HIV and type 2 diabetes: An evolving story.

INTRODUCTION: Diabetes is widely reported to be more common in people living with HIV (PLWH). Much of the data supporting this originated during the earlier HIV era. The perceived increased risk of type 2 diabetes is reflected in HIV clinical guidelines that recommend screening for diabetes in PLWH on anti-retroviral therapy (ART). However, international HIV clinical guidelines do not agree on the best marker of glycaemia to screen for diabetes. This stems from studies that suggest HbA1c underestimates glycaemia in PLWH. METHODS: Within this review we summarise the literature surrounding the association of HIV and type 2 diabetes and how this has changed over time. We also present the evidence on HbA1c discrepancy in PLWH. CONCLUSION: We suggest there is no basis to any international guidelines to restrict HbA1c based on HIV serostatus. We recommend, using the current evidence, that PLWH should be screened annually for diabetes in keeping with country specific guidance. Finally, we suggest future work to elucidate phenotype and natural history of type 2 diabetes in PLWH across all populations.

Differences in neuroinflammation in people who started antiretroviral treatment during primary versus chronic HIV infection: an 18kDa Translocator protein (TSPO) positron emission tomography (PET) study.

Persistent inflammation is described in people with HIV (PWH) on antiretroviral treatment (ART). Early ART initiation is associated with reduced inflammation. We aimed to evaluate neuroinflammation, using translocator protein (TSPO) [11C]PBR28 PET neuroimaging in PWH who initiated ART during acute HIV (aPWH) versus chronic HIV infection (cPWH) versus a control population. This was a cross-sectional, observational study. All participants underwent [11C]PBR28 PET-CT neuroimaging. Using a two-tissue compartment model, total volume of distribution (VT) and distribution volume ratios (DVR) using cortical grey matter as a pseudo-reference region at 20 regions of interest (ROIs) were calculated. Differences in VT and DVR were compared between groups using the Kruskall-Wallis test. Seventeen neuro-asymptomatic male PWH on ART (9 aPWH, 8 cPWH) and 8 male control participants (CPs) were included. Median (interquartile range, IQR) age was 40 (30, 46), 44 (41, 47) and 21 (20, 25) years in aPWH, cPWH and CPs, respectively. Median (IQR) CD4 (cells/µL) and CD4:CD8 were 687 (652, 1014) and 1.37 (1.24, 1.42), and 700 (500, 720) and 0.67 (0.64, 0.82) in aPWH and cPWH, respectively. Overall, no significant difference in VT and DVR were observed between the three groups at any ROIs. cPWH demonstrated a trend towards higher mean VT compared with aPWH and CPs at most ROIs. No significant differences in neuroinflammation, using [11C]PBR28 binding as a proxy, were identified between cPWH, aPWH and CPs. A trend towards lower absolute [11C]PBR28 binding was seen amongst aPWH and CPs, suggesting early ART may mitigate neuroinflammation.

Acceptability of digital vending machines to access STI and HIV tests in two UK cities.

OBJECTIVES: Prompt HIV and STI diagnosis and treatment is a public health priority and relies on accessible testing. Technology-based approaches to distribute test kits have the potential to increase access to testing. We evaluated the acceptability and uptake of vending machines in publicly available settings in Brighton and Hove (BH) and Bristol, North Somerset and South Gloucestershire (BNSSG), to distribute HIV rapid self-test and STI self-sample kits. METHODS: Seven machines were installed in BH and four in BNSSG. User characteristics, proportion of kits returned and test results, taken from the machine database and clinic records, combined with online questionnaires completed by self-recruited users and analysed using Stata and SPSS. RESULTS: 2536 kits were dispensed over 12 months (April 2022 to March 2023). The STI self-sample kits were most popular (74% of vends). 78% of kits dispensed were among users aged 16-35 years and 56% identified as male. 68% and 59% of users had either not tested in the last 12 months or never tested for HIV and STIs, respectively. 51% of STI kits were returned via post, lower than the local online service (65%). 208 users completed questionnaires. Convenience, desire for instant access and increased confidentiality were the most common reasons for using machines. 92% of respondents thought the machines were user-friendly and 97% would recommend the service. Concerns about safety and privacy while using the machine were reported by 42% and 66% of respondents. CONCLUSIONS: This study demonstrates that vending machines are an acceptable and effective means of accessing infrequent or never testers in the general population and can act as a horizontal intervention to tackle HIV and STIs. Research is needed to understand optimal machine locations to assure privacy and safety along with the long-term impact on sexual health services.

A multi-country comparative study of two treponemal tests for the serodiagnosis of syphilis amongst men who have sex with men (MSM): Chemo-luminescent assay vs Treponema pallidum particle agglutination assay.

INTRODUCTION: International guidelines recommend routine screening for syphilis (aetiological agent: Treponema pallidum subspecies pallidum) amongst key populations and vulnerable populations using tests detecting treponemal and non-treponemal antibodies. Whilst treponemal tests have high sensitivities and specificities, they differ regarding subjective or objective interpretation, throughput and workload. Chemiluminescence immunoassays (CLIAs) are cost- and time-effective automated methods for detecting treponemal antibodies. The Treponema pallidum particle agglutination assay (TPPA) has been considered the "gold standard" treponemal assay, however, this includes a highly manual procedure, low throughput and subjective interpretation. The present multi-country study evaluated the ADVIA Centaur® Syphilis CLIA (Siemens Healthcare) assay compared to the reference SERODIA-TP·PA® (Fujirebio Diagnostics) for the serodiagnosis of syphilis amongst men who have sex with men (MSM). METHOD: 1,485 MSM were enrolled in Brighton (UK), Malta, and Verona (Italy) as part of a larger WHO multi-country and multi-site ProSPeRo study. Ethical approval was obtained. Serum was tested with the ADVIA Centaur® Syphilis CLIA assay and SERODIA-TP·PA®, in accordance with the manufacturers' instructions, for a first round of validation. A second round of validation was carried out for discrepant results that were additionally tested with both Western Blot (Westernblot EUROIMMUN®) and an Immunoblot (INNO-LIA, Fujirebio Diagnostics). Sensitivity, specificity, positive and negative predictive value (PPV and NPV), likelihood ratios (positive/negative), and the Diagnostic Odds Ratio (DOR)/pre-post-test probability (Fagan's nomogram) were calculated. RESULTS: Out of 1,485 eligible samples analysed in the first phase, the SERODIA-TP·PA® identified 360 positive and 1,125 negative cases. The ADVIA Centaur® Syphilis CLIA assay (Siemens) identified 366 positives, missclassifying one TPPA-positive sample. In the second phase, the ADVIA Centaur® Syphilis CLIA resulted in 1 false negative and 4 false positive results. Considering the syphilis study prevalence of 24% (95% CI: 22-26.7), The sensitivity of the ADVIA Centaur® Syphilis CLIA assay was 99.7% (95% CI: 98.5-100), and the specificity was 99.4% (95% CI: 98.7-99.7). The ROC area values were 0.996 (95% CI: 0.992-0.999), and both the PPV and NPV values were above 98% (PPV 98.1%, 95% CI: 96.1-99.2; NPV 99.9%, 95% CI: 99.5-100). CONCLUSIONS: The ADVIA Centaur® Syphilis CLIA assay showed similar performance compared to the SERODIA-TP·PA®. Considering the study is based on QUADAS principles and with a homogeneous population, results are also likely to be generalisable to MSM population but potentially not applicable to lower prevalence populations routinely screened for syphilis. The automated CLIA treponemal assay confirmed to be accurate and appropriate for routine initial syphilis screening, i.e. when the reverse testing algorithm is applied.

Independent clinic-based evaluation of dual POCTs for screening for HIV and syphilis in men who have sex with men in Italy, Malta, Peru, and the United Kingdom.

INTRODUCTION: Globally, the incidence of HIV and syphilis can be reduced by the use of validated point of care tests (POCTs). As part of the WHO PRoSPeRo Network, we aimed to evaluate the performance, acceptability, and operational characteristics of two dual HIV/syphilis POCTs (Bioline HIV/Syphilis Duo (Abbott) and DPP® HIV-Syphilis assay (Chembio) for the screening of HIV and syphilis amongst men who have sex with men (MSM). METHOD AND ANALYSES: A cross sectional study of 2,577 MSM in Italy, Malta, Peru, and the United Kingdom (UK) presenting to seven clinic sites, were enrolled. Finger prick blood was collected to perform POCTs and results compared with standard laboratory investigations on venepuncture blood. Acceptability and operational characteristics were assessed using questionnaires. Diagnostic meta-analysis was used to combine data from the evaluation sites. RESULTS: Based on laboratory tests, 23.46% (n = 598/2549) of participants were confirmed HIV positive, and 35.88% of participants (n = 901/2511) were positive on treponemal reference testing. Of all participants showing evidence of antibodies to Treponema pallidum, 50.56% (n = 455/900) were Rapid Plasma Reagin (RPR) test reactive. Of HIV positive individuals, 60.62% (n = 354/584) had evidence of antibodies to T. pallidum, and of these 60.45% (n = 214/354) exhibited reactive RPR tests indicating probable (co)infection. For Bioline POCT, pooled sensitivities and specificities for HIV were 98.95% and 99.89% respectively, and for syphilis were 73.79% and 99.57%. For Chembio pooled sensitivities and specificities for HIV were 98.66% and 99.55%, and for syphilis were 78.60% and 99.48%. Both tests can detect greater than 90% of probable active syphilis cases, as defined by reactive RPR and treponemal test results. These dual POCTs were preferred by 74.77% (n = 1,926) of participants, due to their convenience, and the operational characteristics made them acceptable to health care providers (HCPs). CONCLUSIONS: Both the Bioline and the Chembio dual POCT for syphilis and HIV had acceptable performance, acceptability and operational characteristics amongst MSM in the PRoSPeRo network. These dual POCTs could serve as a strategic, more cost effective, patient and healthcare provider (HCP) friendly alternative to conventional testing; in clinical and other field settings, especially those in resource-limited settings.

Episodic disability questionnaire (EDQ) measurement properties among adults living with HIV in Canada, Ireland, United Kingdom, and United States.

BACKGROUND: The Episodic Disability Questionnaire (EDQ) is a generic 35-item patient-reported outcome measure of presence, severity and episodic nature of disability. We assessed the measurement properties of the Episodic Disability Questionnaire (EDQ) with adults living with HIV. METHODS: We conducted a measurement study with adults living with HIV in eight clinical settings in Canada, Ireland, United Kingdom, and United States. We electronically administered the EDQ followed by three reference measures (World Health Organization Disability Assessment Schedule; Patient Health Questionnaire; Social Support Scale) and a demographic questionnaire. We administered the EDQ only 1 week later. We assessed the internal consistency reliability (Cronbach's alpha; > 0.7 acceptable), and test-retest reliability (Intra Class Correlation Coefficient; > 0.7 acceptable). We estimated required change in EDQ domain scores to be 95% certain that a change was not due to measurement error (Minimum Detectable Change (MDC95%)). We evaluated construct validity by assessing 36 primary hypotheses of relationships between EDQ scores and scores on the reference measures (> 75% hypotheses confirmed indicated validity). RESULTS: Three hundred fifty nine participants completed the questionnaires at time point 1, of which 321 (89%) completed the EDQ approximately 1 week later. Cronbach's alpha for internal consistency ranged from 0.84 (social domain) to 0.91 (day domain) for the EDQ severity scale, and 0.72 (uncertainty domain) to 0.88 (day domain) for the EDQ presence scale, and 0.87 (physical, cognitive, mental-emotional domains) to 0.89 (uncertainty domain) for the EDQ episodic scale. ICCs for test-retest reliability ranged from 0.79 (physical domain) to 0.88 (day domain) for the EDQ severity scale and from 0.71 (uncertainty domain) to 0.85 (day domain) for the EDQ presence scale. Highest precision was demonstrated in the severity scale for each domain (MDC95% range: 19-25 out of 100), followed by the presence (MDC95% range: 37-54) and episodic scales (MDC95% range:44-76). Twenty-nine of 36 (81%) construct validity hypotheses were confirmed. CONCLUSIONS: The EDQ possesses internal consistency reliability, construct validity, and test-retest reliability, with limited precision when administered electronically with adults living with HIV across in clinical settings in four countries. Given the measurement properties, the EDQ can be used for group level comparisons for research and program evaluation in adults living with HIV.

Understanding the lived experience research priorities for improving health-related quality of life in people living with HIV with cognitive impairment.

BACKGROUND: People living with HIV experience higher rates of cognitive impairment (CI), and at younger ages, than the general population. These individuals report poor health-related quality of life (HRQL), however, interventions aimed at assisting people living with HIV to live well with CI do not currently exist and represent an important un-met need in this population. OBJECTIVE: This study aimed to identify the lived experience research priorities for improving HRQL and identify interventions to support priority areas. METHODS: A Research Advisory Group was established with 15 lived experience, academic, healthcare, and third sector professionals. Additionally, two semi-structured focus groups were undertaken, with health and third sector professionals and people living with HIV with CI. Participants were asked to rank factors impacting HRQL, identified in prior research, in terms of priority and intervention development. Findings were analysed using a combination of conventional and summative content analysis. Study findings were feedback to our Research Advisory Group. RESULTS: Five people living with HIV with CI, recruited through third sector agencies [Male 80%; median age 59 (range 56-78); White British 60%; homosexual 60%], and three healthcare and third sector participants (66% third sector professionals from two local HIV charities; 33% HIV-specific clinical psychologist) took part in two focus groups and ranked interventions targeting improvement in physical function, social connectedness, cognition and perceived control over cognitive health as priority areas. Findings were then fed back to the Research Advisory Group who recommended the development of an illness-specific cognitive rehabilitation programme and improved information provision as important avenues for intervention development. CONCLUSION: Given the absence of meaningful patient and public involvement, intervention, and support guidelines for people living with HIV with CI, this provides a roadmap for future research in this important and growing area of HIV clinical care.

Cognitive impairment in people living with HIV: mechanisms, controversies, and future perspectives.

Despite the dramatic decrease in HIV-associated neurocognitive impairment (NCI) in the combined antiretroviral treatment (cART) era, subtler neuropsychological complications remain prevalent. In this review, we discuss the changing pathophysiology of HIV-associated NCI, considering recent evidence of HIV neuropathogenesis, and the pivotal role of cART. Furthermore, we address the multifactorial nature of NCI in people living with HIV, including legacy and ongoing insults to the brain, as well as host-specific factors. We also summarize the ongoing debate about the refinement of diagnostic criteria, exploring the strengths and limitations of these recent approaches. Finally, we present current research in NCI management in people living with HIV and highlight the need for using both pharmacological and nonpharmacological pathways toward a holistic approach.

Switching to dolutegravir plus rilpivirine versus maintaining current antiretroviral therapy regimen in virologically suppressed people with HIV-1 and the Lys103Asn (K103N) mutation: 48-week results from a randomised, open-label pilot clinical trial.

BACKGROUND: The combination of dolutegravir plus rilpivirine has been studied in people with virologically suppressed HIV with no previous history of treatment failure or resistance. We investigated the potential to maintain viral suppression with dolutegravir plus rilpivirine in people with Lys103Asn mutations whose HIV was previously managed with other treatment regimens. METHODS: In this open-label pilot trial at 32 clinical sites in seven European countries, virologically suppressed, HBsAg-negative adults aged 18 years or older with HIV-1 and Lys103Asn mutations were randomly assigned (2:1) to switch to 50 mg dolutegravir plus 25 mg rilpivirine (given as a single tablet) once daily or to continue their current antiretroviral therapy regimen (control group). After 48 weeks, participants in the control group also switched to dolutegravir plus rilpivirine. Randomisation was stratified by country, and a computer-generated randomisation list with permuted blocks within strata was used to assign participants to treatment groups. The primary endpoints were virological failure (ie, two consecutive measurements of 50 copies or more of HIV RNA per mL at least 2 weeks apart) and virological suppression (the proportion of participants with fewer than 50 copies of HIV RNA per mL) at week 48 (week 96 data will be reported separately). Analyses were done in the modified intention-to-treat population, which included all participants who received at least one dose of the study medication. This trial is registered with ClinicalTrials.gov, NCT05349838, and EudraCT, 2017-004040-38. FINDINGS: Between Nov 5, 2018, and Dec 9, 2020, 140 participants were enrolled and randomly assigned, 95 to the dolutegravir plus rilpivirine group and 45 to the control group. Virological failure was recorded in three participants (3·2%, 95% CI 0·7 to 9·0) in the the dolutegravir plus rilpivirine group and one (2·2%, 0·1 to 11·8) in the control group. The proportion of participants in whom virological suppression was maintained at week 48 was 88·4% (80·2 to 94·1) in the dolutegravir plus rilpivirine group versus 88·9% (75·9 to 96·3) in the control group (difference -0·5, -11·7 to 10·7). Significantly more adverse events were recorded in the dolutegravir plus rilpivirine group than in the control group (234 vs 72; p=0·0034), but the proportion of participants who reported at least one adverse event was similar between groups (76 [80%] of 95 vs 33 [73%] of 45; p=0·39). The frequency of serious adverse events was low and similar between groups. INTERPRETATION: Virological suppression was maintained at week 48 in most participants with Lys103Asn mutations when they switched from standard regimens to dolutegravir plus rilpivirine. The results of this pilot study, if maintained when the week 96 data are reported, support conduct of a large, well-powered trial of dolutegravir plus rilpivirine. FUNDING: ViiV Healthcare.

The Social Construction of Aging Among a Clinic-Based Population and Their Healthcare Workers in Zambia.

Objectives: We sought to understand the social construction of aging in a clinic-based population, with and without HIV, to address gaps in care for older individuals living with HIV in Zambia. Methods: Our exploratory qualitative study included 36 in-depth interviews with clinic clients and four focus group discussions with 36 professional and lay healthcare workers providing services to the clients. We identified themes based on social construction theory. Results: At the individual level, aging was multidimensional, perceived both as an achievement in the HIV era and as a period of cognitive, physical, and economic decline. In social interactions, older individuals were often stereotyped and treated as helpless, poor, and "witches." Those living with HIV faced the additional stigma of being labeled as promiscuous. Some of the participants living without HIV refused to take daily medication for non-communicable diseases to avoid being mistaken for taking antiretroviral therapy for HIV. Older individuals wanted quality healthcare and family support to address the intersectional stigma of aging, poverty, and chronic illness. Conclusion: Multifaceted interventions are required to combat age-related prejudice, intersectional stigma, and discriminatory practices, particularly for people living with HIV.

El perfil psicológico de un asesino serial en la ciudad de Medellín / The psychological profile of a serial killer in the city of Medellin

El objetivo de esta investigación,es presentar un análisis de la realización de la evaluación Psicológica Forense de un asesino serial en la ciudad de Medellín. A lo largo de él se señalan algunos aspectos históricos del asesinato serial, sus características y sus diferentes tipos; asi mismo, se hace una descripción de los crímenes, el modus operandi del asesino y, por último su evaluación y perfil de personalidad. Todo ello enmarcado bajo el respeto y la ética ya que este estudio no pretende juzgar al asesino, sino analizar el fenómeno de su personalidad psicopática desde los diversos factores que se interrelacionan.

The goal of this research is to showan analysis of the psychological and forensic assessment carried out to a serial killer in the city of Medellin. In it, some historical aspects of the serial killer are made, including hischaracteristics and different types; as well as a description of the crimes, the killer's modus operandi and his assessment and personality profile. All of this is framed in the respect andthe ethics, since this research does not attempt to judge the murder, but to analyze the phenomenon of his psychotic personality taking into account the diverse factors, whichare interrelated.

Reservorio urinario continente de Indiana modificado en la infancia / Modified Indiana continent urinary reservoir in childhood

Introducción: Con el propósito de mejorar la calidad de vida de una gran cantidad de niños que padecen por tener una vejiga no útil, se realizaron sustituciones vesicales continentes, del tipo de Indiana en pacientes portadores de "incontinencia urinaria" y vías urinarias inferiores no propicias para la reconstrucción satisfactoria o bien portadores de una derivación previa no continente. Material y métodos: Este procedimiento se realizó en 18 pacientes pediátricos durante el periodo comprendido entre enero de 1991 a septiembre de 1994 en el Centro Médico "La raza" y el Hospital Médica Sur, México, D.F. Con el objeto de mejorar los resultados, se agregó a la técnica original de Indiana un segundo mecanismo de continencia mediante invaginación del íleon terminal a través de la válvula ileocecal. Resultados: De los 18 pacientes, 16 se conservaron secos y sólo dos presentaron escurrimiento leve. La función renal se mantuvo estable y ningún paciente presentó reflujo ureteral ni estenosis en el sitio de la reimplantación. Conclusiones: Los resultados obtenidos demostraron que este mecanismo cumple los requisitos de sustitución vesical y ofrece, con sus modificaciones, buenos resultados y una mejor calidad de vida

Tratamiento paliativo del dolor óseo con samario 153-EDTMP en cáncer prostático metastásico: estudio controlado / Palliative pain treatment by means of samarium 143-EDTMP in metastatic prostate cancer: a controled study

Se realizó un ensayo clínico controlado, prospectivo, longitudinal, comparativo y experimental que abarcó el periodo comprendido entre el 26 de septiembre de 1995 y el 27 de marzo de 1996, con 18 pacientes de cáncer prostático metastásico que cursaban con dolor óseo refractario por actividad tumoral. De los 18 pacientes, a nueve se les aplicó el fármaco radiactivo samario 153 como terapia analgésica, y los otros nueve continuaron con el tratamiento analgésico ordinario (grupo testigo). Los resultados muestran una disminución significativa de la intensidad del dolor en los pacientes tratados con samario 153 en comparación con lo observado en los pacientes del grupo testigo. Se concluye que el samario puede ser un agente terapéutico útil para la paliación del dolor óseo que generalmente es refractario a la terapéutica analgésica convencional, lo que se traduce en una mejoría en la calidad de vida de los pacientes con cáncer prostatico en etapa avanzada.