Atripla to Raltegravir Switch Study for CNS Toxicity

• Status: Completed
• Trial end date: 2013-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St Stephens Aids Trust
• Treatments: Efavirenz; Efavirenz, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Emtricitabine; Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; Raltegravir Potassium; Tenofovir

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.