Time to Protection and Adherence Requirements of Raltegravir With or Without Lamivudine in Protection From HIV Infection
Condition: Hiv
MeSH terms: HIV Infections
Study type: Interventional
Phase: Phase 4

Summary: 
      This study evaluates whether a 7-day course of Raltegravir 400mg bd or Raltegravir
      400mg/lamivudine 150mg bd can prevent HIV from infecting genital tissue and will relate the
      level of drug in the blood to the level of drug in genital tissue and to the ability to of
      HIV to infect genital tissue. As well as determining whether these regimes can provide ex
      vivo protection against HIV, this study will also determine speed to provision of protection
      and a 48 hour PK/PD decay profile of Raltegravir following drug cessation after attaining
      steady state concentrations. The results will also inform all future HIV pre-exposure
      prophylaxis studies of Raltegravir and form the basis for large scale clinical trials without
      the need for tissue sampling. To date, efficacy studies assessing PrEP regimens have utilized
      HIV-acquisition endpoints with the consequence being such studies are required to be large in
      subject number in order to power observations. In addition the study will provide for the
      first time data on HIV protection rather than just Raltegravir drug levels in tissue, and
      allow assessment of the possibility of Raltegravir being used as an intermittent dosing
      regimen in PrEP.
    

Detailed description: 
      This is a multi-site, open-label, randomised, pharmacokinetic (PK) and pharmacodynamic (PD)
      trial whereby 36 individuals (18 women and 18 men) will be randomised according to gender
      1:1:1:1:1:1 to one of 6 arms (A 1 A 2 A 3 B 1 B 2 B 3). The result being 3 women and 3 men
      will be in each arm. The letter dictates the ART regimen order and the number dictates the
      time points that tissue sampling will occur on and off ART. Two ART regimes will be
      investigated and all individuals will receive both regimes separated by a one month wash out.

      Arm A (A 1 A 2 A 3): will start with 7 days Raltegravir 400mg bd and then have a one month
      wash out before then starting 7 days Raltegravir 400mg /lamivudine 150mg bd.

      Arm B (B 1 B 2 B 3): will start with 7 days Raltegravir 400mg /lamivudine 150mg bd and then
      have a one month wash out before then starting 7 days Raltegravir 400mg bd. This will remove
      sequential selection bias. All individuals will receive tissue sampling at baseline for ex
      vivo analysis to ensure biopsies are infectable on challenge assays. Sampling from women will
      avoid menstruation and if possible focus on the luteal phase of the menstrual cycle.
      Individuals will receive another set of tissue sampling during and after ART in phase 1, have
      a 4 week wash out period and then have another set of sampling during and after ART in phase
      2. Individuals will therefore have 5 sets of sampling during the trial.
    

Intervention name(s): Raltegravir 400Mg Tab; Lamivudine 150Mg Tablet
Intervention type(s): Drug; Drug
Intervention description(s): bd for 7 days; + Raltegravir 400Mg tablet bd for 7 days
Other intervention name(s): Isentress; Epivir
Intervention MeSH terms: Lamivudine; Raltegravir Potassium
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Prevention