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 emtricitabine. 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 hybridization). 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 profiles. The secondary objective is to determine the pharmacokinetics of Raltegravir in blood and gut tissue; relative tissue/compartment penetration compared to Efavirenz.

NCT00984152

Conditions

1. HIV-1 Infections

Interventions

1. Drug: TDF/FTC Once-Daily + Raltegravir 400 mg Orally Twice-Daily
2. Drug: TDF/FTC + Efavirenz (Atripla) Once-Daily

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 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. --- M41L --- --- D76N ---

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 HIV-1 Infections 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. --- M41L --- --- D76N ---