Trial of TDF/FTC + Raltegravir Versus TDF/FTC + Efavirenz in HIV-1-Infected Women (ICE-002)

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