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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
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.
Khayelitsha Hospital
Cape Town, Western Cape, South Africa
Groote Schuur Hospital
Cape Town, Western Cape, South Africa
Event-free survival at 28 days post-randomization between experimental group and standard of care group
Events defined as Hospitalisation or Death
Time frame: Day 28
Incidence of serious adverse events
Time frame: Day 28
Incidence of adverse events of special interest related to investigational product at time of hospitalisation
Time frame: Day 28
Premature discontinuation of treatment
Time frame: Day 28
Time from treatment initiation to death, ARDS (PF/SF ratio < 300), or mechanical ventilation
Time frame: Day 28
Proportion with moderate and severe ARDS
Time frame: Day 28
Duration of hospitalisation and ICU stay in survivors
Time frame: Day 28
Incidence of Covid-19 in household contacts
Time frame: Day 28
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.