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

Lahiri, Cecile D.a,b; Brown, Nakita L.a,*; Ryan, Kevin J.c; Acosta, Edward P.c; Sheth, Anandi N.a,b; Mehta, Cyra C.d; Ingersoll, Jessicae; Ofotokun, Ighovwerhaa,b

doi: 10.1097/QAD.0000000000001945
CLINICAL SCIENCE

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 = 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 = 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.

aEmory University School of Medicine, Department of Medicine, Division of Infectious Diseases

bGrady Healthcare System Infectious Diseases Program, Atlanta, Georgia

cUniversity of Alabama at Birmingham School of Medicine, Division of Clinical Pharmacology, Birmingham, Alabama

dEmory University, Rollins School of Public Health, Department of Biostatistics and Bioinformatics

eEmory Center for AIDS Research, Virology and Molecular Biomarkers Core, Atlanta, Georgia, USA.

Correspondence to Cecile D. Lahiri, MD, MS, 49 Jesse Hill Jr Drive SE, Atlanta, Georgia 30303, USA. Tel: +1 404 616 6306; fax: +1 404 616 9702; e-mail: cdelill@emory.edu

Received 16 April, 2018

Revised 14 June, 2018

Accepted 15 June, 2018

Copyright © 2018 Wolters Kluwer Health, Inc.