HIV RNA persists in rectal tissue despite rapid plasma virologic suppression with dolutegravir-based therapy

• Type of Material: Article
• Authors: Cecile Lahiri, Emory University; Nakita L Brown, Emory University; Kevin J Ryan, University of Alabama Birmingham; Edward P Acosta, University of Alabama Birmingham; Anandi Sheth, Emory University; Christina Mehta, Emory University; Jessica Ingersoll, Emory University; Ighovwerha Ofotokun, Emory University
• Language: English
• Date: 2018-09-24
• Publisher: Lippincott Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 Wolters Kluwer Health, Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1097/QAD.0000000000001945
• Title of Journal or Parent Work: AIDS
• Volume: 32
• Issue: 15
• Start Page: 2151
• End Page: 2159
• Grant/Funding Information: National Institute of Allergy and Infectious Diseases at the National Institutes of Health [K23AI124913 to C.D.L, K23AI114407 to A.N.S., CFAR P30AI050409, U01 AI103408 to I.O]; National Center for Advancing Translational Sciences at the National Institutes of Health to C.D.L [KL2TR000455 to C.D.L, UL1TR000454]; Emory Medical Care Foundation
• Keywords: LYMPHOID-TISSUE; antiretroviral pharmacology; LEPTIN; dolutegravir; HIV; DOSE PHARMACOKINETICS; Immunology; SINGLE; rectal tissue; reservoirs; GENITAL-TRACT; Life Sciences & Biomedicine; OVERWEIGHT; Science & Technology; Infectious Diseases; Virology
• Research Categories: Biology, Virology; Health Sciences, Immunology

Abstract

Objectives: Despite plasma virologic suppression with antiretroviral therapy (ART), HIV persists in gut tissue. The objectives of this study were to compare plasma and rectal tissue HIV RNA dynamics and to assess relationships with dolutegravir (DTG) plasma and tissue concentrations. Design: A longitudinal cohort study of HIV-infected treatment-naïve individuals initiating DTG-based ART was conducted over 12 weeks with plasma and rectal tissue sampling (Clinicaltrials.gov:NCT02924389).Methods: HIV RNA and DTG concentrations were quantified in plasma and rectal tissue samples collected pre-ART (baseline) and post-ART at weeks 2, 6, and 12 using Abbott Real-Time HIV-1 assays and high-performance liquid chromatography tandem mass spectroscopy, respectively. Relationships between rectal tissue RNA and DTG concentrations were modeled using binary logistic regression, controlling for repeated measures. Results: Twelve participants were enrolled: six (50.0%) women, nine (75.0%) black, median age 42.0 years (Q1 31.2, Q3 52.0). All attained plasma virologic suppression by week 6. 11 of 12 (91.7%) had detectable rectal tissue HIV RNA at baseline, and only three of 11 (27.3%) achieved rectal tissue virologic suppression at any time-point. Compared with rectal tissue nonsuppressors, three of three (100.0%) of rectal tissue suppressors were women, had higher BMI, 35.9 kg/m2 (range 24.9 - 38.5) versus 20.6 (17.7 - 29.9), P ¼ 0.05, and lower baseline log plasma HIV RNA: 3.7 copies/ml (range 3.6 - 4.4) versus 4.7 (3.8 - 5.4), P ¼ 0.02. No significant relationships between rectal tissue RNA suppression and DTG concentrations were seen. Conclusion: Rectal tissue HIV RNA persisted in most participants and was not predicted by DTG concentrations. Impact of host factors, particularly sex, on tissue HIV viral dynamics warrants further exploration.