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

• Status: Unknown status
• Trial end date: 2014-08-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of the study is to examine the effects of adding a drug called hydroxychloroquine, usually used to treat rheumatoid arthritis, to patients' usual antiretroviral combination. HIV causes activation of some parts of the immune system and this immune activation may persist despite effective antiretroviral therapy. Ongoing activation may be responsible for poor CD4 rise on antiretroviral therapy and for some HIV-related complications. Drugs like hydroxychloroquine work by inhibiting immune activation.

The study will primarily investigate the effect of adding this medication on immunological parameters (particularly CD4 count), on other safety parameters (such as cholesterol), patients' side effects and viral load.

If you decide to take part, the duration of your involvement in the study will be 24 weeks plus two screening visits up to 84 days prior to the start of the study and a follow up visit.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St Stephens Aids Trust
• Treatments: Hydroxychloroquine

Criteria

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.