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Second person cured of HIV after 30 months virus-free

The second cure is now taken to mean that the first one (in the Berlin patient) wasn’t an anomaly or a fluke.

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Photo credit: Adam Castillejo / Twitter

A man from London is now considered as the second person ever cured of HIV.

The man’s case was first announced a year ago; and he has now been HIV-free for 30 months, not needing antiretoviral medications (ARVs), according to a report published in The Lancet HIV.

The man was previously known only as the “London patient”; but his identity was revealed just as this development came into view.

Adam Castillejo is a 40-year-old who grew up in Venezuela. He was first diagnosed with HIV in 2003 after moving to London a year earlier, and developed advanced Hodgkin lymphoma in 2012. In 2016, to fight the rare cancer, he received bone marrow stem cells from a donor with a rare genetic mutation that resists HIV infection.

Last year, he experienced “long-term remission” from the virus after undergoing a special bone-marrow transplant. At that time, he was already HIV-free for 18 months. Now, 12 months later, his doctors are “more sure” that his case does indeed represent a cure.

In a statement, Ravindra Kumar Gupta, a professor of clinical microbiology the University of Cambridge and the lead author of the report published in The Lancet HIV, said: “We propose that these results represent the second ever case of a patient to be cured of HIV.”

The first patient to be cured of HIV is Timothy Brown, who was earlier known as the “Berlin patient”. He also received a similar bone-marrow transplant in 2007 and has been HIV-free for more than a decade.

In the two cases, stem cells used for their transplants came from a donor who had a relatively rare genetic mutation that confers resistance to HIV.

The researchers, nonetheless, stressed that such a bone-marrow transplant would not work as a standard therapy for all patients with HIV because: 1. such transplants are risky, and 2. both Castillejo and Brown needed the transplants to treat cancer rather than HIV.

In the new report, doctors found no active viral infection in Castillejo’s body. But they found “remnants” of HIV’s DNA in some cells (traces of DNA that can be considered as “fossils” because they are unlikely to allow the virus to replicate). Such remnants were also found in Brown’s case.

The second cure is now taken to mean that the first one (in the Berlin patient) wasn’t an anomaly or a fluke.

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Kidney transplantation between people with HIV is safe, NIH study finds

Kidney transplantation from deceased donors with HIV to people living with both HIV and end-stage kidney disease is feasible and safe.

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Kidney transplantation from deceased donors with HIV to people living with both HIV and end-stage kidney disease is feasible and safe, investigators supported by the National Institutes of Health have found. Their study demonstrates that the pool of available kidneys for people with HIV can be expanded by including donors with HIV, making more kidneys available for all who are awaiting a transplant.

The new findings build on research from 2019, when scientists from the University of Cape Town and NIH reported that people living with HIV who received kidney transplants from deceased donors with HIV had high overall survival and kidney graft survival after five years.

People living with HIV have a growing prevalence of end-stage kidney disease and are nearly three times more likely to die while on kidney dialysis than people without HIV. Kidney transplantation extends the lives of people with HIV and end-stage kidney disease, but these individuals face a shortage of donors and limited access to donor kidneys.

The HIV Organ Policy Equity (HOPE) Act, passed by the US Congress and signed into law in 2013, allows organ transplants from donors with HIV to recipients with HIV in approved research studies in the US. Experts concurred that kidney transplantation between people with HIV would expand the pool of available organs and save lives. Consequently, investigators sought to explore the safety of this innovative transplantation practice.

People living with HIV have a growing prevalence of end-stage kidney disease and are nearly three times more likely to die while on kidney dialysis than people without HIV. Kidney transplantation extends the lives of people with HIV and end-stage kidney disease, but these individuals face a shortage of donors and limited access to donor kidneys.

The multicenter study was conducted by the HOPE in Action team led by Christine M. Durand, M.D., associate professor of medicine, and Dorry Segev, M.D., professor of surgery at Johns Hopkins University in Baltimore. NIH’s National Institute of Allergy and Infectious Diseases (NIAID) funded the study with additional support from the National Cancer Institute, also part of NIH.

