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3 八月 2022, 09:55
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A woman from Barcelona is still in remission from HIV 15 years after stopping treatment

A woman from Barcelona is still in remission from HIV 15 years after stopping treatment - 图片 1

One case study, presented at the 24th International AIDS Conference (AIDS 2022) in Montreal, has sparked international interest.

A woman from Barcelona has been living with an undetectable viral load for more than 15 years after she stopped taking antiretroviral treatment. The woman cannot be considered “cured” as HIV has not completely disappeared from her body, rather she is in “long-term remission” in the absence of antiretroviral drugs - this is often referred to as a “functional cure”.

Of the few people who have truly been cured of HIV have achieved this through stem cell transplantation in order to treat cancer, the donor cells carried the CCR5-delta-32 mutation which prevents HIV penetrating immune cells. There are, however, a small group of people who can keep HIV under control without treatment - these are referred to as “Elite Controllers”.

This new case of functional cure was presented by Dr Nuria Climent from the IDIBAPS clinic. The woman is being referred to as the ‘Barcelona Patient’. At the age of 59, she was diagnosed with acute HIV infection - at which point her viral load was around 70,000 copies and her CD4 at about 800.

The woman joined a small clinical trial of various immunomodulatory drugs (NCT00979706). In total, 20 people took part in the trial. Participants received standard antiretroviral therapy, consisting of lopinavir/ritonavir, tenofovir (TDF) and lamivudine for nine months, as well as a short course of cyclosporin A (an immunodepressant).

During a short planned treatment break, she received a drug that stimulates the production of leukocytes and interferon-alpha (cytokine that regulates the congenital or non-specific immune system). She then resumed ART, alongside a short course of interleukin-2 (cytokine, which activates T-cells and natural killer cells).

Eight weeks later, at which point she had an undetectable viral load, there was another planned treatment interruption - but this time her viral load remained undetectable. As well as undetectable viral load in blood plasma, the researchers noted “pronounced and progressive” reductions in viral reservoirs. This was evidenced by a 98% decrease in total HIV DNA, and 94% decreased in integrated proviral DNA in CD4 cells.

The researchers conducted a genetic analysis and found that the woman did not have any “classical genetic factors” associated with natural control of HIV - including HLA B*57 or the CCR5-delta-32 mutation. Further analysis also showed that her T-cells were susceptible to penetration by HIV. The virus was also not found to be “defective”, something that is common in people who are elite controllers.

When studying the woman’s immune system more closely, the researchers found that her natural killer cells (NK) and CD8 T-cell killers were playing a key role in the fight against HIV. Moreover, she had higher levels of specific natural killer cells (such as NKG2C+) and T-killer cells (gamma delta CD8 T-cells) - something which is usually observed in people with untreated HIV following a normal progression. These cells types are strongly associated with powerful cytotoxic activity against HIV-infected CD4 cells.

Dr Climent did not provide detailed results on the other 19 people involved in the trial, but did tell reporters that this woman was the “only one who was able to control HIV in the long run”.

This pilot regimen is not suitable for widespread use in HIV treatment, but this case study can help researchers develop new strategies for long-term remission that may be of use to all people living with HIV.

At the current time, all people living with HIV should continue to follow their HIV healthcare team’s advice and take their treatment accordingly.

译者: Tom Hayes

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