ABSTRACT
Antifungal drug resistance is an emerging cause of treatment failure in invasive fungal infections, and antifungal susceptibility testing (AFST) may inform treatment decisions. Currently, there are no established AFST guidelines for Talaromyces marneffei (Tm) or other dimorphic fungi. We developed a colorimetric AFST method using a fluorescent redox indicator alamarBlue, which changes from blue to pink in proportion to cellular metabolic activity. We determined the optimal time for alamarBlue addition to be 24 h post-inoculation and for MIC reading to be 72 h post-inoculation. Our method allows three ways to determine minimum inhibitory concentration (MIC): visual inspection of color change, optical density, and fluorescence intensity. We validated the assay by determining the MICs for seven antifungals against 32 Tm clinical isolates and assessed the essential agreement (EA) and inter-rater reliability between our alamarBlue and the Clinical Laboratory Standard Institute (CLSI) broth microdilution methods. The MIC ranges (from low to high) were: 0.008-0.025 µg/ml for itraconazole, 0.004-0.13 µg/ml for voriconazole, 0.03-0.13 µg/ml for posaconazole, 0.06-0.5 µg/ml for flucytosine, 0.5-1 µg/ml for amphotericin B, 0.5-4 µg/ml for caspofungin, and 0.5-16 µg/ml for fluconazole. The EAs were 100% between all three MIC readouts of the alamarBlue method, and 94%-100% between the alamarBlue and CLSI methods. Our alamarBlue method had substantially higher inter-rater agreement and offers a more reliable method that can be standardized across laboratories in both high- and low-resource settings compared to the established CLSI methodology.
We developed a colorimetric alamarBlue method to determine the susceptibility of antifungal drugs against Talaromyces marneffei. We observed excellent agreement between the alamarBlue method and the Clinical Laboratory Standard Institute broth microdilution method, and the alamarBlue method had substantially higher inter-rater agreement.
Subject(s)
Antifungal Agents , Talaromyces , Animals , Antifungal Agents/pharmacology , Colorimetry/veterinary , Reproducibility of Results , Voriconazole/pharmacology , Microbial Sensitivity Tests/veterinaryABSTRACT
Culture is an important determinant of HIV risk and protective behaviors; yet, we know little about how it is integrated in HIV interventions. This scoping review characterizes the integration of culture in HIV prevention and treatment interventions focused on Black/African Americans. We searched MEDLINE, PsycINFO, CINAHL, and Google Scholar for peer-reviewed manuscripts published between July 1, 2011, and June 28, 2021. Twenty-five interventions were identified, with 96% focused on prevention. Most (40%) targeted men who have sex with men or transgender women. Only three were grounded in cultural theory. Although all interventions were labeled "culturally based," only two explicitly defined culture. Moreover, there was much diversity regarding the ways in which interventions integrated cultural elements, with some conflating race/ethnicity with culture. To improve uptake and HIV-related outcomes, interventions integrating culture are greatly needed. Additionally, HIV interventions purporting to be "culturally based" must include basic information to support rigor and reproducibility.
Subject(s)
Black or African American , Culturally Competent Care , Culture , HIV Infections , Healthcare Disparities , Sexual and Gender Minorities , Female , Humans , Male , HIV Infections/ethnology , HIV Infections/prevention & control , Homosexuality, Male , Reproducibility of Results , Culturally Competent Care/ethnology , Healthcare Disparities/ethnology , Transgender PersonsABSTRACT
Background: Daily pre-exposure prophylaxis (PrEP) regimen of tenofovir/emtricitabine (TDF/FTC) tablet is the standard of care for HIV prevention in Thailand. Event-driven PrEP (ED-PrEP), taking two loading pills 2-24 h prior to sex and two doses afterward, is considered an alternative regimen. This pilot study aimed to describe accuracy of and retention in ED-PrEP use among Thai young men who have sex with men (YMSM).Methods: A cohort of YMSM aged 15-19 years at risk of HIV infection, defined as reporting irregular condom use or having an HIV-positive sexual partner, was enrolled. All participants were provided oral TDF/FTC, condoms, and the "Raincoat" mobile application, which reminds users when to administer ED-PrEP. Participants attended clinic visits at Months 1, 3, and 6 and followed up by phone at Months 2, 4, and 5. Proper use of ED-PrEP was reported in person-months.Results: From August 2020 to July 2021, 36 YMSM with a median age of 18.7 (IQR, 17.5-19.4) years were enrolled. Thirty-two participants (88.9%, 95% CI: 73.9-96.9%) were retained at 6 months. No HIV incidence occurred during this study period. Of 197 person-months of follow-up, 69 (35%) involved sexual activity. In this group, 61% used ED-PrEP correctly. "Unplanned sexual activity" was the most commonly cited reason for incorrect use.Conclusions: YMSM who have infrequent sex had very high retention in ED-PrEP. However, about one-third of the sexually active period, ED-PrEP was not used correctly due to not taking the loading dose, suggesting that this regimen may not be suitable for unanticipated sexual activity.
