Lancet Official: Confirms World’s 22th CASE of HIV Cure

Ravindra K, March 10, 2020. The Gupta team followed up with the latest developments in the magical ‘London patient’ treatment of last year’s case report in Lancet HIV with a study entitled Evidence for HIV-1 cure CCR5 32/32 allogene haemopoietic stem-cell-cell age 30 months post-care: a case report. In the latest study, the authors’ assessment of patient improvement has changed from ‘long-term remission’ to ‘cure’ and confirms that ‘London patients’ are the second case of aids in the world to be cured.

Lancet Official: Confirms World's 22th CASE of HIV Cure

Photo: Lancet HIV

‘Berlin Patient’ Is No Longer Alone

In 1995, a man named Timothy Ray Brown was diagnosed with AIDS. Eleven years after a hard time, poor Brown was diagnosed with acute myeloid leukemia (AML), and the death-of-die sickle finally waved to the surviving AIDS patient.

Lancet Official: Confirms World's 22th CASE of HIV Cure

Optimistic Timothy smiling in the street

But Brown and his doctor didn’t get carried away, and Gero H?tter, a doctor from Berlin, decided to take a bold treatment, picking a special donor from 60 bone marrow donors who carried the CCR5-32 mutation.

CCR5 has previously been proven by Professor Deng Hongkui of Peking University to be the main receptor for HIV virus incursions into cells. One percent of Europeans are born with a mutation of CCR5-32. Subsequent studies have found that this mutation pre-exists to immunize them against CCR5 (R5) hiv.

Lancet Official: Confirms World's 22th CASE of HIV Cure

Professor Deng Hongkui’s previous papers, pictured: Nature

Brown’s bone marrow transplant was a success, and his leukemia recovered. Even more surprising, the virus in his body has dropped to undetectable levels, and he no longer needs to take antiretroviral virus (ART) to suppress the virus, and Brown has survived to this day.

Until March 8, 2019, Brown was considered the world’s first and only cured AIDS patient, hence the name ‘Berlin Patient’.

Ravindra K, University of Cambridge, March 8 last year. Professor Gupta led the team in Nature with a paper entitled HIV-1 remission ces5 32/32 haematopoietic stem-cell-popation, which brought lonely Berlin patients together.

Lancet Official: Confirms World's 22th CASE of HIV Cure

Picture: Nature

The article reported that within 16 months of receiving a hematopoietic stem cell transplant from a CCR5-32 donor, a patient in London, England, had not only recovered from Hodgkin’s lymphoma, but had no further HIV in the patient’s blood.

The patient then stopped taking the alphaRT drug for 18 months and did not find HIV in the blood before the paper was submitted. Researchers believe the ‘London patient’ has received ‘long-term remission’ of AIDS, and he is likely to be the second case of AIDS to be cured.

A year later, the ‘London Patient’ was finally confirmed as the world’s second-best case of AIDS.

‘London patient’ recreates miracle in 30 months

Lancet Official: Confirms World's 22th CASE of HIV Cure

Photo: Lancet HIV

In a previous nature article, the researchers reported only the HIV load in the plasma 18 months after stopping taking ART. This article follows up on progress between March 19 and March 20, extending the time to 30 months.

During the new 12 months, the HIV load in the plasma is still below the detection limit and cannot be detected. The chimeric of transplanted hematopoietic stem cells can still reach 99% of the population, and the number of CD4 cells in patients returns to normal levels.

During this time, the patient sat still had the same type 4 human herpes virus (Epstein-Barr virus, EBV) and cytomegalovirus (Cytomegalovirus, CMV) as reported in Nature, but the CMV virus load decreased after 18 months of transplantation.

The patient did not take immunosuppressive drugs during this period and did not have a transplant anti-host reaction (graft versus host disease). The droplet digital PCR shows that the long end repeat sequence (HIV-1 LTR) of the pre-HIV1 virus cannot be detected in CD4 T cells, but a small amount of HIV-1 LTR is detected in the memory T cell.

Based on testing plasma in the Nature study, the researchers specifically tested for the presence of HIV in multiple HIV latent libraries. The HIV virus load in semen, cerebrospinal fluid and puncture tissue biopsies was lower than the detection limit and was negative.

A small amount of HIV membrane glycoprotein genes (env), LRT, and structural protein genes (gags) were detected in the lymph nodes, but no detected DNA-integrated enzymes proved to be low and incomplete in the HIV genome. THE RT-PCR SHOWS SIMILAR RESULTS AND PROVES THE ABSENCE OF HIV PACKAGING SIGNALS. This means that these small amounts of HIV genes are not enough to cause HIV to recur.

