Trial of TDF/FTC + Raltegravir Versus TDF/FTC + Efavirenz in HIV-1-Infected Women

Launched by RUSH UNIVERSITY MEDICAL CENTER · Sep 24, 2009

Keywords

ClinConnect Summary

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 + Ralte...

Gender

FEMALE

Eligibility criteria

• Inclusion Criteria:
• • 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 infection.
• • 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 to entry).
• 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 equation:
• • 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.
• Exclusion Criteria:
• • 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, T215any, K219Q/E
• • 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