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Introduction: Men who have sex with men (MSM) are one of the most at-risk group for contracting HIV in the USA. However, the HIV epidemic impacts some groups of MSM disproportionately. Latino MSM comprise 25.1% of new HIV infections among MSM between the ages of 13 and 29 years. The daily medication tenofovir/emtricitabine was approved by the Food and Drug Administration for pre-exposure prophylaxis (PrEP) in 2012 and has demonstrated strong efficacy in reducing HIV acquisition., Methods and Analysis: Through extensive formative research, this study uses a pilot randomised controlled trial design and will examine the feasibility and acceptability of a patient navigation intervention designed to address multiple barriers to improve engagement in the PrEP continuum among 60 Latino MSM between the ages of 18 and 29 years. The patient navigation intervention will be compared with usual care plus written information to evaluate the feasibility and acceptability of the intervention and study methods and the intervention's potential in improving PrEP continuum behaviours. The results will be reviewed for preparation for a future full-scale efficacy trial., Ethics and Dissemination: This study was approved by the institutional review board at San Diego State University and is registered at ClinicalTrials.gov. The intervention development process, plan and the results of this study will be shared through peer-reviewed journal publications, conference presentations and healthcare system and community presentations., Registration Details: Registered under the National Institutes of Health's ClinicalTrials.gov (NCT04048382) on 7 August 2019 and approved by the San Diego State University (HS-2017-0187) institutional review board. This study began on 5 August 2019 and is estimated to continue through 31 March 2021. The clinical trial is in the pre-results stage., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: A bridging study was performed to compare the safety, dose delivery, and acceptability of a prefilled plastic and user-filled paper applicator to assess whether a low-cost, user-filled, paper applicator could serve as a delivery option for tenofovir (TFV) 1% vaginal microbicide gel., Methods: The study used a randomized crossover design with 25 healthy women randomized to begin with the prefilled or user-filled applicator. Within each study arm, participants delivered two 4.0-mL doses of TFV 1% gel vaginally for 7 days, with one dose delivered at the clinic each morning and a second dose delivered at home each evening. To assess the primary objective, applicator safety, colposcopy examinations were performed at 2 time points in each study arm., Results: There were no colposcopic findings or adverse events attributable to either applicator. One case of vulvovaginal candidiasis was considered possibly related to gel use. On average, the user-filled applicator delivered 96% of the target dose, with 85% of doses falling within ± 10% of the average dose volume. Participants found both applicators comparable for ease of use, insertion, and dispensing gel, with 60% of participants preferring the user-filled applicator., Conclusions: This study suggests that both applicators are safe, and most women delivered TFV with the user-filled applicator as directed. Participants found both applicators acceptable, with a slight majority preferring the user-filled applicator. Incorporating a low-cost, user-filled, paper applicator to deliver TFV could help reduce costs and improve access to TFV 1% gel, especially in resource-limited settings heavily impacted by HIV.

Background: Large language models (LLMs) that can efficiently screen and identify studies meeting specific criteria would streamline literature reviews. Additionally, those capable of extracting data from publications would enhance knowledge discovery by reducing the burden on human reviewers. Methods: We created an automated pipeline utilizing OpenAI GPT-4 32 K API version "2023–05-15" to evaluate the accuracy of the LLM GPT-4 responses to queries about published papers on HIV drug resistance (HIVDR) with and without an instruction sheet. The instruction sheet contained specialized knowledge designed to assist a person trying to answer questions about an HIVDR paper. We designed 60 questions pertaining to HIVDR and created markdown versions of 60 published HIVDR papers in PubMed. We presented the 60 papers to GPT-4 in four configurations: (1) all 60 questions simultaneously; (2) all 60 questions simultaneously with the instruction sheet; (3) each of the 60 questions individually; and (4) each of the 60 questions individually with the instruction sheet. Results: GPT-4 achieved a mean accuracy of 86.9% – 24.0% higher than when the answers to papers were permuted. The overall recall and precision were 72.5% and 87.4%, respectively. The standard deviation of three replicates for the 60 questions ranged from 0 to 5.3% with a median of 1.2%. The instruction sheet did not significantly increase GPT-4's accuracy, recall, or precision. GPT-4 was more likely to provide false positive answers when the 60 questions were submitted individually compared to when they were submitted together. Conclusions: GPT-4 reproducibly answered 3600 questions about 60 papers on HIVDR with moderately high accuracy, recall, and precision. The instruction sheet's failure to improve these metrics suggests that more sophisticated approaches are necessary. Either enhanced prompt engineering or finetuning an open-source model could further improve an LLM's ability to answer questions about highly specialized HIVDR papers. [ABSTRACT FROM AUTHOR]

