{"id":38414,"date":"2020-07-22T07:47:47","date_gmt":"2020-07-22T07:47:47","guid":{"rendered":"http:\/\/i-base.info\/htb\/?p=38414"},"modified":"2021-02-11T14:36:41","modified_gmt":"2021-02-11T14:36:41","slug":"generic-hepatitis-c-drugs-sofosbuvir-and-daclatasvir-linked-to-faster-recovery-from-covid-19-and-reduced-mortality","status":"publish","type":"post","link":"https:\/\/i-base.info\/htb\/38414","title":{"rendered":"HepC drugs for COVID-19: sofosbuvir\/daclatasvir show faster recovery and reduced mortality"},"content":{"rendered":"

\"\"<\/strong><\/p>\n

NOTE: DAAs have since been shown to NOT work against COVID-19.<\/strong><\/em><\/p>\n

Simon Collins, HIV i-Base<\/span><\/strong><\/p>\n

Tentative results from a small Iranian study using a combination of direct acting antivirals (DAAs) used to treat hepatitis C \u2013 sofosbuvir and daclatasvir (SOF\/DCV) \u2013 led to faster recovery from COVID-19. In a meta-analysis with two other small studies the combination also reduced mortality.<\/strong><\/p>\n

The results were presented by Andrew Hill from Liverpool University at a press conference for the IAS COVID-19 workshop after AIDS2020. The study was presented in full by\u00a0Anahita Sadeghi\u00a0from Tehran University. [1]<\/span><\/p>\n

Both drugs have shown some evidence of in-vitro or in-silico activity against SARS-CoV-2, at equivalent to standard dosing. [2, 3, 4]<\/p>\n

The main study was an open-label multicentre trial in Tehran that randomised 66 adults hospitalised with severe PCR-confirmed COVID-19 to either SOF\/DCV or standard of care, which included lopinavir\/r for both arms. Other entry criteria included fever (\u226537.8\u00b0C) plus at least one of: respiratory rate >24\/min, O2Sat<94% or Pa02\/Fi02 ratio <300mgHg. [5]<\/p>\n

The primary outcome was clinical recovery within 14 days (defined as normalised temperature, respiratory rate or oxygen saturation) with secondary outcomes that includes all-cause mortality.<\/p>\n

Baseline characteristics were reported as similar and included approximate median age 60 (IQR: 25 to 70), 61% vs 42% men, enrolment within 1 day of admission. Although comorbidities were also not reported as significantly different, diabetes was reported more in the active arm (52% vs 33%, p=0.213), and chronic lung disease reported less (18% vs 27%, p=0.558). Median O2 saturation was 91% vs 90%, p=0.225, also in active vs control arm respectively.<\/p>\n

Although <\/span>the percentage of participants with <14 day recovery favoured the active arm: 88% vs 67% (n=29 vs 22), this was not statistically significant (p=0.076). However, i<\/span>n a multivariate analysis using logistic regression (for some reason not presented) the effect was significant after adjustment for baseline characteristics (supplementary data, in press).<\/p>\n

Time to clinical recovery, a secondary endpoint, was significantly faster in the active vs SoC arm: median 6 days (IQR: 4 to 10) vs 11 days (IQR: 6 to 17), p=0.041. <\/span><\/p>\n

When combined in a meta-analysis (n=176) with results from two other similar size studies (the Abadan and Sari studies, n=62 and 48, respectively) time to clinical recovery significantly favoured SOF\/DCV: s<\/span>ubhazard ratio 2.03 (95% CI 1.33 to 3.08); SHR p-value <0.001. However, these studies, both also small, had different designs and also included ribavirin (one in a control arm and one with SOF\/DCV).<\/span><\/p>\n

Mortality in the meta-analysis was significantly reduced in the SOF\/DCV arm: 5.4 % (5\/92) vs 20% (17\/84), p=0.013.<\/p>\n

comment<\/h3>\n

These are small studies and design differences also caution the interpretation of results from the meta-analysis. The tentative results also clearly need to be supported by larger randomised clinical studies, but one of these (n=600) is already underway. [6]<\/strong><\/p>\n

