Could a quarterly injection prevent HIV infection?

PrEP (pre-exposure prophylaxis) is the term used for methods to prevent disease transmission before contact with the disease occurs, thereby preventing infection.

Vaccinations can be an example of this technique. Getting Yellow Fever is a possibility if someone travels to Africa. To protect the traveler, he gets vaccinated against Yellow Fever weeks before the trip. The vaccination may then protect him from the disease should he be exposed to it.

In HIV, PrEP centers around taking an oral medication daily to prevent infection by HIV in conjunction with condom use.

About two years ago, the FDA approved a combination of two antiretroviral medications that can be given together as PrEP for HIV in sexually-active people. These medications are tenofovir disoproxil fumarate plus emtricitabine (TDF/FTC) [Truvada®], which can be given together as a single dose.

In studies, PrEP seems to be quite effective in decreasing HIV transmission in men who have sex with men (MSMs). However, some trials showed that PrEP wasn’t as effective in some cases. This seemed to be due to non-compliance. That is, the patients were not taking the PrEp medication as they were supposed to on a daily basis.

HIV virus attacking cell. 3D render, via Shutterstock.

HIV virus attacking cell. 3D render, via Shutterstock.

However, PrEP isn’t being used as much as was anticipated. There may be a few different reasons for this. Some people, even in higher risk groups, don’t feel that they are at risk to get HIV and therefore don’t even consider PrEP. Some may feel that HIV is now an easily treatable disease and not a major threat, and therefore don’t consider PrEP. Others may not be aware that PrEP even exists. Some may not want to experience the side effects that these drugs can cause. Still others may not like the thoughts of taking a pill every day (as mentioned previously in the trials showing a lower rate of prevention of HIV transmission.) For whatever reason(s), PrEP as a daily dose, isn’t being used much.

Investigators are working on a technique where PrEP can be injected once monthly, or perhaps once every few months.

To date, this research has only been carried out in a small number of male monkeys using an antiretroviral medication, GSK1265744-LAP. This medication is an integrase inhibitor that is already in human clinical trials. To replicate in a host cell, HIV’s RNA needs to be converted to DNA in the host cell (CD4+). Then it needs to be merged with the cell’s own native DNA. Integrase inhibitors block this merger of the two strands of DNA.

The researchers took this drug, in a special formulation, and injected it into monkeys. They chose this drug because it has a long half-life. That is, the drug will remain in the monkey’s plasma for much longer than a dose of some other antiretrovirals. In humans, the half-life can range from about 3 weeks to about 8 weeks, depending on the dose given. After the drug was injected, the scientists attempted to infect the monkeys with SIV, a virus that is similar to HIV and can infect monkeys. The scientists tried to infect the monkeys several times with SIV over about a 2-month period. Control monkeys, who were not given the antiretroviral injection, were also exposed to SIV multiple times.

The results showed that all of the monkeys exposed to SIV, and who weren’t given the integrase inhibitor, became infected with SIV. None of the monkeys who did get the drug developed an infection with SIV.

These results are promising. The investigators feel that this medication, in this formulation, might be the next generation of PrEP. An injection that people will get monthly, or perhaps, quarterly, could help prevent the acquisition of HIV. However, there is still a lot of work to be done before this antiretroviral and this technique can be considered for use in humans.

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Mark Thoma, MD, is a physician who did his residency in internal medicine. Mark has a long history of social activism, and was an early technogeek, and science junkie, after evolving through his nerd phase. Favorite quote: “The most exciting phrase to hear in science... is not 'Eureka!' (I found it!) but 'That's funny.'” - Isaac Asimov

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