Aims: Many transgender and gender diverse (TGD) individuals have expressed concerns about the potential for oral pre-exposure prophylaxis to affect hormonal concentrations achieved from taking gender-affirming hormone therapy (GAHT). The purpose of this study was to understand the bidirectional effects between hormone and intraerythrocytic tenofovir diphosphate concentrations when switching from tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) to tenofovir alafenamide/emtricitabine (TAF/FTC) in TGD users/nonusers of GAHT., Methods: The study evaluated stored blood samples and dried blood spot cards from TGD adults without HIV who took ≥12 weeks of TDF/FTC and then switched to ≥12 weeks of TAF/FTC for pre-exposure prophylaxis., Results: Thirty-nine individuals met the study inclusion criteria. Regardless of sex assigned at birth and the use of GAHT, there were no significant differences in hormone concentrations when individuals taking GAHT were taking TDF/FTC and then switched to TAF/FTC. Further, there was no significant difference in intraerythrocytic tenofovir diphosphate concentrations between users and nonusers of GAHT., Conclusion: There are no bidirectional effects between hormone and intraerythocytic tenofovir diphosphate concentrations when switching from TDF/FTC to TAF/FTC in TGD users/nonusers of GAHT., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: The coronavirus disease 2019 (COVID-19) pandemic continues to put strain on health systems in the United States, leading to significant shifts in the delivery of routine clinical services, including those offering HIV pre-exposure prophylaxis (PrEP). We aimed to assess whether individuals discontinued PrEP use at higher rates during the COVID-19 pandemic and the extent to which disruptions to usual clinical care were mitigated through telehealth., Methods: Using data from an ongoing prospective cohort of men who have sex with men (MSM) newly initiating PrEP in 3 mid-sized cities (n = 195), we calculated the rate of first-time discontinuation of PrEP use in the period before the COVID-19 pandemic and during the COVID-19 pandemic and compared these rates using incidence rate ratios (IRRs). Furthermore, we compared the characteristics of patients who discontinued PrEP use during these periods with those who continued to use PrEP during both periods., Results: Rates of PrEP discontinuation before the COVID pandemic and during the COVID-19 pandemic were comparable [4.29 vs. 5.20 discontinuations per 100 person-months; IRR: 1.95; 95% confidence interval (CI): 0.83 to 1.77]. Although no significant differences in the PrEP discontinuation rate were observed in the overall population, the rate of PrEP discontinuation increased by almost 3-fold among participants aged 18-24 year old (IRR: 2.78; 95% CI: 1.48 to 5.23) and by 29% among participants covered by public insurance plans at enrollment (IRR: 1.29; 95% CI: 1.03 to 5.09). Those who continued to use PrEP were more likely to have had a follow-up clinical visit by telehealth in the early months of the pandemic (45% vs. 17%)., Conclusions: In this study, rates of PrEP discontinuation were largely unchanged with the onset of the COVID-19 pandemic. The use of telehealth likely helped retain patients in PrEP care and should continue to be offered in the future., Competing Interests: Supported by a grant from the National Institute of Mental Health (R01MH114657; MPI: P.A.C. and A.S.N.). B.G.R. has received research project funds from Gilead Sciences, Inc. L.A.M. has received consulting fees and speaker fees from Gilead Sciences, Inc.; GlaxoSmithKline, LLC; Merck Sharp & Dohme Corporation; Roche Molecular Systems, Inc.; Theratechnologies, Inc.; and ViiV Health Healthcare Company. R.R.P. has received consulting fees from Gilead Sciences, Inc. and ViiV Healthcare Company. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Preexisting drug resistance limits the utility of HIV antiretroviral therapy. Studies have demonstrated safety and efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), including in patients with M184V/I substitutions., Setting: We investigated virologic outcomes through 48 weeks of B/F/TAF treatment in individuals with preexisting primary integrase strand transfer inhibitor resistance (INSTI-R)., Methods: Preexisting INSTI-R was retrospectively evaluated from 7 B/F/TAF studies. INSTI-R was assessed by historical genotypes and/or baseline RNA or DNA sequencing. Viral loads were measured at all visits., Results: Preexisting primary INSTI-R substitutions were detected in 20 of the 1907 participants (1.0%). The 20 participants were predominantly male (75%), were Black (65%), had HIV-1 subtype B (85%), and had baseline median CD4 counts of 594 cells/mm3 and median age of 52 years. Most of the participants (n = 19) were virologically suppressed at baseline and had one primary INSTI-R substitution, E92G, Y143C/H, S147G, Q148H/K/R, N155S, or R263K, +/-secondary substitutions. All suppressed participants maintained virologic suppression throughout 48 weeks without any viral blips. One treatment-naive participant had virus with Q148H+G140S that was fully sensitive to bictegravir but only partially to dolutegravir (phenotype <2.5-fold change and >4-fold change, respectively). With a baseline viral load of 30,000 copies/mL, this participant was virologically suppressed by week 4 and maintained <50 copies/mL through week 48., Conclusions: This small cohort with primary INSTI-R achieved and/or maintained virologic suppression through 48 weeks of B/F/TAF treatment. Consistent with the potent in vitro activity of bictegravir against most INSTI-R patterns, B/F/TAF may be a potential treatment option for patients with select preexisting INSTI-R, if confirmed by further studies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Aims: Clinically significant interactions with food occur for more than half of antiretroviral drugs. Different physiochemical properties deriving from the chemical structures of antiretroviral drugs may contribute to the variable food effect. Chemometric methods allow analysing a large number of interrelated variables concomitantly and visualizing correlations between them. We used a chemometric approach to determine the types of correlations among different features of antiretroviral drugs and food that may influence interactions., Methods: Thirty-three antiretroviral drugs were analysed: ten nucleoside reverse transcriptase inhibitors, six non-nucleoside reverse transcriptase inhibitors, five integrase strand transfer inhibitors, ten protease inhibitors, one fusion inhibitor and one HIV maturation inhibitor. Input data for the analysis were collected from already published clinical studies, chemical records and calculations. We constructed a hierarchical partial least squares (PLS) model with three response parameters: postprandial change of time to reach maximum drug concentration (ΔT max ), albumin binding (%) and logarithm of partition coefficient (logP). Predictor parameters were the first two principal components of principal component analysis (PCA) models for six groups of molecular descriptors., Results: PCA models explained 64.4% to 83.4% of the variance of the original parameters (average: 76.9%), whereas the PLS model had four significant components and explained 86.2% and 71.4% of the variance in the sets of predictor and response parameters, respectively. We observed 58 significant correlations between ΔT max , albumin binding (%), logP and constitutional, topological, hydrogen bonding and charge-based molecular descriptors., Conclusions: Chemometrics is a useful and valuable tool for analysing interactions between antiretroviral drugs and food., (© 2023 British Pharmacological Society.)

Objective: To develop and assess an alternative care model using community-based groups for people living with HIV and facilitate by lay personnel., Methods: Geographic locations in the Academic Model Providing Access to Healthcare Kitale clinic catchment were randomized to standard of care versus a community-based care group (ART Co-op). Adults stable on antiretroviral therapy and virally suppressed were eligible. Research Assistant-led ART Co-ops met in the community every 3 months. Participants were seen in the HIV clinic only if referred. CD4 count and viral load were measured in clinic at enrollment and after 12 months. Retention, viral suppression, and clinic utilization were compared between groups using χ2, Fisher exact, and Wilcoxon rank sum tests., Results: At 12 months, there were no significant differences in mean CD4 count or viral load suppression. There was a significant difference in patient retention in assigned study group between the intervention and control group (81.6% vs 98.6%; P < 0.001), with a number of intervention patients withdrawing because of stigma, relocation, pregnancy, and work conflicts. All participants, however, were retained in an HIV care program for the study duration. The median number of clinic visits was lower for the intervention group than that for the control group (0 vs 3; P < 0.001)., Conclusions: Individuals retained in a community-based HIV care model had clinical outcomes equivalent to those receiving clinic-based care. This innovative model of HIV care addresses the problems of insufficient health care personnel and patient retention barriers, including time, distance, and cost to attend clinic, and has the potential for wider implementation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a“work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)

