Hydroxychloroquine (Plaquenil) in Acute Infections
Hydroxychloroquine has no established role in treating acute viral infections, including COVID-19, and should not be used for this purpose based on overwhelming evidence showing lack of benefit and potential harm. 1, 2
Established Indications for Acute Infections
Q Fever (Coxiella burnetii)
Hydroxychloroquine is only indicated for chronic Q fever, not acute Q fever. 3
- Acute Q fever: Treat with doxycycline alone (100 mg twice daily); do not use hydroxychloroquine. 3
- Chronic Q fever: Requires combination therapy with doxycycline (100 mg twice daily) plus hydroxychloroquine (200 mg three times daily) for 18-24 months depending on valve involvement. 3
- The rationale for hydroxychloroquine in chronic Q fever is that it alkalinizes the acidified phagosomal compartment, allowing doxycycline to achieve bactericidal activity against C. burnetii. 3
Malaria
Hydroxychloroquine is FDA-approved for uncomplicated malaria caused by susceptible Plasmodium species. 4
- Treatment dosing: 800 mg initially, then 400 mg at 6,24, and 48 hours (total 2,000 mg). 4
- Prophylaxis dosing: 400 mg once weekly, starting 2 weeks before travel and continuing 4 weeks after leaving endemic area. 4
- Critical limitation: Not effective against chloroquine-resistant strains or complicated malaria. 4
COVID-19: Evidence Against Use
The WHO and CDC do not support hydroxychloroquine use for COVID-19 treatment or prophylaxis. 1
Why Early Enthusiasm Failed
- Initial in vitro studies showed antiviral activity against SARS-CoV-2, leading to premature clinical use. 3
- Early uncontrolled reports from China and France suggested benefit, but these were not reproducible. 2
- Proposed mechanisms included interference with ACE2 receptor binding and lysosomal protease activity. 3
Definitive Evidence of Lack of Benefit
- Multiple randomized controlled trials, meta-analyses, and systematic reviews conclusively demonstrated no mortality benefit or reduction in time-to-recovery in hospitalized COVID-19 patients. 2
- Combination with azithromycin similarly showed no benefit. 2
- The risks of adverse events (cardiac, neuropsychiatric, hematologic, hepatobiliary) outweigh any theoretical benefits. 2
Historical Context
Early 2020 recommendations suggesting hydroxychloroquine as a "secondary drug" for worsening COVID-19 symptoms 3 were based on inadequate evidence and have been superseded by high-quality trials showing no efficacy. These early opinions acknowledged the lack of published data and were explicitly cautious. 3
Patients Already Taking Hydroxychloroquine
Patients with rheumatic diseases on chronic hydroxychloroquine therapy should continue their medication during acute infections, including COVID-19. 3
- The immunomodulatory (not immunosuppressive) effects may be beneficial. 3
- Discontinuation could trigger disease flares. 3
- Standard dosing for rheumatic diseases: 200-400 mg daily (maximum 5 mg/kg actual body weight to minimize retinal toxicity). 3, 1, 4
Safety Monitoring Requirements
For any patient on hydroxychloroquine therapy:
- Baseline ophthalmologic examination before starting treatment. 3, 1, 5
- Annual screening after 5 years for low-risk patients; earlier and more frequent for high-risk patients. 1, 5
- Check G6PD levels in men of African, Asian, or Middle Eastern origin before starting (risk of hemolysis). 1
- Dose adjustment required for renal impairment (reduce by 25% if eGFR <30 mL/min/1.73 m²). 1
- Monitor for photosensitivity, especially when combined with doxycycline. 3
Common Pitfalls to Avoid
- Do not use hydroxychloroquine for acute viral respiratory infections based on outdated 2020 recommendations or in vitro data. 1, 2
- Do not use hydroxychloroquine for acute Q fever—doxycycline monotherapy is the correct treatment. 3
- Do not exceed 5 mg/kg actual body weight daily for chronic indications due to retinal toxicity risk. 1, 4
- Do not discontinue hydroxychloroquine in patients with SLE or rheumatoid arthritis who develop acute infections unless specifically contraindicated. 3