Gestión integral de la farmacoterapia en un paciente hospitalizado con VIH y tuberculosis / Comprehensive medication management in a patient hospitalized with HIV and tuberculosis

Paciente varón de 27 años derivado desde infectología al Servicio de Gestión Integral de la Farmacoterapia para optimizar la administración del tratamiento antifímico. Se encontraba internado en hospital por un absceso submaxilar y axilar, candidiasis esofágica, desnutrición proteico-calórica, infección por VIH, tuberculosis pulmonar y ganglionar. Se analizó la experiencia farmacoterapéutica para lograr una mejor comprensión del uso de la medicación en el paciente y posteriormente lograr establecer un plan de cuidados individualizado para identificar y resolver 7 problemas farmacoterapéuticos mediante el sistema Pharmacotherapy Workup, obteniendo mejoría y estabilidad de su estado de salud. En las 11 condiciones clínicas que padecía el paciente, se realizaron un total de 7 intervenciones, para resolver los 6 problemas farmacoterapéuticos y prevenir la nueva aparición de uno de ellos. Uno de los problemas que consistía en que el paciente no deseaba tomar la medicación debido a los efectos adversos, fue resuelto con el propio paciente mediante la comprensión de su experiencia farmacoterapéutica, de esta forma se llegó a un acuerdo para lograr la tolerancia del fármaco. El resto se resolvieron mediante el trabajo colaborativo con la médica infectóloga y la nutricionista. (AU)

A 27-year-old male patient referred from infectious diseases to the Comprehensive medication Man-agement Service to optimize the administration of antifungal management. He was hospitalized for a submaxillary and axillary abscess, esophageal candida infection, protein-calorie malnutrition, HIV infection, pulmonary and ganglial tuberculosis.The pharmacotherapeutic experience was analyzed to achieve a better understanding of the patient's medication use and subsequently establish an indi-vidualized care plan to identify and solve 7 pharma-cotherapeutic problems through the Pharmacother-apy Workup system, obtaining improvement and stability in the patient's state of health.In the 11 clinical conditions suffered by the patient, a total of 7 interventions were performed to solve the 6 pharmacotherapeutic problems and prevent the new appearance of one of them. 1 of the prob-lems was solved by the patient himself because it was necessary to understand his medication expe-rience. The rest were solved through collaborative work with the infectious disease physician and the nutritionist. (AU)

Actualización 2022 de los indicadores para la calidad asistencial y la atención farmacéutica a las personas que viven con el virus de la inmunodeficiencia humana / 2022 update of the indicators for quality of care and pharmaceutical care for people living with human immunodeficiency virus

Objetivo: actualizar y definir los indicadores para la mejora de la calidad asistencial y la atención farmacéutica a las personas que viven con infección por VIH en España. Método: el presente proyecto, que actualiza la versión anterior del documento de 2013, se desarrolló en 4 fases de trabajo realizadas entre enero y junio de 2022.En la fase 1, de organización, se creó un grupo de trabajo conformado por 7 especialistas en farmacia hospitalaria con amplia experiencia en atención farmacéutica y procedentes de distintos servicios del territorio nacional. Adicionalmente otros 34 especialistas, participaron en la valoración de los indicadores a través de 2 rondas de evaluación online para generación del consenso.Para la fase 2, inicialmente, se llevó a cabo una revisión bibliográfica con el objetivo de establecer una base a partir de la cual poder definir una propuesta de criterios de calidad e indicadores. A continuación, se realizó una propuesta preliminar de criterios y se establecieron revisiones para su ajuste en varias reuniones de trabajo telemáticas.En la fase 3 se estableció el consenso basado en la metodología de consenso Delphi-Rand/UCLA.Adicionalmente todos los indicadores clasificados como adecuados y necesarios fueron agrupados según 2 niveles de recomendación de monitorización, de manera que pueda orientar a los servicios en la prioridad de su medición: claves y avanzados.Por último, en la fase 4 se elaboró el documento final del proyecto, junto con las fichas descriptivas correspondientes para cada indicador con la finalidad de facilitar su medición y evaluación por parte de los servicios de farmacia hospitalaria. Resultados: se obtuvo un listado consensuado de ítems conformado por 79 indicadores adecuados y necesarios que permiten establecer un seguimiento y monitorización de la calidad y actividad de la atención farmacéutica a las personas que viven con VIH. De los mismos, 60 fueron establecidos como clave y 19 avanzados. Conclusiones: (AU)