Background: We investigated whether deep sequencing of archived HIV DNA of antiretroviral-naive persons with acute/early HIV infection could identify transmitted drug resistance mutations (DRM), per the IAS drug resistance algorithm, which are not detected by routine bulk (consensus) sequencing., Methods: Deep sequencing of HIV DNA from peripheral blood mononuclear cells and consensus sequencing from concurrent blood plasma (BP) was performed from antiretroviral (ART)-naive adults with recent infection. We compared the prevalence of low-frequency (2%-20%) and high-frequency (>20%) nonnucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), and protease inhibitor (PI) DRM., Results: Overall, 190 individuals were included, 72 (37.9%) with acute, 20 (10.5%) with very early, and 98 (51.6%) with recent HIV infection. Although all DRM detected in plasma appeared in archived proviral DNA, 9 high-frequency mutations were only detected in HIV DNA. These included 3 NRTI mutations, 4 NNRTI mutations, 1 PI mutation, and 1 H221Y (associated rilpivirine resistance) mutation. When considering DRM <20%, 11 NNRTI, 7 NRTI, 6 PI, and 3 F227L (associated doravirine resistance) mutations were found exclusively in HIV DNA. Interestingly, although 2 high-frequency M184V appeared in both DNA and RNA, low-frequency M184I were exclusive to HIV DNA (n = 6). No participants experienced virologic failure after initiating ART during the median 25.39 ± 3.13 months of follow-up on treatment., Conclusion: Although most high-frequency DRMs were consistently detected in HIV RNA and HIV DNA, the presence of low-frequency DRM in proviral DNA may be relevant for clinicians because these mutations could become dominant under drug selection pressure., Competing Interests: M.L.D. and R.K.A. are employees and shareholders of Gilead. The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: New HIV infections remain higher in women than men in sub-Saharan Africa. Preexposure prophylaxis (PrEP) is an effective HIV prevention measure, currently prioritized for those at highest risk, such as female sex workers (FSWs), for whom it is most cost-effective. However, the greatest number of HIV infections in sub-Saharan Africa occurs in women in the general population. As countries consider wider PrEP scale-up, there is a need to weigh the population-level impact, cost, and relative cost-effectiveness to inform priority setting., Methods: We developed mathematical models of HIV risk to women and derived tools to highlight key considerations for PrEP programming. The models were fitted to South Africa, Zimbabwe, and Kenya, spanning a range of HIV burden in sub-Saharan Africa. The impact, cost, and cost-effectiveness of PrEP scale-up for adolescent girls and young women (AGYW), women 25 to 34 years old, and women 35 to 49 years old were assessed, accounting for differences in population sizes and the low program retention levels reported in demonstration projects., Results: Preexposure prophylaxis could avert substantially more infections a year among women in general population than among FSW. The greatest number of infections could be averted annually among AGYW in South Africa (24-fold that for FSW). In Zimbabwe, the greatest number of infections could be averted among women 25 to 34 years old (8-fold that for FSW); and in Kenya, similarly between AGYW and women 25 to 34 years old (3-fold that for FSW). However, the unit costs of PrEP delivery for AGYW, women 25 to 34 years old, and women 35 to 49 years old would have to reduce considerably (by 70.8%-91.0% across scenarios) for scale-up to these populations to be as cost-effective as for FSW., Conclusions: Preexposure prophylaxis has the potential to substantially reduce new HIV infections in HIV-endemic countries in sub-Saharan Africa. This will necessitate PrEP being made widely available beyond those at highest individual risk and continued integration into a range of national services and at community level to significantly bring down the costs and improve cost-effectiveness.

Background: Study 4030 was a phase 3, randomized, double-blinded study of 565 HIV-1 RNA-suppressed participants switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)+F/TAF. Nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI, and protease inhibitor resistance (-R) was allowed, but integrase strand transfer inhibitor-R was excluded. Here, we describe the detailed resistance analysis., Methods: Historical plasma HIV-1 RNA genotypes and baseline proviral DNA genotypes were analyzed. Documented or investigator-suspected NRTI-R was grouped for stratification into 3 categories of level of resistance. Viral blips were assessed through week 48. Virologic failures had genotypic and phenotypic resistance analyses at week 48, confirmed failure, or last visit, if HIV-1 RNA did not resuppress to <50 copies/mL while on study drug., Results: In total, 83% (470/565) of participants had baseline genotypic data available with NRTI-R detected in 24% (138/565), including 5% (30/565) with K65R/E/N or ≥3 thymidine analog mutations and 19% (108/565) with other NRTI-R mutations. M184V/I was present in 14% (81/565). Pre-existing integrase strand transfer inhibitor-R mutations were found in 4% (20/565) of participants. Primary non-NRTI-R and protease inhibitor-R mutations were present in 21% (118/565) and 7% (38/565) of participants. High rates of viral suppression were maintained in all groups through week 48; blips were observed in only 15 participants (2.7%). Three participants met criteria for resistance analysis (all in DTG+F/TAF arm); none developed treatment-emergent resistance to study drugs., Conclusions: Participants with baseline NRTI resistance, much of which was previously undocumented, maintained suppression 48 weeks after switching to B/F/TAF or DTG+F/TAF triple therapy. Blips and virologic failure were uncommon using either regimen, with no treatment-emergent resistance.

Background: The dapivirine vaginal ring reduces the risk of HIV-1 acquisition in acts of vaginal intercourse (VI), and although it does not offer HIV-1 protection in acts of anal intercourse (AI), it may provide some overall risk reduction for women for whom most sex acts are vaginal. We estimated the protective effect of the ring among women with high ring adherence engaged in both VI and AI., Methods: We developed a microsimulation model using data from the MTN-020/ASPIRE trial. Among women who reported any AI, we estimated the proportion of all sex acts that were AI. Model scenarios varied this proportion among women engaged in both VI and AI from 5% to 30%, including the trial-observed median proportion of 6.3% of all acts being AI. In primary analyses, dapivirine ring efficacy was model-calibrated at 70% for vaginal exposures and assumed to be 0% for anal exposures., Results: Among highly adherent women for whom 6.3% of sex acts were AI, the ring reduced HIV-1 risk by 53% (interquartile range: 44, 60), with a decline to 26% (interquartile range: 16, 36) among women for whom 30% of acts were AI. Ring effectiveness was less than 40% among women for whom AI accounted for greater than 16% of all sex acts, although this represented less than 5% of all women in the ASPIRE trial., Conclusions: For most women, including those who engage in AI, because most HIV-1 risk occurs in acts of vaginal sex, the dapivirine vaginal ring can provide important HIV-1 protection., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Spathodea campanulata stem bark decoction (SCD) has shown hypoglycemic activity in mice. It was separated by column chromatography into different fractions, which were evaluated for their hypoglycemic, anticomplement and anti-HIV activities. The most polar fraction exerted by far the most prominent effect in different biological models.

