The goal of this clinical trial is to learn if hydroxychloroquine works to treat long-term complaints attributed to Lyme borreliosis in adults. The main questions it aims to answer are:

Does addition of hydroxychloroquine reduce physical complaints? Researchers will compare hydroxychloroquine to a placebo (a look-alike substance that contains no drug) to see if hydroxychloroquine works to treat Lyme borreliosis.

Participants will:

Take hydroxychloroquine or a placebo two times a day during 28 days. Visit the clinic 4 times in one year for checkups and tests.

Rationale Assess other strategies for Lyme patients with vexing symptoms.

Objective Provide initial insights as to whether addition of hydroxychloroquine results in reduction of physical complaints and assessing safety and tolerability of hydroxychloroquine in these patients.

Main trial endpoints The primary endpoint is health-related quality of life, as measured by the global score of the 36-item Short-form General Health Survey (SF-36) at EOT (week 4).

Secondary trial endpoints Secondary endpoints are improvement on subscales of SF-36 (pain and physical function) at week 4, safety at week 4 and 12 and global physical health composite score of the 36-item Short-form General Health Survey (SF-36) at week 52. Of note, there are no biochemical or microbiological test available to assess cure.

Trial design This is a monocentre, randomized, double blind pilot study. Treatment last one month, with a follow up at week 52. In total the subject are participating for one year.

Trial population Patients with possible persisting B. burgdorferi s.l. infection or probable or possible post Lyme treatment Lyme borreliosis syndrome (PTLBS) will be recruited. Patients who will start antibiotic treatment can be included.

Interventions The intervention group will be treated with 28 days Doxycycline 2 x 100 mg (standard of care) combined with hydroxychloroquine 2 x 200 mg (two time a day one tablet). The control arm receives 28 days Doxycycline 2 x 100 mg (standard of care) combined with placebo 2 x 1 tablet.

Ethical considerations relating to the clinical trial including the expected benefit to the individual subject or group of patients represented by the trial subjects as well as the nature and extent of burden and risks The combination of doxycycline en hydroxychloroquine is based on expected synergy and probably enhancement of effective therapy. Its combination has been used for years in malaria and Q-fever. Its pro- and con's are well known.

The use of doxycycline and hydroxychloroquine is not associated with increased health risk.

Inclusion Criteria:

• Patients who are 18 years of age or older
• Patients with probable or possible signs and symptoms attributed to Lyme borreliosis
• Patients with probable or possible post Lyme treatment Lyme borreliosis syndrome (PTLBS)
• Males or non-pregnant females (who must agree to use barrier methods of contraception during the study therapy period, women of childbearing age must have a negative urine pregnancy or serum test at baseline).

Exclusion Criteria:

• Known contra-indication for used study medication.
• Women who are pregnant or lactating