Switching HIV Treatment to Doravirine/Islatravir to Study Biological Aging in People With HIV

Trial details

Who runs it

The University of Texas Health Science Center, Houston

Trial code

NCT07871552

Record updated

23 October 2026

Original description

The purpose of this study is to quantify biologic aging (using validated epigenetic clocks) as downstream indicators of Long Interspersed Nuclear Element-1 (LINE-1) retrotransposon activity before and after switch to doravirine (DOR)/Islatravir (ISL) , to estimate whether effects of DOR/ISL on biologic aging vary by entry antiretroviral therapy (ART) regimen, and relative to continued standard of care (SoC) ART and to obtain the tolerability (adverse event profile) associated with switch to DOR/ISL relative to continued SoC ARTRead full original descriptionShow less

A Pilot, Randomized, Open-Label Trial of the Effects of Switch to Doravirine/Islatravir vs. Continued Antiretroviral Therapy on Biomarkers of Aging Among Virologically Suppressed People With HIV

The purpose of this study is to quantify biologic aging (using validated epigenetic clocks) as downstream indicators of Long Interspersed Nuclear Element-1 (LINE-1) retrotransposon activity before and after switch to doravirine (DOR)/Islatravir (ISL) , to estimate whether effects of DOR/ISL on biologic aging vary by entry antiretroviral therapy (ART) regimen, and relative to continued standard of care (SoC) ART and to obtain the tolerability (adverse event profile) associated with switch to DOR/ISL relative to continued SoC ART

Inclusion: Living with HIV-1 and on ART for greater than or equal to 2 years (to allow for epigenetic stabilization after ART initiation; Current ART greater than or equal to 6 months prior to entry. ART must contain 1) FTC or 3TC with TAF or TDF or 2) any NRTI-sparing regimen consisting of greater than or equal to 2 drugs; HIV-1 RNA <50 copies/mL at screening and less than or equal to 200 copies/mL within 6 months of entry (latter according to clinical care records). Repeat HIV-1 RNA within the screening allowed if needed to verify eligibility; Able and willing to provide informed consent and undergo study procedures.

Exclusion: Active AIDS-defining opportunistic infection <30 days prior to entry; Other concomitant chronic inflammatory diseases (e.g., systemic lupus erythematosus, rheumatoid arthritis), in the opinion of the site investigator; Concomitant (current or <45 days of entry) use of any investigational compound or device; Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate Cytochrome P450 3A (CYP3A) inducers from <45 days prior to entry through the study treatment period; HIV-2; Hypersensitivity or other contraindication to DOR or ISL or any of the components of the study product, as determined by the site investigator; Active malignancy (exclusive of basal/squamous cell skin cancer); Active Hepatitis B Virus; Chronic Hepatitis C Virus; Advanced liver disease (Childs-Pugh Class B or C); Concern for risk of virologic failure with switch to DOR, based on participant history and in the opinion of the site investigator; Any condition, therapy, laboratory abnormality or other circumstance that the site investigator feels may confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate; Any of the following laboratory abnormalities:; Alkaline phosphatase (AP), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5x the upper limit of normal (ULN); Calculated creatinine clearance less than or equal to 30 mL/min, as calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) equation -Cluster of Differentiation 4 (CD4+) T cell count <50 cells/mm3; Absolute lymphocyte count <0.650 × 109 cells/L; Hemoglobin (Hb) <9 or <10 g/dL for persons assigned female or male sex at birth, respectively; Pregnant or nursing, or intent to become pregnant during the study period; Documented or known virologic resistance to DOR, as demonstrated by any of the following DOR resistance substitutions in RT: Valine106Alanine/Methionine (V106A/M), Valine108 Isoleucine (V108I), tyrosine 188 leucine (Y188L), Histidine 221 tyrosine (H221Y), Proline 225 histidine (P225H), Phenylalanine 227 cysteine, leucine, or valine (F227C/L/V), Methionine 230 isoleucine/leucine (M230I/L), Leucine 2341 isoleucine (L234I), Proline 236 leucine (P236L) or Tyrosine 318 phenylalanine (Y318F); Use of agents containing glucagon-like peptide-1 receptor agonists during the study or within 24 W of entry.

ClinicalTrials.gov NCT07871552