Two HIV patients have been found to be in remission even after stopping treatment for the disease, hospitals in California and Barcelona announced on Wednesday. The developments come as the Joint United Nations Program on HIV/AIDS (UNAIDS) released a report warning of serious setbacks in the fight against AIDS.
The data on the cases was presented at the pre-conference meetings of the 2022 International AIDS Conference. The main conference is set to take place on Friday.
While modern treatments can reduce the viral load in HIV patients to low enough that they can live a relatively healthy life and cannot infect others, the virus usually can return and replicate into large numbers again if treatment is stopped. There are two types of HIV cures being studied: a "sterilizing cure" which completely eliminates the virus from the body and a "functional cure" or remission which leads to long-term control of the virus without the need for continuous treatment.
The first patient, a 66-year-old man who was diagnosed with HIV in 1988, has been in remission for over 17 months after stopping antiretroviral therapy (ART) for the disease following a stem cell transplant from an unrelated donor for acute leukemia, the City of Hope Medical Center, located in Duarte, California, announced on Wednesday.
The stem cell transplant was conducted in early 2019 at City of Hope after he was diagnosed with acute myelogenous leukemia, a form of the cancer more prevalent in those with HIV later in life. The stem cell donor had a rare genetic mutation, the homozygous CCR5 delta 32 mutation, that makes people resistant to most strains of HIV infection.
The man had lived with HIV for over 31 years, longer than any of the three previous HIV patients who have gone into remission after receiving a stem cell transplant. He is also the oldest patient with HIV and blood cancer to undergo a transplant and achieve remission from both conditions.
Under the care of hematologist Dr. Ahmed Aribi, assistant professor in City of Hope's Division of Leukemia, the patient received three different therapies to get him into remission before the stem cell transplant. Most patients achieve remission after one therapy.'
“This patient had a high risk for relapsing from AML [acute myeloid leukemia], making his remission even more remarkable and highlighting how City of Hope provides excellent care treating complicated cases of AML and other blood cancers,” said Aribi.
Since the transplant, the man has not shown any evidence of having replicated HIV virus in his body and he stopped taking ART in March 2021.
“We were thrilled to let him know that his HIV is in remission and he no longer needs to take antiretroviral therapy that he had been on for over 30 years,” said Jana Dickter, associate clinical professor in the Division of Infectious Diseases, in a press statement. “He saw many of his friends die from AIDS in the early days of the disease and faced so much stigma when he was diagnosed with HIV in 1988. But now, he can celebrate this medical milestone. We can find no evidence of replicating HIV in his system.”
Meanwhile, the Hospital Clinic of Barcelona-August Pi i Sunyer Biomedical Research Institute (IDIBAPS) announced that a female patient had absolute control of the replication of HIV, going 15 years without treatment and with an undetectable viral load.
The patient was enrolled in a clinical trial with antiretroviral treatment after being diagnosed with HIV. She was treated for nine months with the treatment and different immune-modulating interventions with ciclosporin A, an immunosuppressant agent.
“The patient did not have genetic factors associated with control of HIV, she was not an elite controller of the disease, and furthermore, she presented severe acute-phase infection, something that is uncommon in post-treatment controllers (a term for people who manage to keep their viral load suppressed even after halting treatment)," said Josep Miró, Senior Consultant of Infectious Diseases at the Hospital Clinic of Barcelona.
Sonsoles Sánchez-Palomino, a researcher with the IDIBAPS AIDS and HIV Infection group, stated that there was a "pronounced and gradual drop" in the viral load over the years the patient was observed, "which suggests control by the immune response."
The researchers found that the patient's blood cells were highly resistant to infection by the HIV virus, but her purified CD4+ T cells ( a type of T cell that play an important role in the immune system) were susceptible to infection. The researchers stated that this suggests that blood cells were blocking the infection and that this may contribute to controlling HIV.
The study conducted by the Spanish researchers identified natural killer cells, which constitute the first line of defense against different pathogens, and CD8+ T cells, which play a key role in the cell's defense against viruses and bacteria, as having high resistance to HIV infection.
"The major novelty of the study is that we have characterized the cells that achieve control of the virus”, said Núria Climent, a researcher from the group at IDIBAPS, adding that the patient who achieved remission had "very high level" of both of these cells.
“The presented case is exceptional, not just because there are so few people with long-term post-treatment control but also because of the HIV-control mechanism, which is different than that described in elite controllers and other cases documented to date," said Josep Mallolas, co-author of the study.
The researchers stressed that this study opens the door to the development of new potential treatment strategies that focus on increasing the activity of natural killer cells and CD8+ T cells involved in the patient's innate response to the virus.
'The global AIDS response is under threat'
Alongside the news of the patients in remission on Wednesday, UNAIDS warned that "the global AIDS response is under threat," due to instability caused by the novel coronavirus outbreak, the war in Ukraine and other issues in the past two years.
"The new data revealed in this report are frightening: progress has been faltering, resources have been shrinking and inequalities have been widening. Insufficient investment and action are putting all of us in danger: we face millions of AIDS-related deaths and millions of new HIV infections if we continue on our current trajectory," said Winnie Byanyima, the executive director of UNAIDS.
The number of new HIV infections dropped only by 3.6% between 2020 and 2021, the smallest annual decline in new infections since 2016. Eastern Europe and central Asia, Middle East and North Africa, and Latin America have all seen increases in annual HIV infections over several years. In locations in Asia and the Pacific where the rate of HIV infections had been falling, it is now rising.
Over 1.5 million new infections were reported last year, a million more than global targets. The new infections occurred disproportionately among young women and adolescent girls, with a new infection every two minutes in this population in 2021. The spike in infections took place amid disruptions to key HIV treatment and prevention services and the closures of schools amid the pandemic, as well as spikes in teenage pregnancies and gender-based violence, according to UNAIDS.
Men who have sex with men (MSM) are also at a heightened risk of being infected with HIV, with UNAIDS data showing that, as of 2021, MSM have 28 times the risk of acquiring HIV compared to people of the same age and gender identity. People who inject drugs have 35 times the risk, sex workers 30 times the risk and transgender women 14 times the risk.
The number of people on HIV treatment also grew more slowly in 2021 than it has in over a decade. While three-quarters of all people living with HIV have access to antiretroviral treatment, about 10 million people do not, and only half of the children living with HIV have access to lifesaving medicine.
In 2021, the AIDS pandemic took a life every minute, on average, in 2021, with 650,000 AIDS deaths reported despite the existence of effective HIV treatment.
“These figures are about political will. Do we care about empowering and protecting our girls? Do we want to stop AIDS deaths among children? Do we put saving lives ahead of criminalization?” asked Byanyima. “If we do, then we must get the AIDS response back on track.”
On the current track, if action is not taken, the number of new infections per year will be over 1.2 million in 2025 - the year in which United Nations member states have set a goal of fewer than 370 000 new HIV infections.
“We can end AIDS by 2030 as promised,” said Byanyima. “But what it takes is courage.”