Atripla to Raltegravir Switch Study for CNS Toxicity
Condition: HIV Infection
MeSH terms: HIV Infections
Intervention: Truvada/Raltegravir
Intervention description: All subjects currently on Atripla® will switch to Truvada/Raltegravir
Intervention MeSH terms: Tenofovir; Emtricitabine; Efavirenz; Raltegravir Potassium; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 40.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of the study is to investigate the benefits of switching away from efavirenz
      (part of the combination pill, Atripla®) in patients with central nervous system side effects
      (such as insomnia {difficulty with sleeping}, bad dreams etc). The investigators will
      investigate the effect of switching to Truvada (a combination pill of tenofovir and
      emtricitabine, the other two components of Atripla) plus raltegravir.

      Raltegravir is a licensed drug for HIV treatment which showed side effects were fewer in
      number when compared to efavirenz in 2 other clinical studies, where patients were starting
      HIV treatment for the first time.

      This study will also investigate the safety (in terms of other side effects and the routine
      blood tests which the investigators ordinarily use to monitor your treatment) and monitor
      effectiveness, your viral load and CD4 counts, when you switch treatment from Atripla® to
      Truvada/raltegravir.
    

Eligibility criteria:

        Inclusion Criteria:

          1. is male or female aged 18 years or above

          2. has a documented HIV-1 infection

          3. has signed the Informed Consent Form voluntarily

          4. is willing to comply with the protocol requirements

          5. has an HIV-plasma viral load at screening <50 copies/mL

          6. has a CD4 cell count at Screening >50 cells/mm3

          7. has been on a stable ART, with at least 3 licensed agents, one of which being EFV, for
             at least 12 weeks at Screening, and has been on Atripla for at least 4 weeks at
             screening; the subject must be willing to stay on treatment until Baseline

          8. estimated glomerular filtration rate (by MDRD or CG methods) >50 ml/min.

          9. has symptomatic toxicity associated with EFV after at least 12 weeks of therapy

         10. if female and of childbearing potential, she is using effective birth control methods
             (as agreed by the investigator) and is willing to continue practising these birth
             control methods during the trial and for at least 30 days after the end of the trial
             (or after last intake of investigational ARVs); Note: Women who are postmenopausal for
             least 2 years, women with total hysterectomy, and women who have a tubal ligation are
             considered of non-childbearing potential

         11. if a heterosexually active male, he is using effective birth control methods and is
             willing to continue practising these birth control methods during the trial and until
             follow-up visit

        Exclusion Criteria:

          1. is infected with HIV-2

          2. is using any concomitant therapy disallowed as per SPC for the study drugs (section
             5.2)

          3. has a currently active AIDS defining illness (Category C conditions according to the
             CDC Classification System for HIV Infection 1993) with the following exceptions (must
             be discussed with the sponsor prior to enrolment):

               -  Stable cutaneous Kaposi's Sarcoma (no pulmonary or gastrointestinal involvement
                  other than oral lesions) unlikely to require systemic therapy during the trial
                  period

               -  CD4 count less than 200 cells/mm3 Note: Primary and secondary prophylaxis for an
                  AIDS defining illness is allowed

          4. has acute viral hepatitis including, but not limited to, A, B, or C

          5. has chronic hepatitis B and/or C with AST and/or ALT >5 x ULN Note: Subjects
             co-infected with chronic HBV or HCV can enter the trial if clinically stable and not
             expected to require treatment during the trial period.

          6. has received any investigational drug within 30 days prior to the trial drug
             administration

          7. Prior exposure to raltegravir or investigational integrase inhibitors

          8. Any tenofovir or emtricitabine associated resistance mutations

          9. No baseline resistance test available

         10. Clinically significant allergy or hypersensitivity to any trial medication excipients

         11. If female, she is pregnant or breastfeeding

         12. screening blood results with any grade 3 / 4 toxicity according to Division of AIDS
             (DAIDS) grading scale, except: asymptomatic grade 3 glucose, amylase or lipid
             elevation or asymptomatic grade 4 triglyceride elevation (re-test allowed).

         13. Clinical or laboratory evidence of significantly decreased hepatic function or
             decompensation: INR > 1.5 or albumin < 30g/L or bilirubin > 2.5 x ULN

         14. Resolution of their CNS toxicity between Screening and Baseline visits

         15. Any condition (including drug/alcohol abuse) or laboratory results which, in the
             investigator's opinion, interfere with assessments or completion of the trial.