8 ms·

Long-acting injectable is effective in preventing HIV acquisition in women

157 points by _Microft 6y ago

msla 6y ago
> A similar study (HPTN 083) in HIV-uninfected cisgender men who have sex with men and transgender women who have sex with men, was also stopped early by its DSMB in May 2020, after it also demonstrated that CAB LA was highly effective in preventing HIV acquisition in this group. So it works on people who are physiologically male, too, but this study seems to have been specifically about people who are physiologically female. (I guess. They don't mention results for trans men, so I don't know if they're neglecting that group or what's going on there.)
- valarauko 6y ago
  >They don't mention results for trans men, so I don't know if they're neglecting that group or what's going on there Might just be an issue with recruiting enough statistically sufficient numbers of trans men for the study group.
- heavyset_go 6y ago
  There are other trials for HIV vaccines in the US that are recruiting MSM, and some that are specifically recruiting trans people.
PaulHoule 6y ago
That family of drugs is highly promising because in combination with other HIV drugs it may be able to deplete the inactive form of the virus hiding and really curve HIV.
- est31 6y ago
  Why would it deplete the inactive form of the virus? The drug prevents HIV from including itself into the DNA of host cells, but if the virus has already accomplished this and is a provirus inside resting T cells, this drug can't do anything about it. It can only prevent this from happening in the first place.
  - onychomys 6y ago
    In reservoirs, there's ongoing cryptic replication, which would be blocked by drug. That is, the virus wakes up every so often, replicates (killing the host cell), infects another cell nearby, and then goes back to sleep. Blocking any one of those steps would eliminate the reservoir. There's actually some pretty promising work that's been done on how to wake up all the virus at once, because if you do that while the person is on ART, the reservoir would be entirely eliminated!
    - est31 6y ago
      Oh cool, didn't know that. That makes it way more promising then!
    - pmiller2 6y ago
      It seems like waking up all the dormant virus at once could cause some serious problems, especially if ART isn't 100% effective. Is this an actual concern, does it not happen, or is it just not an issue in practice?
est31 6y ago
More info: https://en.wikipedia.org/wiki/Cabotegravir https://en.wikipedia.org/wiki/Cabotegravir Most importantly: > In theory, this would make possible suppression of HIV with dosing as infrequently as once every three months. I guess to attain this, you'll still need multiple drugs of this kind, as due to HIV's incredibly high mutation rate, anything but triple therapy is a lost cause.
- onychomys 6y ago
  PrEP prevents transmission of the virus by having a non-infected person on the medication. So there's no need to worry about mutation, because the only time the virus sees the drug is when it first gets into a new host, at which point it is unable to replicate. You wouldn't want to use this on somebody who is already positive.
  - est31 6y ago
    That makes total sense. Thanks for explaining!
  - postalrat 6y ago
    If it was used on someone positive would HIV mutate and allow that person to spread it to people who took the medication before being exposed to HIV?
    - heavyset_go 6y ago
      The two forms of FDA-approved PrEP are just medications that are already used on people who are HIV positive. Truvada and Descovy are used to treat HIV infections, as well as to prevent it in people who don't have it.
xiphias2 6y ago
Arm A – CAB LA (as an intramuscular injection every 8 weeks) and daily oral TDF/FTC placebo. Arm B – Daily oral TDF/FTC and intramuscular CAB LA placebo every 8 weeks. Taking an oral medication + injection every 8 weeks looks a little bit too hard to follow to me for preventing HIV acquisition. I'm more optimistic for HIV vaccines on the long term, though right now it's not the highest priority for the 2 mRNA vaccine winners. BioNTech has HIV vaccine in preclicical stage though: https://biontech.de/science/pipeline https://biontech.de/science/pipeline
- gizmo686 6y ago
  You don't need both. The new treatment is only a bi-monthly injection. Study participants only needs both the injection and daily oral medication due to the study design. Since they were comparing the new (injection) treatment with an old (oral) treatment, participants needed to go through the motions of both so that they could be properly blinded.
  - xiphias2 6y ago
    Ah sorry, I didn’t read it carefully enough, thanks for the explanation!
- abeppu 6y ago
  > Taking an oral medication + injection every 8 weeks looks a little bit too hard to follow to me for preventing HIV acquisition. In the US, PrEP is normally a daily pill, plus testing (typically an in-office blood draw) for both HIV but also kidney function every 90 days. 8 weeks vs 90 days isn't _that_ different, and visiting a health care provider to get an injection vs a blood draw seems quite similar. So in terms of patient experience, this treatment + placebo combination during their trial doesn't seem that far off from what a lot of people are already doing. The prospect of moving to _only_ the long-term injection (and perhaps supporting tests done at the same time?) would be appealing for many.
jxramos 6y ago
So when we speak of body fluids transmitting STDs during intercourse, particularly HIV, are we talking specifically about semen and preejaculate for men and cervical mucous for women? And do those virus particles wind up in those fluids not through any targeted mechanism but rather are pervasive in the blood and essentially leach out into all tissues and interstitial fluid? So when the semen is generated and collected in the epididymus they've been soaking in virus contaminated fluids lying dormant until release? Is that accurate? Also for the women half I suppose the mucous glands on the cervix make a steady release of virus particles? What's going on here exactly with these viral mechanisms as they relate to tissues and the fluids they produce and precisely how the virus winds up in the fluids.
Angostura 6y ago
This sounded very exciting, but 'long acting' in this case is 8 weeks which, feels quite a frequent interval to have a jab. I wonder whether to what extent the people struggling with daily oral pills will be able to manage goig for injections every two months. Still, every small bit of good news is good news.
- dillondoyle 6y ago
  Maybe bundle with Suboxone doctor visits or other harm reduction sites
- vmception 6y ago
  I mean that’s about the same interval that the sexually active population should be getting tested, which is a blood test, which is a jab. Thats a best practice which mitigates most issues around sex to begin with, so this wouldnt be an abnormal for treatment. I feel like insurance providers could and should reeducate adults on modern sex education, since most adults have a patchwork of outdated best practices based mostly on fear, alongside missing some vaccinations.
  - smnrchrds 6y ago
    > I mean that’s about the same interval that the sexually active population should be getting tested Is that an official recommendation? I cannot find a source for this.
    - stevesimmons 6y ago
      The CDC recommendation for HIV tests is at least every 12 months, and every 3-6 months for gay men with casual partners. In the UK, the Terrence Higgins Trust, the AIDS charity, also recommends every 3-6 months for gay men with new or casual partners. If any people from the UK are reading this, free STD/HIV home test kits are widely available. In London, for instance, order them from https://www.shl.uk https://www.shl.uk. If you're a gay guy and you haven't been tested recently, go do it!
heavyset_go 6y ago
There are several HIV vaccines and monoclonal antibody treatments for HIV that are going, or about to go, through clinical trials in the US if anyone is curious about them or wants to contribute to the research.

