Long-time readers of ERV know that I am not a fan of Pre-Exposure Prophylactics as a regular means of preventing HIV infection. In tightly controlled clinical trials, giving people who might be exposed to HIV anti-HIV drugs does lower infection rates... but when the same protocol is let loose 'out in the wild', the results are not as good. Some are disastrously bad.
And thats just following infection rates-- Thats not even addressing the long-term effects sub-optimal levels of antiretrovirals has on the HIV population.
A major problem with 'The Pill' to prevent HIV is that people do not take the meds as prescribed. Hell, people will lie/forget, even in clinical trials-- scientists can tell via monitoring pill bottles electronically, and monitoring levels of the drugs in trial participants blood-stream.
When people take the meds, like theyre supposed to, the drugs do work.
The same population dynamics are in effect in unexposed adults, as they are in those babies that were treated ASAP-- Even though there are a GAZILLION different genotypes of HIV in an infected individual, usually only ONE genotype is transmitted. ONE. Sometimes 2-4, but usually ONE.
Unless that ONE variant is resistant to the anti-HIV meds the uninfected person is taking, having the drugs there immediately SHOULD stop the infection.
In theory, this should all work!
But people dont take the meds right.
Is there a way to increase compliance?
What if, instead of taking a pill every day, people went into a clinic for a shot every 3-4 months?
Can we do that???
In this paper, they tried out a new anti-retroviral-- an integrase inhibitor. While drug resistance makes a new weapon in our anti-HIV arsenal always welcome, this new drug, GSK744, is metabolized relatively slowly in humans when administered as a shot (the shot formulation makes it 'slow release'. when its taken orally, the half-life is shorter).
For example, AZT has a half-life of 0.5-3 hours.
Injectable GSK744 has a half-life of 21 to 50 days.
While that looks really good on paper, that doesnt mean a shot of this drug could *PREVENT* HIV infection. The drugs have to be at the right place at the right time in the right concentration.
To determine whether this would even be plausible in humans, in this paper, they gave rhesus macaques doses of GSK744 (eight monkeys), or placebo (another eight monkeys). They then exposed them to infectious virus (a SHIV-- part SIV, part HIV) via rectum (not vaginally exposed. though that would have been immensely useful information, these were all male monkeys).
All the placebo monkeys were infected with the SHIV. Researchers could find viral RNA, and antibodies to the virus in the infected monkeys.
All of the GSK744 monkeys remained uninfected. Researchers could not find any viral RNA OR proviral DNA OR antibodies to the virus (meaning there wasnt even a little infection that got nipped in the bud, but not before the virus got the B-cells attention). No infection.
There are some caveats (they challenged with a relatively homogenous viral stock (SHIVs are not like the quasispecies this kind of therapy would have to face out in nature), and, it was only eight monkeys).
But still, nice. Its hard to argue with 'zero experimental monkeys got infected'.
They took this a step further by attempting to determine how long the monkeys could be protected by one dose of the drug-- Now, these monkeys metabolize GSK744 a lot faster than humans would. 12 got one dose of the drug, 4 got none, and then all where exposed to the SHIV on a schedule. As expected, when the concentration of the drug started to go down, the monkeys started getting infected. But this allowed the researchers to determine what is the lowest concentration of drug is necessary to protect against HIV-- Very important when moving forward to human trials.
These plasma concentrations can be readily achieved in humans with quarterly 800-mg IM injections of GSK744...
Get a shot 4 times a year to prevent HIV infection.
This gets around a few obvious obstacles with a daily pill--
1-- People wouldnt have to remember to take a pill every day/multiple times a day. With a shot, you can forget about it for 3-4 months.
2-- Due to the stigma of HIV, people dont want antiretrovirals in their medicine cabinet. With a shot, no one knows anything except the nurse/physician.
3-- Women in Africa prefer the Depovera shot for preventing pregnancy. Getting Depo and your anti-HIV shot at the same time would be *perfect*. Private, discreet, *perfect*!
We have got to up compliance for pre-exposure prophylactics to work well in the real world-- Maybe this shot, or one like it, will help.
Hi Abby, thanks for writing about PrEP. I'm a gay men's HIV prevention education researcher and your blog has been incredibly helpful to me trying to understand the biology of transmission and resistance, so anything you can write about PrEP will be much appreciated. I wanted to make one quick point about adherence in the PrEP studies -- I think it's relevant that we didn't, at the time of the trial, know whether it was effective or not. I'm reminded of people making a similar argument about treatment roll-out in Africa -- 'there's no point, African don't have fridges and wrist-watches' -- and we know how fucked that assumption turned out to be.