Objective: To examine type 2 diabetes mellitus incidence and associated risk factors among people with HIV (PWH)., Design: A retrospective clinical cohort study of PWH at a Southeastern US academic HIV clinic between 2008 and 2018., Methods: PWH who attended at least two clinic visits were evaluated with demographic and clinical data extracted from the electronic medical record (EMR). Diabetes was defined as: hemoglobin A1C ≥6.5% and/or 2 glucose results >200 mg/dl (at least 30 days apart), diagnosis of diabetes in the EMR, or exposure to diabetes medication. Time to diabetes incidence was computed from the entire clinic population for each year. Multivariable Cox proportional hazard regression models with time-dependent covariates were created to evaluate the independent association between covariates and time to incident diabetes., Results: Among 4113 PWH, we identified 252 incident cases of diabetes. Incidence increased from 1.04 incidents per 1000 person years (PY) in 2008, to 1.55 incidents per 1000 PY in 2018. Body mass index (hazard ratio [HR] 10.5 (6.2, 17.7)), liver disease (HR 1.9 (1.2, 3.1)), steroid exposure (HR 1.5 (1.1, 1.9)), and use of integrase inhibitors (HR 1.5 (1.1, 2.0)) were associated with incident diabetes. Additional associated factors included lower CD4 + cell counts, duration of HIV infection, exposure to nonstatin lipid-lowering therapy, and dyslipidemia., Conclusions: Rapidly increasing incident diabetes rates among PWH were associated with both traditional and HIV-related associated risk factors, particularly body weight, steroid exposure, and use of Integrase Inhibitors. Notably, several of the risk factors identified are modifiable and can be targeted for intervention., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: During the COVID-19 pandemic, patients experienced significant care disruptions, including laboratory monitoring. We investigated changes in the time between viral load (VL) checks for people with HIV (PWH) associated with the pandemic., Setting and Methods: This was an observational analysis of VLs of PWH in routine care at a large subspecialty clinic. At pandemic onset, the clinic temporarily closed its onsite laboratory. The exposure was time period (time varying): prepandemic (January 1, 2019-March 15, 2020); pandemic laboratory closed (March 16-July 12, 2020); and pandemic laboratory open (July 13-December 31, 2020). We estimated time from an index VL to a subsequent VL, stratified by whether the index VL was suppressed (≤200 copies/mL). We also calculated cumulative incidence of a nonsuppressed VL following a suppressed index VL, and of resuppression following a loss of viral suppression., Results: Compared with prepandemic, hazard ratios for next VL check were 0.34 (95% CI: 0.30 to 0.37, laboratory-closed) and 0.73 (CI: 0.68 to 0.78, laboratory-open) for suppressed patients, and 0.56 (CI: 0.42 to 0.79, laboratory-closed) and 0.92 (95% CI: 0.76 to 1.10, laboratory-open) for nonsuppressed patients. The 12-month cumulative incidence of loss of suppression was the same in the pandemic laboratory-open (4%) and prepandemic (4%) period. The hazard of resuppression following the loss of suppression was lower during the pandemic laboratory-open versus the prepandemic period (hazard ratio: 0.68, 95% CI: 0.50 to 0.92)., Conclusions: Early pandemic restrictions and laboratory closure significantly delayed VL monitoring. Once the laboratory reopened, nonsuppressed patients resumed normal monitoring. Suppressed patients still had a delay but no significant loss of suppression., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Pre-exposure prophylaxis (PrEP) is proven to be a highly effective HIV prevention method for key populations. However, its scale-up in resource-limited settings remains suboptimal. This paper seeks to describe PrEP initiation and continuation among key populations in Cameroon., Methodology: From June 2019 through October 2020, we collected routine program data on PrEP uptake and continuation among female sex workers (FSWs) and men who have sex with men (MSM) in the Continuum of prevention, care and treatment of HIV/AIDS with Most-at-risk Populations (CHAMP) program in Cameroon. PrEP was offered to clients who tested negative for HIV and were assessed to potentially benefit from PrEP. Using survival analysis, we identified factors associated with PrEP discontinuation over time with significance set at 5%., Results: Overall, 27,750 clients were sensitized for PrEP of whom 3,138 persons were eligible to start PrEP and 1,409 (45%; FSW: 691 and MSM: 718) initiated PrEP. The PrEP continuation rate was 37% at 3 months, 28% at 6 months and 19% at 12 months. PrEP discontinuation was significantly higher among FSW than MSM [adjusted hazard ratio (aHR) 1.5 (95% CI: 1.2 to 1.9)] in Yaounde [aHR 1.5 (95% CI: 1.2 to 1.9)] and Bafoussam/Bertoua [aHR 3.1 (2.2-4.5)] relative to Douala. Discontinuation was lower among those with moderate [aHR 0.3 (0.3-0.4)] or good adherence [aHR 0.4 (0.3-0.6)] compared with poor adherence (all P < 0.001)., Conclusion: Differentiated approaches to deliver PrEP, create demand, and provide more intensive support for adherence and continuation may support scale-up of PrEP in Cameroon for equitable and prolonged impact on HIV prevention., Competing Interests: A.L.B., W.P., D.C. and S.B. disclose that they received payments through their institutions for their efforts in this study. The other authors have no conflict of interest to disclose., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Sexual health clinics (SHCs) serve large numbers of patients who might benefit from preexposure prophylaxis (PrEP). Integrating longitudinal PrEP care into SHCs can overburden clinics. We implemented an SHC PrEP program that task shifted most PrEP operations to nonmedical staff, disease intervention specialists (DIS)., Methods: We conducted a retrospective cohort analysis of PrEP patients in an SHC in Seattle, WA, from 2014 to 2020 to assess the number of patients served and factors associated with PrEP discontinuation. Clinicians provide same-day PrEP prescriptions, whereas DIS coordinate the program, act as navigators, and provide most follow-up care., Results: Between 2014 and 2019, 1387 patients attended an initial PrEP visit, 93% of whom were men who have sex with men. The number of patients initiating PrEP per quarter year increased from 20 to 81. The number of PrEP starts doubled when the clinic shifted from PrEP initiation at scheduled visits to initiation integrated into routine walk-in visits. The percentage of visits performed by DIS increased from 3% in 2014 to 45% in 2019. Median duration on PrEP use was 11 months. PrEP discontinuation was associated with non-Hispanic black race/ethnicity [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.02 to 1.76], age <20 years (HR 2.17, 95% CI: 1.26 to 3.75), age between 20 and 29 years (HR 1.55, 95% CI: 1.06 to 2.28), and methamphetamine use (HR 1.98, 95% CI: 1.57 to 2.49). The clinic had 750 patients on PrEP in the final quarter of 2019., Conclusions: A demedicalized SHC PrEP model that task shifts most operations to DIS can provide PrEP at scale to high priority populations., Competing Interests: J. C. Dombrowski, L. A. Barbee, C. M. Khosropour, and M. R. Golden have received research support, unrelated to this work, from Hologic. L. A. Barbee has received research support outside of this work from SpeeDx and Nabriva and received consulting fees from Nabriva. M. R. Golden received research support unrelated to this work from GlaxoSmithKline. M. S. Ramchandani owns stock in Gilead and Merck. The remaining authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pre-exposure prophylaxis (PrEP) is essential to ending HIV. Yet, uptake remains uneven across racial and ethnic groups. We aimed to estimate the impacts of alternative PrEP implementation strategies in Los Angeles County., Setting: Men who have sex with men, residing in Los Angeles County., Methods: We developed a microsimulation model of HIV transmission, with inputs from key local stakeholders. With this model, we estimated the 15-year (2021-2035) health and racial and ethnic equity impacts of 3 PrEP implementation strategies involving coverage with 9000 additional PrEP units annually, above the Status-quo coverage level. Strategies included PrEP allocation equally (strategy 1), proportionally to HIV prevalence (strategy 2), and proportionally to HIV diagnosis rates (strategy 3), across racial and ethnic groups. We measured the degree of relative equalities in the distribution of the health impacts using the Gini index (G) which ranges from 0 (perfect equality, with all individuals across all groups receiving equal health benefits) to 1 (total inequality)., Results: HIV prevalence was 21.3% in 2021 [Black (BMSM), 31.1%; Latino (LMSM), 18.3%, and White (WMSM), 20.7%] with relatively equal to reasonable distribution across groups (G, 0.28; 95% confidence interval [CI], 0.26 to 0.34). During 2021-2035, cumulative incident infections were highest under Status-quo (n = 24,584) and lowest under strategy 3 (n = 22,080). Status-quo infection risk declined over time among all groups but remained higher in 2035 for BMSM (incidence rate ratio, 4.76; 95% CI: 4.58 to 4.95), and LMSM (incidence rate ratio, 1.74; 95% CI: 1.69 to 1.80), with the health benefits equally to reasonably distributed across groups (G, 0.32; 95% CI: 0.28 to 0.35). Relative to Status-quo, all other strategies reduced BMSM-WMSM and BMSM-LMSM disparities, but none reduced LMSM-WMSM disparities by 2035. Compared to Status-quo, strategy 3 reduced the most both incident infections (% infections averted: overall, 10.2%; BMSM, 32.4%; LMSM, 3.8%; WMSM, 3.5%) and HIV racial inequalities (G reduction, 0.08; 95% CI: 0.02 to 0.14)., Conclusions: Microsimulation models developed with early, continuous stakeholder engagement and inputs yield powerful tools to guide policy implementation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Integrase strand transfer inhibitors (InSTIs) decrease HIV plasma viral load faster than other antiretroviral classes. More rapid viral load decline has been associated with higher risk of immune reconstitution inflammatory syndrome (IRIS). There are conflicting reports on the association between InSTI and IRIS. We performed a systematic review and meta-analysis to compare the risk of IRIS among treatment-naive HIV-positive patients starting InSTI versus non-InSTI regimens., Methods: We searched PubMed, Scopus, Web of Science, Africa-Wide, and Cochrane databases from earliest available date to 26 November 2021, for randomized controlled trials (RCTs) having intervention arms with InSTI versus control arms without InSTI in patients initiating first-line antiretroviral therapy. The primary outcome was relative risk (RR) of IRIS, whereas the secondary outcome was RR of paradoxical tuberculosis-associated IRIS (TB-IRIS). Data were combined by random-effects meta-analysis according to the Mantel-Haenszel method. The protocol for this study is registered with PROSPERO, CRD42020213976., Results: We included 14 RCTs comprising 8696 participants from 6 continents for the primary outcome of IRIS and a subset of 674 participants (from 3 RCTs) for the secondary outcome of paradoxical TB-IRIS. Risk of IRIS was similar between InSTI and non-InSTI regimens (RR, 0.93; 95% confidence interval: 0.75 to 1.14). There was a trend towards a lower risk of paradoxical TB-IRIS with InSTI versus efavirenz regimens that was not statistically significant (RR, 0.64; 95% confidence interval: 0.34 to 1.19)., Conclusions: In this meta-analysis among treatment-naive patients commencing first-line antiretroviral therapy, InSTI regimens were not associated with higher risk of IRIS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

