In Didier Raoults recent open label study in France
1 , 24 SARS-COV-2 positive patients were given 600 mg Hydroxychloroquine (HC) once daily with our without Azithromycin (A) – dosage unknown:
After 6 days 5% in the HC+A group tested positive, 40% in the HC group and 90% in the control group (it's known A has both anti-inflammatory and anti-viral activity), see the reddit discussion for more detail. HC is being used in several countries and there seems to be no debate about its or Chloroquine's efficacy in China.
We know the combination of Lopinavir/Ritonavir (LR) + Ribavirin (R) is effective against SARS-COV
In one study the adverse clinical outcome (ARDS or death) was significantly lower in the treatment group than in the historical controls (2.4% v 28.8%, p<0.001), dosage LR 400 / 100 mg twice daily for 14 days + a 4 g R oral loading dose followed by 1.2 g R every 8 hours.
There's been one recent study in 18 SARS-COV-2 positive patients where LR was tested, but they used half the dose compared to the above SARS-COV trial and no R which could explain the disappointing results: no observable improvement in the time course of nasopharyngeal virus clearance.3
EDIT: Another study with 199 patients was published today showing no improvement from LR 400 / 100 mg used for 14 days – note that these were severe cases.4
For a more in depth discussion see the Emcrit blogpost https://emcrit.org/pulmcrit/lopinavir/
Could the combination of HC, A, LR and R be an optimal easily available drug cocktail for SARS-COV-2?
Are there any known detrimental interactions between them? Potentially used in stages where LR+R is saved for last given R's side effect profile. In no way an expert on this.
@david87 says the following in his thread about LR+R used against SARS-COV-2
"The two problems that would come up in large scale ribavirin use are hemolytic anemia (can be profound, and in the presence of cardiac comorbidities cause real problems) and serious teratogenicity (FDA labeling is not to get pregnant or get anyone pregnant for 6 months after treatment).
I also wonder what would happen if a G6PD deficient person suddenly was given loading doses of chloroquine/hydroxychloroquine and ribavirin both of which can lead to hemolysis. I'm not sure whether this interaction has been studied."
Raoults et al. Hydroxychloroquine as a treatment of COVID-19: results of an open-label non-randomized clinical trial. PDF from presentation. March 16, 2020.
Chu CM, Cheng VCC, Hung IFN, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004;59:252-256.
Young BE, Ong SWX, Kalimuddin S, et al. Epidemiologic Features and Clinical Course of Patients Infected With SARS-CoV-2 in Singapore. JAMA. Published online March 03, 2020. doi:10.1001/jama.2020.3204
Bin Cao et al. A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19. NEJM. March 18, 2020 DOI: 10.1056/NEJMoa2001282
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