A Two Year Study of the Clinical Efficacy of the Combination of Emtricitabine, Tenofovir, and Nevirapine
Information source: University of Maryland
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV
Intervention: Nevirapine, FTC, and Tenofovir (Drug)
Phase: Phase 4
Status: Active, not recruiting
Sponsored by: University of Maryland
Official(s) and/or principal investigator(s):
Robert R Redfield, MD, Principal Investigator, Affiliation: University of Maryland, School of Medicine, IHV
Charles E Davis, MD, Principal Investigator, Affiliation: University of Maryland, School of Medicine, IHV
Open label, two year study of the clinical efficacy of the combination of FTC, Tenofovir, and
Nevirapine. Sixty HIV infected patients without previous exposure to antiretroviral therapy
will be enrolled. Study will include a pharmacokinetic substudy to evaluate the interaction
of FTC and Nevirapine. Truvada may be used.
Official title: Cell Cycle Independent Antiretroviral Therapy: Combination of Nevirapine, FTC, and Tenofovir
Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
Primary outcome: The primary endpoint will be evidence of viral failure as determined by two consecutive viral load measurements of >500 copies/ml.
proportion of patients with grade 2, 3 and 4 adverse events and laboratory toxicities
proportion of patients with plasma HIV RNA < 50 copies/mL
proportion of patients with plasma HIV RNA < 400 copies/mL
change from baseline in plasma HIV RNA at 24, 48, 72, and 96 weeks
changes in CD4 cell counts, in each group, from baseline, and at weeks 24, 48, 72, and 96
changes in Mitochondrial DNA to Cellular DNA ratio
Description of study design This is an open-labeled clinical trial evaluating an
antiretroviral treatment regimen in which the drugs have demonstrated in vitro activity in
both, resting and activated mononuclear cells. These drugs include: FTC 200 mg p. o. qd, and
Tenofovir 300 mg p. o. qd, and Nevirapine 200 mg b. i.d.
Eligible patients must be at least 18 years of age, be referred by their primary HIV provider
for antiretroviral therapy or if the patient is self referred, have a CD4 cell count of <
250/mm3 and have a viral load >5,000c/ml. Eligibility requirement for women is that they
must have a CD4 cell count of <250 at the time of enrollment. This cutoff for women is based
on unpublished data that there may be increased hepatotoxicity in women with a CD4 cell count
> 250 cell/mm3. The screening evaluation will take place the day the informed consent is
signed. During that screening evaluation, the patient will undergo a history and physical
examination, and will have study labs drawn. Within 60 days of the screening evaluation and
meeting all eligible criteria, the patient will be placed on the study treatment regimen.
Patients will be evaluated at the clinic on Day 0 (therapy initiation), weeks 2, 4, 6, 8, 12,
16, and then every 8 weeks until 48 weeks and thereafter every 12 weeks through week 96. At
the end of the study, all patients may continue their current antiretroviral treatment
regimen at the discretion of the patient and their primary care provider.
Pharmacokinetic Analysis Sub Study A pharmacokinetic evaluation will be performed in first 7
volunteers to assess the impact of FTC on Nevirapine and vice versa. Pharmacokinetic
analysis will be performed at end of week 2 ( day 14) during 200mg qd start up period.
Samples will be obtained at baseline and 1, 3, 6, 12 and 24 hours post Nevirapine dosing.
Pharmacokinetic analysis will be repeated at the week 8 visit. Samples will be obtained at
baseline and 1, 3, 6, 12 and 24 hours post Nevirapine.
Assignment of patients There will be 60 patients involved in this clinical trial. This is an
open-labeled study. There are no placebos involved in this study.
Dose and dose selection The dosages of medications are those that are currently used as
standard clinical practice: Nevirapine 200 mg b. i.d. (1-200 mg tablet b. i.d.); Emtricitabine
(FTC) 200mg po qd.(1-200mg capsule); Tenofovir 300 mg once-a-day (1-300 mg tablet qd).
Justification of study design All study patients require treatment for their HIV infection.
All of the drugs used in this study are FDA-Approved. Tenofovir and FTC are approved as a
once-a-day treatment medication. Nevirapine (NVP) is approved for BID dosing.
NOTE: That whenever Nevirapine is being prescribed, there will be a lead-in period of 14
days in which Nevirapine will be prescribed as 200 mg once a day followed by 200 mg BID as is
the recommended standard of care.
Minimum age: 18 Years.
Maximum age: 75 Years.
1. HIV-1 infection, as documented by any licensed ELISA test kit, and confirmed by
Western blot, positive HIV-1 blood culture, positive HIV serum antigen, or plasma
viremia at any time prior to study entry. If no record exists, testing must occur at
2. Male or female, age 18 to 75 years of age.
3. Able to sign the informed consent, and is willing to comply with the requirements of
this clinical trial.
4. Available for at least 96 weeks of follow up.
5. Males: deemed a candidate for antiretroviral therapy per referring primary care
provider. (If patient is self referred, CD4 cell count must be <400 cells/mm3 and
viral load>5,000c/ml) Females: CD4 cell count must be less than 250 cells/mm3 and
viral load >5,000 c/mL at time of enrollment.
6. If female and of child bearing potential must consent to using at least two forms of
7. Participants will be "treatment naive" as no prior antiretroviral therapy or
antiretroviral therapy for less than 7 days in the past.
1. Evidence of mutation associated with primary drug resistance to Nevirapine (K103N,
Y181C, Y188L, G190S), Tenofovir (M41L, T69 insertion, Q151M, L210W,and K65R), and/or
FTC (184V) previously documented, or at time of screening.
2. Patients with any of the following laboratory parameters at the screening visit:
estimated creatinine clearance of <60 ml/min; aspartate aminotransferase (AST) or
alanine aminotransferase (ALT) >2. 5 times the upper limits of normal; total bilirubin
>1. 5 mg/dL.
3. Women with CD4 cell count > 250 cells/ mm3 at time of entry or in males with a CD4
cell count less than 400/mm3, along with a viral load greater than 5,000c/ml. for both
males and females.
4. Pregnant women or women who are breast feeding.
5. Unwillingness to use effective barrier contraception.
6. Patients with current alcohol abuse or illicit drug use that in the opinion of the
Principal Investigator may interfere with the patient's ability to comply with the
7. Patients with malabsorption or severe chronic diarrhea for more than 30 days.
8. Current treatment for malignancy other than basal or squamous cell carcinoma of the
skin or carcinoma in situ of the cervix.
9. History of any chronic illness or other condition that in the opinion of the
investigator would interfere with the conduct or completion of the study.
10. Patient who is, in the opinion of the investigator, unable to complete the 96-week
dosing period and protocol evaluations and assessments.
11. Experimental vaccines, to include HIV vaccines.
12. Patient who is currently enrolled in an experimental protocol, or is receiving an
Locations and Contacts
University of Maryland, Institute of Human Virology, Baltimore, Maryland 21201, United States
Starting date: March 2004
Ending date: July 2008
Last updated: May 16, 2008