Hydroxychloroquine fails to prevent COVID-19 or SARS-CoV-2 transmission when used as PEP

Simon Collins, HIV i-Base

Results from a large randomised open-label phase 3 study reported hydroxychloroquine (HCQ) had no impact as prophylaxis against COVID-19 and didn’t reduce symptoms in participants who did become infected.

The Barcelona PEP study was run in three regions in Catalonia, and reported in 24 November edition of NEJM. [1]

Between 17 March and 28 April 2020 the study enrolled 2314 adults in who had been in contact with 672 index case patients with confirmed COVID-19. Participants were randomised to open label HCQ (n=1116) or standard of care (n=1198) (based on hand hygiene, face masks, social distancing, and isolation of case patients and contacts).

Contact risk was defined as being within two metres for >15 minutes to 7 days before enrollment and who were at high risk (a health care worker, a household contact, a nursing-home worker, or a nursing-home resident). Participants connected to the same index case were randomised together as a group.

The primary endpoint of incidence of symptomatic COVID-19 confirmed by PCR was similar in both groups: 5.7% vs 6.2%, respectively (risk ratio: 0.86 [95% CI: 0.52 to 1.42]). There were also no differences in SARS-CoV-2 transmission: 18.7% vs 17.8%, respectively.

However, side effects were significantly higher (56.1% vs 5.9%) although these were not related to higher rates of discontinuations from the study.

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Another randomised, double-blind, placebo-controlled clinical study of HCQ as PEP in 132 health workers also found no benefit in preventing infection, but with higher side effects reported in the HCQ arm. [4]

And as this issue of HTB was being compiled, a multicentre US randomised controlled study also reported no benefit of HCQ as PEP (400 mg/day for 3 days followed by 200 mg/day for 11 days) at preventing SARS-CoV-2 infection by day 14. [5] This study had been presented as a late breaker abstract at IDWeek in October 2020.

Other large well-publicised studies have reported that HCQ also has no benefit as treatment from COVID-19 in moderate or advanced infection. [6, 7, 8]

With definitive studies now finding no benefit before infection or in moderate (hospitalised infection) it is difficult to believe that a new study planned in 13 African countries – the ANTICOV study – is likely to find any benefit hydroxychoroquine in early confirmed infection. [9]

References

1. Mitjà et al. A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19. NEJM. DOI: 10.1056/NEJMoa2021801. (24 November 2020).
   https://www.nejm.org/doi/full/10.1056/NEJMoa2021801
2. ClinicalTrials.gov. Treatment of non-severe confirmed cases of COVID-19 and chemoprophylaxis of their contacts as prevention strategy: a cluster randomized clinical trial (PEP CoV-2 Study). NCT04304053.
   https://www.nejm.org/doi/full/10.1056/NEJMoa2021801?query=RP
3. Boulware DR et al. A randomized trial of hydroxychloroquine as postexposure prophylaxis for Covid-19. N Engl J Med 2020;383:517-525. (6 August 2020).
   https://www.nejm.org/doi/full/10.1056/NEJMoa2016638
4. Abella BS et al. Efficacy and safety of hydroxychloroquine vs placebo for pre-exposure SARS-CoV-2 prophylaxis among health care workers: a randomized clinical trial. JAMA Intern Med. DOI:10.1001/jamainternmed.2020.6319. (30 September 2020).
   https://jamanetwork.com/article.aspx?doi=10.1001/jamainternmed.2020.6319
5. Barnabas RV et al. Hydroxychloroquine as postexposure prophylaxis to prevent severe acute respiratory syndrome coronavirus 2 infection. Annals of Internal Medicine. DOI: 10.7326/M20-6519. (8 December 2020).
   https://www.acpjournals.org/doi/full/10.7326/M20-6519
6. UK RECOVERY study stops hydroxychloroquine (HCQ) for COVID-19: more than 1100 deaths question ethics and safety overall. HTB (26 June 2020).
   https://i-base.info/htb/38188
7. UK RECOVERY study stops hydroxychloroquine (HCQ) for COVID-19: more than 1100 deaths question ethics and safety overall. HTB (26 June 2020).
   https://i-base.info/htb/38188
8. No survival benefit from remdesivir hydroxychloroquine lopinavir/r or interferon-β1a in moderate and severe COVID-19: interim results from the WHO SOLIDARITY study. HTB (11 November 2020).
   https://i-base.info/htb/39223
9. International COVID-19 study launches in Africa but with drugs that have little chance of working (ANTICOV). HTB (25 November 2020).
   https://i-base.info/htb/39419

This article was first posted on 30 November 2020.