Objective: To update and define indicators for improving the quality of care and pharmaceutical care for people living with HIV infection in Spain. Method: The present project, which updates the previous version of the 2013 document, was developed in four work phases carried out between January and June 2022.In phase 1, the organization phase, a working group was created, made up of seven hospital pharmacy specialists with extensive experience in pharmaceutical care and from different SFHs in Spain. In addition, another 34 specialists participated in the evaluation of the indicators through two rounds of online evaluation to generate consensus.For phase 2, initially, a review of the identified reference literature was carried out with the aim of establishing a basis from which to define a proposal for quality criteria and indicators. Then, a preliminary proposal of criteria was made and revisions were established for their adjustment in several telematic work meetings.In phase 3, consensus was established based on the Delphi-Rand/UCLA consensus methodology.In addition, all the indicators classified as appropriate and necessary were grouped according to two levels of monitoring recommendation, so as to guide the hospital pharmacy services in the priority of their measurement: key and advanced.Finally, in phase 4, the final project document was prepared, along with the corresponding descriptive sheets for each indicator in order to facilitate the measurement and evaluation of the indicators by the hospital pharmacy services. Results: Following the consensus methodology used, a list of items made up of 79 appropriate and necessary indicators was drawn up to establish a follow-up and monitoring of the quality and activity of pharmaceutical care for people living with HIV. Of these, 60 were established as key and 19 advanced. Conclusions ... (AU)

Acute interstitial nephritis due to dolutegravir: The first case reported / Nefritis intersticial aguda por dolutegravir: primer caso notificado

Kidney disease is frequent in HIV-patients. We present a case of a 44-year-old woman, with known uncontrolled HIV infection and chronic kidney disease due to HIV-associated nephropathy. After starting dolutegravir, the patient developed eosinophilia and worsening kidney function. A kidney biopsy confirmed the diagnosis of acute interstitial nephritis. Given the time relation with dolutegravir introduction, it was deemed the culprit medication. Dolutegravir was stopped, and corticosteroids were initiated, with moderate improvement in renal function. To our knowledge, this is the first reported case of acute interstitial nephritis to dolutegravir, which should raise awareness of previously undocumented renal effects of antiretroviral therapy. (AU)

La enfermedad renal es frecuente en pacientes con VIH. Presentamos el caso de una mujer de 44 años, con infección por VIH no controlada conocida y enfermedad renal crónica por nefropatía asociada al VIH. Después de comenzar con dolutegravir, el paciente desarrolló eosinofilia y empeoramiento de la función renal. Una biopsia de riñón confirmó el diagnóstico de nefritis intersticial aguda. Dada la relación temporal con la introducción de dolutegravir, se consideró al medicamento el culpable. Se interrumpió el tratamiento con dolutegravir y se iniciaron corticosteroides, con una mejoría moderada de la función renal. Hasta donde sabemos, este es el primer caso notificado de nefritis intersticial aguda por dolutegravir, lo que debería crear conciencia sobre los efectos renales previamente indocumentados de la terapia antirretroviral. (AU)

Atencion Farmaceutica al paciente VIH en tratamiento con Dolutegravir y Lamivudina / Pharmaceutical Care for HIV patients on treatment with Dolutegravir and Lamivudine

