Human Cells Infected with HIV
Steve Gschmeisner/Science Photo Library
A man has become the seventh individual to rid himself of HIV after receiving a stem cell transplant for blood cancer. Notably, he was the second case among seven to receive stem cells that weren’t resistant to the virus, reinforcing the idea that resistant cells may not be essential for HIV treatment.
“Understanding that treatment can occur without this resistance offers us additional avenues for combating HIV,” remarks Christian Gabler at the Free University of Berlin.
So far, five individuals have been cleared of HIV following transplants from donors possessing mutations in both copies of a gene responsible for CCR5, a protein that HIV targets to infect immune cells. Scientists have drawn conclusions that having two copies of a mutation that eradicates CCR5 from immune cells is crucial for eliminating HIV. “It was previously thought that the use of HIV-resistant stem cells was key,” states Gabler.
However, last year, a sixth instance emerged, known as the Geneva patient, who was declared free of the virus. His infection persisted for over two years after receiving stem cells that lacked the CCR5 mutation, indicating that CCR5 might not be the complete narrative, though many scientists suggest that two years without viral infection may not suffice to confirm an actual cure, Gabler notes.
The recent cases bolster the hypothesis that the Geneva patient has indeed been cured. The research includes a male who received stem cells in October 2015 to address leukemia, a blood cancer characterized by uncontrolled growth of immune cells. At the time, the patient was 51 years old and was infected with HIV. During the treatment, he underwent chemotherapy to eliminate a majority of his immune cells, allowing the donor’s stem cells to generate a healthier immune system.
Ideally, the man would have received HIV-resistant stem cells; however, these were unavailable, leading doctors to use cells with one typical and one mutated copy of the CCR5 gene. During this time, the patient was undergoing conventional HIV care known as antiretroviral therapy (ART), a regimen of medications that suppress the virus to undetectable levels, preventing transmission and reducing the likelihood of donor cells becoming infected.
Approximately three years post-transplant, he opted to discontinue ART. “He felt that he had waited long enough after the stem cell transplant and believed his cancer was in remission, so he anticipated a positive outcome from the transplant,” Gabler explained.
Shortly thereafter, tests revealed no traces of the virus in the man’s blood samples. Since then, he has remained free of the virus for seven years and three months, qualifying him as “cured.” He holds the record for the second-longest duration HIV-free amongst the seven declared cases, achieving this status longer than some by around a dozen years. “It’s astonishing that a decade ago he was very likely facing death from cancer, and now he has conquered a terminal diagnosis of a lingering viral infection without any medication. He is in good health,” Gabler remarked.
This discovery challenges our perceptions of what it entails to treat HIV through this method. “We once believed that transplantation required a donor without CCR5, but now it seems that’s not the case,” points out Ravindra Gupta from the University of Cambridge, who was not part of the study.
It’s generally assumed that the success of such treatments hinges on the inability of the virus to hide within remaining immune cells of the recipient after chemotherapy, thus preventing infection or replication in the donor’s cells. “Essentially, you deplete the pool of host cells that the virus can infect,” argues Gabler.
Nevertheless, Gabler speculates that the latest cases imply a potential cure can be achieved as long as non-resistant donor cells can eliminate the recipient’s remaining original immune cells before the virus has a chance to spread. Such immune responses often arise from variations in the proteins that the two cell sets display. These, he notes, enable donor cells to recognize the remaining recipient cells as a threat that must be eradicated.
The findings indicate a wider array of stem cell transplants might offer the possibility of curing HIV than previously believed, including those that do not exhibit two copies of the CCR5 mutation, according to Gabler.
However, for this to be effective, several factors must align, such as the genetic compatibility between the recipient and donor to ensure the donor’s cells can swiftly eradicate the recipient’s cells. Additionally, in the most recent case, the man possessed one copy of the CCR5 mutation, which may have modified his immune cell dynamics throughout his body, aiding in the eradication of the virus, Gabler noted.
This suggests that most individuals undergoing stem cell transplants for HIV or blood cancers should ideally receive HIV-resistant stem cells, as emphasized by Gabler.
It’s crucial to recognize that individuals with HIV who do not have cancer will not gain from stem cell transplants, as these procedures are highly risky and prone to life-threatening infections, Gabler warns. Most experts agree that adhering to ART (typically taken in pill form daily) is substantially safer and more practical for halting HIV’s spread. This approach allows many to lead longer, healthier lives. Moreover, a newly available medication, lenacapavir, offers nearly complete protection against HIV with just two injections annually.
Despite this, research continues on treating HIV through gene editing of immune cells and exploring preventive vaccines.
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Source: www.newscientist.com
