5 ms·

Lancet isn't the only paper that has raised issues with HCQ treatment. Sciencemag [1] has this to say: However, both HCQ and AZ have potential cardiac toxicit

by pen2l 6y ago

Lancet isn't the only paper that has raised issues with HCQ treatment. Sciencemag [1] has this to say: However, both HCQ and AZ have potential cardiac toxicity (QT prolongation, which can lead to fatal arrhythmia), and HCQ additionally has the potential for negative effects on the eye. Understanding risk-benefit ratios is paramount if these drugs are to become a standard of care for COVID-19. Several post hoc analyses carried out in the United States and Europe suggest modest benefit, at best, from HCQ monotherapy for COVID-19 patients; one large post hoc analysis among U.S. veterans suggests that there is harm to patients from HCQ. Given the mechanistic rationale but lack of well-designed clinical studies and potential for drug-induced toxicity, there is a key need for controlled, randomized trials to test the efficacy and safety of these drugs for COVID-19 patients. [1]: https://science.sciencemag.org/content/sci/368/6493/829.full.pdf https://science.sciencemag.org/content/sci/368/6493/829.full... I don't think it's a "shame" that some have decided to stop wtih HCQ when other viable treatments seem to have less concerning side-effects. Either way, we will know very soon with greater certainty as ongoing randomized trials finish up.

lbeltrame 6y ago
Most of these analyses were done in late-stage COVID-19 patients, when any antiviral won't work (same results with remedisivir, lopinavir/ritonavir/ribavirin), that's why the discussion won't stop. Didier Raoult in his very controversial paper suggested prophylaxis after exposure to the virus. And guess what, no one (save the U of Minnesota trial, AFAICS) has done a RCT on that. EDIT: I think it's a "shame" because all analyses so far focused on the late-stage disease, as I said, and because hopefully real RCT results will be out soon (like, real soon, or so I hope).
- mxcrossb 6y ago
  It seems like we’re in trouble if we try to pursue a drug that has to be administered early in the disease process. Such a large percentage of people recover on their own that even a very effective drug has limited returns. And of course you need the infrastructure to detect the disease early and deliver huge supplies. It makes me worry that all antivirals we try will fail.
  - lbeltrame 6y ago
    > It seems like we’re in trouble if we try to pursue a drug that has to be administered early in the disease process. This is the same for remedisivir, and also for ritonavir/lopinavir/ribavirin: they must be given within 7 days of symptom onset to be effective. In fact, the latter was deemed unsuccesful in a first paper, because it was given late, then it was reconsidered when given earlier during the disease. This is not surprising, given how the disease works (outlined also by the Cell paper from yesterday): at some point the consequences of the highly altered inflammatory reaction greatly surpass the effects of the replication of the virus itself. This calls more for extensive and early testing, IMO.
    - ceejayoz 6y ago
      Remdesivir doesn't have the sudden cardiac death side effect, though, does it? HCQ's issue may be a bad combination of "has to be taken early" and "has significant side effects".
      - ytNumbers 6y ago
        HCQ has been around for 70 years. Remdesivir's issue is that everyone gets to be the guinea pig. Sometimes it's better to go with the devil you know.
        ceejayoz 6y ago
        > HCQ has been around for 70 years. Not in an antiviral context, and certainly not for SARS-CoV-2.
        dpoochieni 6y ago
        So? The point here is the safety of it, plus there's research going back to 2006 about its effectiveness for other Coronaviruses. I mean do whatever you want to do, but there's a reason most people in government are taking it. In my country they privately take it, while publicly not endorsing it to prevent shortages
- Yoric 6y ago
  > Didier Raoult in his very controversial paper suggested prophylaxis after exposure to the virus. To be fair, Didier Raoult has changed his own claims several times (including dosage, drug mix and he even switched from chloroquine to hydroxychloroquine – afait, these are different molecules). Including after the studies were started. This doesn't mean that he's wrong, but at this stage, there are so many red flags that it's hard to take anything he said seriously.
  - marvin 6y ago
    For the purposes we're discussing here, Raoult et al. are front-line clinicians working to save lives under extreme uncertainty, with every decision scrutinized with the benefit of hindsight. You shouldn't hold them to the same standard as pure research scientists. Research scientists have all the time in the world, clinicians don't. Once again, it's a peacetime army of bureaucrats vs. an unknown enemy that doesn't have the decency to wait for understanding to catch up with reality. Decisions have to be made with an imperfect understanding, in a reality that changes every day. The truth will seem obvious afterwards, but right now it doesn't. Those not on the front lines should keep to their very important job of improving prospects for the future, and keep the judgement out of it.