157 points by _Microft 6y ago

msla 6y ago

> A similar study (HPTN 083) in HIV-uninfected cisgender men who have sex with men and transgender women who have sex with men, was also stopped early by its DSMB in May 2020, after it also demonstrated that CAB LA was highly effective in preventing HIV acquisition in this group. So it works on people who are physiologically male, too, but this study seems to have been specifically about people who are physiologically female. (I guess. They don't mention results for trans men, so I don't know if they're neglecting that group or what's going on there.)

valarauko 6y ago
>They don't mention results for trans men, so I don't know if they're neglecting that group or what's going on there Might just be an issue with recruiting enough statistically sufficient numbers of trans men for the study group.
heavyset_go 6y ago
There are other trials for HIV vaccines in the US that are recruiting MSM, and some that are specifically recruiting trans people.

PaulHoule 6y ago

That family of drugs is highly promising because in combination with other HIV drugs it may be able to deplete the inactive form of the virus hiding and really curve HIV.

est31 6y ago
Why would it deplete the inactive form of the virus? The drug prevents HIV from including itself into the DNA of host cells, but if the virus has already accomplished this and is a provirus inside resting T cells, this drug can't do anything about it. It can only prevent this from happening in the first place.
- onychomys 6y ago
  In reservoirs, there's ongoing cryptic replication, which would be blocked by drug. That is, the virus wakes up every so often, replicates (killing the host cell), infects another cell nearby, and then goes back to sleep. Blocking any one of those steps would eliminate the reservoir. There's actually some pretty promising work that's been done on how to wake up all the virus at once, because if you do that while the person is on ART, the reservoir would be entirely eliminated!
  - est31 6y ago
    Oh cool, didn't know that. That makes it way more promising then!
  - pmiller2 6y ago
    It seems like waking up all the dormant virus at once could cause some serious problems, especially if ART isn't 100% effective. Is this an actual concern, does it not happen, or is it just not an issue in practice?

est31 6y ago

More info: https://en.wikipedia.org/wiki/Cabotegravir https://en.wikipedia.org/wiki/Cabotegravir Most importantly: > In theory, this would make possible suppression of HIV with dosing as infrequently as once every three months. I guess to attain this, you'll still need multiple drugs of this kind, as due to HIV's incredibly high mutation rate, anything but triple therapy is a lost cause.

