Are We Standing in Our Own Way on the Path to a Cure for HIV/AIDS
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PROFILE Are we standing in our own way on the path to a cure for HIV/AIDS lthough there are many reasons to celebrate the life-extending benefits from antiretroviral Atherapeutics (ART) for HIV/AIDS and the ability to chronically manage patients’ disease for decades, the majority of people around the world living with the virus do not have access to ART and those that do, have over decades developed life-threatening side effects. Our inability to identify a cure to HIV lies not only in the as-of- yet failure of the medical research community to identify and develop appropriate means of ridding the body of the virus but also government and industrial policies that promote public opinion exclusively focused on chronic management scenarios instead of broadly exploring innovation for cure. “An inconvenient truth” (Davis Guggenheim) mates of the magnitude of the global forced government policy for early epidemic. As the majority of Ameri - and expanded access to experimental There are approximately 37 million cans are not rountinely tested for HIV, drugs, the medical community and people living with HIV and 39 million the virus can go years without being society are struggling with the fact have died of AIDS-related diseases diagnosed in an HIV positive person. that we are barely managing the HIV since the start of the epidemic in 1981. With these statistics it is no wonder epidemic and AIDS crisis. For years we As of March 2015, only 15 million that every day an estimated 5,600 have been locked into thinking of people have access to treatments for people globally become newly infected solutions in terms of a chronic disease HIV. It is estimated that one fifth of with the virus. Importantly, the statis - with life-long treatment. The past 30 people infected with HIV in the USA tics we are analysing are biased for years in which anti retroviral drugs have not been diagnosed and only populations who can or are willing to (ARV) have been identified and treat - half the patients with access to ART in access HIV testing/treatment programs ment modalities have been refined the USA take prescribed medication. and where government policies or are remarkable in their success in pro - Durable suppression of HIV is only cultural beliefs allow the health status longing the lives of people infected achieved in 25% of the patients who of individuals to be revealed. with HIV. These years also have the are linked to medical care and inconvenient truth that they reflect receiving ART. The etiologies for these Despite the research on HIV and AIDS with one exception, the Berlin patient, statistics are hotly debated but as from academic institutions, industry failure to discover a cure or achieve concerning as these numbers are, and advocacy groups and dedicated sustained viral suppression without they are likely to be gross underesti - efforts of AIDS treatment activists that ever changing drug regimens. 32 PROFILE Cocktails, cascades and a industry that adjudicates and ranks conundrum research proposals submitted to gov - At this time, decision makers speak of ernment and private foundations. A an ‘HIV Care Continuum’, underwritten majority of those who served in peer as policy by a United States Federal review have been in lockstep with the initiative and supported by the Center dogma that a cure was not possible for Disease Control (CDC) and the and they put the ‘thumbs down’ on National Institutes of Health (NIH). priority scores that determine grant This four-part recommendation funding for hypotheses for the eradi - includes comprehensive HIV testing cation of HIV. Simply put, if one could and diagnosis, linking and maintaining not state a hypothesis for a cure, then all HIV positive individuals to a health - specific research objectives could not Dr. Harold Charles Smith care provider, providing all HIV be articulated in a funding proposal positive patients with life-long access for testing opportunities to cure HIV. to ART and ensuring that for each to advocating that ‘everyone be given Eventually word got out and such patient, viral loads remain suppressed. ART immediately after diagnosis’. The ideas no longer were submitted for The impracticality of this manage - recommendations go further to consideration or they were couched ment model as a solution to the global include pre-exposure prophylactic as being for therapy. In that way, KOL’s AIDS pandemic can be appreciated in ART treatment (PrEP) for HIV negative and rank and file scientists them - both social and economic considera - individuals who are at high risk of selves influenced capitalisation and tions. In fact, while the ink is still wet infection. We now are faced with the development of new concepts. I on the HIV Care Continuum initiative, conundrum of an expanded and hasten to add that in this era gone by, we already know that its goals are not global