HIV prevention and treatment with injectable cabotegravir and/or rilpivirine administered once every 4 to 8 weeks is an attractive alternative to daily therapy. Prescribed dosage and drug concentrations in plasma are based on patient data collected in clinical trials, but actual patients are expected to exhibit more variability in drug concentrations, which is important to quantify. Here, we demonstrate the first quantitative point-of-care assay with a miniature mass spectrometer to assess these drug concentrations in whole blood. Quantitative performance is obtained using paper spray ionization in combination with tandem mass spectrometry (MS/MS) in the clinically relevant concentration range of both drugs. Limits of quantitation (LoQs) of cabotegravir and rilpivirine are measured to be 750 ng/mL and 20 ng/mL, respectively. The assay turnaround time is < 4 min, and strong linear relationships are established between MS/MS responses and concentration, with percentage of relative standard deviations (RSDs) that are <15% at concentrations above the LoQs. The speed, portability, low power consumption, and specificity offered by the miniature instrument should make it an appropriate platform for measuring drug concentrations in a walk-in clinic using small volumes of patient blood., (© 2022. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Health care worker (HCW) training using standardized patient actors (SPs) is an evidence-based approach for improving patient-provider interactions. We evaluated whether SP training among HCWs in Western Kenya improved the quality of pre-exposure prophylaxis (PrEP) counseling for adolescent girls and young women (AGYW)., Methods: We conducted a 2-day SP training intervention among HCWs providing PrEP counseling for AGYW. Six trained SPs role played one encounter each with HCWs following scripts depicting common PrEP-seeking scenarios. SPs used checklists to report and discuss domains of adherence to national PrEP guidelines, communication, and interpersonal skills using validated scales after each encounter. HCWs presented to each case in a random order. Overall and domain-specific mean score percentages were compared between the first and subsequent case encounters using generalized linear models, clustering by HCWs., Results: During 564 training cases among 94 HCWs, the overall mean quality of PrEP counseling score was 83.1 (SD: 10.1); scores improved over the course of the 6 encounters (P < 0.001). Compared with the first case encounter, the mean scores for the fourth were significantly higher (79.1 vs. 85.9, P < 0.001). The mean scores plateaued from the fourth to the sixth case (85.2). Although HCWs demonstrated high baseline communication (95.3) and interpersonal skills (83.7), adherence to PrEP guidelines at baseline was suboptimal (57.6). By the fourth case, scores increased significantly (P < 0.001) for all domains., Conclusions: SP training improved PrEP counseling overall and in domains of interpersonal skills, use of guidelines, and communication with AGYW and could be useful in efforts to improve the quality of PrEP counseling for AGYW., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: AIDS Drug Assistance Programs (ADAPs) provide financial support for medical care for people living with HIV (PLWH) in the United States. Federal policy requires that clients recertify for the program every 6 months, which has been described as a barrier to care access. Our objective was to describe the prevalence of and factors associated with ADAP disenrollment in Washington State., Methods: Between 2017 and 2019, we categorized ADAP clients by the success of their recertification applications as follows: (1) continuously enrolled, (2) ruled ineligible, or (3) disenrolled if they failed to recertify. We compared individuals who were disenrolled with those who were continuously enrolled by demographic and socioeconomic characteristics and engagement with case management using data from the Washington State HIV Surveillance and Ryan White data systems., Results: From 2017 to 2019, 5480 clients were enrolled in ADAP, of whom 1423 (26%) were disenrolled and 984 (18%) were ruled ineligible at least once. Compared with those who were continuously enrolled, disenrolled PLWH were more likely to be Black [unadjusted prevalence ratio (PR) vs White 1.31, 95% confidence interval (CI): 1.17 to 1.46], uninsured (PR vs private insurance 1.24, 95% CI: 1.10 to 1.40), and younger (PR 25-34 vs 35-44 years 1.23, 95% CI: 1.08 to 1.41). The median time to return after disenrollment was 12 months (95% CI: 8 to 19 months)., Conclusions: Disenrollment after failure to recertify was the most common reason why PLWH lost ADAP coverage in Washington State. ADAP recertification procedures disproportionately affect Black, young, and uninsured PLWH and may contribute to disparities in HIV outcomes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pre-exposure prophylaxis (PrEP) delivery to adolescent girls and young women (AGYW) is scaling up in sub-Saharan African countries. Understanding how AGYW learn about PrEP is needed to inform programs seeking to reach AGYW with HIV prevention tools., Methods: AGYW (ages 15-24), attending routine family planning and maternal child health clinics in Kisumu, Kenya, participated in in-depth interviews. AGYW were recruited if they either declined or accepted PrEP when offered that day in clinic or were currently or previously on PrEP. Thematic analysis was used to identify key themes related to the type and quality of knowledge sources from which AGYW first became aware of PrEP., Results: Overall, 140 in-depth interviews were conducted with AGYW. The median age was 21.5 years (interquartile range: 20.0-23.0), 65% of participants were married, and almost half (45.7%) were currently taking PrEP. Participants reported learning about PrEP from 3 primary sources: (1) clinic-based education; (2) friends, family, or other PrEP users; and (3) media and community outreach. Participants who reported learning about PrEP from friends or family were highly enthusiastic about PrEP. The accuracy and completeness of knowledge varied with most inaccuracies around the cost, dosing, and who benefits from PrEP. Community outreach campaigns provided fewer details, resulting in more inaccurate information and distrust of information received., Conclusion: PrEP information reaches AGYW through many sources with variable accuracy and completeness. Training providers and peer leaders to disseminate thorough and accurate PrEP information when counseling AGYW could positively impact acceptance and proper use., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The number and characteristics of pre-exposure prophylaxis (PrEP) health care providers in the United States have not been reported., Methods: We analyzed a national pharmacy database that included >90% of all prescriptions dispensed by retail pharmacies and 60%-86% dispensed by mail-order outlets. We estimated the number of PrEP providers by year, provider type, physician specialty, and geographic location. We also measured the Gini coefficients for the distribution of PrEP patients among providers., Results: The number of PrEP providers increased from 9621 in 2014 to 65,822 in 2019. In 2019, 68.1% of PrEP providers were physicians. The proportion of nurse practitioners or physician assistants increased from 18.0% in 2014 to 29.7% in 2019. Among all the US health care providers, those who prescribed PrEP increased from 0.7% in 2014 to 4.3% in 2019. Among all general practice/family medicine physicians, the percentage of who prescribed PrEP increased from 1.8% in 2014 to 13.6% in 2019 and from 14.2% to 34.2% among infectious disease physicians. The ratio of PrEP providers to 100 persons with PrEP indications was lowest in the South with 4.4. The Gini coefficient for the distribution of PrEP patients among providers was 0.75 in 2019, with 50% of the PrEP patients prescribed PrEP by 2.2% of PrEP providers., Conclusions: An increasing number of providers prescribed PrEP during 2014-2019. The South had the largest number of new HIV diagnoses and greatest need for HIV prevention but had less PrEP service capacity compared with other regions. Expanded access to PrEP services is needed in the United States., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: We assessed the impact of the coronavirus disease 2019 (COVID-19) pandemic on HIV suppression rates in people living with HIV (PLWH) attending a large Italian HIV clinic., Setting: The HIV outpatient clinic of the Infectious Diseases Department of Luigi Sacco Hospital, Milan, Italy, which serves more than 5000 PLWH per year., Methods: A before and after quasi-experimental study design was used to make a retrospective assessment of the monthly trend of HIV-RNA determinations of ≥50 among the PLWH attending our clinic, with "before" being the period from January 1, 2016 to February 20, 2020, and "after" being the period from February 21, 2020 to December 31, 2020 (the COVID-19 period). Interrupted time series analysis was used to evaluate any changes in the trend., Results: During the study period, 70,349 HIV-RNA viral load determinations were made, and the percentage of HIV-RNA viral load determinations of <50 copies/mL increased from 88.4% in 2016 to 93.2% in 2020 (P < 0.0001). There was a significant monthly trend toward a decrease in the number of HIV-RNA determinations of ≥50 copies/mL before the pandemic (β -0.084; standard error 0.015; P < 0.001), and this did not significantly change after it started (β -0.039, standard error 0.161; P = 0.811)., Conclusions: A high prevalence of viral suppression was maintained among the PLWH referring to our clinic, despite the structural barriers raised by the COVID-19 pandemic. The use of simplified methods of delivering care (such as teleconsultations and multiple antiretroviral treatment prescriptions) may have contributed to preserving this continuum., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Quantile regression offers an invaluable tool to discern effects that would be missed by other conventional regression models, which are solely based on modeling conditional mean. Quantile regression for mixed-effects models has become practical for longitudinal data analysis due to the recent computational advances and the ready availability of efficient linear programming algorithms. Recently, quantile regression has also been extended to additive mixed-effects models, providing an efficient and flexible framework for nonparametric as well as parametric longitudinal forms of data analysis focused on features of the outcome beyond its central tendency. This study applies the additive quantile mixed model to analyze the longitudinal CD4 count of HIV-infected patients enrolled in a follow-up study at the Centre of the AIDS Programme of Research in South Africa. The objective of the study is to justify how the procedure developed can obtain robust nonlinear and linear effects at different conditional distribution locations. With respect to time and baseline BMI effect, the study shows a significant nonlinear effect on CD4 count across all fitted quantiles. Furthermore, across all fitted quantiles, the effect of the parametric covariates of baseline viral load, place of residence, and the number of sexual partners was found to be major significant factors on the progression of patients' CD4 count who had been initiated on the Highly Active Antiretroviral Therapy study., (© 2021. The Author(s).)

