Next year in Jerusalem?

Will AIDS 2018 give us any further strategies towards a cure

Cody Petterson, Ph.D. and Chris Romano

It’s been more than a decade since, in 2007, a German oncologist named Dr. Gero Hütter performed a risky surgical procedure on a willing patient with both HIV and leukaemia that would result in the first and only person to date cured of HIV. In the years since, the details of the procedure have been well documented, publicized, and scrutinized, leaving little doubt that Timothy Ray Brown (formerly known as the “Berlin Patient”) has indeed been cured of HIV (and leukaemia).

Although successful, Timothy Ray Brown’s treatment may provide proof of concept but not a functional way to generalize the cure to a widespread population of people living with HIV. It remains unclear whether Brown’s cure methodology could be replicated at all, given similar circumstances and unlimited funds. To date, it sadly has not.

The procedure is relatively simple to understand. The immune system is destroyed by using chemotherapy and radiation, killing the HIV, and the cancer along with it. Blood cord cells (transplanted bone marrow cells) from a compatible donor are then used to rebuild the immune system. In Brown’s case, these cells were donated by a man with a genetic mutation that confers resistance to HIV, as the mutation of the CCR5 “doorway” that HIV typically uses to enter and infect a cell is physically incompatible with the virus.

This procedure is not without risk; one in every five people who undergo a regular blood cord transplant do not survive. Brown received his HIV cure because his leukaemia was life threatening, necessitating radical intervention. Dr. Hütter struck upon the idea of using stem cells resistant to HIV, as well as matched for blood-type, for the transplant

It is astounding that more than a decade after the successful cure of one person, it has neither been replicated nor inspired a precise medical breakthrough for curing other people infected, if not hundreds, thousands, or millions. Brown continues to live as the only person granted a new and hopeful future. He has become iconic as a symbol of hope in this pandemic.

With thousands of clinicians, scientists, researchers, doctors, bureaucrats, and activists working hard to advance an HIV cure strategy, will AIDS 2018 go down in history as a turning point in the struggle for the cure? We can only hope. Timothy Ray Brown often speaks of feeling lonely as the singular cured person; many would love to stand with him – and give him company.

 

Advertisements

This House of Ash and Sand

At the first International AIDS Society Conference since Durban, the AIDS crisis in Venezuela went without notice

By Chris Romano and Cody Petterson

Editors note: This article was originally posted in August of 2017 but due to site issues was mistakenly deleted from PanAware. However, in light of AIDS 2018 which begins tomorrow (July23) we’ve decided to repost it in order to bring attention to this important issue.

At IAS 2017 in Paris last July, delivering treatment, medicines, and other HIV-related services to the most vulnerable patient populations in resource-poor, distressed, and unstable nations should have been a matter of urgency. But there were no declarations, no condemnations, and no calls for immediate action.

More than a decade ago, Venezuela was lauded for its treatment program. Now, more than a decade into its political and economic crisis, Venezuela’s oil revenues account for 95% of the country’s export earnings and the precipitous decline in oil prices has helped plunge Venezuela ever deeper into crisis. The corrupt and increasingly dictatorial regime of President Nicolás Maduro Moros, has only accelerated the country’s decline.

Venezuela’s economic crisis is a tragic example of impact of domestic instability on the testing, treatment, and care of people living with HIV and on the worsening global HIV pandemic. Venezuela’s entire healthcare system is critically short of medication, including life-saving anti-HIV drugs.  Despite pleas for immediate assistance from the Global Fund to Fight AIDS, Tuberculosis and Malaria, no measurable degree of help has arrived.  The World Bank continues to classify Venezuela as a high-income nation and the Global Fund “is not in a position to grant any exceptions from its rules,” according to its Executive Director Mark Dybul and Norbert Hauser.

An estimated 110,000 people in 2015 were living with HIV in Venezuela, and at least 63,000 of them had started antiretroviral (ARV) treatment, says Feliciano Reyna Ganteaume, whose Caracas-based nonprofit Acción Solidaria supplies HIV-infected people with ARVs. “[The situation] is much worse than one can describe,” he says. “When the government does take action, drug orders are placed late and not paid for on time, causing interruptions that have lasted more than  months… There is not even 1 month without our receiving complaints of lack of one or more ARVs from one or more Venezuelan states,” he says. In addition, reagents for the tests needed to monitor people on treatment are in short supply.