Introducción: De acuerdo con la Organización Mundial de la Salud el Virus de la Inmunodeficiencia Humana (VIH) continúa siendo uno de los mayores problemas para la salud pública mundial. A día de hoy, la importancia de la adherencia al tratamiento continúa siendo el centro de atención de todos los profesionales sanitarios. La falta de adherencia supone un gran problema económico y sanitario. Método: Este estudio se centra en el servicio de atención farmacéutica (AF) realizado a los pacien-tes VIH en tratamiento con el comprimido coformulado dolutegravir/lamivudina (DTG/3TC) desde su comercialización en julio de 2019 hasta mayo 2021.Variables estudiadas: sexo, edad, adherencia, carga viral, recuento de linfocitos CD4, terapia anti-rretroviral (TAR) previa en paciente no naive, tratamientos concomitantes, interacciones, en pacientes no naive el motivo que ha conducido al cambio de TAR y los efectos adversos (EA) desarrollados. Fuente de datos: programa informático dispensación pacientes externos e historia clínica electrónica. Resultados: En el servicio de AF en la primera entrevista con el farmacéutico se tratan cinco aspectos: adherencia, EA, tratamientos y/o productos de herboristería concomitantes, interacciones y motivo de cambio de TAR. 62 pacientes iniciaron tratamiento con DTG/3TC: 24,1% (15/62) naive y 75,8% (47/62) no naive. El 100% de los pacientes naive presentaron una alta adherencia, solamente el 6,4% de los pacientes pretratados fueron identificados como no adherentes. Se encontró una contraindicación: hipérico. Conclusiones: Los pacientes presentan una alta adherencia, el tratamiento es efectivo y seguro. Se realiza el servicio de AF de forma eficaz. Conocemos la adherencia de nuestros pacientes y realizamos un estrecho seguimiento farmacoterapéutico. (AU)

Introduction: According to the World Health Organization, Human Immunodeficiency Virus (HIV) continues being one of the world's major public health problems. Currently, the importance of adherence to treatment continues being the focus of attention of health professionals. Lack of adherence is a major economic and health problem. Method: This study focuses on the pharmaceutical care service performed on all HIV patients (naive and non-naive) on treatment with the coformulated tablet dolutegravir/lamivudine (DTG/3TC) from its commercialization in July 2019 until May 2021. Variables studied: sex, age, adherence, viral load, CD4 lymphocyte count, previous antiretroviral therapy (ART) in non-naïve patients, concomitant treatments, interactions, the reason that led to the change of ART in non-naïve patient and the adverse effects developed. Results: In the first interview with the pharmacist in the pharmaceutical care service, five fundamental aspects are discussed: adherence, adverse effects, concomitant treatments and/or herbal products, interactions and reason for changing antiretroviral drugs in non-naive patients. 62 patients started treatment with DTG/3TC: 24.1% (15/62) naive and 75.8% (47/62) no naive. 100% of naive patients were highly adherent, only 6.4% of pre-treated patients were identified as non-adherent. Only one contraindication was found: hypericum. Conclusions: Patients are highly adherent, the treatment is effective and safe. The pharmaceutical care service is carried out efficiently. We are aware of our patients' adherence and carry out close phar-macotherapeutic monitoring. (AU)

Variation in renal parameter values after a change in antiretroviral therapy from elvitegravir/cobicistat/emtricitabine/tenofovir-alafenamide to bictegravir/emtricitabine/tenofovir-alafenamide / Variación de los valores de los parámetros renales tras un cambio en la terapia antirretroviral de elvitegravir/cobicistat/emtricitabina/tenofoviralafenamida a bictegravir/emtricitabina/ tenofovir-alafenamida

El cambio de EVG/COBI/FTC/TAF a BIC/FTC/TAF es una estrategia para optimizar la terapia antirretroviral. Nuestro objetivo fue analizar cómo variaban los parámetros analíticos renales tras cambiar tratamiento. Los objetivos secundarios fueron determinar si edad y sexo de los pacientes y el tiempo que habían tomado cobicistat previamente condicionaba la posible variación de los parámetros renales. Se realizó un estudio piloto observacional, descriptivo y ambispectivo. Los parámetros renales se obtuvieron de las analíticas previas más cercanas al cambio (considerándose este valor el basal) y después de 12, 24 semanas y 12 meses tras cambiar tratamiento. Se incluyeron 60 pacientes. En los niveles de creatinina sérica, se observó cambio a las 24 semanas (aumento medio de 0,06 mg/dL, p=0,025) y a los 12 meses (aumento medio de 0,03 mg/dL, p=0,05). Considerando la tasa de filtración glomerular (CKD-EPI), hubo bajada en los 3 períodos analizados, pero sin significación estadística. No hubo influencia del sexo, edad ni tiempo que los pacientes habían tomado cobicistat previamente. (AU)

