The slowdown of new infections by human retroviruses has reached a plateau in Spain.

The 2022 annual meeting of the HTLV & HIV-2 Spanish Network was held in Madrid on December 14. We summarize here the main information presented and discussed at the workshop and review time trends for human retroviral infections in Spain. As transmissible agents, infections by human retroviruses are of obligatory declaration. Until the end of 2022, the Spanish national registry had recorded 451 cases of HTLV-1, 821 of HTLV-2, and 416 of HIV-2. For HIV-1, estimates are of 150 000 people currently living with HIV-1 and 60 000 cumulative deaths due to AIDS. During year 2022, new diagnoses in Spain were of 22 for HTLV-1, 6 for HTLV-2, and 7 for HIV-2. The last updated figures for HIV-1 are from 2021 and counted 2786 new diagnoses. The slowdown in yearly infections for HIV-1 in Spain points out that new strategies are needed to achieve the United Nations 95-95-95 targets by 2025. For the remaining neglected human retroviral infections, their control might be pushed throughout four interventions: (1) expanding testing; (2) improving education and interventions aimed to reduce risk behaviors; (3) facilitating access to antiretrovirals as treatment and prevention, including further development of long-acting formulations; and (4) increasing vaccine research efforts. Spain is a 47 million population country in South Europe with strong migration flows from HTLV-1 endemic regions in Latin America and Sub-Saharan Africa. At this time universal HTLV screening has been implemented only in the transplantation setting, following the report of 5 cases of HTLV-associated myelopathy shortly after transplantation of organs from HTLV-1 positive donors. There are four target populations for expanding testing and unveiling asymptomatic carriers responsible for silent HTLV-1 transmissions: (1) migrants; (2) individuals with sexually transmitted infections; (3) pregnant women; and (4) blood donors.

Treatment of hepatitis delta and HIV infection.

Hepatitis delta virus (HDV) is a defective agent that only infects individuals with hepatitis B virus (HBV). Around 5-10% of chronic hepatitis B patients worldwide are superinfected with HDV, which means 15-25 million people. Hepatitis delta is the most severe of all chronic viral hepatitis, leading to cirrhosis, liver cancer and/or transplantation in most patients. Despite it, many HDV patients remain undiagnosed. The only treatment available until recently was peginterferon alfa, with poor results and significant side effects. The recent approval of bulevirtide, a lipopeptide that blocks HBV/HDV entry, has revolutionized the field. Another drug, lonafarnib, already approved to treat progeria, is expected to be available soon as HDV therapy. Since there is no cell reservoir for the HDV RNA genome, hypothetically viral clearance could be achieved if complete blocking of viral replication occurs for a minimum time frame. This is what happens in hepatitis C using direct-acting antivirals, with the achievement of cure in nearly all treated patients. We envision the cure of hepatitis delta using combination antiviral therapy. Given that sexual and parenteral transmission routes are the most frequent for the acquisition of HBV and HDV, shared with HIV infection and HBV/HDV and HIV coinfection. The clinical outcome of hepatitis delta is worst in the HIV setting, with more frequent liver complications. Since most persons infected with HIV are on regular health care follow-up, we propose that HIV-HDV patients should be prioritized for moving forward new and potentially curative treatments for hepatitis delta.

Susceptibility to hepatitis B virus infection in adults living in Spain.

BACKGROUND: A protective hepatitis B virus (HBV) vaccine has been available for four decades. Universal HBV vaccination of infants is recommended by the WHO since the 1990s. Furthermore, HBV immunization is advised for all adults with high-risk behaviours and no seroprotection. However, HBV vaccine coverage remains globally suboptimal. The advent of new more efficacious trivalent HBV vaccines has renewed the interest in HBV vaccination. At present, the extent of current HBV susceptibility in adults remains unknown in Spain. METHODS: HBV serological markers were assessed on a large and representative sample of adults in Spain, including blood donors and individuals belonging to high-risk groups. Serum HBsAg, anti-HBc and anti-HBs were tested in specimens collected during the last couple of years. RESULTS: From 13 859 consecutive adults tested at seven cities across the Spanish geography, overall 166 (1.2%) had positive HBsAg. Past HBV infection was recognized in 14% and prior vaccine immunization in 24%. Unexpectedly, 37% of blood donors and 63% of persons belonging to high-risk groups had no serum HBV markers and therefore were potentially HBV susceptible. CONCLUSION: Roughly 60% of adults living in Spain seem to be HBV susceptible. Waning immunity might be more common than expected. Hence, HBV serological testing should be performed at least once in all adults regardless of risk exposures. HBV vaccine full courses or boosters should be administered to all adults lacking serological evidence of HBV protection.

