Equipoise for hydroxychloquine was lost

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).

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

Data collected from this study may be made available to other international researchers and institutions who are working to control this Public Health Emergency, but in a fully anonymized way. No personal identifiers will be available anywhere in the data. Dates will either not be included or will be shifted by a random interval so as to not make it possible to trace any identity.

Recruitment period is planned for a maximum of 12 months, rate dependent on patient numbers. Additional sites will be opened after initial approvals.