Closing the knowledge-implementation gap in HIV treatment
Christian Ramers writes on the disparity between research advances in HIV treatment and what treatment is actually available.
In a recent keynote speech at the 48th annual meeting of the Infectious Diseases Society of America, Dr. Kevin DeCock, HIV/AIDS director at WHO noted, “paradoxically, [anti-retroviral] drugs are most available where the diseases are the least prevalent.” Referring to the stark differences in the variety and availability of highly active anti-retroviral therapy (HAART) in the developed and the developing world, DeCock alluded to the great paradox of the AIDS epidemic, that despite amassing substantial knowledge in treatment and care, it has yet to be thoroughly implemented in the populations which need it the most.
At this meeting in Washington DC, nearly 15,000 gathered to review the latest advances in Infectious Diseases and HIV medicine. To my young mind the conference was exhilarating and the mood was buoyant. Undoubtedly, there have been remarkable advances in Infectious Diseases and HIV. Researchers developed 7 new anti-retroviral agents, several from entirely novel classes. (1) These new additions bring our available armamentarium to unprecedented complexity, effectiveness, and tolerability. Never before has such a wealth of knowledge helped us improve the lives of HIV-infected patients.
As a North American HIV clinician, my initial reaction to these therapeutic advances was euphoric. I imagined how my predecessors felt in the mid-1990’s with the advent of protease inhibitors. Life expectancy projections in the HAART era are now approaching that of the general population, (2) and as we move to the ‘extended-HAART era’ this gap will surely shrink further. But my daydreaming ended abruptly with a simple, pointed question.
“In reality, will we ever have access to these new medicines?” whispered a colleague from over my shoulder. Startled, I asked her to repeat the question, but as I did a harsh reality set in that would temper my enthusiasm for the rest of the conference. The words of Dr. DeCock were immediately with me again. My colleague was a developing world physician, working within the budget of a financially deprived Ministry of Health that relied on wealthy donors for anti-retroviral drugs. Firmly bound within the ‘public health strategy’ of HIV care, her choices were limited to two or three anti-retroviral regimens at most. Despite a large increase in HIV programs, she still could provide only very basic HAART to a fraction of those who required it to stave off an AIDS-related death. It would be decades before these newer anti-retroviral drugs would be available to her patients. She had been prescribing HAART for several years-and quite skillfully given her limited resources-but the HAART she was using was merely a sliver of the HAART available to me.
Through a new perspective in my current role as a student of Global Health, the remainder of my conference experience was coloured by that heightened awareness of disparity all too common in any serious study of the health of nations. The following are a few more examples pertaining to HIV:
- The 2008 International AIDS Society-USA guidelines eliminated older nucleoside reverse transcriptase inhibitors ddI and d4T due to ‘unacceptable toxicities’, yet in developing countries these drugs still serve as first line and widely used agents (3)
- In the US, fewer than 200 infants are perinatally infected due to the provision of HAART to pregnant women, yet only one third of the hundreds of thousands of pregnant African women who are known to be HIV positive, actually receive ART to prevent transmission of HIV to their infants.
- Starting HAART at CD4 counts over 350 may result in a 71% mortality benefit; yet WHO and many high-burden country guidelines still recommend withholding treatment until CD4 nears 200 for most patients (4)
JW Lee, former director general of WHO, coined the term ‘know-do gap’ for the distance between proven effective interventions and their implementation. The above are vivid examples of this ‘knowledge-implementation gap’; while our vast knowledge of HIV therapy marches on to the metronome of scientific discovery, implementation of simple, proven, effective therapies-just getting basic generic HAART drugs to those in need-lags behind, especially in the developing world.
I wish not to trivialize the extraordinary efforts of the global community thus far in response to the HIV epidemic. Surely, the 3 million people now receiving HAART have benefited greatly from our actions to date. But we must not rest while HAART is still not available to most of those who need it. In their most recent report, UNAIDS estimates that despite massive roll-out campaigns, we still are only treating roughly 31% of eligible Africans. (5) If we have decided that it is morally unacceptable to allow our fellow humans to die of treatable diseases, let us not cease our efforts until we close the knowledge-implementation gap.
We know what to do…now it’s time to do it.
Christian B. Ramers, MD, MPH candidate at the Department of Global Health, University of Washington, Seattle, WA, USA
ramers@u.washington.edu
References
1. Hughes A, Barber T, Nelson M. New treatment options for HIV salvage patients: an overview of second generation PIs, NNRTIs, integrase inhibitors and CCR5 antagonists. J Infect. 2008 Jul;57(1):1-10.
2. Lohse N, Hansen A, Pedersen G, Kronborg G, Gerstoft J, Sørensen H, et al. Survival of persons with and without HIV infection in Denmark, 1995-2005. Ann Intern Med. 2007 Jan;146(2):87-95.
3. Hammer S, Eron JJ, Reiss P, Schooley R, Thompson M, Walmsley S, et al. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA. 2008 Aug;300(5):555-70.
4. Kitahata M, Gange S, Moore R. Initiating rather than deferring HAART at a CD4+ count between 351-500 cells/mm3 is associated with improved survival. 48th Annual International Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Washington, DC2008.
5. UNAIDS. 2008 Report on the Global AIDS Epidemic. Geneva, Switzerland 2008.