Although both drugs are still in-patent high-cost medicines (approx. list price $18,000 and $7,000 for a 14-day treatment in the US and UK respectively), generic versions of a combined dual formulation are available for $7 or less. [7, 8]<\/strong><\/p>\n

The study has also been selected as one of five clinical highlights selected by Anthony Fauci from the IAS virtual COVID-19 workshop that will take place directly after AIDS2020. [9]<\/strong><\/p>\n

References<\/p>\n

    \n
  1. Wentzel et al. Sofosbuvir and daclatasvir for the treatment of\u00a0COVID-19: Results from a randomised controlled trial. IAS COIVD-19 Conference, 10-11 July 2020.
    \nhttps:\/\/cattendee.abstractsonline.com\/meeting\/9307\/presentation\/3933<\/a><\/li>\n
  2. Elfiky AA et al. Quantitative structure-activity relationship and molecular docking revealed a potency of anti-hepatitis C virus drugs against human corona viruses. J Med Virol 2017; 89: 1040-7.
    \n    https:\/\/pubmed.ncbi.nlm.nih.gov\/27864902<\/a><\/li>\n
  3. Beck BR et al. Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model. Comput Struct Biotechnol J 2020; 18: 784-90.
    \n    https:\/\/www.biorxiv.org\/content\/10.1101\/2020.01.31.929547v1<\/a><\/li>\n
  4. Sacramento CQ et al. The in vitro antiviral activity of the anti-hepatitis C virus (HCV) drugs daclatasvir and sofosbuvir against SARS-CoV-2. bioRxiv. 2020 [preprint].
    \n    https:\/\/www.biorxiv.org\/content\/10.1101\/2020.06.15.153411v1<\/a><\/li>\n
  5. Iranian Trial Registry. A prospective randomized controlled trial comparing antiviral Sovodak (sofosbuvir+daclatasvir) in participants with moderate to severe Coronavirus disease (COVID-19) compared to standard of care treatment.IRCT20200128046294N2.
    \n    https:\/\/en.irct.ir\/trial\/46463<\/a><\/li>\n
  6. Iranian Trial Registry. Evaluation of the effect of sofosbuvir\/daclatasvir in COVID-19 patients: A randomized double-blind clinical trial (DISCOVER study).
    \n    https:\/\/en.irct.ir\/trial\/49198<\/a><\/li>\n
  7. Hill A et al. Minimum costs to manufacture new treatments for COVID-19. J Virus Erad 2020; 6: 61-9.
    \n    https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC7213074<\/a><\/li>\n
  8. Clayden P. Potential treatments for COVID-19 could be manufactured for $1 a day or less. HTB (17 April 2020).
    \n    https:\/\/i-base.info\/htb\/37606<\/a><\/li>\n
  9. Fauci A. IAS COVID-19 workshop. 10-11 July 2020.<\/li>\n<\/ol>\n

    This article was first posted on 9 July 2020.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"

    NOTE: DAAs have since been shown to NOT work against COVID-19. Simon Collins, HIV i-Base Tentative results from a small Iranian study using a combination of direct acting antivirals (DAAs) used to treat hepatitis C \u2013 sofosbuvir and daclatasvir (SOF\/DCV) …<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4,283,278],"tags":[297],"class_list":["post-38414","post","type-post","status-publish","format-standard","hentry","category-conference-reports","category-covid-19-investigational-drugs","category-covid-19","tag-ias-covid-19"],"_links":{"self":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/38414","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/comments?post=38414"}],"version-history":[{"count":0,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/posts\/38414\/revisions"}],"wp:attachment":[{"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/media?parent=38414"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/categories?post=38414"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/i-base.info\/htb\/wp-json\/wp\/v2\/tags?post=38414"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}