Trial of TDF/FTC + Raltegravir Versus TDF/FTC + Efavirenz in HIV-1-Infected Women
Information source: Rush University Medical Center
Information obtained from ClinicalTrials.gov on October 04, 2010
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV-1 Infections
Intervention: TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily (Drug); TDF/FTC + Efavirenz (Atripla) Once-Daily (Drug)
Phase: Phase 3
Status: Not yet recruiting
Sponsored by: Rush University Medical Center
Official(s) and/or principal investigator(s):
Alan L. Landay, Ph.D., Principal Investigator, Affiliation: Rush University Medical Center
Raltegravir not only has a unique mechanism of action, but may also have other unique
effects on suppression of viral replication, viral reservoir, and immune reconstitution in
blood and other important compartments. This may in part be due to the pharmacokinetics of
Raltegravir in blood and gut tissue. Efavirenz will be the comparator antiretroviral drug
in this study, with both drugs being used as part of a three-drug regimen with tenofovir and
The primary objectives are to determine differences in the effects of 2 anti-retroviral
regimens, Raltegravir + Truvada versus Atripla, with respect to:
1. Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ
2. Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract.
3. Immune effects (CD4/CD8 immunophenotypes) in gut and PBMCs and plasma cytokine
The secondary objective is to determine the pharmacokinetics of Raltegravir in blood and gut
tissue; relative tissue/compartment penetration compared to Efavirenz.
Official title: Open Label, Randomized Trial of TDF/FTC+Raltegravir Vs. TDF/FTC+Efavirenz in HIV-1-Infected Women: Differential Effects on Viral Suppression/Reservoir, & Immune Parameters in Different Compartments, Including Gut & Genital Tract
Study design: Allocation: Randomized, Control: Active Control, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Viral load in plasma, genital tract (vaginal secretions), and gut (by in situ hybridization)
Latent viral reservoir (pro-viral DNA) in the peripheral blood and genital tract
Immune effects (CD4/CD8 immunophenotypes) in gut and PBMCs and plasma cytokine profiles
Secondary outcome: Determine the pharmacokinetics of Raltegravir in blood and gut tissue; relative tissue/compartment penetration compared to Efavirenz
This is a phase III, prospective, randomized (1: 1), multicenter, open label study comparing
the effects of two HAART regimens:
- Arm A: Raltegravir 400 mg PO BID + TDF/FTC (Truvada, 300/200 mg) One PO Daily
- Arm B: Efavirenz + TDF/FTC (Atripla) Once PO Daily
The following local sites: Mt. Sinai, Rush University Medical Center, Stroger Hospital,
University of Chicago and University of Illinois will work together to enroll 10 eligible
women meeting all eligibility criteria (5 per study arm) over a one year time period. These
10 women will be randomized 1: 1 to receive either TDF/FTC + Raltegravir or TDF/FTC +
Efavirenz (Atripla). There will be 2 baseline evaluations prior to initiation of study
therapy. Subjects will be followed for 48 weeks after initiation of study treatment.
Minimum age: 18 Years.
Maximum age: 60 Years.
1. Eligible subjects will be antiretroviral naïve (< 7 days of HAART at any time prior
to entry) with plasma HIV-1 RNA > 50,000 copies/mL (obtained within 90 days prior to
study entry by any laboratory that has a CLIA certification or its equivalent) and
moderate immune suppression within 90 days prior to study entry.
2. HIV-1 infected, as documented by any licensed ELISA test kit and confirmed by Western
blot at any time prior to study entry. HIV-1 culture, HIV-1 antigen, plasma HIV-1
RNA, or a second antibody test by a method other than ELISA is acceptable as an
alternative confirmatory test. Alternatively, if a licensed ELISA is not available,
two HIV-1 RNA values >2000 copies/mL at least 24 hours apart performed by any
laboratory that has CLIA certification or its equivalent may be used to document
3. Female sex, Age > 18 and < 60 years, Pre-menopausal.
4. Screening CD4+ T-cell count between 200-350 cells/mm3 obtained within 90 days prior
to study entry by any laboratory that has a CLIA certification or its equivalent.
5. The absence of exclusionary resistance mutations on a genotypic resistance assay
(absence of exclusionary NRTI or NNRTI resistance mutations by genotype testing)
6. Antiretroviral (ARV) drug-naïve (defined as 7 days of ARV treatment at any time prior
7. Laboratory values obtained within 45 days prior to study entry:
- Absolute neutrophil count (ANC) 500/mm3
- Hemoglobin 8. 0 g/dL
- Platelet count 40,000/mm3
- AST (SGOT), ALT (SGPT), and alkaline phosphatase 5 ULN
- Total bilirubin 2. 5 x ULN
- Calculated creatinine clearance ≥60 mL/min as estimated by the Cockcroft-Gault
- For women, multiply the result by 0. 85 = CrCl (mL/min)
8. Negative serum or urine pregnancy test within 48 hours prior to initiating study
medications unless otherwise specified by product labeling.
- Female candidates of reproductive potential is defined as women who have had
regular menses over the preceding 24 months
9. Contraception requirements for women who have not undergone surgical sterilization
(e. g., hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation).
10. Female candidates of reproductive potential, who are participating in sexual activity
that could lead to pregnancy, must agree to the following:
- If the regimen does not include EFV, they must agree to use at least one
reliable method of contraception while receiving the protocol-specified drugs
and for 6 weeks after stopping the medications.
- If the regimen includes EFV, they must agree to use two reliable methods of
contraception: a barrier method of contraception (e. g., condoms, diaphragm, or
cervical cap with or without spermicide) together with another reliable form of
contraceptive (e. g., a second barrier method, an IUD, or a hormone-based
contraceptive) while receiving EFV and for 6 weeks after stopping EFV.
1. Menopausal (may affect quantity of genital tract secretions) or any serious illness
that requires treatment and/or hospitalization until the patient completes therapy
2. Any active infection, including co-infection with hepatitis B or C
3. Any neoplasm
4. Immunosuppressive therapy
5. Requirement for any medications that are prohibited by any of the study treatments
6. Significant liver or renal dysfunction
7. Baseline resistance to any of the study drugs by genotypic testing
- NRTI: M41L, K65 R, D76N, T69D, K70R, L74V/I, y115F, Q151M, M184V, L210W,
- NNRTI: L100I, K103N, V106A/M, V108I, Y181C/I, Y188C/L/H, G190anyA/S
8. Alcohol or substance abuse problems or psychiatric conditions that impair the ability
of the subject to comply with the study protocol
Locations and Contacts
Mt. Sinai Hospital, Chicago, Illinois 60608, United States
University of Chicago, Chicago, Illinois 60637, United States
Rush University Medical Center, Chicago, Illinois 60612, United States
University of Illinois at Chicago, Chicago, Illinois 60612, United States
The Ruth M. Rothstein CORE Center (of Cook County), Chicago, Illinois 60622, United States
Starting date: June 2010
Last updated: April 9, 2010