Economic instability has greatly affected basic HIV treatment and care for people living with HIV in Venezuela. Diagnostics such as CD4 and drug resistance testing have become all but non-existent and stocks experience a lack of resupply, lasting a month or two, approximately every two to three months. Basic laboratory services and drugs such as antibiotics have become unavailable. HIV testing for mothers and ARVs to prevent mother to child transmission are in inadequate supply, resulting in late-stage diagnosis and contributing to an increased rate of mother to child transmission. Maria Eugenia Landaeta, the chief of infectious disease at the teaching hospital who oversees the HIV program for 5,600 patients, reports that a small group of AIDS physicians has been scrambling to hold it together for years. “The HIV and TB programs were the last to deteriorate,” she said. “We have tried to defend the program in all possible ways.” (https://www.theglobeandmail.com/news/world/in-venezuela-a-once-leading-aids-program-lies-inruins/article35417359/)

At IAS 2017, while the refugee crisis in Europe was a key issue of reference, with numerous posters and presentations featuring the challenges of internally displaced persons, the Venezuelan crisis went virtually unmentioned, despite the knowledge that tens of thousands were going without life-saving medications. The Venezuelan Society of Infectious Diseases (SIV) issued a statement back in November of 2016 announcing that supplies of key drugs used for the treatment of HIV were dangerously low and in danger of stock-out. These drug shortages mean that there are currently no treatment options considered first-rate under international guidelines. “The shortage of antiretroviral drugs and reagents makes it impossible to control the HIV/AIDS epidemic in the country, making it difficult to control the transmission of the virus from the mother to her children and in the general population,” Maritza Landaeta, a senior member of SIV, said. “We are seeing a collapse in the public health system. Venezuela is witnessing a miracle, a miracle of destruction.”

Vulnerabilities continue to mount for displaced persons, who are increasingly exposed to the social drivers of HIV, Hep C, and co-infections. In addition, instability in countries throughout Africa and South America also contributes to an unsteady state of universal access to HIV testing and treatment which drive the continued spread of HIV.

We have learned the hard way the consequences of complacency in the response to global pandemics. The epidemiological dimensions of Venezuela’s current descent into chaos should concern all researchers, activists, and policy makers in the Americas. HIV and its co-morbidities thrive on poverty, instability, and displacement.   Several presentations at IAS 2017 focused on the impact of specific instabilities and policies on the treatment and care of its citizens, in particular, at-risk populations such as refugees, migrants and asylum seekers.

One study found a wide range of disparities negatively affecting access to testing and treatment of key at risk and populations.  The disparities centered mainly on migrants, asylum seekers, and refugees. The study resulted in a website called “Barring the Way To Health” (https://www.gnpplus.net/our-solutions/barring-the-way-to-health/)

Another study at IAS 2017 analyzed a pilot program  initiated by Medecins Sans Frontiere in rural areas of Yambio South, Sudan, to test the feasibility of providing HIV testing and counselling and ARV initiation in regions of chronic conflict. Five mobile teams offered testing and counselling and same day ART initiation to those who tested positive and data over a 17- month period was analyzed. Counseling sessions were provided which included instructions on what to do during times of active conflict including a constituency plan that provided access to ‘go bags’ containing a three-month supply of ARVs. During the study, there were several episodes of instability where the contingency plan was activated.

Results of this study found that levels of ARV retention (86% at 6 months and 81% at 12 months) and viral load suppression (85% below 1000 copies) were comparable to clinic settings. Throughout the study, 13,872 people were tested for HIV, of which 442  (3.2%) tested positive. Of the 442 positive individuals, 344  (77.8%) were started  on  ART.

A third study assessed the feasibility of providing home-based HIV testing in sub- Saharan refugee camps. Visits were made to 319 homes that reported a total of 566 individuals living in the homes, during a one- month period of time in the Nakivale Refugee Settlement. During a total of three visits per home, researchers were able to reach 507 individuals in 292 homes. Of these, 378 (75%) agreed to be home-tested and received their results. There were 7 (1.9%) individuals who tested positive for HIV. Researchers found that people were more likely to agree to be tested if there were others present. The authors concluded that home-based HIV testing is feasible in refugee camp settings.

There is robust data demonstrating that effective service delivery can be conducted for large HIV patient populations struggling in distressed economic and political circumstances. Global Fund’s ban on HIV-related assistance to ostensibly high-income countries is contributing to several regions of risk. The policy has previously led to cuts in HIV/AIDS funding to several Eastern European countries, a move heavily criticized by advocates in those countries. As international assistance for HIV/AIDS has steadily dropped over the past few years, the Global Fund has pushed harder on governments to foot their own bills. The unfolding crisis in Venezuela, and its dire implications for the diagnosis, treatment, and prevention of HIV, should shake the complacency of the Global Fund and other international aid organizations. In an ever more global community, Venezuela’s humanitarian crisis will not long stay Venezuela’s alone. We will help ease Venezuela’s pain, or we will eventually feel it ourselves.

