All posts by PanAware

Absorb This!

New data shows high benefit from HIV-related diarrhea treatment
By Gary Blick, MD, and Jeannie Wraight

HIV-related diarrhea is a damaging condition that can greatly affect quality of life, as well as increase the risk of mortality in people living with HIV and AIDS (PLHWA), both receiving antiretroviral therapy (ART) and those not on ART. New data, released at the IAS 2017 conference, shows an FDA-approved medication for HIV-related diarrhea is more effective than previously believed.

In the early HAART days prior to 2005, as many as sixty percent of PLWHA in the developed world experienced diarrhea. Currently, in the developing world, it is estimated that close to 100 percent of PLWHA have experienced chronic diarrhea either from infectious or noninfectious causes.

Although AIDS-related diarrhea has decreased significantly with the global use of ART, the incidence of noninfectious diarrhea (NID) has increased. HIV enteropathy—or gastrointestinal damage related to HIV infection—as well as the use of ART are the main causes of NID in PLWHA. Over 750,000 newborns, infants and children die annually from potentially treatable HIV-associated infectious diarrhea.

New data from the ADVENT study, which analyzed Mytesi (formally known as crofelemer), shows a potential treatment that can significantly decrease incidents of noninfectious HIV-related diarrhea. Mytesi is an anti-secretory agent that is the only FDA-approved therapy in the U.S. for treatment of noninfectious diarrhea in PLWHA on ART. It is also currently available on formulary in Zimbabwe. Although the source of crofelemer, which is extracted and purified from a tree in the Amazon rainforest, is a timely and expensive process, its manufacture is currently working on processes that could make Mytesi more cost-effective for African countries where, many can argue, it is needed most.

Researchers for the ADVENT study evaluated Mytesi or placebo in 272 PLWHA for a four-week period, after which, all of the participants were offered the opportunity to take Mytesi for an additional twenty weeks. This study, which ultimately led to the FDA-approval of crofelemer, showed that significantly more PLWHA who received Mytesi achieved a clinical response verses those on placebo. Clinical response was defined as a reduction in watery stools from an average of twenty per week at study entry, to less than two watery stools per week during the four-week placebo-controlled phase.

However, the original analysis of the ADVENT study only included results from the four-week placebo controlled study and not the entire twenty to twenty-four weeks that participants took crofelemer. Since the results do not characterize the reduction in diarrhea among all of the participants in the study over the entire duration of the study, and as there is a substantial benefit from a fifty percent or greater reduction in watery stools, a supplemental analysis was performed to review the long-term efficacy of crofelemer. This analysis was presented at the 9th IAS Conference on HIV Science in Paris.

In this analysis of ADVENT, researchers reviewed the entirety of data in study participants. The endpoints analyzed included:

• average change in watery stools over four to twenty-four weeks in crofelemer-treated patients

• proportion of study participants with greater than a fifty percent, seventy-five percent, and 100 percent reduction in the number of watery stools

Participants in the study had NID for at least one month while taking a stable ART regimen and had CD4 cell counts over 100. Almost eighty percent had evaluable stool diary data and completed the placebo-free extension phase.

Of the participants, the average age was forty-five years, sixteen percent were female, and sixty percent were non-Caucasian (thirty-eight percent Blacks/African-Americans, twenty percent Hispanics/Latinos). On average, participants had had diarrhea for six years and reported an average of twenty watery stools per week. Additionally, fifty-nine percent had used at least one antidiarrheal medication.

The proportion of people with ≥50%, ≥75%, and 100% reduction in number of watery stools was forty-eight, thirty-five, and fifteen percent by week 4; seventy-two, sixty, and forty-one percent by week 12; and seventy-three, sixty-three, and fifty percent by week 20, respectively.

The proportion of people achieving clinically relevant reductions in watery stools at any time point was not significantly different whether analyzed by concomitant protease inhibitor use (sixty-six percent were taking protease inhibitors) or by diarrhea etiology (seventy-five percent attributed diarrhea to ART while twenty-five percent to HIV infection and/or other causes).

None of the participants on the study reported serious adverse events attributed to crofelemer. Mytesi has no clinically relevant drug-drug interactions, and does not affect CD4 counts or viral load.

In the supplemental analysis, the researchers concluded that Mytesi was associated with clinically relevant and sustained reductions in NID that were not apparent from the ADVENT trial primary responder analysis.

Mytesi represents a therapy which is direly needed throughout both the industrial world and developing nations to reduce HIV-related noninfectious diarrhea. A reduction in incidences of diarrhea has been found to have an important impact on a person’s quality of life, their physical health and the absorption of ARVs. With HIV ARVs, as well as HIV itself, known to cause diarrhea in a large number of PLWHA, Mytesi should be considered an obvious adjunct therapy for those prescribed ARVs throughout the world.

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Questioning the Cure

By Jeannie Wraight and Noreen Griffin

When first discussing the potential of writing a monthly column on HIV cure, my editor here at A&U Magazine asked a very valid question. He wanted to know if I thought I would be able to find enough material for a monthly column. At that time, nearly five years ago, information on cure-related issues was somewhat scarce. This was the main reason I wanted to write Destination: Cure—to be able to gather and report the bits of scattered news, research, and breakthroughs on what was becoming an emerging field of research.