Switching of EVG/COBI/FTC/TAF to BIC/FTC/TAF is a valid strategy for antiretroviral therapy optimization. Our aim was to analize how the variation of analytical parameters for renal function estimation after the change of their treatment. Secondary objectives were to determine if age and sex of the patients and the time they have previously taken cobicistat conditions the possible variation in renal parameters. An observational, descriptive and ambispective pilot study was performed. The renal laboratory parameters were obtained from the previous laboratory tests closest in time to the change (this value being considered the baseline) and after 12, 24 weeks and 12 months after a change in treatment with BIC/FTC/TAF. 60 patients were included. Regarding serum creatinine levels, a change in serum creatine levels was observed at 24 weeks (mean increase of 0.06 mg/dL, p=0.025) and at 12 months (mean increase of 0.03 mg/dL, p=0.05). Considering glomerular filtration (CKD-EPI), there was downward trend in the 3 periods analyzed, but statistical significance was not reached. There was no influence of sex, age and the length of time that the patients had taken cobicistat before the change. (AU)

Tigliane-Type Diterpene Esters from the Fruits of Shirakiopsis indica and Their Anti-HIV Activity.

Four new diterpene esters, shirakindicans A-D (1-4), along with eight related known diterpene esters (5-12), were isolated from the fruits of the Bangladeshi medicinal plant Shirakiopsis indica. The structures of 1-4 were elucidated by spectroscopic data analysis and electronic circular dichroism (ECD) calculations. Shirakindican A (1) was assigned as a tigliane-type diterpene ester possessing an unusual 6ß-hydroxy-1,7-dien-3-one structure, while shirakindican B (2) exhibits a tiglia-1,5-dien-3,7-dione structure. The anti-HIV activities of the isolated diterpene esters were evaluated and showed significant activities for sapintoxins A (5) and D (11), with EC50 values of 0.0074 and 0.044 µM, respectively, and TI values of 1 100 and 5 290. Sapatoxin A (12) also exhibited anti-HIV activity with an EC50 value of 0.13 µM and a TI value of 161.

Potential HIV latency-reversing agents with STAT1-activating activity from the leaves of Wikstroemia chamaedaphne.

Developing highly effective HIV latency-reversing agent is an inportmant approach for the treatment of AIDS via the "shock and kill" of latent HIV. In this study, two unreported modified daphnane-type diterpenes (chamaedaphnelide A and epi-chamaedaphnelide A) and one unreported tigliane-type diterpene (chamaedaphnelide B), along with four known daphnane-type diterpenes and one known tigliane-type diterpene were obtained from the leaves of Wikstroemia chamaedaphne. Chamaedaphnelide A and epi-chamaedaphnelide A represents the first A ring cleavage daphnane-type backbone. Chamaedaphnelide A, epi-chamaedaphnelide A, chamaedaphnelide B, and 6α,7α-epoxy-5ß-hydroxy-12-deoxyphorbol-13-decanoate showed HIV latency-reversing activity, especially chamaedaphnelide B and 6α,7α-epoxy-5ß-hydroxy-12-deoxyphorbol-13-decanoate displayed equally potential to positive drugs prostratin with reversing latent HIV on more than 100-fold compared to unstimulated cells. Furthermore, the activation of STAT1 was involved in the HIV latency-reversing activity of these diterpenes, firstly demonstrating that daphnane- and tigliane-type diterpenes can rapidly activate STAT1 activity. Indeed, these results also supported that activating STAT1 activity is a pathway for reversing latent HIV.

Guidelines on long-acting injectable cabotegravir for HIV prevention

In this guideline, WHO recommends that long-acting injectable cabotegravir (CAB-LA) may be offered as an additional HIV prevention option for people at substantial risk of HIV infection. CAB-LA is an injectable form of pre-exposure prophylaxis (PrEP) that has been shown to be highly effective at reducing the risk of HIV acquisition. This guideline provides implementation considerations to support Member States, programme managers, policy makers, researchers, health workers, communities, and other stakeholders in the implementation of projects and programmes for CAB-LA. It also outlines critical research gaps for CAB-LA

Synergic effect of metabolic syndrome and lipodystrophy on oxidative stress and inflammation process in treated HIV-patients / Efecto sinérgico del síndrome metabólico y la lipodistrofia en el estrés oxidativo y el proceso de inflamación en pacientes con VIH que reciben tratamiento

