Therapeutic Interfering Particles (TIPs)
A team of researchers at the University of California at San Francisco (UCSF) has developed a completely different approach to control HIV and have recently published the results of experiments with monkeys and human cells. This approach is called therapeutic interfering particles, or TIPs.
An over-simplified explanation of TIPs follows. Researchers have created highly mutated but harmless versions of HIV and its analogue SIV (simian immunodeficiency virus; this causes an AIDS-like disease in susceptible monkeys). These mutated viruses, called TIPs, are unable to cause disease because they have vital information deleted from their genetic information.
When HIV-infected cells are exposed to TIPs, their ability to produce infectious HIV is greatly diminished. The UCSF scientists say that this effect happens because TIPs reproduce faster than infectious HIV, and in the process, TIPs “steals essential viral proteins” from HIV-infected cells. The scientists also said that another way to think about TIPs is that they are a “molecular parasite” of HIV-infected cells.
Monkey research
The UCSF scientists cooperated with scientists in Oregon who work with monkeys. The team of scientists developed a hybrid virus called SHIV, using elements of HIV and SIV. The reason for using this hybrid virus is that it can cause an AIDS-like disease in monkeys within a few months after infection (rather than more than a year with SIV). This way, scientists can determine in a relatively shorter time if their intervention against SIV is working.
A single intravenous infusion of TIPs protected five out of six monkeys infected with SHIV from developing AIDS-like disease for at least six months (the length of the experiment). TIPs had this effect on the course of disease because it greatly suppressed production of SHIV in blood and lymph nodes.
Tests revealed that the immune systems of TIPs-treated monkeys were fully functional and there was no increased level of inflammation. Analysis of SHIV samples from TIPs-treated monkeys found that the hybrid virus was unable to evade TIPs or mutate to avoid it.
TIPs reduced the amount of SHIV in monkeys by a factor of approximately 10,000. This and other effects were maintained for just over six months.
Additional research with monkeys is needed whereby SHIV-infected monkeys are treated with HIV treatment (antiretroviral therapy, ART) to suppress the virus. They can then be given TIPs and ART can be withheld. This research is important because it might mimic what some humans would like to do if they were given TIPs.
Potential in humans with just one dose
Based on results in monkeys with SHIV, the researchers developed computer simulations of the effect of one dose of TIPs in people with HIV.
The simulations predicted that TIPs could reduce the HIV viral load in the blood to less than 1,000 copies/mL. At this level of viral load, previous research suggests that people would be extremely unlikely to pass on HIV via sex.
Human research needed
Based on promising experiments with monkeys and T-cells in the lab, the scientists developing TIPs hope to enroll people with HIV to test the effect of an infusion of TIPs. Although there is no evidence of harm in monkeys that have received TIPs, scientists are unsure about its safety in people and its potential to cause unwanted effects, perhaps even cancer (though so far there is no evidence of cancer-causing potential from TIPs in lab experiments with cells and in monkeys). So, the scientists want to recruit people with HIV who have a diagnosis of terminal cancer for the first infusion of TIPs. After the participants die from complications caused by cancer, the researchers hope to conduct autopsies to assess the impact of TIPs on their organs and immune system.
In the future, if TIPs is found to be safe, it is possible that some people given TIPs could pass on the particles the same way that HIV is most commonly transmitted—through condomless intercourse. This possibility needs to be better understood. Professor Leor Weinberg, the scientist behind TIPs, has mused that the transmission of TIPs from one person to another could be seen as a public health benefit, as it would block the spread of HIV. However, this issue needs to be examined by ethicists. Also, much more information about the long-term safety of TIPs is needed.
Bear in mind
It is still early days with TIPs. Much research lies ahead, and it will be several years before large studies in healthy people with HIV can begin.
—Sean R. Hosein
REFERENCES:
- Pitchai FNN, Tanner EJ, Khetan N, et al. Engineered deletions of HIV replicate conditionally to reduce disease in nonhuman primates. Science. 2024 Aug 9;385(6709):eadn5866.
- Cohen J. Fire-against-fire HIV therapy passes key test in monkeys. Science. 2024 Aug 9;385(6709):586-587.