Background: Preexposure prophylaxis (PrEP) prevents HIV infection but relies on good adherence at times of risk, termed "prevention-effective adherence." Most studies assess adherence without reference to sexual behaviur, making it challenging to determine if poor adherence coincides with HIV risk., Setting: We examined data from a behavioral substudy of a large-scale PrEP implementation trial in New South Wales, Australia., Methods: Trial participants completed optional brief quarterly surveys, reporting the number of pills taken and sexual behavior with male partners for each day of the "last full week" before each survey. Condomless sex (CLS) was defined as "higher risk" for HIV when with HIV-positive men with detectable/unknown viral loads or unknown HIV status men. Adequate PrEP protection was defined as ≥4 pills for participants assigned male sex at birth and ≥6 pills for participants assigned female sex at birth (including transgender men)., Results: Of 9596 participants dispensed PrEP, 4401 completed baseline and ≥1 follow-up survey. Participants reported on 12,399 "last full weeks": 7485 weeks (60.4%) involved CLS and 2521 weeks (33.7% of CLS-weeks) involved higher risk CLS. There were 103 weeks in which participants did not have adequate PrEP protection and had higher risk CLS: 4.1% of higher-risk CLS weeks (n = 103/2521), 1.4% of all CLS weeks (n = 103/7485), and 0.8% of all observed weeks (n = 103/12,399)., Conclusions: In a large PrEP trial, prevention-effective adherence to PrEP was very high at 99%. Our findings illustrate the importance of measuring pill-taking and sexual behavior in the same period so that prevention-effective adherence can be better estimated., Competing Interests: The authors have no conflict of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Both tenofovir disoproxil fumarate (TDF)/emtricitabine and tenofovir alafenamide (TAF)/emtricitabine demonstrate excellent efficacy and safety overall, but concerns remain over specific changes in markers of bone and renal function. Lower plasma tenofovir concentrations are seen with TAF and in unboosted regimens. We assess TAF vs. TDF safety with and without booster coformulation., Methods: A previous systematic review was updated with recent clinical trials. TAF vs. TDF efficacy and safety were compared in boosted and unboosted subgroups. Efficacy was measured by viral suppression. Key safety endpoints included all adverse events, serious adverse events, Grades 3-4 adverse events and adverse event discontinuation. Further specific renal and bone markers were also assessed., Results: A total of 14 clinical trials comparing TDF and TAF regimens were identified. A significant difference (P = 0.0004) in efficacy was shown in the boosted subgroup in favour of TAF, but no difference was seen in the unboosted subgroup. There were no significant differences between TAF and TDF for any of the key safety endpoints analysed. No differences were seen for the bone markers analysed. No difference was found for renal tubular events. There was a difference in risk for discontinuation due to renal adverse events when boosted (P = 0.03), but none when unboosted., Conclusion: Across all main safety endpoints, no differences between TAF and TDF are seen. Boosted TDF regimens were associated with lesser comparative efficacy than boosted TAF and a higher risk of renal event discontinuation. However, modern antiretroviral regimens are more commonly unboosted. This study finds no difference in efficacy or safety in unboosted TAF vs. TDF.

