Antiretroviral Activity and Pharmacokinetics of Deferiprone in Healthy Volunteers and Asymptomatic HIV-infected Subjects

A Double Blind, Placebo-controlled, Dose-escalating, Multiple Dose Study, Investigating the Safety, Antiretroviral Activity, Tolerability and Pharmacokinetic Profile of Deferiprone When Administered in Healthy Volunteers and Asymptomatic HIV Infected Subjects

The purpose of this study was to examine the safety, efficacy, and pharmacokinetics of different dosages of deferiprone in subjects with or without HIV infection.

Three cohorts were enrolled: two of individuals who were asymptomatically infected with HIV and one of healthy volunteers. Dosages were as follows:

• Cohort 1 (asymptomatic HIV infected subjects): 33 mg/kg deferiprone three times daily for a total of 99 mg/kg/day
• Cohort 2 (healthy volunteers): 50 mg/kg deferiprone three times daily for a total of 150 mg/kg/day
• Cohort 3 (asymptomatic HIV infected subjects): 50 mg/kg deferiprone three times daily for a total of 150 mg/kg/day

Inclusion Criteria:

• Male or female aged ≥18 years and ≤ 60 years.
• Absolute neutrophil count (ANC) of >1000/mm3 for African black population and ≥ 1600/mm3 for all other races.
• For Cohort 2: HIV-negative
• For Cohorts 1 and 3: HIV-1 positive; CD4 count of at least 300/mm3; HIV-1 RNA copies (viral load) >10 000 copies/mL serum; and current physical health stable and not requiring antiretroviral treatment
• For Cohorts 1 and 3: Chest x-ray showing absence of active infectious diseases (such as tuberculosis, viral or atypical bacteria or parasitic infection).

Exclusion Criteria:

• Presence of any severe concomitant disease.
• History of or current, recurrent or recent (4 weeks) febrile disease.
• History of opportunistic infections, neoplasm or AIDS-defining conditions.
• Inability to discontinue any medication from screening onwards, or for at least 2 weeks before the first admission; in particular any antiviral or therapy with immunosuppressive activity.
• Significant liver impairment: aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≥ 2.5 times the upper normal limit.
• Significant kidney impairment: serum creatinine ≥ two times the upper normal limit.
• Any concomitant disorder or resultant therapy likely to have interfered with subject compliance or with study procedures.
• Known hypersensitivity to any of the test materials or related compounds.
• Positive test for Hepatitis B and/or C antibodies.
• A history of multiple and/or severe allergies to drugs or foods or a history of anaphylactic reactions.
• History of seizures or epilepsy.