Atazanavir/Ritonavir and Zinc Pharmacokinetic Study
Condition: HIV Infection
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 4

Summary: 
      The study is being conducted as the most common side effect of the HIV drug atazanavir (taken
      with ritonavir) is hyperbilirubinaemia. Bilirubin is a normal waste product from the body and
      gets broken down in the liver so it can leave the body through the gut. Atazanavir slows the
      breakdown of this chemical, which can cause jaundice (yellowing of the skin) and/or scleral
      icterus (yellowing of the eyes). This is completely harmless; in fact up to 1 in 10 of the UK
      population have an inherited condition that causes the same yellowing. However, some patients
      don't like this side effect and it is the commonest reason for switching off the drug.

      A study in people with Gilberts syndrome (the inherited condition that causes the same
      changes in the chemical bilirubin) showed that a mineral supplement (zinc sulphate) reduced
      the levels of bilirubin in the blood. The aim of this study is to see if using zinc
      supplements can achieve the same effect in patients with high bilirubin due to atazanavir
      use.
    

Detailed description: 
      Atazanavir is a protease inhibitor (PI) and, like other agents in this class, requires
      pharmacological 'boosting' with the cytochrome p450 inhibitor ritonavir. Ritonavir slows the
      hepatic clearance of PIs, increasing plasma concentration and allowing the us eof lower, and
      less frequent doses. Atazanavir, boosted with ritonavir, is approved for once-daily use, is
      an internationally preferred first-line agent (in combination with a backbone of two
      nucleosides [NRTI]) and the most commonly prescribed PI in the UK. Once-daily
      atazanavir/ritonavir with two NRTI is an effective and well-tolerated therapeutic option for
      people living with HIV infection. The most common adverse event associated with atazanavir
      use is unconjugated hyperbilirubinaemia. This is observed in over 40% of patients and up to
      5% of patients discontinue the drug due jaundice and/or scleral icterus.

      Truvada is a fixed dose combination of two NRTI, tenofovir (245mg) and emtricitabine (200mg),
      administered as one tablet once daily. Truvada is a preferred NRTI backbone in national and
      international guidelines and the first line, therefore most commonly used, NRTI backbone in
      our unit.

      Benefits of atazanavir/ritonavir compared with alternative agents include once daily dosing,
      low pill burden, low rates of gastro-intestinal toxicity and, importantly in a patient
      population already at an elevated risk of cardiovascular disease, a favourable lipid profile.
      If a simple intervention could reduce the incidence of hyperbilirubinaemia this could reduce
      the risk of treatment discontinuation/switch. The aim of this study is to explore the
      benefit, and safety, of adding zinc sulphate in patients on a stable regimen of Truvada,
      atazanavir and ritonavir.
    

Intervention name(s): 1 Solvazinc tablet, day 2 to day 15; 1 Solvazinc tablet, day 15 to day 28
Intervention type(s): Drug; Drug
Intervention description(s): Zinc sulphate 125mg, day 2 to day 15; Zinc sulphate 125mg, day 15 to day 28
Other intervention name(s): Zinc sulphate; Zinc sulphate
Intervention MeSH terms: Zinc; Zinc Sulfate
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HIV; Bilirubin