ACTG 5257: A Phase III Comparative Study of Three Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-Sparing Antiretroviral Regimens for Treatment-Naïve HIV-1-Infected Volunteers

Key Inclusion Criteria:

1. HIV-1 infection, as documented by any licensed enzyme-linked immunosorbent assay (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.

2 No evidence of any exclusionary resistance mutations based on results from any genotype assay from any laboratory that has a CLIA certification or its equivalent. The result must either be available from previous testing or must be obtained prior to entry and have been reviewed by the site investigator. (The protocol will not provide the resistance assay.)
An exclusionary resistance mutation is defined as evidence of any major NRTI or PI resistance-associated mutation on any genotype, or evidence of significant NRTI or PI resistance on any phenotype performed at any time prior to study entry. Any pending resistance testing ordered prior to entry must be available for review by the site investigator prior to enrollment. Refer to the PSWP for a list of the major NRTI or PI resistance-associated mutations.

NOTE: NNRTI-associated resistance mutations are not exclusionary.

3 ARV drug-naïve (defined as >10 days of ART at any time prior to entry*).

*The only exceptions are:

• Use of ARV drugs as part of post-exposure prophylaxis (PEP) provided the subject did not acquire HIV-1 infection from the event that required PEP.
• ART use during pregnancy that resulted in virologic suppression to <50 copies/mL in HIV-1 RNA and was not complicated either by detectable HIV-1 RNA following suppression or the development of resistance while on therapy. ART must have been stopped within 4 weeks of delivery and can not have been received within 6 months of screening.
• Therapy with an investigational ARV drug that was not an INI, NRTI, NNRTI, or PI. The total duration of this therapy could not have exceeded 24 weeks and cannot have been received within 6 months of screening.
4 Screening HIV-1 RNA >1000 copies/mL obtained within 90 days prior to study entry by any FDA-approved test for quantifying HIV-1 RNA at any laboratory that has a CLIA certification or its equivalent.
5 Laboratory values obtained within 30 days prior to study entry.

• Absolute neutrophil count (ANC) >500/mm3
• Hemoglobin >8.0 g/dL
• Platelet count >40,000/mm3
• aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase < 5 x ULN
• Total bilirubin <2.5 x ULN
• CrCl >60 mL/min as estimated by the Cockcroft-Gault equation.
6 For women of reproductive potential, negative serum or urine pregnancy test with a sensitivity of < 25 mIU/mL at screening and within 48 hours prior to initiating study medications.

Female subjects of reproductive potential are defined as women who have not been post-menopausal for at least 24 consecutive months (i.e., who have had menses within the preceding 24 months) or have not undergone surgical sterilization (e.g., hysterectomy, or bilateral oophorectomy, or bilateral tubal ligation).
7 Contraception requirements:
- Female Subjects of Reproductive Potential
Female subjects of reproductive potential, who are participating in sexual activity that could lead to pregnancy, must agree to use at least one reliable method of contraception while receiving the study drugs and for 6 weeks after stopping the medications. Acceptable methods of contraception include:

• Condoms (male or female) with or without a spermicidal agent
• Diaphragm or cervical cap with spermicide
• Intrauterine device (IUD)
• Hormone-based contraceptive (must contain at least 35 mcg of ethinyl estradiol)
NOTE: If an oral contraceptive is administered with ATV/r, it is recommended that the oral contraceptive contain at least 35 mcg of ethinyl estradiol. Women who use birth control pills containing progestagens, other than norethindrone or norgestimate or less than 35 mcg of ethinyl estradiol; the patch; vaginal rings; or injectable contraceptives should choose a different kind of contraception. ATV/r may affect the safety and effectiveness of these birth control pills or the patch. Therefore, for this study, when used alone, oral contraceptives with less than 35 mcg of ethinyl estradiol and transcutaneous contraceptives will not be considered to be reliable methods of contraception.

- Female Subjects Who Are Not of Reproductive Potential

Women who are not of reproductive potential or whose male partner(s) has azoospermia are eligible to start study drugs without requiring the use of contraceptives. Any statement of self-reported sterility or that of her partner’s must be entered in the source documents.
NOTE:Acceptable documentation of lack of reproductive potential is the woman’s self-reported history of surgical sterilization, menopause, or male partner’s azoospermia.

8 Men and women age >18 years.
9 Ability and willingness of subject or legal guardian/representative to give written informed consent.
10 Ability to obtain RTV by prescription.
11 Cardiovascular risk assessment completed