AIDS 347: IL-6 Blockade in Treated HIV Infection

Inclusion Criteria

4.1.1 Men and women age 18-60 years.

4.1.2 Ability and willingness to communicate in English or Spanish

4.1.3 Ability and willingness of subject to provide informed consent.

4.1.4 Ability and willingness to provide adequate locator information.

4.1.5 HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test at any time before study entry and confirmed by a licensed Western blot, a second antibody test by a method other than rapid HIV or E/CIA; HIV-1 antigen; or plasma HIV-1 RNA viral load.

4.1.6 Receiving a stable antiretroviral regimen consisting of 3 or more drugs belonging to two or more classes, one of which must be a protease inhibitor, an integrase inhibitor, or a non-nucleoside reverse transcriptase inhibitor, without any changes due to virologic failure in the past 24 weeks, and with no plans to change antiretroviral regimen in the 40 weeks following enrollment. If the regimen includes a protease inhibitor, ritonavir or an approved boosting agent known to increase trough levels of the protease inhibitor by at least 50% must also be a part of the regimen.

NOTE A: Changes to the antiretroviral regimen 8 weeks or more prior to enrollment are allowed if the plasma HIV RNA was 200 copies/mL on two or more consecutive occasions; b) the treating physician determines that any given plasma HIV RNA value is indicative or suggestive of virologic failure, and recommends that the patient's regimen be modified as a result; c) a genotypic or phenotypic antiretroviral resistance test identifies the presence of resistance to any component of a patient's regimen that was not present before, and a physician recommends that the patient's regimen be modified as a result.

4.1.7 For subjects who have a positive HBcAb only:

• An antiretroviral regimen containing one or more of the following medications: lamivudine, emtricitabine, or tenofovir.

4.1.8 Screening CD4+ T-cell count ≥350 cells/mm3 but ≤1,000 cells/mm3 performed in a laboratory that has a Clinical Laboratory Improvement Amendments (CLIA) certification or its equivalent.

4.1.9 HIV-1 RNA 100,000/mm3

• Absolute neutrophil count (ANC) ≥2,000 cells/mm3
• Aspartate aminotransferase (AST) [serum glutamic oxaloacetic transaminase (SGOT)] <1.5x ULN
• Alanine aminotransferase (ALT) [serum glutamic pyruvic transaminase (SGPT)] <1.5x ULN
• For subjects who consent to undergo rectal tissue sampling only: International normalized ratio (INR) < 1.7
• Total bilirubin <3.0 mg/dL, EXCEPT for subjects receiving atazanavir
• For subjects receiving atazanavir: Direct bilirubin ≤1.0 mg/dL
• Calculated GFR ≥60 mL/min/1.73m2

4.1.11 Female subjects of reproductive potential must have a negative serum or urine pregnancy test at study entry and must affirm that they do not intend to become pregnant for the duration of the study.

NOTE: For the purposes of this protocol, a female subject of reproductive potential is defined as one who has reached menarche, has not been post-menopausal for at least 24 consecutive months (i.e., has had menses within the preceding 24 months), and has not undergone surgical sterilization (e.g., hysterectomy, tubal ligation, or bilateral oophorectomy).

4.1.12 Female subjects of reproductive potential participating in sexual activity that could lead to pregnancy must agree to use at least one of the following forms of birth control for at least 30 days prior to study entry through 30 days after the final study visit:

• Condoms (male or female) with or without a spermicidal agent
• Diaphragm or cervical cap with spermicide

PLUS at least one of the following:

• An FDA-approved copper intrauterine device (IUD), e.g. ParaGard®, or an FDA-approved hormone-releasing IUD, e.g. Mirena®
• An FDA-approved transdermal hormonal contraceptive, e.g. Ortho-Evra®
• An FDA-approved injectable hormonal contraceptive, e.g. Depo-Provera®
• An FDA-approved hormonal contraceptive in vaginal ring form, e.g. Nuv