Time to Protection and Adherence Requirements of Raltegravir With or Without Lamivudine in Protection From HIV Infection
Condition: Hiv
MeSH terms: HIV Infections
Intervention: Raltegravir 400Mg Tab; Lamivudine 150Mg Tablet
Intervention description: bd for 7 days; + Raltegravir 400Mg tablet bd for 7 days
Intervention MeSH terms: Lamivudine; Raltegravir Potassium
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 38.0
Sex: All
Minimum age: 18 Years
Maximum age: 60 Years
Healthy volunteers: Accepts Healthy Volunteers

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.
    

Eligibility criteria:

        Inclusion Criteria:

          1. The ability to understand and sign a written informed consent form prior to
             participation in any screening procedures and must be willing to comply with all trial
             requirements.

          2. Male or non-pregnant, non-lactating females

          3. Age between 18 to 60 years, inclusive.

          4. Body Mass Index (BMI) of 16 to 35 kg/m2, inclusive.

          5. Negative antibody/antigen combined test for HIV.

          6. Absence of any significant health problems (in the opinion of the investigator) on the
             basis of the screening procedures; including medical history, physical examination,
             vital signs.

          7. Women participating in sexual intercourse that could result in pregnancy -must use an
             adequate form of contraception throughout the study and for two weeks after the study.
             This includes intrauterine device, condoms, anatomical sterility in self or partner.
             Oral hormonal methods and implant contraceptives are allowed but only in combination
             with the additional protection of a barrier method.

          8. Female participants may not use any vaginal products or objects or have vaginal sex
             for 48 hours before and after the collection of vaginal fluid and vaginal biopsies.
             This list includes tampons, female condoms, cotton wool, rags, diaphragms, cervical
             caps (or any other vaginal barrier method),douches, lubricants, vibrators/dildos, and
             drying agents.

          9. Males participating in sexual intercourse that could result in pregnancy must use
             condoms during the duration of the study.

         10. Men and women cannot use anal products or objects including but not exclusive to
             douches, lubricants and vibrators/dildos, butt plugs or urethral sounds or have
             receptive anal intercourse for 48 hours before and after the collection of rectal
             biopsies.

         11. Willing to abstain from multivitamins and antacids for the study duration.

        Exclusion Criteria:

          1. Any significant acute or chronic medical illness.

          2. Evidence of organ dysfunction or any clinically significant deviation from normal in
             physical examination, vital signs or clinical laboratory determinations.

          3. Positive blood screen for syphilis, hepatitis B (HBs Ag) and/or C antibodies.

          4. Positive blood screen for HIV antibodies.

          5. Positive screen for sexually transmitted infections at screening visit

          6. High-risk behaviour for HIV infection which is defined as having one of the following
             within three months before trial day 0 (first dose): had unprotected vaginal or anal
             sex with a known HIV infected person or a casual partner. engaged in sex work for
             money or drugs. acquired a bacterial sexually transmitted disease in the past 3
             months. having a known HIV positive partner either currently or in the previous six
             months Females who are pregnant or breast-feeding.

          7. Clinically significant laboratory abnormalities (according to normal range as defined
             by central laboratory).

          8. Participation in a clinical trial of an Investigational product within 1 month of
             planned baseline enrolment in this study.

          9. Ingestion of H2 receptor antagonists or proton pump inhibitor drugs in the preceding
             14 days

         10. Current of planned use of anti-epileptics