 'yes.'  
Treat HIV earlier, prevent HIV transmission.
In fact, early initiation of ARVs reduced the risk of transmission by an astonishing 96%.  This study compared transmission rates in sero-discordant couples (one person with HIV, the other without) that were put in two groups: the 'delayed treatment group' who received the current standard of care which was to receive ARVs when their CD4 count was between 200-250, and the 'early treatment group' who received ARVs when their CD4 count was between 350-500. 
In case of fire!  Chulaimbo Sub-District Hospital, Kenya
~~~

A few months ago I was having lunch with Dr Joe Mamlin, the Field Director of AMPATH, who has worked in HIV care for many decades all around the world.  A good, hearty Kenyan lunch invariably consists of sukuma wiki (kale) and ugali.  Ugali and sukuma wiki are a must.  When runners travel abroad to race, their suitcases are filled with a few sacks of ugali flour; journalist covering the ICC trials at The Hague complain eloquently at astonishing absence of ugali there.  When I sat down with Joe I jokingly said, 'I wonder if its more difficult to change people's eating habits or sexual habits?'  Joe looked up at me and replied, "That's not what we are tying to do!  The best we can do is to take the bullets out of the AK-47."


Prevention of HIV has been stymied over the past few decades primarily because at their core, these initiatives rely on behavior change.  The "Treatment as Prevention" study provides a new alternative that was not a part of the prevention armamentarium: a way to take the bullets out of the AK-47.
HIV Care center, Jagat, Manang District, Nepal
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This study is very hard not to pay attention to.  Although it doesn't bring us any closer to curing HIV, we can treat HIV as though we could, in terms of community transmission.  In the same way that we treat TB immediately to prevent infection (and subsequently cure it), we can treat HIV early to prevent transmission.  
No longer is the ability to cure linked with the ability to prevent.
What I find intriguing about this study is how is merges, for the first time, the treatment of HIV with the prevention of HIV.  What impact will this have on how the HIV care community approaches prevention strategies?    

The importance of this study is undeniable.  Its findings will prevent the transmission of HIV all around the world.  The basic structure of this intervention finds elegance in simplicity.  Give drugs sooner.  But I wonder if it is too simple.  This promising study will no doubt guide the research priorities of the the HIV community for the coming years and serve as the foundation for USAID/PEPFAR-led initiatives for years to come, and rightly so, given the current structure of American involvement in international health.  
It is my hope that this simple intervention will not overshadow more comprehensive initiaties aimed at solving this very complex problem.  
Although important in our fight against HIV/AIDS, this 'top-down' approach will not address the core structural issues that perpetuate HIV/AIDS in communities around the world and limit access to basic health care services.

I had the opportunity to interview Dr. Fauci while working on a larger project exploring the shift in global health initiatives from traditional 'vertical' initiaties that focus on single diseases, to 'horizontal' approaches that emphasis primary care, service integration, and infrastructure development.  I am interested in primary care in global health because I view it as the first step towards empowering emerging health systems to become sustainable.  To achieve this, I believe that primary care needs to figure more strongly into the research priorities of institutions such as the National Institutes of Health.  Research drives policy.


Although we are experiencing what I believe is some very positive momentum towards integrating services and taking advantage of the healthcare infrastructure that disease-specific programming has developed, we still have a long way to go.  


Clinical research is currently the most powerful driving force in global health in the US: this study is the most powerful expression of what we are able to find out and then later implement with our current approach to 'global health.'

Importantly, one thing this study does not show, is how early treatment of HIV would compare to the transmission rates in a developing country that has benefited from decades of foreign aid and research focused supporting & improving the foundational pillars of a modern health system: primary care and public health services.  


Findings from such a study would likely be the scientific breakthrough of the decade. 

Neighbor kids: Alan and his buddies, Eldoret, Kenya






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