Pharmacokinetics of Antiretroviral Drugs in Older People Living with HIV: A Systematic Review.

BACKGROUND AND OBJECTIVE: The life expectancy of people living with HIV (PLWHIV) has significantly improved in recent decades, mostly due to antiretroviral (ARV) therapy. Aging can affect the pharmacokinetics of drugs and, as a consequence, increase the risk of drug interactions and toxicity that may impact treatment. The aim of this study was to carry out a systematic review of the literature on the effect of aging on ARV pharmacokinetics. METHODS: Searches were performed in the BVS, EMBASE and PUBMED databases until November 2022. All studies available in English, Spanish and Portuguese investigating the pharmacokinetics of ARV approved by the US Food and Drug Administration (FDA) from 2005 to 2020 were selected. Peer-reviewed publications were included if they met all criteria: adults (≥ 18 years of age) living with or without HIV; report any pharmacokinetic parameter or plasma concentration of at least one of the following ARVs: tenofovir alafenamide fumarate (TAF); doravirine (DOR), rilpivirine (RIL) and etravirine (ETR); darunavir (DRV), tipranavir (TPV) and fostemsavir (FTR); dolutegravir (DTG), raltegravir (RAL), bictegravir (BIC) and elvitegravir (EVG); maraviroc (MVC); ibalizumab (IBA); cobicistat (COBI). Pharmacokinetic parameters were reported stratified per age group: young adults (aged 18-49 years) or older (age ≥ 50 years) and all studies were evaluated for quality. The review protocol was registered in the PROSPERO database (registration number CRD42021236432). RESULTS: Among 97 studies included, 20 reported pharmacokinetic evaluation in older individuals (age ≥ 50 years). Twenty five percent of the articles were phase I randomized clinical trials with HIV-negative participants and non-compartmental pharmacokinetic analysis presenting the parameters area under the curve (AUC) and peak drug concentration (Cmax). Seven age-stratified studies evaluated BIC, ETR, DRV, DTG, DOR and RAL. We found publications with discordant results for ETR and DTG pharmacokinetics in different age groups. DRV exposure was highly variable but modestly increased in aging PLWHIV. In contrast, no influence of age on BIC, DOR and RAL exposure was observed. A variability in pharmacokinetic parameters could be observed for the other ARVs (TAF and MVC) in different age groups. CONCLUSION: Exposure to DRV increases modestly with age, while exposure to BIC, DOR and RAL appears to be unaffected by age. As the available evidence to confirm a potential effect of aging on ARV pharmacokinetics is limited, further studies are necessary.

Risks related to the domestic laundering of filling station attendant uniforms: advances and uncertainties.

Gasoline is the most common transportation fuel in Brazil, with up to 1% of benzene. Benzene is a health-damaging organic solvent that is extensively used worldwide, being classified as a human carcinogen by the International Agency for Research on Cancer (Group 1). Many workers at filling stations are exposed to benzene, present in gasoline. The main routes of exposure and absorption of benzene are inhalation, oral, and dermal routes. The penetration and maintenance of benzene and other chemicals on personal protective equipment and clothing of workers who manipulate these solvents may increase their levels of exposure and offer risks to their family members, since contaminated clothing is laundered at their homes, which goes against legislative framework (Annex 2, Regulatory Standard No. 9). This way, the objective of this work was to discuss the importance of periodic changes and cleaning of filling station attendant uniforms performed by employers as preventive measures against the deterioration of the health of workers and their family members. We performed a narrative review; no systematic criteria were used in the search for national and international studies. After critical reading, we observed a lack of consistent data on this theme. Laundering of uniforms worn by filling station attendants should take place outside the domestic environment in order to protect the health of workers and their family members and avoid possible cross-contamination.