Clinical manifestations of Covid-19 are poorly characterised in HIV co-infection, which may predispose to more severe disease. Reducing hospitalisation and severe illness in this population has important individual and public health benefits. The investigators propose a pragmatic multi-centre, randomized controlled trial in South Africa to evaluate the efficacy and safety of chloroquine or hydroxychloroquine to prevent progression of disease and hospitalisation amongst HIV-positive people with Covid-19 not requiring hospitalisation at initial assessment.
The trial objective is to compare chloroquine (or hydroxychloroquine) versus standard of care
for the primary endpoint of hospitalisation or death at 28 days. Consenting adults who meet
criteria for a Covid-19 person under investigation and who are ≥18 years, known to be
HIV-positive, not requiring immediate hospitalisation and are not at risk of cardiac
toxicities related to the study drug will be enrolled. The total sample size will be 560
participants (280 in each arm).
Drug: Chloroquine or hydroxychloroquine
Chloroquine has in vitro antiviral activity against many viruses, including SARS-CoV-1 and SARS-CoV-2. Chloroquine inhibits coronavirus replication at in vitro concentrations that are not cytotoxic and within a range of blood concentrations achievable during standard antimalarial treatment. Chloroquine inhibits viral replication through interference with glycosylation of coronavirus ACE2 receptors, required for viral entry, and downstream phagolysosome alkalisation, interfering with the low-pH-dependent steps of viral fusion and uncoating. Chloroquine also has anti-inflammatory properties and could provide benefit through this mechanism in Covid-19, where a cytokine storm has been described in critically ill patients. Hydroxychloroquine is a less toxic metabolite of chloroquine, has similar anti-inflammatory properties, and is more potent against SARS-CoV-2 in vitro.
Inclusion Criteria:
- Tested for Covid-19 at a trial recruitment site as an outpatient;
- Age 18 years or older;
- Not requiring immediate hospitalisation;
- Mild disease, defined as respiratory rate <25/min, pulse rate <120/min, SpO2 >94%;
- HIV-positive by rapid test or documented history;
- Suspected or confirmed Covid-19;
- Signed informed consent.
Exclusion Criteria:
- Covid-19 diagnosed > 5 days prior to randomization;
- Active tuberculosis;
- Need for concomitant drugs that are contraindicated with the use of
Chloroquine/hydroxychloroquine;
- QTcF interval > 480 ms;
- Known glomerular filtration rate < 10 ml/min;
- Known with glucose-6-phosphate dehydrogenase deficiency (G6PD);
- Previous adverse drug reaction to investigational product;
- Concurrent involvement in other research or use of chloroquine, hydroxychloroquine or
any other 4-aminoquinolone or another experimental investigational medicinal product
that is likely to interfere with the study medication.
Note: Pregnancy and breastfeeding are not exclusions for entry
Khayelitsha Hospital
Cape Town, Western Cape, South Africa
Groote Schuur Hospital
Cape Town, Western Cape, South Africa