Between March 2016 and July 2019, investigators at 14 clinical research sites enrolled 75 adults with end-stage kidney disease and HIV whose virus was reliably suppressed by anti-HIV therapy. Twenty-five participants received kidney transplants from deceased donors with HIV, and 50 participants received kidney transplants from deceased donors without HIV. The latter group included 22 donors who had false-positive HIV tests, another new organ source that has been an unexpected benefit of the HOPE Act.

All participants survived transplantation at a median follow-up of 1.4 years for recipients of HIV-positive kidneys and 1.8 years for recipients of HIV-negative kidneys. One year after transplantation, overall graft survival was excellent and comparable between recipients of HIV-positive kidneys (91%) and HIV-negative kidneys (92%). In addition, there were no differences in the rates of infections requiring hospitalization, serious adverse events (1.1 per person year) or HIV-related complications, which were rare.

Dr. Durand also is leading the HOPE in Action Multicenter Kidney Study, a large-scale, NIAID-sponsored clinical trial to further study the safety of kidney transplantation between people with HIV.

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Brazilian man is first-ever person ‘cured’ of HIV with medication alone; case still ‘not proven’

A 36-year-old man in Brazil – now called the “São Paulo Patient” – seemingly cleared an HIV infection after receiving an aggressive combination of antiretroviral (ARV) drugs and nicotinamide (vitamin B3). He went off all HIV treatment in March 2019 and has not had the virus return to his blood.

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A 36-year-old man in Brazil – now called the “São Paulo Patient” – seemingly cleared an HIV infection after receiving an aggressive combination of antiretroviral (ARV) drugs and nicotinamide (vitamin B3). He went off all HIV treatment in March 2019 and has not had the virus return to his blood.

Most people who suppress HIV with ARVs and later stop treatment see their viral load race back to high levels within weeks. What’s interesting in the case of the “São Paulo Patient” is he did not experience a rebound, and – better yet – his HIV antibodies also dropped to “extremely low levels”, which hints at the possibility that he may have cleared infected cells in the lymph nodes and gut (some of the “reservoirs” where HIV may be “hiding” even for people with undetectable viral load).

Now this is important: According to Ricardo Diaz of the Federal University of São Paulo, the clinical investigator running the study, he doesn’t know whether the patient is cured.

Discussing the case at a press conference of the pay-to-access International AIDS Conference (IAC) 2020, which is being held virtually because of the Covid-19 pandemic, Diaz said that the “São Paulo Patient” “has very little antigen” (referring to HIV proteins that trigger the production of antibodies and other immune responses). But they have not yet sampled the man’s lymph nodes or gut for the virus since he stopped treatment.

Only two people are known to have been cured of their HIV infections: Timothy Ray Brown and Adam Castillejo. Both received bone marrow transplants as part of a treatment for cancers, with the transplants clearing their infections and giving them new immune systems that resist infection with the virus.

However, bone marrow transplants are expensive, complicated interventions that can have serious side effects, making them an impractical cure for over 38 million people living with HIV.

HIV is difficult to eliminate because the virus weaves its genetic material into human chromosomes, where it can lie dormant and so escape the immune surveillance that typically eliminates foreign invaders. Researchers have come up with various strategies to “flush” the reservoirs of cells that harbor latent HIV infections, but so far none have proved effective.

Diaz and his team wanted to compare different reservoir-clearing strategies in 2015, leading to the recruitment of the “São Paulo Patient” and other individuals who had controlled their HIV infections with ARVs.

For this study, the most aggressive approach was used in the “São Paulo Patient” and four others, which added two ARVs to the three they were already taking, hoping this would rout out any HIV that might have dodged the standard treatment. The study group also received nicotinamide that can (in theory) prod infected cells to “wake up” the latent virus. So when those cells make new HIV, they either self-destruct or are vulnerable to immune attack.

After 48 weeks on this intensified treatment, the five participants returned to their regular three-drug regimen for three years, and then stopped all treatments.

