Hydroxychloroquine for Discordant CD4 Responders on Highly Active Antiretroviral Therapy (HAART) (SSAT039)

Inclusion Criteria:

• Documented HIV infection
• Age 18 to 65 years.
• On stable antiretroviral therapy for at least 96 weeks
• CD4 count less than 350 on screening blood test and on one other test performed within 4 months prior to screening and less than 150 cell rise in CD4 count in last 3 years
• Expression of CD38 on CD8+ T cells >10%
• Plasma HIV RNA viral load less than 50 copies/ml on screening blood test and for at least 72 weeks prior to screening (blips defined as a single viral load >50 and <500 copies/ml preceded and followed by an undetectable result will be permitted)
• Willing and able to provide written informed consent
• Females of child-bearing potential will need to use effective contraception

• Satisfactory ophthalmological assessment including:

  • visual acuity
  • careful ophthalmoscopy
  • fundoscopy
  • central visual field testing with a red target
  • colour vision.

Exclusion Criteria:

• History of psoriasis, porphyria cutanea tarda, epilepsy, myasthenia gravis, myopathy, cardiac arrhythmias or glucose 6-phosphate dehydrogenase (G6PD) deficiency.
• Insulin-dependent or non-insulin-dependent diabetes mellitus.
• Chronic liver disease of any cause or alcoholism (investigator defined)
• Pneumonia, meningitis, septicaemia or any other serious infection in the 2 months prior to screening.
• Any acute infection with fever and systemic symptoms in the last 24 hours.
• Any vaccinations in the 2 months prior to screening.
• Active malignancy (patients are eligible if treatment for the malignancy was completed more than 2 years prior to screening and there has been no subsequent clinical evidence of active disease or localised completely excised cutaneous cancers and low volume Kaposi's sarcoma) or any active immune-mediated or inflammatory disease.
• Any known suicide attempts (at any time in the past) or current or past history of depression requiring treatment within the 2 years prior to screening.
• A woman who is currently pregnant or breastfeeding.
• Use of systemic corticosteroids or other immunomodulatory drugs within the 12 months prior to screening.
• Current use of medication with known serious hepatotoxic effects or known interaction with hydroxychloroquine (section 5.2)
• Evidence of cardiac conduction defects or cardiac arrhythmia on screening ECG.
• Hepatitis B surface antigen (HBsAg) positive or Hepatitis C PCR positive (patients who are Hepatitis C antibody positive are allowed to enter if PCR is negative).

• Any of the following laboratory abnormalities on screening blood test:

  • Haemoglobin less than 10.5g/dl
  • Absolute neutrophil count less than 1.0x109/L
  • Platelet count less than 100 X 109/L
  • ALT or AST, or alkaline phosphatase above 2.5 x upper limit of normal (ULN) Template V 2.0, 06 April 2008 SSAT039 Page 23 of 73 Version 6.0, 17 October 2011
  • Serum creatinine greater than 1.5xULN
  • Estimated creatinine clearance (MDRD equation*) below 60ml/min
• Inability to attend or comply with treatment or follow-up scheduling.
• Current participation in any other clinical intervention trial.