The aim of this study was to assess the effect of lipodystrophy (LD) associated to metabolic syndrome (MS) on oxidative stress and inflammation in a cohort of 243 HIV-infected patients with MS, all of them under three different antiretroviral regimens. We collected immunovirological, biochemical and metabolic data, as well as anthropometric measurements. In addition, cardiovascular risk was also assessed by means of Atherogenic Index of Plasma (API) and Framingham Risk Score. The MS-LD patient set was characterized by a lower initial lymphocyte CD4 count and CD4/CD8 ratio and a higher initial viral load than the group without LD. We also found worse lipidic and glycaemic profiles (with lower HDL-cholesterol and higher triglyceride and glucose levels) in the MS-LD group. BMI, systolic blood pressure and Framingham score were significantly increased compared to MS-Non LD. In addition, patients with MS and LD had significantly higher levels of carbonylated proteins, lipid peroxidation, IL-6 and IL-8, as well as a significant decrease in the levels of leptin, adiponectin and antioxidant activities of catalase, super oxide dismutase and glutathione associated enzymes. In MS-LD HIV-1 patients, a significant negative correlation was found between Framingham Risk Score and the antioxidant biomarkers, however a positive association was found between API and protein-C reactive and carbonylated proteins. Segregating by ART, the above-mentioned conditions were worse within the MS-LD group whose treatment contained protease inhibitors, such as lopinavir. In conclusion, HIV-1 infected patients treated for at least six months, especially with regimens including PIs, showed a worsening of inflammatory process and oxidative stress.(AU)

El objetivo de este estudio fue evaluar el efecto de la lipodistrofia (LD) asociada al síndrome metabólico (SM) en el estrés oxidativo y la inflamación en una cohorte de 243 pacientes con VIH y SM, todos en tratamiento con pautas antirretrovirales diferentes. Recopilamos datos inmunovirológicos, bioquímicos y metabólicos, así como medidas antropométricas. Además, el riesgo cardiovascular también se evaluó mediante el índice de plasma aterogénico (API) y la puntuación de riesgo de Framingham. El grupo de pacientes con SM-LD se caracterizó por un recuento inicial de linfocitos CD4 y una relación CD4/CD8 inferiores y una carga vírica inicial más alta que el grupo sin LD. También observamos peores perfiles lipídicos y glucémicos (con menor colesterol HDL y niveles más altos de triglicéridos y glucosa) en el grupo de SM-LD. El IMC, la presión arterial sistólica y la puntuación de Framingham aumentaron significativamente en comparación con el grupo de SM-sin LD. Además, los pacientes con SM y LD tenían niveles significativamente más altos de proteínas carboniladas, peroxidación lipídica, IL-6 e IL-8, así como una disminución significativa de los niveles de leptina, adiponectina y actividades antioxidantes de la catalasa, superóxido dismutasa y enzimas asociadas al glutatión. En los pacientes con SM-LD VIH-1, se observó una correlación negativa significativa entre la puntuación de riesgo de Framingham y los biomarcadores antioxidantes, sin embargo, se observó una asociación positiva entre el API y la proteína C reactiva y las proteínas carboniladas. Al segregarse por ART, las condiciones mencionadas anteriormente fueron peores en el grupo de SM-LD, cuyo tratamiento incluía inhibidores de la proteasa, como el lopinavir. En conclusión, los pacientes con VIH-1 tratados durante al menos seis meses, especialmente con pautas que incluían IP, mostraron un empeoramiento del proceso inflamatorio y el estrés oxidativo.(AU)

Reducing sexually transmitted infections

This guideline covers interventions to prevent sexually transmitted infections (STIs) in people aged 16 and over. It aims to reduce the transmission of all STIs, including HIV, and includes ways to help increase the uptake of STI testing and vaccines for human papillomavirus (HPV) and hepatitis A and B.