Four participants saw the virus quickly return, but the “São Paulo Patient” has now gone 66 weeks without signs of being infected, with tests that detect viral genetic material not finding HIV in his blood.

A more sensitive test was done, mixing his blood with cells that are susceptible to HIV infection, and it produced no newly infected cells.

There are also numerous unknowns, e.g.:

  1. Whether the man indeed stopped taking his ARVs, which has yet to be confirmed with blood examination/s.
  2. How soon the man started ARVs after becoming infected with HIV.
  3. How nicotinamide would awaken silent infected cells.
  4. And if this canoe done/replicated in controlled environment with multiple participants.

“I’m always trying to be a little bit the devil’s advocate, but in this case, I’m optimistic,” Diaz said. “Maybe this strategy is not good for everybody because it only worked in one out of five here. But maybe it did get rid of virus. I don’t know. I think this is a possibility.”

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Antiretroviral meds at risk of running out due to Covid-19 – World Health Organization

More than a third of the world’s countries are at risk of running out of life-saving AIDS drugs because of disruptions to supply lines and other problems caused by COVID-19. Twenty-four nations already reported critically low ARV supplies.

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Yes, PLHIVs should worry.

Seventy-three countries warned that they are “at risk of stock-outs of antiretroviral (ARV) medicines as a result of the COVID-19 pandemic”. This is according to a new survey from the World Health Organization (WHO), which also found that 24 countries already reported having “either a critically low stock of ARVs or disruptions in the supply of these life-saving medicines.”

While there is still no cure for HIV, ARVs can control the virus and prevent onward sexual transmission to other people.

WHO did not name the affected countries in its survey.

According to Dr. Tedros Adhanom Ghebreyesus, WHO Director-General, this is “deeply concerning.” “Countries and their development partners must do all they can to ensure that people who need HIV treatment continue to access it. We cannot let the COVID-19 pandemic undo the hard-won gains in the global response to this disease.”

About 38 million people worldwide are currently infected with HIV.

As FYI: Even prior to the release of the WHO statement, on July 2, Outrage Magazine already sent an email to the office of Department of Health (DOH) Sec. Francisco Duque III, with the National AIDS and STD Prevention and Control Program (NASPCP) and Philippine National AIDS Council (PNAC) Cc’d.

Four days later – and as of press time – no response/s has/have been received.

Various HIV-related services offered in the Philippines have been stalled – e.g. community-based HIV screening, with HIV service providers lamenting the lack of clear guidelines/protocols on how to do this coming from the DOH.

But DOH itself already admitted the ill effects of Covid-19 to HIV-related services in the Philippines.

In June, a letter signed by Usec. Dr. Myrna Cabotaje from Department of Health (DOH) to Outrage Magazine noted the impact of Covid-19 on HIV program implementation. Specifically: Prevention services were reduced by 20% to 30%; HIV testing services reduced by 20% to 80%; viral load testing reduced by 42%; and ARV refill services reduced by 5%.

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Community-led responses must be formally recognized in responses to HIV and COVID-19

UNAIDS, APN+ and APCASO issue a joint statement to emphasize the key role that the HIV response can play in developing and implementing equitable systems for health, including sustainable HIV and COVID-19 programming.

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In the context of the COVID-19 pandemic, UNAIDS, APN+ and APCASO issue a joint statement to emphasize the key role that the HIV response can play in developing and implementing equitable systems for health, including sustainable HIV and COVID-19 programming.

Vulnerable and marginalized people are often the most affected by COVID-19, physically, economically and socially. They are the least able to protect themselves, often living in crowded conditions without sufficient hygiene facilities or on the street. In the context of lockdowns, women have faced increased rates of gender-based violence. Vulnerable and marginalized people are also the least likely to be able to access social protection measures designed to ensure access to basic food, hygiene and livelihood support.