Background: Long-acting (LA) injectable regimens are a potential therapeutic option in people living with HIV-1., Setting: ATLAS (NCT02951052) and FLAIR (NCT02938520) were 2 randomized, open-label, multicenter, multinational phase 3 studies., Methods: Adult participants with virologic suppression (plasma HIV-1 RNA <50 copies/mL) were randomized (1:1) to continue with their current antiretroviral regimen (CAR) or switch to the long-acting (LA) regimen of cabotegravir (CAB) and rilpivirine (RPV). In the LA arm, participants initially received oral CAB + RPV once-daily for 4 weeks to assess individual safety and tolerability, before starting monthly injectable therapy. The primary endpoint of this combined analysis was antiviral efficacy at week 48 (FDA Snapshot algorithm: noninferiority margin of 4% for HIV-1 RNA ≥50 copies/mL). Safety, tolerability, and confirmed virologic failure (2 consecutive plasma HIV-1 RNA ≥200 copies/mL) were secondary endpoints., Results: The pooled intention-to-treat exposed population included 591 participants in each arm [28% women (sex at birth), 19% aged ≥50 years]. Noninferiority criteria at week 48 were met for the primary (HIV-1 RNA ≥50 copies/mL) and key secondary (HIV-1 RNA <50 copies/mL) efficacy endpoints. Seven individuals in each arm (1.2%) developed confirmed virologic failure; 6/7 (LA) and 3/7 (CAR) had resistance-associated mutations. Most LA recipients (83%) experienced injection site reactions, which decreased in incidence over time. Injection site reactions led to the withdrawal of 6 (1%) participants. The serious adverse event rate was 4% in each arm., Conclusion: This combined analysis demonstrates monthly injections of CAB + RPV LA were noninferior to daily oral CAR for maintaining HIV-1 suppression.

