How Many Have Been Cured?
By Rowena Johnston, Ph.D.
It’s a sure sign of cure research progress that today it can be hard to keep track of the various cases of HIV having been cured or controlled in the absence of antiretroviral therapy (ART). The cases that tend to make headlines are those resulting from high-risk stem cell transplants, which are only an option for a very small number of people with both HIV and certain blood cancers. More numerous are those cases where virus still remains but is somehow kept in check by the immune system. While we’re still some distance from having a cure that’s easy to administer, affordable and, above all, widely available, researchers are learning from all of these cases.
So today, we’re curing some people, some of the time, the first step toward curing most people, most of the time. To help you make sense of it all, we’ve put together this summary of cure, or treatment-free control, cases to date, and we’ll add to it as others come to light.
Stem cell transplantation
City of Hope patient – At the AIDS 2022 conference in Montreal in July, researchers reported that a man living with HIV had been treated for acute myeloid leukemia using stem cells from a donor with the CCR5 delta32 genetic mutation, which renders cells almost impervious to HIV infection. The man had stopped taking antiretroviral therapy (ART) for 14 months with no sign of rebounding HIV. He is the oldest person to date to receive a stem cell transplant that appears to have resulted in an HIV cure, and had been living with HIV the longest—since 1988.
Berlin patient – The first known case of HIV cure was Timothy Ray Brown, who had been living with HIV for over a decade when he developed acute myeloid leukemia. He received chemotherapy, total body irradiation, and two stem cell transplants. Each transplant came from the same donor, who had the CCR5 delta32 genetic mutation. The case was published in 2009 and was subject to intense scrutiny before scientists agreed he was likely cured. Although he remained free of any signs of HIV infection, Timothy passed away in September 2020 following a relapse of his leukemia.
London patient – More than 10 years after Timothy Brown’s cure, in 2019 Adam Castillejo was reported likely cured following a CCR5 delta32 stem cell transplant to treat his Hodgkin lymphoma. He received a reduced intensity preparatory chemotherapy but no irradiation prior to his transplant. He stopped taking ART under close supervision in 2017 and remains HIV-free.
Düsseldorf patient – Like the London patient, the Düsseldorf patient is a member of amfAR’s ICISTEM cohort of people living with HIV and cancer who received stem cell transplants. His acute myeloid leukemia was treated with a CCR5 delta32 stem cell transplant in 2013. A few months after the transplant he experienced a relapse of his leukemia, which was treated successfully without additional stem cell transplantation. His case was reported at the same conference as the London patient case. Despite discontinuing ART in 2018, again under closely monitored conditions, he continues to show no signs of HIV infection.
New York patient – In February 2022, researchers reported that a woman living with HIV in New York had been treated for her acute myeloid leukemia using CCR5 delta32 stem cells from cord blood combined with adult stem cells from a relative, the first such haplo-cord blood transplant leading to a potential HIV cure. At the time of the report, the woman had stopped ART for 14 months with no sign of HIV infection.
Exceptional elite control
At the AIDS 2022 conference, Dr. Javier Martinez-Picado discussed the phenomenon of exceptional elite control—people who, without the use of ART, control HIV viral replication and do not experience immune dysfunction. There is no disease progression and they have extraordinarily low burdens of HIV, which can be detected only using specialized laboratory tests. They may experience a loss of anti-HIV antibodies over time, and have relatively weak immune responses against HIV, both signs that the body is no longer fighting HIV infection. Six such individuals have been followed for more than 30 years, and Dr. Martinez-Picado proposed that they may be considered a good model for an HIV cure.
San Francisco patient – Loreen Willenberg was diagnosed with HIV in 1992. Unlike almost all people living with HIV, she has never needed to take antiretroviral therapy to control her HIV infection. In 2020, Drs. Xu Yu and Mathias Lichterfeld (both amfAR grantees) announced that they were unable to find any intact HIV in her body despite searching in more than one billion cells, raising the intriguing possibility that her immune system not only controls the virus but may have, for all intents and purposes, eliminated it.
Esperanza patient – A second such case was announced in 2022 in a woman named after her hometown in Argentina. She was diagnosed with HIV in 2013 and has taken antiretroviral therapy only for brief periods during two pregnancies. Nonetheless, researchers including Drs. Yu and Lichterfeld, as well as collaborators in Argentina, have been unable to find intact or replication-competent virus in her.
Post-treatment control (PTC)
Barcelona patient – Researchers from Barcelona reported at AIDS 2022 that a woman who had participated in a clinical trial of several immune-modifying interventions that variously suppress and stimulate immune function had stopped taking ART with no rebound of HIV for 15 years. She was diagnosed with HIV early during infection and took ART for several months in combination with the immune treatments. Her HIV can still be detected in laboratory tests, but her immune system appears to be keeping it under control without the use of ART. Several measures of her reservoir indicate a decline over time in the amount of persistent virus in her body.
VISCONTI cohort – A study published in 2013 described 14 individuals who had started ART early during HIV infection and stayed on treatment for 1–8 years. These individuals subsequently maintained control of the virus without treatment, either at low levels or undetectable, for a median of around 7.5 years at the time of the report.
CHAMP study – The Control of HIV After Antiretroviral Medication Pause (CHAMP) study identified 67 post-treatment controllers from across 14 clinical studies, of whom about 20% maintained control of their virus without ART for more than 5 years. Other academic centers have also identified some of these rare individuals, and studies are ongoing to find mechanisms that may mediate ART-free control.
South African child – An update was provided at AIDS 2022 on an infant who was born HIV-positive and was enrolled in an NIH clinical trial testing the effect on the reservoir of early ART. He started ART soon after birth and was treated for 40 weeks, during which time his viral load decreased to undetectable after around 40 days of treatment. ART was then stopped and the child has maintained undetectable HIV for more than 13 years. Researchers are unable to find any intact HIV in his body. He was the only one of 227 infants enrolled in the study to achieve this outcome.
Mississippi child – A child born in the U.S. to a mother living with HIV received ART for the first 18 months of her life, and was then lost to follow-up, during which time she did not take ART. When the child re-entered medical care five months later, doctors were surprised to find no HIV in her viral load tests. Researchers carefully monitored her for several months and believed she might have cleared her HIV infection, but the virus rebounded just over two years after stopping ART and she restarted medication.
Figuring out how to fine-tune or supercharge the immune system to unleash its full potential could hold the key to inducing treatment-free control of HIV. Similarly, CCR5, the portal that enables HIV to enter and infect cells and has been central to the stem cell transplantation cures to date, remains a prime target for cure researchers.
amfAR continues to support studies that build on all of these cases and attack HIV, and the persistent HIV reservoir, from every possible angle. Additional studies are testing cell and gene therapy, immunotherapy and other approaches to curing HIV. We will continue to pursue every possible avenue until we have a cure, or cures, that can be made available to all 38 million people living with HIV.
Dr. Johnston is an amfAR vice president and director of research.