Working around the border: Shared experiences of art therapists working with families impacted by immigration and political realities in Mexico and the United States.

This art-based, participatory action research sought to foster dialog between art therapists working on both sides of the US (Southern California)-Mexico (Tijuana) border in 2019. The paper summarizes the narratives from three initial focus groups, highlighting main findings arising from systematic analyses of verbal, creative and reflective writing input of participants. Identified themes include therapists' need to respond to immigration crisis; the realities of being a part of a border town; observing differences between communities; learning from the art of art therapists working with immigrants and refugees; and identifying challenges as a therapist. These themes inspired the creation of preliminary guidelines and are discussed within the context of mental health services around the border at this time.

Drug resistance mutations in HIV-2 patients failing raltegravir and influence on dolutegravir response.

Background: A broader extent of amino acid substitutions in the integrase of HIV-2 compared with HIV-1 might enable greater cross-resistance between raltegravir and dolutegravir in HIV-2 infection. Few studies have examined the virological response to dolutegravir in HIV-2 patients that failed raltegravir. Methods: All patients recorded in the HIV-2 Spanish cohort were examined. The integrase coding region was sequenced in viraemic patients. Changes associated with resistance to raltegravir and dolutegravir in HIV-1 were recorded. Results: From 319 HIV-2-infected patients recorded in the HIV-2 Spanish cohort, 53 integrase sequences from 30 individuals were obtained (20 raltegravir naive and 10 raltegravir experienced). Only one secondary mutation (E138A) was found in one of the 20 raltegravir-naive HIV-2 patients. For raltegravir-experienced individuals, the resistance mutation profile in 9 of 10 viraemic patients was as follows: N155H + A153G/S (four); Y143G + A153S (two); Q148R + G140A/S (two); and Y143C + Q91R (one). Of note, all patients with Y143G and N155H developed a rare non-polymorphic mutation at codon 153. Rescue therapy with dolutegravir was given to 5 of these 10 patients. After >6 months on dolutegravir therapy, three patients with baseline N155H experienced viral rebound. In two of them N155H was replaced by Q148K/R and in another by G118R. Conclusions: A wide repertoire of resistance mutations in the integrase gene occur in HIV-2-infected patients failing on raltegravir. Although dolutegravir may allow successful rescue in most HIV-2 raltegravir failures, we report and characterize three cases of dolutegravir resistance in HIV-2 patients, emerging variants Q148K and Q148R and a novel change G118R.

CD4 cell count response to first-line combination ART in HIV-2+ patients compared with HIV-1+ patients: a multinational, multicohort European study.

Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models. Results: We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm3 were 203 (95% CI 100-290) in HIV-2+ patients and 223 (95% CI 100-353) in HIV-1+ patients. Mean observed CD4 cell count changes from start of cART to 12 months were +105 (95% CI 77-134) in HIV-2+ patients and +202 (95% CI 199-205) in HIV-1+ patients, an observed difference of 97 cells/mm3 in 1 year. In adjusted analysis, the mean CD4 cell increase was overall 25 CD4 cells/mm3/year lower (95% CI 5-44; P = 0.0127) in HIV-2+ patients compared with HIV-1+ patients. Conclusions: A poorer CD4 cell increase during first-line cART was observed in HIV-2+ patients, even after adjusting for pretreatment pVL and other potential confounders. Our results underline the need to identify more potent therapeutic regimens or strategies against HIV-2.

Potential gingival crevicular fluid and serum biomarkers by stage of HIV infection.