Winnie Byanyima, UNAIDS Executive Director in her remarks at the UNAIDS Programme Coordinating Board Meeting, held in Geneva, Switzerland, from 23 to 25 June 2020, recalled that the hard-learned lessons of the struggle against AIDS provide an invaluable practical guide as we confront Covid-19. Such lessons are the importance of empowering communities; that human rights do not hinder but enable pandemic response; that pandemic responses must go beyond health interventions, and address economic and social drivers and impacts, including providing social protection; that pandemic responses must tackle inequalities in rights and in access to services.

“The HIV response has demonstrated that where communities are able to fully participate in decision-making and service delivery, and human rights protections are strengthened, HIV outcomes and impacts have improved. UNAIDS will continue to work with regional community networks, to reach the people who are left the furthest behind and to tackle gender inequalities and human rights violations that place people at greater risk of both HIV and COVID-19,” says Eamonn Murphy, UNAIDS Regional Director for Asia and the Pacific.

With the joint statement, UNAIDS, APN+ and APCASO emphasize that community-led responses must be a formally recognized element of any country’s responses to HIV and COVID-19. They also call on governments and donors to ensure sufficient funding and political and legal support to networks of people living with HIV and key populations, community-based health services, and community and civil society service and advocacy organizations.

“Beyond fighting the virus, we are also battling social inequities, injustices, and rights violations that make pandemics like COVID-19, and HIV, disproportionately impact and further marginalise key populations and vulnerable communities. We need strengthened communities and civil society working alongside governments, highlighting community, rights, and gender dimensions of issues, as a legitimate part of country health responses,” says RD Marte, APCASO Executive Director.

Communities are at the heart of any effective and equitable public health response. “A robust and enabled civil society was an essential element of the HIV response. As we face the challenges of COVID-19 in the short and longer term, communities and civil society must be resourced and enabled to play a legitimate role in delivering sustainable, gender-based, rights-based responses,” points out Shiba Phurailatpam, Director of the Asia Pacific Network of People Living with HIV/AIDS (APN+).

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‘Love on Wheels’ launched as community-based approach in delivery of HIV services

With the end of the COVID-19 pandemic still nowhere in sight, said Ico Rodulfo Johnson, who helms Project Red Ribbon, “we took it upon ourselves to develop an ingenious way for HIV services to still be delivered. The fight against HIV despite COVID-19 must continue. The country needs to innovate to continue the years of successes of the HIV programs.”

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With the COVID-19 pandemic continuing to pose a challenge to the HIV programs in the Philippines, Project Red Ribbon – with the Joint United Nations Programme on HIV and AIDS (UNAIDS) – came up with a pilot program, the “Love on Wheels”, that eyes to continue delivering HIV services in the country. 

Via this program, health facilities in local government units (LGUs) will be provided with at least three electric motor bikes to allow HIV service providers to reach PLHIVs (like getting their antiretroviral medicines), those who want to get tested, or those requiring safer sex materials. The pilot is being done in the City of Manila.

With the end of the COVID-19 pandemic still nowhere in sight, said Ico Rodulfo Johnson, who helms Project Red Ribbon, “we took it upon ourselves to develop an ingenious way for HIV services to still be delivered. The fight against HIV despite COVID-19 must continue. The country needs to innovate to continue the years of successes of the HIV programs.”

The move is also much-needed, considering Department of Health’s (DOH) continuing focus on COVID-19 that seem to be relegating other health services, including those related to HIV.

In a June 10 letter sent to Outrage Magazine by the DOH, the impact of Covid-19 on HIV program implementation has been noted. Specifically: Prevention services were reduced by 20% to 30%; HIV testing services reduced by 20% to 80%; viral load testing reduced by 42%; and ARV refill services reduced by 5%.

Over three months since COVID-19 lockdowns were imposed in the Philippines, the only existing protocol from DOH related to HIV only tackles ARV distribution; and service providers continue to lament the absence of clear-cut, B&W policies re testing, as well as link to treatment of those who may test HIV-positive.