Impacto de la implementación de inicio temprano de terapia antirretroviral en nuevos diagnósticos de VIH: estudio de casos y controles / Impact of the implementation of early initiation of antiretroviral therapy in new HIV diagnoses: case-control study

Antecedentes: En Honduras aún se prioriza asegurar la aceptación del diagnóstico de Virus de Inmunodeficiencia Humana (VIH) y la adherencia al tratamiento del Terapia Anti Retroviral (TAR), provocando retraso en su inicio, consecuencias negativas y alto riesgo de muerte. Objetivo: Evaluar el impacto del inicio temprano de TAR en pacientes con nuevos diagnósti- cos de VIH en el Hospital Nacional Mario Catarino Rivas (HNMCR). Pacientes y Métodos: Investigación analítica, observacional de casos y controles. Muestra: 62 casos que iniciaron TAR temprano, de enero a agosto del 2019 y 62 controles que iniciaron TAR en el 2018, fuera de la estrategia de inicios tempranos. Se tomaron datos de expedientes clínicos y se vacío la información en instrumento tipo cuestionario. Resultados: Se encontró más rápida vinculación al servicio y más inicios tempranos de TAR en el grupo casos (OR 19.6, IC 95% 7.2-53.0, p=0.000), una mayor captación en etapa temprana A1 (OR 3.45, IC 95% 1.36-8.59, p=0.006), un menor cambio de estadio clínico (OR 2.35, IC 95% 0.92-5.98, p= 0.070), mayor cumplimiento de evaluación psicológica (OR 8.15, IC 95% 3.42-19.4, p=0.000), menor riesgo de infecciones oportunistas (OR 3.01, IC 95% 1.34-6.74, p=0.006), menor riesgo de hospita- lización (OR 1.33, IC 95% 0.46-3.84, p=0.596), mayor tamizaje de IO (p=0.000). Conclusión /Recomendación: El inicio del TAR en los primeros 7 días posterior al diagnóstico aporta beneficios clínicos y profilácticos, mejorando la calidad de vida y disminuyendo la transmisibilidad del virus. Se recomienda protocolizar los inicios tempranos como estrategia de atención a los nuevos diagnósticos de VIH...(AU)

Isolation, Synthesis, and Structure-Activity Relationship Study on Daphnane and Tigliane Diterpenes as HIV Latency-Reversing Agents.

Three new diterpenes, stellejasmins A (1) and B (2) and 12-O-benzoylphorbol-13-heptanoate (3), were isolated from the roots of Stellera chamaejasme L. The structures of 1-3 were elucidated by extensive NMR and mass spectroscopic analyses. Compounds 1 and 2 are the first derivatives containing a hydroxy group at C-2 in the family of daphnane and tigliane diterpenes. The presence of a chlorine atom in 1 is unique in the plant metabolite. Compound 3 has an odd-number acyl group, which is biosynthetically notable. Human immunodeficiency virus (HIV) LTR-driven transcription activity was tested with 1-3 and 17 known diterpenes isolated from S. chamaejasme L. and Wikstroemia retusa A.Gray. Among these, gnidimacrin (4), stelleralide A (5), and wikstroelide A (20) were highly potent, with EC50 values of 0.14, 0.33, and 0.39 nM, respectively. The structure-activity relationship (SAR) was investigated using 20 natural and eight synthetic diterpenes. This is the first SAR study on natural daphnane and tigliane diterpenes.

Infectious RNA: Human Immunodeficiency Virus (HIV) Biology, Therapeutic Intervention, and the Quest for a Vaccine.

Different mechanisms mediate the toxicity of RNA. Genomic retroviral mRNA hijacks infected host cell factors to enable virus replication. The viral genomic RNA of the human immunodeficiency virus (HIV) encompasses nine genes encoding in less than 10 kb all proteins needed for replication in susceptible host cells. To do so, the genomic RNA undergoes complex alternative splicing to facilitate the synthesis of the structural, accessory, and regulatory proteins. However, HIV strongly relies on the host cell machinery recruiting cellular factors to complete its replication cycle. Antiretroviral therapy (ART) targets different steps in the cycle, preventing disease progression to the acquired immunodeficiency syndrome (AIDS). The comprehension of the host immune system interaction with the virus has fostered the development of a variety of vaccine platforms. Despite encouraging provisional results in vaccine trials, no effective vaccine has been developed, yet. However, novel promising vaccine platforms are currently under investigation.

Baseline HIV drug-resistance testing: 12 US jurisdictions, 2014-2019.