by pen2l 6y ago

lbeltrame 6y ago

Most of these analyses were done in late-stage COVID-19 patients, when any antiviral won't work (same results with remedisivir, lopinavir/ritonavir/ribavirin), that's why the discussion won't stop. Didier Raoult in his very controversial paper suggested prophylaxis after exposure to the virus. And guess what, no one (save the U of Minnesota trial, AFAICS) has done a RCT on that. EDIT: I think it's a "shame" because all analyses so far focused on the late-stage disease, as I said, and because hopefully real RCT results will be out soon (like, real soon, or so I hope).

mxcrossb 6y ago
It seems like we’re in trouble if we try to pursue a drug that has to be administered early in the disease process. Such a large percentage of people recover on their own that even a very effective drug has limited returns. And of course you need the infrastructure to detect the disease early and deliver huge supplies. It makes me worry that all antivirals we try will fail.
- lbeltrame 6y ago
  > It seems like we’re in trouble if we try to pursue a drug that has to be administered early in the disease process. This is the same for remedisivir, and also for ritonavir/lopinavir/ribavirin: they must be given within 7 days of symptom onset to be effective. In fact, the latter was deemed unsuccesful in a first paper, because it was given late, then it was reconsidered when given earlier during the disease. This is not surprising, given how the disease works (outlined also by the Cell paper from yesterday): at some point the consequences of the highly altered inflammatory reaction greatly surpass the effects of the replication of the virus itself. This calls more for extensive and early testing, IMO.
  - ceejayoz 6y ago
    Remdesivir doesn't have the sudden cardiac death side effect, though, does it? HCQ's issue may be a bad combination of "has to be taken early" and "has significant side effects".
    - ytNumbers 6y ago
      HCQ has been around for 70 years. Remdesivir's issue is that everyone gets to be the guinea pig. Sometimes it's better to go with the devil you know.
      - ceejayoz 6y ago
        > HCQ has been around for 70 years. Not in an antiviral context, and certainly not for SARS-CoV-2.
        dpoochieni 6y ago
        So? The point here is the safety of it, plus there's research going back to 2006 about its effectiveness for other Coronaviruses. I mean do whatever you want to do, but there's a reason most people in government are taking it. In my country they privately take it, while publicly not endorsing it to prevent shortages
Yoric 6y ago
> Didier Raoult in his very controversial paper suggested prophylaxis after exposure to the virus. To be fair, Didier Raoult has changed his own claims several times (including dosage, drug mix and he even switched from chloroquine to hydroxychloroquine – afait, these are different molecules). Including after the studies were started. This doesn't mean that he's wrong, but at this stage, there are so many red flags that it's hard to take anything he said seriously.
- marvin 6y ago
  For the purposes we're discussing here, Raoult et al. are front-line clinicians working to save lives under extreme uncertainty, with every decision scrutinized with the benefit of hindsight. You shouldn't hold them to the same standard as pure research scientists. Research scientists have all the time in the world, clinicians don't. Once again, it's a peacetime army of bureaucrats vs. an unknown enemy that doesn't have the decency to wait for understanding to catch up with reality. Decisions have to be made with an imperfect understanding, in a reality that changes every day. The truth will seem obvious afterwards, but right now it doesn't. Those not on the front lines should keep to their very important job of improving prospects for the future, and keep the judgement out of it.