Brief Report: Urine Emtricitabine and Tenofovir Concentrations Provide Markers of Recent Antiretroviral Drug Exposure Among HIV-Negative Men Who Have Sex With Men.

BACKGROUND: Urine provides a minimally invasive specimen that may allow for development of rapid tests to detect antiretroviral drugs and provide opportunities to improve individual adherence. This study sought to determine whether urine could provide a biomarker of adherence for currently approved pre-exposure prophylaxis and HIV treatment regimens. METHODS: Urine and blood were collected from 34 HIV-negative men who have sex with men aged 18-49 years, enrolled in a clinical trial comparing 2 antiretroviral regimens. Specimens were collected 4 and 24 hours after a single oral dose of tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) (n = 10) or tenofovir alafenamide (TAF)/FTC/cobicistat (COBI)/elvitegravir (EVG) (n = 8), or after 4 and 10 days of daily oral TDF/FTC (n = 9) or TAF/FTC/COBI/EVG (n = 7). Tenofovir (TFV), FTC, and EVG were measured by high-performance liquid chromatography-mass spectrometry. RESULTS: Median urine FTC concentrations at 4 and 24 hours were similar between men receiving TDF/FTC (4 hours 147 µg/mL; 24 hours 10 µg/mL) and men receiving TAF/FTC/COBI/EVG (4 hours 333 µg/mL, P = 0.173; 24 hours 13 µg/mL, P = 0.681). Median urine TFV concentrations were lower among men receiving TAF/FTC/COBI/EVG (4 hours 1.2 µg/mL; 24 hours 0.8 µg/mL) compared with men receiving TDF/FTC (4 hours 17 µg/mL, P < 0.001; 24 hours 7 µg/mL, P = 0.001). Urine TFV concentrations remained reduced among men receiving TAF/FTC/COBI/EVG compared with men receiving TDF/FTC after daily dosing. EVG was not consistently measurable in urine. CONCLUSIONS: High urine FTC and TFV concentrations could provide an indication of adherence to daily oral dosing with TDF or TAF-based regimens used for treatment and prevention.

Behavioral and Serotonergic Changes in the Frontal Cortex Following Methamphetamine Self-Administration.

BACKGROUND: Methamphetamine use is associated with a variety of negative health outcomes, including psychosis. The frontal cortex serotonin receptors are thought to contribute to psychosis-like behaviors. This study investigated changes in serotonergic markers in the frontal cortex following methamphetamine self-administration and hallucinogenic drug-induced behavior. METHODS: Consistent with previously published studies, freely cycling male and female rats were allowed to self-administer methamphetamine (males: 0.12 mg/infusion; females: 0.09 mg/infusion) or saline (10 µL) for 7 days. On the day following self-administration or following 10 days of extinction training, animals were given the serotonin 2A/2C agonist, 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (2 mg/kg, i.p.), and head twitches were analyzed. Autoradiography was also used to assess serotonin receptors and transporters in the frontal cortex following self-administration. RESULTS: Methamphetamine self-administration led to an increase in DOI-induced head-twitch behavior compared to saline only on the day following self-administration. Increases in serotonin receptors in the orbitofrontal cortex and decreases in serotonin transporters in the orbitofrontal cortex and infralimbic cortex were observed following methamphetamine self-administration as assessed by autoradiography. CONCLUSIONS: Methamphetamine self-administration was associated with serotonergic alterations in the frontal cortex, which may underlie behavioral changes related to methamphetamine-associated psychosis.