OBJECTIVE: To understand recent patterns in reported baseline HIV drug-resistance testing over time in the United States. DESIGN: Data from the National HIV Surveillance System for persons who were aged at least 13 years at the time of HIV diagnosis during 2014-2019 and resided in one of 12 US jurisdictions with high levels of reporting in 2014 and 2015. METHODS: Among persons included in the analysis, we calculated the total proportion of HIV diagnoses occurring during 2014-2019 with a reported baseline sequence by year of diagnosis and sequence type. A baseline sequence was defined as any protease/ reverse transcriptase (PR/RT) or integrase sequence generated from a specimen collected 90 days or less after diagnosis. RESULTS: During 2014-2019, reported levels of baseline PR/RT (with or without integrase) testing varied by year from 46.9% to 51.8% without any clear pattern over time. PR/RT with integrase testing increased (8.3-19.4%) and integrase-only testing remained low (1.9-1.3%). CONCLUSION: While reported levels of baseline PR/RT (with or without integrase) testing have remained sufficiently high for the purposes of molecular cluster detection, higher levels would strengthen jurisdictions' and the Centers for Disease Control and Prevention's ability to monitor trends in HIV drug-resistance and detect and respond to HIV molecular clusters. Efforts to increase levels of reported baseline testing likely need to address both gaps in testing as well as reporting.

Adherence to contemporary antiretroviral treatment regimens and impact on immunological and virologic outcomes in a US healthcare system.

BACKGROUND: Only a few recent reports have examined longitudinal adherence patterns in US clinics and its impact on immunological and virological outcomes among large cohorts initiating contemporary antiretroviral therapy (ART) in US clinics. METHODS: We followed all persons with HIV (PLWH) in a California clinic population initiating ART between 2010 and 2017. We estimated longitudinal adherence for each PLWH by calculating the medication possession ratio within multiple 6-month intervals using pharmacy refill records. RESULTS: During the study, 2315 PWLH were followed for a median time of 210.8 weeks and only 179 (7.7%) were lost-to-follow-up. The mean adherence was 84.9%. Age (Hazard Ratio (HR): (95% confidence interval): 1.25 (1.20-1.31) per 10-year increase) and Black race (HR: 0.62 (0.53-0.73) vs. White) were associated with adherence in the cohort. A 10% percent increase in adherence increased the odds of being virally suppressed by 37% (OR and 95% CI: 1.37 [1.33-1.41]) and was associated with an increase in mean CD4 count by 8.54 cells/ul in the next 6-month interval (p-value <0.0001). CONCLUSIONS: Our study shows that despite large improvements in retention in care, demographic disparities in adherence to ART persist. Adherence was lower among younger patients and black patients. Our study confirmed the strong association between adherence to ART and viral suppression but could only establish a weak association between adherence and CD4 count. These findings reaffirm the importance of adherence and retention in care and further highlight the need for tailored patient-centered HIV Care Models as a strategy to improve PLWH's outcomes.

Mapping and population size estimates of people who inject drugs in Afghanistan in 2019: Synthesis of multiple methods.

INTRODUCTION: Mapping and population size estimates of people who inject drugs (PWID) provide information needed for monitoring coverage of programs and planning interventions. The objectives of this study were to provide the locations and numbers of PWID in eight cities in Afghanistan and extrapolate estimates for the country as a whole. METHODS: Multiple population size estimation methods were used, including key informant interviews for mapping and enumeration with reverse tracking, unique object and service multipliers, capture-recapture, and wisdom of the crowds. The results of the several methods were synthesized using the Anchored Multiplier-a Bayesian approach to produce point estimates and 95% credible intervals (CI). Using the prevalence of PWID in the eight cities and their correlation with proxy indicators, we extrapolated the PWID population size for all of Afghanistan. RESULTS: Key informants and field mapping identified 374 hotspots across the eight cities from December 29, 2018 to March 20, 2019. Synthesizing results of the multiple methods, the number of male PWID in the eight study cities was estimated to be 11,506 (95% CI 8,449-15,093), corresponding to 0.69% (95% CI 0.50-0.90) of the adult male population age 15-64 years. The total number of women who injected drugs was estimated at 484 (95% CI 356-633), corresponding to 0.03% (95% CI 0.02-0.04) of the adult female population. Extrapolating by proxy indicators, the total number of PWID in Afghanistan was estimated to be 54,782 (95% CI 40,250-71,837), men and 2,457 (95% CI 1,823-3,210) women. The total number of PWID in Afghanistan was estimated to be 57,207 (95% CI 42,049-75,005), which corresponds to 0.37% (95% CI 0.27-0.48) of the adult population age 15 to 64 years. DISCUSSION: This study provided estimates for the number of PWID in Afghanistan. These estimates can be used for advocating and planning services for this vulnerable at-risk population.

