Comparing Immune Activation and Latent HIV Reservoir Size Between People Living With HIV on Tenofovir-containing Versus NRTI-free ART

The study will be open-label, cross-sectional, two-cohort study (20 participants per cohort will be recruited).

Cohort 1: Tenofovir-containing ART (tenofovir disoproxil fumarate [TDF] OR tenofovir alafenamide [TAF] PLUS any other ART drugs) prescribed for daily use by participants' primary care providers.

Cohort 2: NRTI-sparing ART (specifically: rilpivirine PLUS dolutegravir OR rilpivirine PLUS cabotegravir) prescribed for daily use by participants' primary care providers.

The investigators plan to test type I/III IFN (interferon) pathway activation using Crystal digital PCR (Crystal-dPCR) to quantify mRNA copy numbers of ISG15 (ISG15 ubiquitin-like modifier), MX1 (MX dynamin like GTPase 1) and IFI6 (interferon alpha inducible protein 6). RNA will be isolated from the rectal and duodenal biopsies stored in RNALater using the RNeasy Fibrous Tissue Mini Kit (Qiagen) and from the PBMC using the RNeasy Plus Mini Kit (Qiagen). Crystal-dPCR will be performed on a 6-color Naica Crystal digital PCR instrument (Stilla Technologies).

The latent HIV reservoir will be measured in DNA derived from peripheral blood mononuclear cells (PBMCs) using a novel intact/defective proviral HIV DNA Crystal-dPCR assay developed jointly by the Hladik and Jerome groups in Seattle.

Inclusion criteria

• Confirmed HIV infection, by two different positive antibody tests and/or detectable plasma HIV RNA on two different dates
• ≥18 and ≤65 years of age
• Stable use of ART medication for ≥ 1 year
• No switch of ART regimen within the past 180 days
• CD4 > 350/mm3 within the past 180 days
• HIV RNA <40 copies / mL on ≥ 2 occasions during continuous ART of ≥ 1 years, with no blip of >1000 HIV RNA copies / mL
• Karnofsky score ≥80
• Willingness and ability to provide informed consent for study participation
• Willingness to undergo all required study procedures

Exclusion criteria

• Active malignancy including myelodysplastic syndrome, or myeloproliferative disease within 24 weeks prior to study entry
• Prior organ or bone marrow transplantation
• Diagnosed autoimmune disease
• Medical need for ongoing treatment with an immunosuppressive drug
• Diagnosis of AIDS (defined as any AIDS-defining opportunistic infection or cancer, or a history of blood CD4+ T cell count < 200/μL)
• Active opportunistic infection
• Vomiting or diarrhea which prohibits consistent use of ART
• Pregnant or breastfeeding
• Excessive ingestion of ethanol determined by an AUDIT score of >8
• Substance abuse
• History of medical non-compliance
• The following laboratory values (< 30 days before enrollment):

• Hemoglobin < 8.5 mg/dL
• Platelet count < 100,000/μL
• Coagulation (PT/PTT) tests above the normal reference
• Creatinine clearance < 60 mL/min
• Using disallowed medications:

• Systemic corticosteroids
• Other immunosuppressive medications (e.g., cyclosporine, sirolimus, tacrolimus, pimecrolimus, tofacitinib)
• BMI > 40
• Pulmonary dysfunction.
• Use of narcotics.