All posts by Jeannie Wraight

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.

 

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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.

 

 

Cure Research: CROI 2018

By Jeannie Wraight

The Conference on Retroviruses and Opportunistic Infections (CROI) provides an annual snapshot of the year’s most interesting and progressive data on HIV cure and remission research. Here’s a quick run down of some of the highlights presented at this year’s conference.

Kick and Kill
“Kick and kill” is a strategy that proposes to wake up or activate and then eliminate cells that are latently infected with HIV. Active replication allows the immune system to recognize these cells as a danger, making them a target for therapeutic agents. Researchers evaluated in Rhesus monkeys the combination of GS-9620, a TLR antagonist used to activate latent cells, and PGR121, a broadly neutralizing antibody, to kill off the awakened cells. The monkeys had been virally suppressed for two years. ARVs were discontinued before beginning the dual therapy. Viral suppression was maintained for over three months with this combination. At least half the monkeys remained suppressed at six months. In some cases, the virus remerged but the monkeys’ immune systems were able to re-suppress the virus without the need for additional doses. Additionally, researchers found that, even after viral rebound, the virus was at a lower level (viral setpoint) than it had originally been before the monkeys were given the combo, and the monkeys had lower viral DNA levels in their lymph nodes. This study suggests that the duo may have depleted viral reservoirs and allowed for some level of immune control of the virus.

More Validation of U=U
A study relevant to our understanding of viral reservoirs set out to determine if HIV replication occurs in lymph nodes in the presence of viral suppression. Its results are also important to our understanding of the U=U (undetectable equals untransmissable) premise. It has been conclusively established that when a person is undetectable and on sustained treatment for at least six months, he or she can’t transmit HIV to someone else. However, there remains a question as to whether HIV replication occurs elsewhere in the body, such as the lymph nodes, despite it not occurring in the blood, or if ongoing replication in a virally suppressed person stemmed solely from activated latent HIV in viral reservoirs. In this study, Dr. Mary Kearney of NIH’s National Cancer Institute found no evidence of ongoing HIV replication in the lymph node. This study contradicts a previous study published in 2016 that found that HIV replicates in the lymph nodes, helping to replenish viral reservoirs.

CD32+ as a Biomarker?
A major barrier to curing HIV is determining which cells harbor latent HIV. Biomarkers are needed to distinguish latently infected cells from cells not harboring the virus. CD32+ was recently suggested as a biomarker to differentiate the two in CD4 cells. Several studies evaluated this hypothesis and determined CD32+ did not identify latently infected reservoir cells. Studies continue to evaluate other surface markers that can be used as biomarkers, allowing researchers to target these cells.

Early ART in Infants
The “Mississippi baby” first made us aware that very early treatment with ARVs in infants could produce viral suppression for prolonged periods of time. Several studies were conducted to explore the effects of early initiation of ARVs in infants, two of which were reported at CROI 2018. Both studies found that beginning ARVs shortly after birth was safe, feasible and lead to smaller viral reservoirs.

The first study was conducted in Thailand and compared babies aged four to twenty-three weeks who received uninterrupted triple prophylactic ARV therapy since birth and those who did not receive uninterrupted prophylactic ARV therapy. The study also examined virally suppressed babies, with a median age of 2.7 years, who had initiated prophylactic ARV therapy at or after birth. Evaluating markers of HIV persistence, researchers found the infants who received continuous therapy had significantly lower viral loads and lower levels of integrated DNA, than those who didn’t receive continuous therapy. Also lower were the frequency of latently infected cells and the frequencies of cells producing msRNA spontaneously and after stimulation. In the older babies, after ART initiation, those who had started ARVs at birth had significantly lower total and integrated HIV DNA than children starting treatment later and the size of the inducible reservoir correlated with the age at which they began continuous therapy.

In the second study, infants in Botswana were given antiretroviral therapy before the age of seven days old. They were compared to children who started therapy later. Researchers set out to measure immune responses and discover if early treatment limits the size of viral reservoirs and measure immune responses. They found that those treated within seven days had lower viral reservoirs both at the beginning of the study and after eighty-four weeks. Five of the six children who initiated therapy with the first week of life had a negative qualitative HIV DNA PCR and a negative HIV ELISA test after eighty-six weeks.

Originally published in A&U Magazine http://aumag.org/2018/05/21/cure-research-croi-2018/