Development of a risk assessment profile tool to determine appropriate use of SARS-CoV-2 rapid antigen detection tests for different activities and events in Ireland, since October 2021.

We describe the development of a risk assessment profile tool that incorporates data from multiple domains to help determine activities and events where rapid antigen detection tests (Ag-RDT) could be used to screen asymptomatic individuals to identify infectious cases as an additional mitigation measure to reduce transmission of SARS-CoV-2. The tool aims to stratify, in real time, the overall risk of SARS-CoV-2 transmission associated with common activities and events, and this can be matched to an appropriate Ag-RDT testing protocol.

Weight gain before and after switch from TDF to TAF in a U.S. cohort study.

INTRODUCTION: Although weight gain has been reported with the use of integrase strand transfer inhibitors (InSTI), concurrent use of tenofovir alafenamide (TAF) has been implicated in recent studies. This study examined weight changes in people living with HIV (PLWH) who switched from tenofovir disoproxil fumarate (TDF) to TAF, to clarify the relative contribution to weight gain of core agents versus TDF to TAF switch. METHODS: Antiretroviral-experienced, virologically suppressed PLWH in the U.S. OPERA cohort were included if they switched from TDF to TAF (5NOV2015-28FEB2019) and either maintained all other antiretrovirals or switched from a non-InSTI to an InSTI. Linear mixed models were used to assess weight changes before/after the switch to TAF (restricted cubic splines on time) and rates of change over time (linear splines on time, based on the shape of the weight change curves). Changes in weight on TDF or TAF were assessed among those who maintained other antiretrovirals (overall, by core class), and those who maintained an InSTI or switched to an InSTI (by core agent). All models were adjusted for age, sex, race, (age-sex, race-sex interactions), BMI, CD4 cell count, endocrine disorders and concurrent medications that could affect weight. RESULTS: A total of 6908 PLWH were included, with 5479 maintaining all other antiretrovirals (boosted protease inhibitor: 746, non-nucleoside reverse transcriptase inhibitor: 1452, InSTI: 3281) and 1429 switching from a non-InSTI to an InSTI (elvitegravir/cobicistat: 1120, dolutegravir: 174, bictegravir: 129). In adjusted models, modest weight gain was observed over time on TDF for most (0.24 to 0.71 kg/year); raltegravir was the exception with weight loss. Switching to TAF was associated with early, pronounced weight gain for all (1.80 to 4.47 kg/year). This effect with TAF switch was observed both in PLWH maintaining other antiretrovirals and those switching to an InSTI, regardless of which InSTI agent was used. Weight gain tended to slow down or plateau approximately nine months after switch to TAF. CONCLUSIONS: In this large, diverse U.S. cohort of PLWH, switching from TDF to TAF was associated with pronounced weight gain immediately after switch, regardless of the core class or core agent, suggesting an independent effect of TAF on weight gain.

Cognitive function, depressive symptoms and syphilis in HIV-positive and HIV-negative individuals.

We evaluated associations between history of syphilis infection and both cognitive function and depressive symptoms in people living with HIV (PLHIV) and comparable HIV-negative controls. Syphilis serological tests, cognitive function and depression were assessed in PLHIV and controls participating in the Pharmacokinetic and Clinical Observations in People Over Fifty study. Cognitive test scores were converted to demographically adjusted T-scores (mean = 50, SD = 10) and then averaged to obtain a global T-score. Severity of depressive symptoms was assessed via the Patient Health Questionnaire-9. Associations of syphilis with global T-scores and depression were assessed using median regression. The 623 PLHIV and 246 HIV-negative controls were predominantly male (89.3% and 66.5%) with median age (interquartile range [IQR]) of 57 (53-63) and 58 (53-63) years, respectively. PLHIV had lower global cognitive T-scores (median [IQR] 48.7 [45.1, 52.1] versus 50.5 [47.0, 53.9], p < 0.001), more severe depressive symptoms (median [IQR] 4 [1, 10] versus 1 [0, 3], p < 0.001) and were more likely to report history of syphilis infection (22.0% versus 8.1%) than controls. There was no significant association between history of syphilis and global cognitive function in either PLHIV (p = 0.69) or controls (p = 0.10). Participants with a history of syphilis had more severe depressive symptoms (median [IQR] 4 [1, 9] versus 2 [0, 8], p = 0.03); however, the association became non-significant (p = 0.62) after adjusting for HIV status and potential confounders. Despite the higher prevalence of syphilis infection in PLHIV, there was no evidence of an association between history of syphilis infection and impaired cognitive function nor depressive symptoms after accounting for potential confounders.

The clinical pharmacology of antiretrovirals in development.

Drugs in development for the management of HIV type 1 (HIV-1) infection include agents in existing classes and agents of novel classes. Of existing classes, new protease inhibitors, nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors are in development. Novel therapeutic approaches include the development of chemokine receptor (CCR)5 antagonists, integrase inhibitors and maturation inhibitors. CCR5 antagonists are thought to inhibit HIV-1 entry into host cells by occupying a specific site on the CCR5 receptor, preventing attachment of the HIV-1 envelope protein gp120. Integrase inhibitors are small synthetically prepared molecules that block RNA/DNA interactions and modify protein or enzyme synthesis. Data on the pharmacokinetics and pharmacodynamics of these new antiretroviral agents continue to generate interest. This review reports the known data on the pharmacokinetics of experimental antiretrovirals, and describe the main drug-drug interactions studied so far.