onychomys 6y ago
PrEP prevents transmission of the virus by having a non-infected person on the medication. So there's no need to worry about mutation, because the only time the virus sees the drug is when it first gets into a new host, at which point it is unable to replicate. You wouldn't want to use this on somebody who is already positive.
- est31 6y ago
  That makes total sense. Thanks for explaining!
- postalrat 6y ago
  If it was used on someone positive would HIV mutate and allow that person to spread it to people who took the medication before being exposed to HIV?
  - heavyset_go 6y ago
    The two forms of FDA-approved PrEP are just medications that are already used on people who are HIV positive. Truvada and Descovy are used to treat HIV infections, as well as to prevent it in people who don't have it.

xiphias2 6y ago

Arm A – CAB LA (as an intramuscular injection every 8 weeks) and daily oral TDF/FTC placebo. Arm B – Daily oral TDF/FTC and intramuscular CAB LA placebo every 8 weeks. Taking an oral medication + injection every 8 weeks looks a little bit too hard to follow to me for preventing HIV acquisition. I'm more optimistic for HIV vaccines on the long term, though right now it's not the highest priority for the 2 mRNA vaccine winners. BioNTech has HIV vaccine in preclicical stage though: https://biontech.de/science/pipeline https://biontech.de/science/pipeline

gizmo686 6y ago
You don't need both. The new treatment is only a bi-monthly injection. Study participants only needs both the injection and daily oral medication due to the study design. Since they were comparing the new (injection) treatment with an old (oral) treatment, participants needed to go through the motions of both so that they could be properly blinded.
- xiphias2 6y ago
  Ah sorry, I didn’t read it carefully enough, thanks for the explanation!
abeppu 6y ago
> Taking an oral medication + injection every 8 weeks looks a little bit too hard to follow to me for preventing HIV acquisition. In the US, PrEP is normally a daily pill, plus testing (typically an in-office blood draw) for both HIV but also kidney function every 90 days. 8 weeks vs 90 days isn't _that_ different, and visiting a health care provider to get an injection vs a blood draw seems quite similar. So in terms of patient experience, this treatment + placebo combination during their trial doesn't seem that far off from what a lot of people are already doing. The prospect of moving to _only_ the long-term injection (and perhaps supporting tests done at the same time?) would be appealing for many.

jxramos 6y ago

So when we speak of body fluids transmitting STDs during intercourse, particularly HIV, are we talking specifically about semen and preejaculate for men and cervical mucous for women? And do those virus particles wind up in those fluids not through any targeted mechanism but rather are pervasive in the blood and essentially leach out into all tissues and interstitial fluid? So when the semen is generated and collected in the epididymus they've been soaking in virus contaminated fluids lying dormant until release? Is that accurate? Also for the women half I suppose the mucous glands on the cervix make a steady release of virus particles? What's going on here exactly with these viral mechanisms as they relate to tissues and the fluids they produce and precisely how the virus winds up in the fluids.

Angostura 6y ago

This sounded very exciting, but 'long acting' in this case is 8 weeks which, feels quite a frequent interval to have a jab. I wonder whether to what extent the people struggling with daily oral pills will be able to manage goig for injections every two months. Still, every small bit of good news is good news.

dillondoyle 6y ago
Maybe bundle with Suboxone doctor visits or other harm reduction sites
vmception 6y ago
I mean that’s about the same interval that the sexually active population should be getting tested, which is a blood test, which is a jab. Thats a best practice which mitigates most issues around sex to begin with, so this wouldnt be an abnormal for treatment. I feel like insurance providers could and should reeducate adults on modern sex education, since most adults have a patchwork of outdated best practices based mostly on fear, alongside missing some vaccinations.
- smnrchrds 6y ago
  > I mean that’s about the same interval that the sexually active population should be getting tested Is that an official recommendation? I cannot find a source for this.
  - stevesimmons 6y ago
    The CDC recommendation for HIV tests is at least every 12 months, and every 3-6 months for gay men with casual partners. In the UK, the Terrence Higgins Trust, the AIDS charity, also recommends every 3-6 months for gay men with new or casual partners. If any people from the UK are reading this, free STD/HIV home test kits are widely available. In London, for instance, order them from https://www.shl.uk https://www.shl.uk. If you're a gay guy and you haven't been tested recently, go do it!

heavyset_go 6y ago

There are several HIV vaccines and monoclonal antibody treatments for HIV that are going, or about to go, through clinical trials in the US if anyone is curious about them or wants to contribute to the research.