Dataset Information

Antiretroviral drug exposure in urethral and glans surface sampling of the penis.

ABSTRACT:

Background

HIV exposure to penile tissues provides a risk of acquisition among men, yet studies evaluating penile antiretroviral (ARV) drug distribution have been lacking. We measured ARVs on urethral and glans surface swabs collected following a dose of tenofovir alafenamide, emtricitabine, elvitegravir, darunavir and cobicistat.

Methods

Thirty-five HIV-negative male participants provided urethral swabs, glans swabs, rectal swabs, blood and urine up to 96 h following a single dose of tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat and darunavir. ARVs were measured by liquid chromatography-mass spectrometry with a lower limit of detection (LOD) of 1 ng/swab for swabs and 10 ng/mL for plasma and urine. Concentrations are reported as median and range.

Results

Urethral swab emtricitabine and darunavir concentrations peaked at 4 h for emtricitabine (36 ng/swab; 3-307 ng/swab) and 8 h for darunavir (25 ng/swab; 2-52 ng/swab). Glans swab emtricitabine and darunavir concentrations peaked 24 h after dosing (emtricitabine 14 ng/swab, ConclusionsWe document ARV dosing in the urethra and on the glans surface with high drug concentrations noted for emtricitabine and darunavir and lower tenofovir and elvitegravir concentrations. Data suggest a potential protective role of urethral emtricitabine or darunavir against penile HIV acquisition.

SUBMITTER: Haaland RE

PROVIDER: S-EPMC10134741 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Antiretroviral drug exposure in urethral and glans surface sampling of the penis.

Haaland Richard E RE Fountain Jeffrey J Dinh Chuong C Lupo L Davis LD Martin Amy A Conway-Washington Christopher C Hall LaShonda L Kelley Colleen F CF Garcia-Lerma J Gerardo JG Heneine Walid W

The Journal of antimicrobial chemotherapy 20210801 9

<h4>Background</h4>HIV exposure to penile tissues provides a risk of acquisition among men, yet studies evaluating penile antiretroviral (ARV) drug distribution have been lacking. We measured ARVs on urethral and glans surface swabs collected following a dose of tenofovir alafenamide, emtricitabine, elvitegravir, darunavir and cobicistat.<h4>Methods</h4>Thirty-five HIV-negative male participants provided urethral swabs, glans swabs, rectal swabs, blood and urine up to 96 h following a single dos ...[more]

PMID: 34007982

Similar Datasets

Project description:IntroductionGlans penis augmentation (GPA) using hyaluronic acid (HA) gel has been developed for treating premature ejaculation (PE) with penile hypersensitivity. The injected HA filler creates a barrier that reduces the tactile stimuli to the hypersensitive dorsal nerve. Although the HA filler is biodegradable and is believed to not cause permanent loss of sexual function, the current International Society for Sexual Medicine guideline for PE does not recommend this procedure owing to concerns regarding sexual dysfunction.AimTo investigate the practice patterns for GPA using HA filler among Korean urologists, and to identify whether urologist experienced patient reports of sexual dysfunction post-treatment.MethodsBetween March 2016 and July 2016, a specially designed questionnaire was mailed to 86 selected Korean urologists who had used injectable materials to treat PE.Main outcome measuresThe prevalence and awareness of sexual dysfunction after GPA using HA filler were evaluated.ResultsOverall, 56 urologists completed the survey (response rate: 69.2%), of which 36 (64.3%) had performed GPA using HA filler. They reported having performed a combined total of 4,344 such GPA procedures. Most urologists (72.7%) performed GPA using HA filler in patients who benefit from topical anesthetics. Patients with a history of failed pharmacotherapy (59.1%) and selective dorsal nerve neurotomy (45.5%) were selected for GPA using HA filler. The respondents (44.4%) encountered overall 206 (4.7%) cases of patients reports of recurrence of PE. Interestingly, only 36 (0.8%) cases of glans pain or paresthesia and no cases of erectile dysfunction post-treatment were reported.ConclusionKorean urologists performed GPA using HA filler when pharmacotherapy failed or if there was a response to topical treatment. Paresthesia and hypoesthesia after GPA using HA filler are rare, and no cases of erectile dysfunction were encountered by Korean urologists. Jeong HG, Ahn ST, Kim JW, et al. Practice Patterns Among Korean Urologists for Glans Penis Augmentation Using Hyaluronic Acid Filler in the Management of Premature Ejaculation. Sex Med 2018;6:297-301.

Project description:IntroductionHIV reservoirs and infected cells may persist in tissues with low concentrations of antiretrovirals (ARVs). Traditional pharmacology methods cannot assess variability in ARV concentrations within morphologically complex tissues, such as lymph nodes (LNs). We evaluated the distribution of six ARVs into LNs and the proximity of these ARVs to CD4+ T cells and cell-associated RT-SHIV viral RNA.MethodsBetween December 2014 and April 2017, RT-SHIV infected (SHIV+; N = 6) and healthy (SHIV-; N = 6) male rhesus macaques received two selected four-drug combinations of six ARVs over 10 days to attain steady-state conditions. Serial cryosections of axillary LN were analysed by a multimodal imaging approach that combined mass spectrometry imaging (MSI) for ARV disposition, RNAscope in situ hybridization for viral RNA (vRNA) and immunohistochemistry for CD4+ T cell and collagen expression. Spatial relationships across these four imaging domains were investigated by nearest neighbour search on co-registered images using MATLAB.ResultsThrough MSI, ARV-dependent, heterogeneous concentrations were observed in different morphological LN regions, such as the follicles and medullary sinuses. After 5-6 weeks of infection, more limited ARV penetration into LN tissue relative to the blood marker heme was found in SHIV+ animals (SHIV+: 0.7 [0.2-1.4] mm; SHIV-: 1.3 [0.5-1.7] mm), suggesting alterations in the microcirculation. However, we found no detectable increase in collagen deposition. Regimen-wide maps of composite ARV distribution indicated that up to 27% of SHIV+ LN tissue area was not exposed to detectable ARVs. Regions associated with B cell follicles had median 1.15 [0.94-2.69] -fold reduction in areas with measurable drug, though differences were only statistically significant for tenofovir (p = 0.03). Median co-localization of drug with CD4+ target cells and vRNA varied widely by ARV (5.1-100%), but nearest neighbour analysis indicated that up to 10% of target cells and cell-associated vRNA were not directly contiguous to at least one drug at concentrations greater than the IC50 value.ConclusionsOur investigation of the spatial distributions of drug, virus and target cells underscores the influence of location and microenvironment within LN, where a small population of T cells may remain vulnerable to infection and low-level viral replication during suppressive ART.

Dataset Information

Antiretroviral drug exposure in urethral and glans surface sampling of the penis.

Background

Methods

Results

Publications

Antiretroviral drug exposure in urethral and glans surface sampling of the penis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets