Parenteral platforms for tunable, long-acting administration of a highly hydrophobic antiretroviral drug.

GSK2838232 (GSK8232) is a second-generation maturation inhibitor (MI) developed for the treatment of HIV with excellent broad-spectrum virological profiles. The compound has demonstrated promising clinical results as an orally administered agent. Additionally, the compound's physical and pharmacological properties present opportunities for exploitation as long-acting parenteral formulations. Despite unique design constraints including solubility and dose of GSK8232, we report on three effective tunable drug delivery strategies: active pharmaceutical ingredient (API) suspensions, ionic liquids, and subdermal implants. Promising sustained drug release profiles were achieved in rats with each approach. Additionally, we were able to tune drug release rates through a combination of passive and active strategies, broadening applicability of these formulation approaches beyond GSK8232. Taken together, this report is an important first step to advance long-acting formulation development for critical HIV medicines that do not fit the traditional profile of suitable long-acting candidates.

Development of a physiologically-based pharmacokinetic model to simulate the pharmacokinetics of intramuscular antiretroviral drugs.

There is growing interest in the use of long-acting (LA) injectable drugs to improve treatment adherence. However, their long elimination half-life complicates the conduct of clinical trials. Physiologically-based pharmacokinetic (PBPK) modeling is a mathematical tool that allows to simulate unknown clinical scenarios for LA formulations. Thus, this work aimed to develop and verify a mechanistic intramuscular PBPK model. The framework describing the release of a LA drug from the depot was developed by including both the physiology of the injection site and the physicochemical properties of the drug. The framework was coded in Matlab® 2020a and implemented in our existing PBPK model for the verification step using clinical data for LA cabotegravir, rilpivirine, and paliperidone. The model was considered verified when the simulations were within twofold of observed data. Furthermore, a local sensitivity analysis was conducted to assess the impact of various factors relevant for the drug release from the depot on pharmacokinetics. The PBPK model was successfully verified since all predictions were within twofold of observed clinical data. Peak concentration, area under the concentration-time curve, and trough concentration were sensitive to media viscosity, drug solubility, drug density, and diffusion layer thickness. Additionally, inflammation was shown to impact the drug release from the depot. The developed framework correctly described the release and the drug disposition of LA formulations upon intramuscular administration. It can be implemented in PBPK models to address pharmacological questions related to the use of LA formulations.

Antiretroviral adherence and treatment outcomes among patients living with HIV at an Indonesian HIV clinic: a cross-sectional study / Cumplimiento de los antirretrovirales y resultados del tratamiento entre pacientes que viven con el VIH en una clínica de VIH de Indonesia: un estudio transversal

Objective: This study assessed antiretroviral adherence and treatment outcomes among outpatients with human immunodeficiency virus (HIV). Methods: A cross-sectional study was performed on patients with HIV over 18 years old receiving antiretroviral therapy for at least six months at an Indonesian clinic, from January to March 2021. The previously validated self-reported adherence questionnaire was used to recall antiretroviral use. Viral load and CD4 were indicators of treatment outcomes. Binary logistic regression was used to explore factors associated with nonadherence and poor treatment outcomes. Results: Ninety-five patients were included in the study (male 70.5%, median [interquartile range, IQR] age 35 [29–42] years, and median [IQR] treatment duration 29 [15–49] months). Adherence greater than 95% was observed in 89.5%, 88.4%, 95.8% of the patients in the past week, month, and three months, respectively. Patients with secondary education or lower were associated with low adherence (adjusted odds ratio, aOR: 7.73, 95%CI: 1.12– 53.19). Viral suppression and improved CD4 were observed in 83.2% and 68.4% of the patients, respectively. Taking non-nucleoside reverse transcriptase inhibitors (NNRTIs)-based regimen was associated with viral suppression (aOR: 0.01, 95%CI: 0.00–0.14) as well as high CD4 count (aOR: 0.16, 95%CI: 0.03– 0.83). Being diagnosed with stage 4 of HIV (aOR: 72.38, 95%CI: 3.11–1687.28) and having adherence of 95% or lower (aOR: 68.84, 95%CI: 4.86–974.89) were associated with non-suppressed viral load, and having HIV stage 3 (aOR: 7.81, 95%CI: 1.26–48.40) or 4 (aOR: 26.15, 95%CI: 3.42–200.10) at diagnosis was associated with low CD4. Conclusion: Rates of self-reported adherence and treatment outcomes were high. Secondary education or lower was a predictor of low adherence. Using NNRTIs-based therapy was associated with good treatment outcomes; meanwhile, stage 3 or 4 of HIV at diagnosis and low adherence were predictors of poor outcomes. Therefore, strategies to improve adherence and treatment outcomes are warranted.(AU)

Analysis of antiretroviral therapy interruption in people living with HIV during the 2010-2021 period.

INTRODUCTION: In the context of the advancement of antiretroviral therapy and as the characteristics of people living with HIV progress toward an ageing population, understanding the causes of treatment interruption becomes crucial. The aim of the study was to determine the change in reasons for antiretroviral treatment discontinuation for 12 years. Secondarily, compare annual antiretroviral regimen discontinuation rate and factors associated. METHODS: We conducted an analysis using data from people living with HIV who were receiving antiretroviral therapy and discontinued it for any reason. The study included people with HIV infection who visited an outpatient hospital pharmacy clinic from January 2010 to December 2021. Two periods were differentiated for the analysis: 2010-2015 and 2016-2021. The reasons for antiretroviral treatment discontinuation followed classification described by Swiss cohort. In the context of this study, it is pertinent to note that the term "discontinuation" is employed synonymously with "interruption". The term "discontinuation" will be consistently used in this article to refer to the act of switching or stopping antiretroviral treatment. To examine factors associated with antiretroviral therapy discontinuation, we utilised Kaplan-Meier methods and Cox proportional models. RESULTS: We included 789 people living with HIV, predominantly male (81.5%). The main reason for discontinuation was clinical decision (50.2%) followed by adverse effects (37.9%). Focusing on clinical decision, we observed a trend change that went from antiretroviral treatment simplification regimen (56.1%) in the first part of the period analysed to the therapeutic optimisation (53.6%) in the second half. Furthermore, factors that were statistically significantly associated with antiretroviral treatment discontinuation were people with HIV≥50 years (HR 1.60; 95%CI 1.25-2.04), post-discontinuation single-tablet regimen (HR 1.49; 95%CI 1.06-2.11) and antiretroviral drug classes. CONCLUSION: Over the 12 years, there has been a change in the main cause of antiretroviral treatment discontinuation, currently therapeutic optimisation being the main reason. Integrase inhibitors-based regimens and single-tablet regimen strategies were less likely to be discontinued than others antiretroviral drug classes, allowing for better clinical management due to the efficacy profile, especially in people living with HIV≥50 years with comorbidities.

Evolución temporal de la terapia antirretroviral (2017-2021): análisis de la modificación del tratamiento y su impacto económico / Temporal evolution of antiretroviral therapy (2017-2021): analysis of treatment change and its economic impact

Objetivos. Analizar las modificaciones de la terapia antirre troviral (TAR) y su impacto económico en la práctica clínica diaria. Material y métodos. Estudio observacional, retrospectivo de los pacientes que iniciaron TAR entre 01/2017-12/2021 (se guimiento hasta 12/2022). Variables recogidas: TAR, duración, motivo del cambio y costes del tratamiento. Resultados. 280 pacientes iniciaron TAR. La mediana de durabilidad de la 1ª línea fue: 19,9 meses en 2017 (IC95% 13,9-25,9), 12,2 meses en 2018 (IC95% 4,7-19,7), 27,4 meses en 2019 (IC95% 6,8-48,1) y no se alcanzó la mediana para los años 2020 y 2021 (p p<0,001). De un total de 541 líneas prescri tas, la triple terapia con inhibidores de la proteasa se modificó en el 63,8% (81/127), seguido de los inhibidores de la integrasa 52,1% (159/305), mientras que, la terapia dual (DTG/3TC) solo en el 8,3% (7/84). De un total de 261 modificaciones, la simpli ficación/optimización 47,5% (124/261) fue el principal motivo, seguido de efectos adversos 21,8% (57/261), siendo el 2017 el único año donde ambos motivos se encontraban al mismo nivel. El impacto económico de los cambios supusieron una re ducción del coste medio de 34,0€ [-391,4 a +431,4] al mes/ paciente. El año 2019 es el único año donde estos cambios se asociaron con un incremento del coste adicional medio (23,4€ [-358,3 a +431,4]). Conclusiones. Dejando atrás el fracaso virológico, la sim plificación a regímenes de un solo comprimido y de mayor tolerancia han marcado la nueva la era TAR. Con un impacto económico que, a pesar del punto de inflexión del 2019, refleja una reducción progresiva de costes mantenida en el tiempo (AU)

Objectives. To analyze the modifications of antiretrovi ral therapy (ART) and their economic impact on daily clinical practice. Material and methods. Observational, retrospective study of patients who started ART between 01/2017-12/2021 (follow-up until 12/2022). Variables collected: prescribed ART, duration, the reason for the change, and treatment costs. Results. A total of 280 patients initiated ART therapy. The median durability of 1st line was: 19.9 months in 2017 (95%CI 13.9-25.9), 12.2 months in 2018 (95%CI 4.7-19.7), 27.4 months in 2019 (95%CI 6.8-48.1) and the median was not reached for the years 2020 and 2021 (p<0.001). Triple therapy with protease inhibitors was changed in 63.8% (81/127) of cases, followed by integrase inhibitors 52.1% (159/305), while dual therapy (DTG/3TC) only in 8.3% (7/84). The main cause of dis continuation was simplification/optimization 47.5% (124/261), followed by adverse effects 21.8% (57/261), with 2017 being the only year where simplification/optimization was at the same level as adverse effects. The economic impact of ART changes resulted in an average cost reduction of 34.0€ [-391.4 to +431.4] per month per patient. The year 2019 stands out as the only year where these changes were associated with an increase in mean additional cost (23.4€ [-358.3 to +431.4]). Conclusions. Optimization/simplification accounts for almost half of the reasons for TAR change, with an econom ic impact that, despite the inflection point of 2019, each year manages to exceed the previous one, achieving a progressive cost reduction maintained over time (AU)

Perfil clinico-epidemiológico e factores associados à não supressão viral em pacientes vivendo com hiv/sida assistidos no centro integrado de tratamento no hospital militar de maputo (citra/hmm), 2019 à 2020 / Clinical-epidemiological profile and factors associated with viral non-suppression in patients living with hiv/aids assisted at the integrated treatment center at the maputo military hospital (citra/hmm), 2019 to 2020

: Introdução: O HIV e SIDA é um problema de saúde pública global, responsável por cerca de 32.7 milhões de mortes de doenças relacionadas à SIDA desde o início da epidemia até o final de 2019, comprometendo a saúde, a força de produção e produtividade. Esse cenário tende a ser mais grave, quando se trata de forças militares, cuja a responsabilidade da defesa e manutenção da paz, recai sobre eles. O objectivo foi avaliar o perfil clinico-epidemiológico e factores associados a não supressão viral em pacientes vivendo com HIV/SIDA assistidas no Centro Integrado de Tratamento no Hospital Militar de Maputo (CITRA/HMM). Métodos: Tratou-se de um estudo transversal analítico com uma abordagem quantitativa, utilizando dados secundários de pacientes em seguimento entre os anos de 2019-2020 no CITRA/HMM. A amostra foi composta por 9.015 indivíduos com idade igual ou superiora 15 anos de idade. A analise de dados foi feita com pacote estatístico STATA versão 16, onde recorreu-se os testes Qui-quadrado de Pearson e a razão de chances/OR com Intervalos de Confiança/IC de 95% e p<0,05, para verificar as diferenças entre às proporções e a associação entre as variáveis em análise, considerando como desfecho o estado de supressão viral: suprimido (<1000 cópias de RNA do HIV/ml) e não suprimido (≥1000 cópias de RNA do HIV/ml). Para o modelo de regressão logística múltipla, apenas foram seleccionadas as variáveis que se mostraram estatisticamente significativas na análise bivariada. Resultados: Dos 9.105 indivíduos inclusos na análise, 4.808 (52,8%) eram do sexo feminino e 1.235 (13,6%) eram militares. A média de idade foi de 47,9 anos (DP±12,1), sendo o grupo etário mais prevalente composto por indivíduos com idades entre 25 e 59 anos, totalizando 7.297 (80,2%) participantes. Entre os analisados, 5.395 (53,3%) tinham resultados de última carga viral, e destes, 4.148 (76,9%) tinham a carga viral suprimida. Embora a maior proporção de supressão viral tenha sido verificada em civis, quando ajustada, essa diferença não demonstrou significância estatística…

Introduction: HIV and AIDS is a global public health problem, responsible for about 32.7 million deaths from AIDS-related diseases from the beginning of the epidemic to the end of 2019, compromising health, workforce and productivity. This scenario tends to be more serious when it comes to military forces, whose responsibility for the defense and maintenance of peace falls on them. The objective was to evaluate the clinical and epidemiological profile and factors associated with viral load non-suppression in patients living with HIV/AIDS at the Military Hospital (CITRA/HMM). Methods: This is a analytic cross-sectional study with a quantitative approach, using secondary data from patients being followed up between the years 2019-2020 at CITRA/HMM. The sample consisted of 9,015 individuals aged 15 years and over. Data analysis was performed with the statistical package STATA, Version 16. Pearson's chi-square test and odds ratio/OR with a confidence interval of 95%CI and p<0,05 were used to verify the differences between the proportions and association between the variables under analysis, considering the state of viral suppression as an outcome: suppressed (<1000 HIV RNA copies/ml) and non-suppressed (≥1000 HIV RNA copies/ml). For the multiple logistic regression model, only the variables that proved to be statistically significant in the bivariate analysis were selected. Results: Of the 9,105 individuals included in the analysis, 4,808 (52.8%) were female and 1,235 (13.6%) were military personnel. The average age was 47.9 years (SD±12.1), with the most prevalent age group being individuals aged between 25 and 59, totalling 7,297 (80.2%) participants. Among those analysed, 5,395 (53.3%) had their last viral load results, and of these, 4,148 (76.9%) had a suppressed viral load. Although the highest proportion of viral suppression was seen in civilians, when adjusted, this difference was not statistically significant…

Preexposure Prophylaxis to Prevent Acquisition of HIV: US Preventive Services Task Force Recommendation Statement.

Importance: An estimated 1.2 million persons in the US currently have HIV, and more than 760 000 persons have died of complications related to HIV since the first cases were reported in 1981. Although treatable, HIV is not curable and has significant health consequences. Therefore, effective strategies to prevent HIV are an important public health and clinical priority. Objective: The US Preventive Services Task Force (USPSTF) commissioned a systematic review to evaluate the benefits and harms of preexposure prophylaxis with antiretroviral therapy for the prevention of HIV acquisition, and the diagnostic accuracy of risk assessment tools to identify persons at increased risk of HIV acquisition. Population: Adolescents and adults who do not have HIV and are at increased risk of HIV. Evidence Assessment: The USPSTF concludes with high certainty that there is a substantial net benefit from the use of effective antiretroviral therapy to reduce the risk of acquisition of HIV in persons at increased risk of acquiring HIV. Recommendation: The USPSTF recommends that clinicians prescribe preexposure prophylaxis using effective antiretroviral therapy to persons at increased risk of HIV acquisition to decrease the risk of acquiring HIV. (A recommendation).

Host Immunity to Mycobacterium tuberculosis Infection Is Similar in Simian Immunodeficiency Virus (SIV)-Infected, Antiretroviral Therapy-Treated and SIV-Naïve Juvenile Macaques.

Pre-existing HIV infection increases tuberculosis (TB) risk in children. Antiretroviral therapy (ART) reduces, but does not abolish, this risk in children with HIV. The immunologic mechanisms involved in TB progression in both HIV-naive and HIV-infected children have not been explored. Much of our current understanding is based on human studies in adults and adult animal models. In this study, we sought to model childhood HIV/Mycobacterium tuberculosis (Mtb) coinfection in the setting of ART and characterize T cells during TB progression. Macaques equivalent to 4 to 8 year-old children were intravenously infected with SIVmac239M, treated with ART 3 months later, and coinfected with Mtb 3 months after initiating ART. SIV-naive macaques were similarly infected with Mtb alone. TB pathology and total Mtb burden did not differ between SIV-infected, ART-treated and SIV-naive macaques, although lung Mtb burden was lower in SIV-infected, ART-treated macaques. No major differences in frequencies of CD4+ and CD8+ T cells and unconventional T cell subsets (Vγ9+ γδ T cells, MAIT cells, and NKT cells) in airways were observed between SIV-infected, ART-treated and SIV-naive macaques over the course of Mtb infection, with the exception of CCR5+ CD4+ and CD8+ T cells which were slightly lower. CD4+ and CD8+ T cell frequencies did not differ in the lung granulomas. Immune checkpoint marker levels were similar, although ki-67 levels in CD8+ T cells were elevated. Thus, ART treatment of juvenile macaques, 3 months after SIV infection, resulted in similar progression of Mtb and T cell responses compared to Mtb in SIV-naive macaques.

Association of Race and Ethnicity With Initial Prescription of Antiretroviral Therapy Among People With HIV in the US.

Importance: Integrase strand transfer inhibitor (INSTI)-containing antiretroviral therapy (ART) is currently the guideline-recommended first-line treatment for HIV. Delayed prescription of INSTI-containing ART may amplify differences and inequities in health outcomes. Objectives: To estimate racial and ethnic differences in the prescription of INSTI-containing ART among adults newly entering HIV care in the US and to examine variation in these differences over time in relation to changes in treatment guidelines. Design, Setting, and Participants: Retrospective observational study of 42 841 adults entering HIV care from October 12, 2007, when the first INSTI was approved by the US Food and Drug Administration, to April 30, 2019, at more than 200 clinical sites contributing to the North American AIDS Cohort Collaboration on Research and Design. Exposures: Combined race and ethnicity as reported in patient medical records. Main Outcomes and Measures: Probability of initial prescription of ART within 1 month of care entry and probability of being prescribed INSTI-containing ART. Differences among non-Hispanic Black and Hispanic patients compared with non-Hispanic White patients were estimated by calendar year and time period in relation to changes in national guidelines on the timing of treatment initiation and recommended initial treatment regimens. Results: Of 41 263 patients with information on race and ethnicity, 19 378 (47%) as non-Hispanic Black, 6798 (16%) identified as Hispanic, and 13 539 (33%) as non-Hispanic White; 36 394 patients (85%) were male, and the median age was 42 years (IQR, 30 to 51). From 2007-2015, when guidelines recommended treatment initiation based on CD4+ cell count, the probability of ART initiation within 1 month of care entry was 45% among White patients, 45% among Black patients (difference, 0% [95% CI, -1% to 1%]), and 51% among Hispanic patients (difference, 5% [95% CI, 4% to 7%]). From 2016-2019, when guidelines strongly recommended treating all patients regardless of CD4+ cell count, this probability increased to 66% among White patients, 68% among Black patients (difference, 2% [95% CI, -1% to 5%]), and 71% among Hispanic patients (difference, 5% [95% CI, 1% to 9%]). INSTIs were prescribed to 22% of White patients and only 17% of Black patients (difference, -5% [95% CI, -7% to -4%]) and 17% of Hispanic patients (difference, -5% [95% CI, -7% to -3%]) from 2009-2014, when INSTIs were approved as initial therapy but were not yet guideline recommended. Significant differences persisted for Black patients (difference, -6% [95% CI, -8% to -4%]) but not for Hispanic patients (difference, -1% [95% CI, -4% to 2%]) compared with White patients from 2014-2017, when INSTI-containing ART was a guideline-recommended option for initial therapy; differences by race and ethnicity were not statistically significant from 2017-2019, when INSTI-containing ART was the single recommended initial therapy for most people with HIV. Conclusions and Relevance: Among adults entering HIV care within a large US research consortium from 2007-2019, the 1-month probability of ART prescription was not significantly different across most races and ethnicities, although Black and Hispanic patients were significantly less likely than White patients to receive INSTI-containing ART in earlier time periods but not after INSTIs became guideline-recommended initial therapy for most people with HIV. Additional research is needed to understand the underlying racial and ethnic differences and whether the differences in prescribing were associated with clinical outcomes.

Factores que influenciam a utilização de serviços pré-natais num contexto urbano: estudo de caso do centro de saúde 1º de maio, cidade de maputo / Factors influencing the use of antenatal services in an urban setting: a case study of the case study of the 1º de maio health center, maputo city

Os cuidados pré-natais são fundamentais para assegurar uma boa saúde da gestante e da futura criança. Foram objectivos deste estudo, analisar os factores que influenciam a utilização de serviços pré-natais definida como a realização de pelo menos quatro consultas pré-natais. Foi realizado um estudo descritivo transversal com uma abordagem quantitativa e qualitativa no Centro de Saúde 1º de Maio, na Cidade de Maputo. A componente quantitativa foi baseada num questionário aplicado às puérperas na maternidade e na consulta pós-parto. A componente qualitativa foi baseada na observação participativa e em entrevistas em profundidade às Enfermeiras de Saúde Materno-Infantil. Foram submetidas ao questionário um total de 271 puérperas, com idades entre os 16 e os 42 anos. Destas, 233 (86%) realizaram mais do que quatro consultas pré-natais. O início do tratamento anti-retroviral na consulta pré-natal foi o único factor associado a menor utilização dos serviços pré-natais (p ≤ 0,05). Os dados qualitativos mostraram que, no geral, o Centro de Saúde apresentou condições para a prestação dos serviços pré-natais, com a excepção da falta de água potável para a toma de medicamentos sob observação directa e um stock insuficiente de suplemento de ferro e ácido fólico. Embora existam algumas deficiências na oferta de alguns serviços neste Centro de Saúde, a utilização dos serviços pré natais é, em geral, alta. Esta alta utilização dos serviços pode ser explicada pela localização - zona urbana, onde o acesso a informação e aos serviços de saúde é mais facilitado.

Antenatal care is essential to ensure a good health for pregnant women and for expected offspring. The objectives of this study were to analyze factors that influence the utilization of antenatal services, defined as at least four antenatal visits. A cross-sectional descriptive study, using both quantitative and qualitative methods, was carried out at 1o de Maio Health Center in Maputo City. The quantitative component was based on a questionnaire administered to postpartum women in the maternity ward and in the postpartum consultation. The qualitative component was based on participatory observation and in-depth interviews with providers of maternal and child health services. A total of 271 postpartum women, with ages ranging from 16 and 42 years, were responded to a questionnaire. Among them, 233 (86%) had complete more than four antenatal visits. Initiation of anti-retroviral treatment at antenatal care was the only factor associated with lower use of antenatal services (p≤ 0.05). The qualitative data show that overall, the health Center was ready to provide antenatal services, with the exception of lack of drinking water for the direct observation treatment, and an insufficient stock of iron and folic acid supplementation. Although there are some deficiencies in the provision of some services at the health Center level, the use of antenatal services is, in general, high. This high utilization of services may be explained by the location - an urban area, where access to information and health services is easier.

Proporción de infecciones oportunistas y factores de riesgo asociados a su aparición en pacientes con VIH / Proportion of opportunistic infections and risk factors associated with its appearance in patients with HIV

Antecedentes: Las infecciones oportunistas son la principal causa de morbilidad, discapaci- dad y mortalidad en pacientes con VIH, aumentando el número de hospitalizaciones y costos en la atención. Objetivo: Estimar la proporción de infecciones oportunistas e identificar los factores asociados a su aparición en pacientes con VIH atendidos en el Servicio de Atención Integral del Hospital Nacional Dr. Mario Catarino Rivas, San Pedro Sula, 2019-2020. Métodos: Estudio no experimental, analítico de casos (infección oportunista presente) y controles. Se evaluaron 40 casos y 120 controles, con un nivel de confianza de 95%, poder estadístico de 80%, con muestreo tipo aleatorio simple. Se utilizó la distribución de variables entre casos y controles para la obtención de Odds Ratio. Resultados: Las infecciones oportunistas incluyeron: 52.5% (21) tuberculosis, 15.0% (6) histoplasmosis, 12.5% (5) citomegalovirus, 10.0% (4) toxoplasmosis, 10.0% (4) candidiasis, 7.5% (3) criptococosis. El conteo de linfocitos T CD4 fue <200 cel/mm3 en 60.0% (24) de grupo casos y 10.8% (13) de grupo control. La carga viral ˃1000 copias/ml (OR 14.500 IC95% 6.109-34.415), el antecedente de abandono (OR 4.363 IC95% 1.928-9.872) y el no tomar tratamiento antirretroviral (OR 64.076 IC95% 8.063-509.165) se asociaron a infecciones oportunistas. La carga viral mayor de 1000 copias/mL predominó en el grupo de casos, y se encontró asociación de esta con la presencia de infecciones oportunistas con OR 14.500 (IC 95% 6.109-34.415, p=.0001). Conclusión: El no tomar ARV aumenta 64 veces más el riesgo de desarrollar infecciones oportunistas y el haber abandonado el tratamiento antirretroviral aumenta 4 veces más la probabilidad de desarrollar una infección oportunista. El tratamiento antirretroviral de gran actividad y el apego al mismo es la mejor estrategia para prevenir las infecciones oportunistas en pacientes infectados por el VIH...(AU)

Progress towards controlling the HIV epidemic in urban Ethiopia: Findings from the 2017-2018 Ethiopia population-based HIV impact assessment survey.

INTRODUCTION: In 2014, the Joint United Nations Programme on HIV/AIDS set an 'ambitious' 90-90-90 target for 2020. By 2016, there were disparities observed among countries in their progress towards the targets and some believed the targets were not achievable. In this report, we present the results of data from the Ethiopia Population-based HIV Impact Assessment survey analyzed to assess progress with the targets and associated factors. METHODS: We conducted a nationally representative survey in urban areas of Ethiopia. Socio-demographic and behavioural data were collected from consenting participants using a structured interview. HIV testing was done following the national HIV rapid testing algorithm and seropositivity confirmed using a supplemental laboratory assay. HIV viral suppression was considered if the viral load was <1,000 RNA copies/ml. Screening antiretroviral drugs was done for efavirenz, lopinavir, and tenofovir, which were in use during the survey period. In this analysis, we generated weighted descriptive statistics and used bivariate and logistic regression analysis to examine for associations. The 95% confidence interval was used to measure the precision of estimates and the significance level set at p<0.05. RESULTS: Of 19,136 eligible participants aged 15-64 years, 614 (3% [95% CI: 0.8-3.3]) were HIV-positive, of which 79.0% (95% CI: 4.7-82.7) were aware of their HIV status, and 97.1% (95% CI: 95.0-98.3 were on antiretroviral therapy, of which 87.6% (95% CI: 83.9-90.5) achieved viral load suppression. Awareness about HIV-positive status was significantly higher among females (aOR = 2.8 [95% CI: 1.38-5.51]), significantly increased with age, the odds being highest for those aged 55-64 years (aOR = 11.4 [95% CI: 2.52-51.79]) compared to those 15-24 years, and was significantly higher among those who used condom at last sex in the past 12 months (aOR = 5.1 [95% CI: 1.68-15.25]). Individuals with secondary education and above were more likely to have achieved viral suppression (aOR = 8.2 [95% CI: 1.82-37.07]) compared with those with no education. CONCLUSION: Ethiopia made encouraging progress towards the UNAIDS 90-90-90 targets. The country needs to intensify its efforts to achieve the targets. A particular focus is required to fill the gaps in knowledge of HIV-positive status to increase case identification among population groups such as males, the youth, and those with low education.

Time to lost to follow-up and its predictors among adult patients receiving antiretroviral therapy retrospective follow-up study Amhara Northwest Ethiopia.

Antiretroviral therapy lowers viral load only when people living with HIV maintain their treatment retention. Lost to follow-up is the persistent major challenge to the success of ART program in low-resource settings including Ethiopia. The purpose of this study is to estimate time to lost to follow-up and its predictors in antiretroviral therapies amongst adult patients. Among registered HIV patients, 542 samples were included. Data cleaning and analysis were done using Stata/SE version 14 software. In multivariable Cox regression, a p-value < 0.05 at 95% confidence interval with corresponding adjusted hazards ratio (AHR) were statistically significant predictors. In this study, the median time to lost to follow-up is 77 months. The incidence density of lost to follow-up was 13.45 (95% CI: 11.78, 15.34) per 100 person-years. Antiretroviral therapy drug adherence [AHR: 3.04 (95% CI: 2.18, 4.24)], last functional status [AHR: 2.74 (95% CI: 2.04, 3.67)], and INH prophylaxis [AHR: 1.65 (95% CI: 1.07, 2.56) were significant predictors for time to lost to follow-up. The median time to lost was 77 months and incidence of lost to follow-up was high. Health care providers should be focused on HIV counseling and proper case management focused on identified risks.

Effect of single tablet regimen on prescription trends for treatment-naïve patients with HIV/AIDS in Korea.

Single-tablet regimens (STRs) should be considered for patients with HIV/AIDS to increase medication compliance and improve clinical outcomes. This study compared variations in the prescription trends between STRs and multiple-tablet regimens (MTRs) for treatment-naïve patients with HIV/AIDS after the approval of the new STRs, a proxy indicator for improvement in medication adherence. The medical and pharmacy claim data were retrospectively obtained from the Health Insurance Review and Assessment service, which contains basic information on the patients' sociodemographic characteristics and treatment information for the entire Korean population. From 2013 to 2018, a total of 6737 patients with HIV/AIDS were included. Most patients were men (92.8%, n = 6251) and insured through the National Health Insurance (95.1%, n = 6410). The mean number of pills in their antiretroviral treatment regimens decreased from 2.8 ± 1.2 in 2013 to 1.2 ± 1.0 in 2018. After the first STR (EVG/c/TDF/FTC) was approved in 2014, prescription transitions from MTR to STR were observed among more than 38% of patients. In 2018, most treatment-naïve patients were prescribed STRs (91.2%). There was a time lag for STR prescription trends in non-metropolitan hospitals compared with those in metropolitan cities. Our data provide a valuable perspective for evaluating ART regimen prescription patterns on a national scale.

Implants for HIV prevention in young women: Provider perceptions and lessons learned from contraceptive implant provision.

Preventing new HIV infections, especially amongst young women, is key to ending the HIV epidemic especially in sub-Saharan Africa. Potent antiretroviral (ARV) drugs used as pre-exposure prophylaxis (PrEP) are currently being formulated as long-acting implantable devices, or nanosuspension injectables that release drug at a sustained rate providing protection from acquiring HIV. PrEP as implants (PrEP Implants) offers an innovative and novel approach, expanding the HIV prevention toolbox. Feedback from providers and future users in the early clinical product development stages may identify modifiable characteristics which can improve acceptability and uptake of new technologies. Healthcare workers (HCWs) perspectives and lessons learned during the rollout of contraceptive implants will allow us to understand what factors may impact the roll-out of PrEP implants. We conducted eighteen interviews with HCWs (9 Nurses and 9 Community Healthcare Workers) in rural KwaZulu-Natal, South Africa. HCWs listed the long-acting nature of the contraceptive implant as a key benefit, helping to overcome healthcare system barriers like heavy workloads and understaffing. However, challenges like side effects, migration of the implant, stakeholder buy-in and inconsistent training on insertion and removal hampered the roll-out of the contraceptive implant. For PrEP implants, HCWs preferred long-acting products that were palpable and biodegradable. Our findings highlighted that the characteristics of PrEP implants that are perceived to be beneficial by HCWs may not align with that of potential users, potentially impacting the acceptability and uptake of PrEP implants. Further our data highlight the need for sustained and multi-pronged approaches to training HCWs and introducing new health technologies into communities. Finding a balance between the needs of HCWs that accommodate their heavy workloads, limited resources at points of delivery of care and the needs and preferences of potential users need to be carefully considered in the development of PrEP implants.

"The research assistants kept coming to follow me up; I counted myself as a lucky person": Social support arising from a longitudinal HIV cohort study in Uganda.

BACKGROUND: Participation in longitudinal research studies in resource-limited settings often involves frequent interactions with study staff and other participants, as well as receipt of incentives and transportation reimbursements. Social support-receipt of material and emotional resources from one's social network-has been linked to antiretroviral adherence in sub-Saharan Africa. The extent to which social support arises from study participation, its range and depth, and its implications for observational study conduct, have not been extensively described. METHODS: We conducted individual open-ended and semi-structured interviews with participants in a longitudinal, observational antiretroviral therapy adherence monitoring study in Mbarara, Uganda. Participants were asked about their experiences in the longitudinal study and their interactions with research staff. We also interviewed study research assistants (RAs). Deductive and inductive coding were used to identify content related to the experience of study participation. Codes were organized into themes, and relationships between themes were used to develop overarching categories. RESULTS: Sixty longitudinal study participants and 6 RAs were interviewed. Instrumental and emotional social support emerged as pervasive and valued aspects of longitudinal study participation. Instrumental support that participants received consisted of enhanced linkage to medical care, health education, and direct and indirect material benefits. Emotional support consisted of perceptions of feeling "cared for" and social interactions that permitted escape from HIV-related stigma. Both instrumental and emotional support often arose through the close relationships participants formed with research staff and with each other. Study-derived social support motivated some participants to adhere to antiretroviral therapy-an unanticipated effect potentially influencing the longitudinal study's primary observational outcome. CONCLUSIONS: Longitudinal study participation resulted in instrumental and emotional social support for participants. The depth of support participants experienced has implications for observational study design in resource-limited settings, including need to assess potential effects on study outcomes; consideration of social support during risk/benefit assessment in study ethics review and consent; and vigilance for consequences of social support loss when studies end.

Association of HIV status and treatment characteristics with VIA screening outcomes in Malawi: A retrospective analysis.

BACKGROUND: Although evidence from high-resource settings indicates that women with HIV are at higher risk of acquiring high-risk HPV and developing cervical cancer, data from cervical cancer "screen and treat" programs using visual inspection with acetic acid (VIA) in lower-income countries have found mixed evidence about the association between HIV status and screening outcomes. Moreover, there is limited evidence regarding the effect of HIV-related characteristics (e.g., viral suppression, treatment factors) on screening outcomes in these high HIV burden settings. METHODS: This study aimed to evaluate the relationship between HIV status, HIV treatment, and viral suppression with cervical cancer screening outcomes. Data from a "screen and treat" program based at a large, free antiretroviral therapy (ART) clinic in Lilongwe, Malawi was retrospectively analyzed to determine rates of abnormal VIA results and suspected cancer, and coverage of same-day treatment. Multivariate logistic regression assessed associations between screening outcomes and HIV status, and among women living with HIV, viremia, ART treatment duration and BMI. RESULTS: Of 1405 women receiving first-time VIA screening between 2017-2019, 13 (0.9%) had suspected cancer and 68 (4.8%) had pre-cancerous lesions, of whom 50 (73.5%) received same-day lesion treatment. There was no significant association found between HIV status and screening outcomes. Among HIV+ women, abnormal VIA was positively associated with viral load ≥ 1000 copies/mL (aOR 3.02, 95% CI: 1.22, 7.49) and negatively associated with ART treatment duration (aOR 0.88 per additional year, 95% CI: 0.80, 0.98). CONCLUSION: In this population of women living with HIV with high rates of ART coverage and viral suppression, HIV status was not significantly associated with abnormal cervical cancer screening results. We hypothesize that ART treatment and viral suppression may mitigate the elevated risk of cervical cancer for women living with HIV, and we encourage further study on this relationship in high HIV burden settings.