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.


This finding support those from other RCTs.

A randomised study in 821 participants that also found no benefits from hydroxychoroquine used as post exposure prophylaxis (PEP) for COVID-19 after moderate or high risk of exposure, although fewer index cases had PCR-confirmed infection. [3]

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]


  1. Mitjà et al. A cluster-randomized trial of hydroxychloroquine for prevention of Covid-19. NEJM. DOI: 10.1056/NEJMoa2021801. (24 November 2020).
  2. 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.
  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).
  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).
  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).
  6. UK RECOVERY study stops hydroxychloroquine (HCQ) for COVID-19: more than 1100 deaths question ethics and safety overall. HTB (26 June 2020).
  7. UK RECOVERY study stops hydroxychloroquine (HCQ) for COVID-19: more than 1100 deaths question ethics and safety overall. HTB (26 June 2020).
  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).
  9. International COVID-19 study launches in Africa but with drugs that have little chance of working (ANTICOV). HTB (25 November 2020).

This article was first posted on 30 November 2020.

Links to other websites are current at date of posting but not maintained.