“Love on Wheels” will be implemented by social hygiene clinics (SHCs) of LGUs, involving medical practitioners like nurses, case managers and medical technologists, among others. This way, confidentiality is ensured (e.g. when accessing HIV testing, or when PLHIVs get their medicines via “Love on Wheels”).

The longer-term plan is to expand this to other LGUs in Metro Manila by July, and eventually to provinces after July.

For those who may want to avail of the services of the “Love on Wheels” in the City of Manila, coordinate with the Manila Social Hygiene Clinic and Treatment Hub, located at 667 Earnshaw St., Sampaloc, via 5310-1326, 749-8273 or 09455102130.

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Brain cells can harbor and spread HIV to the body

Researchers found that the transplanted HIV-infected astrocytes were able to spread the virus to CD4+ T cells in the brain. These CD4+ T cells then migrated out of the brain and into the rest of the body, spreading the infection to peripheral organs such as the spleen and lymph nodes.

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Researchers have found that astrocytes, a type of brain cell can harbor HIV and then spread the virus to immune cells that traffic out of the brain and into other organs. HIV moved from the brain via this route even when the virus was suppressed by combination antiretroviral therapy (cART), a standard treatment for HIV.

The study, conducted by researchers at Rush University Medical Center in Chicago and published in PLOS Pathogens, was funded by the National Institutes of Health.

“This study demonstrates the critical role of the brain as a reservoir of HIV that is capable of re-infecting the peripheral organs with the virus,” said Jeymohan Joseph, Ph.D., chief of the HIV Neuropathogenesis, Genetics, and Therapeutics Branch at NIH’s National Institute of Mental Health, which co-funded the study. “The findings suggest that in order to eradicate HIV from the body, cure strategies must address the role of the central nervous system.”

HIV attacks the immune system by infecting CD4 positive (CD4+) T cells, a type of white blood cell that is vital to fighting off infection. Without treatment, HIV can destroy CD4+ T cells, reducing the body’s ability to mount an immune response – eventually resulting in AIDS.

cART, which effectively suppresses HIV infections, has helped many people with HIV live longer, healthier lives. But some studies have shown that many patients receiving antiretroviral drugs also show signs of HIV-associated neurocognitive disorders, such as thinking and memory problems. Researchers know that HIV enters the brain within eight days of infection, but less is known about whether HIV-infected brain cells can release virus that can migrate from the brain back into the body to infect other tissues.

The brain contains billions of astrocytes, which perform a variety of tasks — from supporting communication between brain cells to maintaining the blood-brain barrier. To understand whether HIV can move from the brain to peripheral organs, Lena Al-Harthi, Ph.D., and her research team at Rush University Medical Center transplanted HIV-infected or noninfected human astrocytes into the brains of immunodeficient mice.

The researchers found that the transplanted HIV-infected astrocytes were able to spread the virus to CD4+ T cells in the brain. These CD4+ T cells then migrated out of the brain and into the rest of the body, spreading the infection to peripheral organs such as the spleen and lymph nodes. They also found that HIV egress from the brain occurred, albeit at lower levels, when animals were given cART. When cART treatment was interrupted, HIV DNA/RNA became detectable in the spleen — indicating a rebound of the viral infection.

“Our study demonstrates that HIV in the brain is not trapped in the brain — it can and does move back into peripheral organs through leukocyte trafficking,” said Dr. Al-Harthi. “It also shed light on the role of astrocytes in supporting HIV replication in the brain — even under cART therapy.”

This information has significant implications for HIV cure strategies, as such strategies need to be able to effectively target and eliminate reservoirs of HIV replication and reinfection, Dr. Al-Harthi added.

“HIV remains a major global public health concern, affecting 30 to 40 million people across the globe. To help patients, we need to fully understand how HIV affects the brain and other tissue-based reservoirs,” said May Wong, Ph.D., program director for the NeuroAIDS and Infectious Diseases in the Neuroenvironment at the NIH’s National Institute of Neurological Disorders and Stroke, which co-funded the study. “Though additional studies that replicate these findings are needed, this study brings us another step closer towards that understanding.”

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