The Eastern View from AIDS 2018

By Chad S. Johnson

Many AIDS 2017 attendees in Paris were disappointed by the neglect of a timely, critical focus on the HIV challenges in Venezuela caused by the abject failure of governance, human rights, and the rule of law in Caracas.  With the country falling apart and people unable to obtain essential HIV medications and basic medical supplies, the lack of a concerted effort to address this urgent human tragedy at AIDS 2017 seemed like an astounding failure by the most powerful stakeholders in the epidemic.  However, an equally pressing dynamic has existed for years without mainstream media coverage in many countries in Eastern Europe and Central Asia (EECA).  While not making the daily headlines, the EECA region has the highest new HIV infection rate in the world at 57% between 2010 and 2015 according to AVERT, a statistic highlighted at the AIDS 2017 teaser session on the upcoming 22nd International AIDS Conference in Amsterdam, Netherlands underway during the next days in July 2018 (AIDS 2018).

The AIDS 2017 session emphasized that one of Amsterdam’s top five objectives is to change the dynamic in the EECA where governments, institutions, orthodox religions, society, law enforcement and criminality, and international organizations fail vulnerable populations.  Session participants noted that this EECA problem was on the agenda during the 19th IAC in Vienna in 2010, a conference now deemed a failure in this regard.  Leading up to AIDS 2010, the WHO reported that the epidemic in Eastern Europe “… can be ascribed to government intransigence, public ignorance and the criminalization of risky behaviors, compounded by poverty, social exclusion and political and economic turmoil.”  These conditions have not significantly changed in Eastern Europe and continued to be mirrored in Central Asia.

Consequently, AIDS 2018 Local Co-Chair Dr. Peter Reiss of Amsterdam and International Co-Chair Dr. Linda Gail-Bekker of Cape Town, South Africa, committed to shine a spotlight on people left behind in the international response to the AIDS epidemic and to prompt a vigorous discussion about the reasons that the EECA region is an outlier in the progress seen around the world.  The theme of AIDS 2018, “Breaking Barriers, Building Bridges,” speaks to some of the unique contributing factors beyond unsafe sexual practices, including language, culture, lack of human rights and freedom of information, and “relative” prosperity (and with it, non-qualification for various international assistance programs for middle-income nations).  Additional factors on the rise in the EECA region include IV drug use in countries disapproving of needle-exchange programs, migration of female sex workers who are shamed into the shadows by conservative societies, and the refugee crisis and its health consequence.

The organizer of the session, the Dutch Ministry of Foreign Affairs, represented by Mr. Lambert Grijus, the Dutch Ambassador for Sexual and Reproductive Health & Rights and HIV/AIDS, articulated rights- and community-based approaches to more effectively reach key populations in the EECA region, along with putting mechanisms in place to hold politicians accountable in regional and international diplomatic settings for shortcomings in HIV-related awareness, funding and policy.  Dr. Michel Kazatchkine, former Director of the Global Fund and currently the UN Secretary-General Special Envoy on HIV/AIDS in Eastern Europe and Central Asia, also underscored the importance of aggressive work with top-level politicians as key to breaking the log jam in the region.  Unless governments acknowledge and take ownership of the growing HIV problem, outside efforts will continue to fail.  In some EECA nations, leaders are in denial that HIV/AIDS even exist in their countries – typifying the difficulties that stand between an increasing epidemic and effective solutions.

On top of government inaction and denial, several avenues of international support are not available as policy enticements since median incomes disqualify funding and assistant for many EECA countries – incomes that are by no means truly prosperous.  Traditional and orthodox populations in rights-limited societies add to the slow demand for and pace of change.  Communication and the free flow of HIV-related information are limited, and a lack of historical commitment to Russian language-based prevention and treatment programs is recognized as a problem for much of the EECA region.

The eastern view from Amsterdam is gloomy but there are glimmers of light.  AIDS 2018 will lead to critical analysis of potential solutions for the epidemic in the EECA.  Having hit the ground running on this 19th Day of July, 2018, we hope for an effective conference.  If the welcome provided at Amsterdam’s Schiphol Airport to conference participants is any sign, maybe this IAC will come closer to meeting its goals than previous conferences.  The response to this epidemic is constrained by resources and shaped by priorities, funding and discrimination and always will be.  It is disappointing, for example, that there are no sessions on the impact of HIV on war veterans around the world who suffer disproportionately.  The IAS community does not even recognize HIV veterans as a key population group for study and focus.  While different, this is reminiscent of AIDS 2017’s lack of programmatic flexibility and basic resolve to act on the dire circumstances in Venezuela, discussed above, when we assembled in Paris.

 

AIDS 2018 in Amsterdam has an opportunity for real success.  The next week will test us all, and we remain cautiously hopeful.

 

 

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.

Your Haven for Global Pandemic Awareness