Lancet Official: Confirms World's 22th CASE of HIV Cure

Photo: Lancet HIV

The researchers then tested the specific immune response of CD4 and CD8 T cells to HIV gag, EBV, and CMV in patients. It was found that the patient’s T-cells had only an immune response to EBV and CMV and no response to HIV gag.

Lancet Official: Confirms World's 22th CASE of HIV Cure

Photo: Lancet HIV

Further studies have found that although there is still a certain amount of HIV antibodies in the patient’s body, there has been a significant decrease in these antibody affinity, and this evidence, together, proves that the patient’s AIDS has been clinically cured.

Lancet Official: Confirms World's 22th CASE of HIV Cure

Photo: Lancet HIV

Using mathematical models to simulate the probability of patient remission, the researchers concluded that the probability of ‘long-term remission’ in the case of 90 percent chimiworst was higher than 99 percent. At present, the patient’s chimeric rate has stabilized at 99% for a long time, the authors believe that the ‘London patient’ AIDS has been cured, based on the previous ‘Berlin patient’ treatment history.

The paper once again demonstrates the possibility of treating AIDS with hematopoietic stem cell transplantation with CCR5 mutation, and provides experience and guidance for the clinical implementation of related therapies in the future.

What’s more, in a world where HIV vaccine and drug research has failed, the miracle of ‘Berlin Patients’ has been recreated by ‘London Patients’, giving new hope to the world’s 38 million people living with AIDS.

The story of CCR5 continues.

Because AIDS currently has no effective cure, people’s views on AIDS have reached the point of talking about ‘Ai’ color change. Every time the progress of AIDS can lead to heated discussions both inside and outside the academic world, and in recent years the story of CCR5 has been ups and downs.

Before the ‘London Patient’ was reported, Professor He Jiankui of the Southern University of Science and Technology used CRISPR technology to genetically edit the fetuses of AIDS patients.

He knocks out CCR5 in the baby’s body to give the baby the same HIV immunity as the ‘Berlin patient’ and CCR5-32 mutation carriers. But his aggressive behavior has sparked shockins in the world’s scientific community and the claims of all scientists because of ethical controversy and falsified experimental ethics approval procedures. Last year, He Wasan-kui was sentenced to three years in prison.

Lancet Official: Confirms World's 22th CASE of HIV Cure

Photo: Nature Medicine

Following the heckenkui incident and the publication of the ‘London Patients’, the safety of the CCR5-32 mutation was studied.

Rasmus Nielsen and Xinzhu Wei from the University of California, Berkeley, published at Nature Medicine entitled CCR5-s32 is deleterious in the homozygous state in humans  The paper, which reports that CCR5-32 pure hem will lead to a 21% increase in all-cause mortality. The paper sparked a heated debate after data and other research conflicts and analysis methods were eventually withdrawn.

Lancet Official: Confirms World's 22th CASE of HIV Cure

Photo: Nature Medicine

Dramatically, a few months later, researchers, including the original author of this article, re-analysed the data and again published at Nature Medicine entitled No-statistical evidence for an effect of CCR5-?32 on-lifespan in The UK Biobank cohort article, which states that there is no evidence that the CCR5-32 mutation affects the life of the carrier, clears some of the obstacles to the study.

Lancet Official: Confirms World's 22th CASE of HIV Cure

Picture: NEJM

In addition to the hematopoietic stem cells of the carriers of the CCR5-32 mutation, the discoverers of CCR5, the research team of Professor Deng Honggui of Peking University, the Chen Hu Research Group of the Fifth Medical Center of the PLA General Hospital, and the Wu Wei Research Group of Beijing You’an Hospital, affiliated with the Capital Medical University, published a report entitled CRISPR-Edited in the company. Stem Cells in a Patient with HIV and Acute Lymphocy Leukemiatic, a study that reports on ways to circumvent ethics and safety concerns by using CRISPR technology to edit CCR5 in hematopoietic stem cells. The method is expected to produce ‘Berlin patients’ and ‘London patients’ in mass production, helping more AIDS patients. Although the editing efficiency of the study is inefficient, the safety and potential of the technology have been proven in the study.

The cure of the ‘London patient’ is further proof that Professor Deng Hongkui and Professor Chen Hu, who had tragically passed away, chose the right path.