epidemic with a need to supply had academic scientists inadvertently broadly achievable due to significant ART and access to medical care for found a cure to HIV, it is unlikely that attrition from care and treatment decades on a planetary scale. Given they would have suppressed findings dubbed as the ‘care cascade’. the improbability of this course of simply based on government or foun - action, discovering a cure to HIV/AIDS dation funding priorities. But cure has Two potential limitations of the new has to become an overriding priority. the potential of being a disruptive policy are the magnitude of chemical technology for the pharmaceutical production that will be necessary to A challenge to the industry and Wall Street. So it is not meet the global demand for ARV (i.e. imagination for those who clear how industries would manage how do we produce this quantity of could make a difference the impact of a cure on sales of life- chemistry, for that many people, for Key opinion leaders (KOLs) have in long ART that have held reliable billion all years that their disease will need to recent years said that they now “dare dollar profits from the sales of so-called be managed) and an inadequate to imagine” a cure yet others say we ‘block buster’ drugs. mechanism in place that can ensure cannot go there because ‘there be long term compliance (i.e. uninter - dragons’ in charting a course to cure, “A rose by any other name rupted access to healthcare and ART i.e. a cure is not possible. The HIV would smell as sweet” to a diverse global community with community is encouraged by talk (William Shakespeare) disparate education, infrastructure, about HIV eradication but are con - cultural and religious beliefs). The fused over the course that is being Many members of the drug discovery limitations of this model will be exac - prescribed. The negative outlook and drug development communities erbated by the recent announcement toward curing HIV/AIDS actually has remain astonished by the about-face from the World Health Organization held back adequate funding for cure that is now referred to as ‘cure (WHO) that they have reversed research by actively discouraging it for research’. The past structure leaves their policy from one of ‘don’t treat many years as ‘intellectually unsound’. many scientists uncomfortable with with ART until individuals become There is a peer review system com - the direction for and implementation significantly immune-compromised’ prised of experts from academia and of this change in emphasis. The many 33 PROFILE years of the chronic therapeutic man - before the recent glasnost on cure FDA-approved ARVs can have serious agement mindset has left the map for research. A vaccine strategy that is side effects that will almost certainly ideation with many information voids. capable of neutralising one or multiple manifest in chronically treated patients. The years required for exploration strains of HIV and does so for have been squandered. Confusion is extended periods of time has not For decades the efficacy of a new drug a typical symptom of deep shock that been achieved. Clearly there is prece - candidate has been assessed pre-clin - may explain why eradication research dent in other diseases that justifies ically by the ability of HIV to evolve has become mired in a debate over continued pursuit of a broadly drug resistance to it in the laboratory. what the word ‘cure’ means? Recent neutralising vaccine strategy. These This policy is based on the premise media blitzes have tragically rushed to endeavors have yielded a fascinating that if a drug is interacting with an be first to proclaim (define) a cure that understanding of the acquired important viral target, the virus will turned out not to be. Trying to define immune system relative to HIV that figure out a way to become drug- cure as what can or cannot be achieved may yet triangulate investigators resistant. Said in a different way, all has been distracting. We certainly will toward a curative vaccine strategy. ARVs that have been brought to know a cure when we find the overt market are already known to select evidence in someone like the Berlin “There are approximately 37 for minority subspecies of HIV and patient. million people living with therefore they have anticipated ‘use HIV and 39 million have died until dates’ (i.e. not curative). The We have to accept and stop arguing of AIDS-related diseases since industry and venture capital firms about whether a cure can only be the start of the epidemic in demand this proof and failure to ‘functional’ (no replicating virus 1981. As of March 2015, only establish it evokes silence in the room. detectable but genetic analysis will 15 million people have demonstrate the presence of HIV access to treatments for These policies certainly will become genomes) or what most would under - HIV know as antiretroviral fodder for future debates on how to stand to be an absolute cure (the therapy (ART).” eradicate HIV.