A single tablet regimen (STR) of efavirenz, emtricitabine and tenofovir disoproxil fumarate
(tenofovir DF) is the first complete HAART that is offered as one tablet once a day. The
individual components of this HAART regimen have demonstrated efficacy and safety in HIV
treatment-naive patients and offer simplification that in turn may increase adherence and
improve clinical outcomes. This study aims to evaluate the effectiveness (efficacy, safety
and tolerability) of a STR simplification strategy in patients on HAART who have achieved
viral suppression in a real world clinical setting.
Within the Chelsea and Westminster hospital approximately 540 subjects have been identified
who are currently receiving the individual components of Atripla and who would eventually
switch to Atripla. The Royal Sussex County Hospital will be included to ensure that
recruitment timelines are met.
A minimum of 150 subjects will be switched within the first 6 months allowing initial 24 week
data for these subjects to be available approximately 12 months post launch.
Inclusion Criteria:
- Patient must have documented HIV 1 infection by Roche Amplicor (Version 1. 5 Ultra
sensitive) or equivalent assay - either at screening or previously documented in the
patient's medical record.
- Stable HAART regimen of efavirenz, emtricitabine and tenofovir DF for equal to or
greater than 24 weeks prior to Screening and must be on their first HAART regimen.
- Undetectable plasma HIV 1 RNA (less than 50 copies/mL) at Screening and greater than
or equal to 12 weeks prior to Screening.
- Greater than or equal to 18 years old.
- Adequate renal function by: Estimated creatinine clearance greater than or equal to
60 mL/min according to the Cockcroft Gault formula
- Hepatic transaminases (AST and ALT) less than or equal to 5 times upper limit of
normal (ULN)
- Total bilirubin less than or equal to 1. 5 mg/dL
- Adequate hematologic function (absolute neutrophil count greater than or equal to
1,000/mm3; platelets greater than or equal to 25,000/mm3; hemoglobin greater than or
equal to 8. 0 g/dL
- Serum amylase less than or equal to 1. 5 times ULN (subjects with serum amylase greater
than 1. 5 times ULN will remain eligible if serum lipase is less than or equal to 1. 5
times ULN)
- Negative serum pregnancy test (females of childbearing potential only i. e., not
surgically sterile or at least two years post-menopausal)
- Women of childbearing potential (WOCBP) must be willing to use two methods of
contraception to avoid pregnancy throughout the study and for up to 12 weeks after the
last dose of study drugs in such a manner that the risk of pregnancy is minimized.
Subjects may choose two (a barrier and highly effective method) of the birth control
methods listed below: Hormonal birth control drugs, Male or female condoms with or
without spermicidal gels, Diaphragm cervical cap with or without spermicidal gels,
Intrauterine device
- Female subjects who utilize hormone contraceptive as one of their birth control
methods must have used the same methods for at least three months prior to study
dosing.
- Female subjects who are postmenopausal for less than two years are required to have
FSH greater than or equal to 40 mIU/mL. If the FSH is less than 40 mIU/mL, the subject
must agree to use highly effective method of birth control (as described above) to
participate in the study.
- Male subjects who are sexually active must be willing to use effective barrier
contraception (e. g., condom with spermicide) during heterosexual intercourse from
screening through completion of the study and continuing for up to 12 weeks after the
last dose of study drugs.
- Life expectancy greater than or equal to 1 year.
- The ability to understand and sign a written informed consent form, which must be
obtained prior to initiation of study procedures.
Exclusion Criteria:
- Known hypersensitivity or toxicities to emtricitabine (FTC), tenofovir DF (TDF) or
Truvada
- Known hypersensitivity or toxicities to Sustiva
- Have a history of resistance to any of the study agents at the time of screening
(documented presence of resistance mutation(s) as defined by the IAS-USA 2007
Guidelines
- A new AIDS-defining condition diagnosed within the 30 days prior to the Baseline
visit.
- Pregnant/lactating or breastfeeding females
- Severe hepatic impairment (greater than 5 times upper limit of normal as defined by
laboratory transaminases) or deemed clinically significant by investigator.
- Any currently known clinical or laboratory parameter of GSI Grade 4. However
asymptomatic grade 4 abnormalities will be permitted at the discretion of the
investigator if deemed clinically appropriate (excluding AEs and laboratory parameters
mentioned elsewhere in the inclusion/exclusion criteria). Abnormalities deemed
insignificant by the investigator must be discussed with the sponsor prior to
enrollment.
- Receiving on-going therapy with any of the prohibited medications. Administration of
any of the medications must be discontinued at least 30 days prior to the Baseline
visit and for the duration of the study period.
- Active, serious infections (other than HIV infection) requiring parenteral antibiotic
therapy within 30 days prior to Screening visit.
- Current acute illness or infection (e. g., opportunistic) - including an active AIDS
defining condition within the previous six months.
- Hepatitis B coinfection or Hepatitis C coinfection
- Malignancy other than cutaneous Kaposi's sarcoma (KS) or basal cell carcinoma.
Subjects with biopsy-confirmed cutaneous KS are eligible, but must not have received
any systemic therapy for KS with 30 days of Baseline visit and are not anticipated to
require systemic therapy during the study.
- Prior history of renal or bone disease deemed significant by the investigator.
- Subjects currently taking part in any other clinical trial using an investigational
product, with the exception of studies where the treatment studied has been stopped
for more than 1 month.
- Evidence of alcohol and/or drug or substance abuse that in the judgment of the
investigator would likely result in the patient being unreliable in fulfilling the
conditions of the protocol.
- History of psychological illness or conditions that in the judgment of the
investigator might interfere with the patient's ability to understand the requirements
of the study.
- Any other clinical condition or prior therapy that, in the opinion of the
investigator, would make the subject unsuitable for the study or unable to comply with
the dosing requirements and cause the patient to be unable to complete the study
protocol.
