By Ritika Sakhuja
New Delhi: People with human immunodeficiency virus (HIV) experience the associated taboo, inciting an ‘out of sight, out of mind’ response among the general public. As per World Health Organisation (WHO), globally, 38.4 million people were living with HIV at the end of 2021, amounting to 0.4 per cent of the total world population, which is a significant number that cannot be overlooked. Despite a widespread lack of awareness among the masses, healthcare professionals and scientists all around the world are actively searching for a cure.
At the International AIDS Conference in Montreal, held in July’22, scientists reported that an American man with HIV had possibly been cured of the virus through a stem cell transplant (SCT). This approach has demonstrated apparent success in four other cases. Although experts adamantly suggest that a stem cell transplant is an extremely risky treatment for anyone who isn’t already facing a fatal health condition that would make such treatment viable for them, no progress can be ignored if it’s against a fatally infectious disease that has been prevalent for four decades and still doesn’t have a cure.
Stem cell transplant: potential HIV treatment
The healthcare industry accidentally stumbled upon SCT as a potential treatment for HIV. Calling it a blessing in disguise, Dr Neha Rastogi, Consultant, Infectious Disease, Fortis Memorial Research Institute, spoke to ETHealthworld on World AIDS Day about the mechanics behind an SCT indicated for a patient living with HIV. Dr Rastogi shared, “When the first case came in of the ‘Berlin patient,’ he was also diagnosed with acute myeloid leukaemia, which is a type of blood cancer. To treat blood cancer, the patient received a donor-derived stem cell transplant, where the donor was already deficient in a CCR-5 gene which is an entry receptor for HIV (this information was discovered after the patient was accidentally cured of HIV). So when the diseased bone marrow was replaced with CCR-5 deficient bone marrow, it cured the patient of HIV.”
Explaining how HIV actually spreads throughout the body, Dr Ankita Baidya, Consultant Infectious Disease, HCMCT Manipal Hospitals, said, “HIV attaches to a cell through the CCR-5 receptor, through which it goes inside the cell and starts multiplying. HIV then attaches to a separate receptor that is called CXCR4 receptor which is predominantly on the lymphocyte CD4 cell from where it attaches, multiplies and kills the CD4 cell.”
When HIV infects a body, it forms miniature particles that bury deep into hidden sanctuary sites within the body, mainly in the bone marrow. To rid the body of HIV, all these hidden sites need to be cleaned as well, and that is the exact function that a stem cell transplant performs, by removing the existing source and replacing it with new bone marrow which doesn’t take up new HIV cells.
Viability of SCT
Dr Baidya warns that SCT should not be offered anywhere globally just for the cure of HIV. She said, “The person who undergoes a bone marrow transplant (BMT) needs immuno-modulators, steroids, or some other heavy medicines to ensure that the body doesn’t reject the transplant. These medications hamper immunity, making the patient susceptible to more infections. Secondly, CCR-5 mutated bone marrow donors are also limited. It was just a matter of chance that in the case where HIV was cured or remitted after BMT, the donor was deficient in the CCR-5 gene. Additionally, the healthcare system does not screen for this mutation in all bone marrow donors.”
Reciprocating the above sentiment, Dr Rastogi said, “Providing an SCT to a patient infected with HIV, who is otherwise healthy, is totally a medico-legal process. SCT is not a definitive indication for HIV. SCT for exclusively curing HIV is only possible when you have the CCR-5 gene mutations. So, firstly you will need a pre-transplant workup. Talking in terms of medical science intervention, studies are ongoing about this mechanism.”
“Stem cell transplant is additionally an extremely costly procedure. Both SCT and HIV potentially suppress the immune system. So post-transplant recovery and complications can further increase the financial burden,” added Dr Rastogi.
Promise of gene editing
Although SCT seems plausible only for HIV patients with comorbidities, the genetic mutation that allows SCT to remit HIV suggests how gene therapy may be a promising cure for HIV.
Gene editing refers to modifying a certain gene to alter its function or phenotype. The gene editing techniques used in HIV therapy mainly include RNA interference, programmable nuclease-based editing, and recombinant enzymes in vitro, which are the most advanced systems currently available for effectively, and in some cases, permanently tackling HIV genomes.
It was recently reported that scientists at Northwestern Medicine are using new advances in CRISPR gene-editing technology to discover longer-lasting treatments and new therapeutic strategies for curing HIV. The team successfully identified human genes that were important for HIV infection in the blood, finding 86 genes that may play a role in the way HIV replicates and causes disease, including over 40 that have never been looked at in the context of HIV infection.
With more understanding of how the virus replicates, finding a cure seems a likely possibility in the near future.
Shrouded by lack of awareness
With HIV still being taboo, it becomes increasingly essential to spread awareness about the possible treatment options available for HIV patients who often lose hope after diagnosis. The community needs to be sensitised and made aware of the many modes of transmission of HIV, to make sure that infected people seek timely treatment. A gap in treatment and recorded cases further hampers the healthcare system to take relevant strides in advancing the research around HIV.
Dr Baidya provided insights that many patients diagnosed with HIV often enquire about SCT. Hence, it is essential for the masses to be aware of the potential threats and efficacy of various treatment options, especially for a disease like HIV which is shrouded in a rampant lack of awareness, to ensure that patients all around the world receive appropriate and more importantly safe treatments.