Over the years I’ve had little trouble finding cure-related topics to focus on. In addition to scientific research, there were and still are many political, ethical, social, funding and policy issues that encompass “HIV cure.” Since beginning this column in 2013, I’ve attempted to focus on these issues as they continue to evolve.

A lot has changed since my first column. We’ve come a long way, particularly in HIV reservoir research, scientific collaboration, and heightened funding. However, we still have a vast road ahead of us with many unanswered questions and dilemmas.

For example, how do we know when we’ve found a cure or remission? Several researchers are working on biomarkers that can measure trace amounts of HIV in certain cells and reservoirs. Until these biomarkers are available, it would be difficult to declare a person cured or know if a therapy or cure strategy is successful.

Debate continues about how long a person must remain off ARVs until they are considered in remission. HIV remission is different from an eradication cure, where HIV is completely removed from the body. HIV remission is currently defined similarly to cancer remission in terms of a person being able to remain illness-free without the use of ongoing treatment. Some researchers suggest borrowing the timeframe instituted in cancer patients to define when HIV remission has been achieved. This is normally five years.

Perhaps one of the most important questions that continues to be asked by some is: Do we really still need a cure and is it ethical to continue to search for one? For many this is a no-brainer. However, there are those that argue about the necessity and fairness of spending money on an HIV cure. Some claim that since the approval of over thirty HIV antiretroviral medications have succeeded in turning HIV/AIDS from a deadly disease to a “manageable chronic illness,” that it’s time for HIV to take a backseat to other life- threatening illnesses.

There are over 7,000 “rare diseases” affecting people in the United States. According to a fact sheet from The National Organization for Rare Disorders (NORD), “There are more Americans who live with a rare disease than ALL of those who have either HIV, Heart Disease or Stroke.” Only five percent of rare diseases have FDA-approved treatments. It’s likely that a tiny fraction of the HIV research budget, since the discovery of HIV, could have either cured or found treatments for a number of these diseases.

This argument may be strengthened as U=U and PrEP allow HIV to become untransmittable and easier to protect against, respectively, particularly as ARVs become more available to a greater number of people in the developing world.

So then, is it fair or necessary that such a large amount of resources, including those from government, commercial, foundation and private sector finances, continue to be used for HIV cure and remission efforts?

On an ethical level, few of us are qualified to answer that. However, on a financial level, and in terms of human lives lost, the answer is unequivocally yes.

Despite a massive decrease of forty-eight percent in AIDS-related deaths since the global scale-up of ARVs, there were still 1.1 million deaths from HIV/AIDS-related causes in 2015. Despite over thirty years of research and many HIV therapies, millions of people will continue to die of AIDS and HIV- related illnesses.

The U.S. government currently invests approximately $26 billion domestically, and $6.6 billion globally, to the fight against HIV/AIDS. The need for funding both in the U.S. and abroad is likely to only grow greater with each year. A cure or remission for HIV is the only means of eventually eliminating this financial burden and freeing up funding for other diseases.

As such, the search must continue and questions regarding scientific, ethical, financial and logistic considerations of cure research will need to be fairly, intelligently and timely asked, confronted and resolved. Many questions remain, but as the puzzle slowly takes shape, we must maintain the momentum so many have come together to create.

 

 

An Unseen Storm

Despite the success of ARV’s, Toxoplasmosis still remains a serious medical concern for people with HIV/AIDS
By Christopher Romano & Timothy Ray Brown

The protozoan intracellular parasite, toxoplasma gondii (toxo), is still one of the most causative agents of disease and death in HIV/AIDS patients even in the post combination antiretroviral therapy era. Estimates indicate that 30 to 50 percent of humans carry the parasite which often causes toxoplasmic encephalitis in immunocompromised populations. Toxoplasmosis remains profoundly under studied and underfunded as evidenced by the fact no one will be talking about this devastating pathogen at this year’s IAS International Conference on HIV Science.

Continue reading An Unseen Storm

Dollars and Sense in the Era of Tooth and Claw

Chad S. Johnson and Chris Romano

The emergence of another fiscal cliff bogyman has been deterred for a few weeks, as the House, allowing a welcome reprieve from countdown clocks and diatribes about the end of western civilization as we know it, prepares for summer recess. We were all thoroughly distracted by the ache and convolutions of our elected officials bemoaning one another’s consistent failure to produce solutions that don’t devalue the gratuity of their corporate benefactors. People living with HIV/AIDS around the country, and around the world – and their family and friends – sat before the late night glare of 24/7 media outlets, wondering if the rational, genuine commitment to saving the essential benefits of millions of people is even a slight priority for the Trump Administration and its congressional allies.

Continue reading Dollars and Sense in the Era of Tooth and Claw

Other Dragons at our Feet

The impact of the economic policies of a crazed administration on “Getting to Zero” and other necromancy at IAS 2017

Chad S. Johnson and Chris Romano

At IAS2016 in Durban, South Africa, we never truly anticipated being witnesses to the specter of an unprecedented economic and political unraveling of progress towards defeating this generation’s signature epidemic. The well-intentioned speeches, proclamations, and community building in Durban, realized on that idyllic Indian Ocean coast, now seem distant and naïve, as U.S. communities like Baltimore, Rochester, and the South Bronx fight against the threatened regressive policies of Washington.  As poverty and AIDS have come to be constant companions, without effective advocacy and scientific breakthroughs, scarcity and disease are settling in for an unwelcome, extended stay.

Continue reading Other Dragons at our Feet