Prevalence and factors associated with hypertension among adults with and without HIV in Western Kenya.

INTRODUCTION: The burden of cardiovascular disease (CVD) is increasing in sub-Saharan Africa with untreated hypertension being a major contributing factor. Understanding the magnitude of the problem and risk factors associated with HIV and long-term antiretroviral therapy (ART) is critically important for designing effective programs for diagnosing and treating hypertension in Kenya. METHODS: In this cross-sectional study, we enrolled 300 persons with HIV (PWH) on long term ART (≥6 months) and 298 HIV-negative adults seeking care at the Kisumu County Hospital between September 2017 and May 2018. Hypertension was defined as blood pressure of ≥140/90mmHg or a previous hypertension diagnosis. Multivariate regression was used to assess the association between hypertension and HIV adjusting for age, sex, and known CVD risk factors. RESULTS: Overall prevalence of hypertension was 22%. PWH had a lower prevalence of hypertension than HIV-negative persons (16% vs 27% respectively; p<0.002). In multivariate analyses, persons with HIV were 37% less likely to have hypertension compared to HIV-negative individuals (adjusted prevalence ratio 0.63; 95% confidence interval: 0.46-0.86). Other factors that were associated with hypertension in all participants included older age >40 years, body mass index (BMI) >25 kg/m2 and low-density lipoproteins ≥130mg/dL. Among PWH, being older than 40 years and higher BMI >30 kg/m2 were associated with hypertension. CONCLUSION: Prevalence of hypertension was high, affecting nearly one in every 4 adults, and associated with older age, higher BMI and high low-density lipoproteins. PWH on long-term ART had significantly lower prevalence of hypertension compared to HIV-negative individuals, potentially due to increased access to healthcare services and interaction with prevention messaging. Interventions to increase screening for and prevention of hypertension in the community for all adults are warranted.

The Effect of Treatment-Associated Mutations on HIV Replication and Transmission Cycles.

HIV/AIDS mortality has been decreasing over the last decade. While promising, this decrease correlated directly with increased use of antiretroviral drugs. As a natural consequence of its high mutation rate, treatments provide selection pressure that promotes the natural selection of escape mutants. Individuals may acquire drug-naive strains, or those that have already mutated due to treatment. Even within a host, mutation affects HIV tropism, where initial infection begins with R5-tropic virus, but the clinical transition to AIDS correlates with mutations that lead to an X4-tropic switch. Furthermore, the high mutation rate of HIV has spelled failure for all attempts at an effective vaccine. Pre-exposure drugs are currently the most effective drug-based preventatives, but their effectiveness is also threatened by viral mutation. From attachment and entry to assembly and release, the steps in the replication cycle are also discussed to describe the drug mechanisms and mutations that arise due to those drugs. Revealing the patterns of HIV-1 mutations, their effects, and the coordinated attempt to understand and control them will lead to effective use of current preventative measures and treatment options, as well as the development of new ones.

Expanding the known structure space for RNA binding: a test of 2,5-diketopiperazine.

As the importance of RNA as a therapeutic target has become increasingly recognized, the need for new chemotypes able to bind RNA has grown in significance. We hypothesized that diketopiperazines (DKPs), common substructures in natural products and protein-targeting therapeutic agents, could serve as effective scaffolds for targeting RNA. To confirm this hypothesis, we designed and synthesized two analogs, one incorporating a DKP and one not, of compounds previously demonstrated to bind an RNA critical to the life cycle of HIV-1 with high affinity and specificity. Prior to compound synthesis, calculations employing density functional methods and molecular mechanics conformational searches were used to confirm that the DKP could present functionality in a similar (albeit not identical) orientation to the non DKP-containing compound. We found that both the DKP-containing and parent compound had similar affinities to the target RNA as measured by surface plasmon resonance (SPR). Both compounds were found to have modest but equal anti-HIV activity. These results establish the feasibility of using DKPs to target RNA.