Background: Lesotho adopted the test-and-treat approach for HIV treatment in June 2016, which increased antiretroviral treatment (ART) clinic volume. We evaluated community-based vs. facility-based differentiated models of multimonth dispensing of ART among stable HIV-infected adults in Lesotho., Methods: Thirty facilities were randomized to 3 arms, facility 3-monthly ART (3MF) (control), community ART groups (3MC), and 6-monthly community distribution points (6MCD). We estimated risk differences (RDs) between arms using population-averaged generalized estimating equations, controlling for baseline imbalances and specifying for clustering. The primary outcome was retention in ART care by intention-to-treat and virologic suppression as a secondary outcome (ClinicalTrials.gov: NCT03438370)., Results: A total of 5,336 participants were enrolled, with 1898, 1558, and 1880 in 3MF, 3MC, and 6MCD, respectively. Retention in ART care was not different across arms and achieved the prespecified noninferiority limit (-3.25%) between 3MC vs. 3MF (control); 6MCD vs. 3MF; and 6MCD vs. 3MC, adjusted RD = -0.1% [95% confidence interval (CI): -1.6% to 1.5%], adjusted RD = -1.3% (95% CI: -3.0% to 0.5%), and adjusted RD = -1.2% (95% CI: -2.9% to 0.5%), respectively. After 12 months, 98.6% (n = 1503), 98.1% (n = 1126), and 98.3% (n = 1285) were virally load (VL) suppressed in 3MF, 3MC, and 6MCD, respectively. There were no differences in VL between 3MC vs. control and 6MCD vs. control, risk ratio (RR) = 1.00 (95% CI: 0.98 to 1.01) and RR = 1.00 (95% CI: 0.98 to 1.01), respectively., Conclusions: There were no differences in retention and VL suppression for stable HIV-infected participants receiving multimonth dispensing of ART within community-based differentiated models when compared with the facility-based standard-of-care model.

Background: People living with HIV (PLWH) are at high cardiovascular disease (CVD) risk. Traditional CVD risk scores do not accurately reflect their CVD risk. Noninvasive subclinical vascular damage (SVD) biomarkers are valid surrogates of CVD and able to stratify CVD risk., Setting: We tested whether 4 widely applied CVD risk scores [Framingham (FRS), Atherosclerotic CVD, Data Collection on Adverse Effects of Anti-HIV Drugs Study (D:A:D), and Greek-specific European Society of Cardiology (ESC) risk scores] are associated with or detect the presence, incidence, and progression of arteriosclerosis, atheromatosis, and arterial hypertrophy in PLWH and uninfected individuals., Methods: We prospectively examined (at baseline and 3-year follow-up) 10 different arterial sites applying 5 different noninvasive vascular biomarkers and measured all 4 CVD risk scores at baseline., Results: In both PLWH (n = 138) and uninfected (n = 664) individuals, the CVD risk scores (except the ESC) performed differently but reasonably well in identifying the presence of SVD, but all scores failed to predict the incidence/progression of overall SVD. The most clinically useful biomarkers (carotid plaque/atheromatosis) revealed that in PLWH, only the FRS was able to stratify the progression (11% of the low-risk, 33.3% of the medium-risk, and 0% of the high-risk group)., Conclusions: This extensive vascular phenotyping study demonstrated the clear need to incorporate vascular imaging in CVD risk stratification, in addition to designing more accurate HIV-specific CVD risk models. The use of FRS would further enable treatment optimization and CVD prevention strategies in PLWH at medium CVD risk because one-third of carotid atheromatosis progresses within 3 years.

Objective: Prices of antiretroviral (ARV) drugs in lower income countries have decreased substantially over the past two decades, helping to facilitate greatly expanded access to antiretroviral therapy (ART). However, ART coverage in many parts of the world remains low. We investigate the extent of epidemiological benefits that might be expected if ARV drug prices decline further., Design: A modeling study using data from seven countries in West and Central Africa (Cameroon, Democratic Republic of the Congo, Côte d'Ivoire, Niger, Nigeria, Senegal, and Togo)., Methods: We investigated how the timing of ARV cost reductions could affect the impact and compared three different possible investment strategies: reinvesting in ART, reinvesting in the HIV response according to historical allocations, and reinvesting with the aim of minimizing HIV incidence and mortality., Results: If ARV drug prices fell by 37% relative to 2018 levels (i.e. following continued trend declines), we calculate ART unit costs could decrease by ∼20% (holding other cost components constant). If this could be achieved by 2020 and the savings were reinvested into ART, we estimate that an additional 8% of HIV infections and 11% of HIV-related deaths could be averted over 2020-2030 across the seven countries. Slightly greater gains could be attained if funds were reinvested in ART in combination with primary prevention. Delays in the year of introduction of ARV price reductions would reduce the impact by about 1% per year., Conclusion: ARV price reductions could free up funds that - if strategically invested - would help countries move closer toward the elimination of HIV.

Natural products have long been a cornerstone of drug discovery, providing diverse and biologically relevant chemical scaffolds. This work aims to guide newcomers to natural product research and, specifically, drug discovery by presenting a curated list of 30 key publications selected through an international survey of experts and critical evaluation by the authors. The selected works span textbooks, review articles, and original research papers, covering various aspects of natural product research, including chemistry, pharmacology, analytical sciences, emerging open science, and computational approaches. We discuss historical milestones in natural product drug discovery, highlighting the specific contributions of the U.S. National Cancer Institute in developing anticancer and anti-HIV agents. The present work also addresses current challenges and innovations in the field, emphasizing the importance of data quality, interdisciplinary collaboration, and the integration of artificial intelligence. By providing this carefully selected reading list and accompanying analysis, we aim to offer a comprehensive yet accessible entry point for researchers new to natural product-based drug discovery and highlight future directions and opportunities in this dynamic field. [ABSTRACT FROM AUTHOR]

Given the ease of synthetic accessibility and the promising biological profile demonstrated by both imidazo[1,2-a]pyridine and Chalcone derivatives, a series of Chalcone-based imidazo[1,2-a]pyridine derivatives were synthesized and characterized using 1 H NMR, 13 C NMR, Mass Spectrometry and FTIR techniques. Density functional theory (DFT) was employed to investigate the structural and electronic properties, providing insights into potential reactive sites. The synthesized compounds were evaluated in vitro for their antiviral properties against human immunodeficiency virus type-1 (HIV-1) and human immunodeficiency virus type-2 (HIV-2) in MT-4 cells. Furthermore, Molecular docking studies show strong binding affinities with HIV-1 reverse transcriptase and HIV-2 protease. To further understand the dynamic behavior and stability of these interactions, molecular dynamics (MD) simulations were conducted. The MD results indicated stable binding conformations of the ligands within the active sites, with low RMSD and RMSF values throughout the simulation, confirming the robustness of these interactions. ADME predictions suggested acceptable pharmacokinetic profiles, though solubility remains a limitation for these compounds. Although the in vitro antiviral activity was limited, the combination of in vitro and in silico approaches provided valuable insights, guiding further structural optimization to improve bioavailability and enhance the therapeutic potential of these derivatives., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)