OBJECTIVE: This study evaluates the potential of gingival crevicular fluid and serum cytokines as HIV stage biomarkers. METHODS: Gingival crevicular fluid (GCF) and serum samples from 78 HIV-positive adult male subjects (cases) and 39 HIV-negative male subjects (controls) from Mexico were examined for 17 cytokines using multiplex ELISA. Participants were divided into five subgroups by HIV stage of infection on age-specific CD4+ T-lymphocyte count and antiretroviral therapy (ART), and further correlated to the cytokine levels. RESULTS: GCF concentrations of IL-6, IL-7, IL-10, IL-12, G-CSF and MCP-1, as well as serum concentrations of IL-1ß, IL-2 and IL-6 showed a statistically significant difference among subgroups. We found a significant effect size correlation on cytokines expression levels. Subjects who were not in ART showed significantly higher levels of some of the analyzed cytokines compared to the rest. We found that GCF IL-8 was a significant predictor for the Non-ART HIV status (p<0.05). We observed the same result for GCF G-CSF in the ART Short-term group and serum GM-CSF in the ART Long-term subgroup. CONCLUSION: Results indicate a high variability of GCF and serum cytokines concentrations and low frequency of their detection in different HIV/ART stages. However, within the limits of the present study, some GCF and serum cytokine concentrations correlate positively. Oral and periodontal innate immunity is affected by HIV viremia and ART. GCF IL-8, G-CSF, as well as serum IL-8, MCP-1 and GM-CSF may be useful biomarkers for the detection of disease presence and/or its severity due to HIV infection and ART use.

Repeatability of ocular biometry with IOLMaster 700 in subjects with clear lens.

PURPOSE: The purpose of the study was to assess the reproducibility of ocular biometry using the IOLMaster-700 in a healthy population. METHODS: This is a prospective, cross-sectional, observational reproducibility study. Ocular biometry was performed three times on each of 45 studied eyes. Flattest meridian (Kf) and the steepest meridian (Ks), central corneal thickness, axial length, anterior chamber depth, aqueous depth, lens thickness, and white-to-white distances were recorded. Reproducibility was evaluated using the coefficient of variation (CV), the within subject standard deviation, and the intraclass correlation coefficient (ICC). RESULTS: There was a high reproducibility in all parameters; CV was between 0.3 and 1 %, and the ICC was higher than 0.87 in all measurements. CONCLUSIONS: IOLMaster-700 showed high reproducibility for ocular biometry.

Reporting guidelines for implementation and operational research.

In public health, implementation research is done to improve access to interventions that have been shown to work but have not reached many of the people who could benefit from them. Researchers identify practical problems facing public health programmes and aim to find solutions that improve health outcomes. In operational research, routinely-collected programme data are used to uncover ways of delivering more effective, efficient and equitable health care. As implementation research can address many types of questions, many research designs may be appropriate. Existing reporting guidelines partially cover the methods used in implementation and operational research, so we ran a consultation through the World Health Organization (WHO), the Alliance for Health Policy & Systems Research (AHPSR) and the Special Programme for Research and Training in Tropical Diseases (TDR) and developed guidelines to facilitate the funding, conduct, review and publishing of such studies. Our intention is to provide a practical reference for funders, researchers, policymakers, implementers, reviewers and editors working with implementation and operational research. This is an evolving field, so we plan to monitor the use of these guidelines and develop future versions as required.

Dans le domaine de la santé publique, des recherches sur la mise en œuvre sont menées pour améliorer l'accès aux interventions qui se sont révélées efficaces, mais qui n'ont pas touché toutes les personnes qui auraient pu en bénéficier. Les chercheurs identifient les difficultés pratiques qui compromettent les programmes de santé publique et s'efforcent de trouver des solutions pour améliorer les résultats sanitaires. Les données de programme systématiquement collectées dans le cadre des recherches opérationnelles, sont utilisées pour mettre en lumière des moyens de rendre les soins de santé plus efficaces, efficients et équitables. D'autre part, comme il est possible que les recherches sur la mise en œuvre portent sur de nombreux types de questions, différents plans de recherche peuvent s'avérer appropriés. Les directives existantes concernant l'établissement de rapports traitent en partie des méthodes utilisées dans le cadre des recherches sur la mise en œuvre et des recherches opérationnelles. Nous avons donc mené une consultation au sein de l'Organisation mondiale de la Santé (OMS), de l'Alliance pour la recherche sur les politiques et les systèmes de santé (AHPSR) et du Programme spécial de recherche et de formation concernant les maladies tropicales (TDR) et élaboré des directives pour faciliter le financement, la conduite, la révision et la publication de ce type de recherches. Notre objectif est de fournir une référence pratique pour les bailleurs de fonds, les chercheurs, les décideurs, les responsables de la mise en œuvre, les réviseurs et les éditeurs associés aux recherches sur la mise en œuvre et aux recherches opérationnelles. Ce domaine étant en constante évolution, nous prévoyons de suivre l'utilisation de ces directives et de rédiger, si besoin est, de futures versions.

En la salud pública, las investigaciones sobre la ejecución se llevan a cabo para mejorar el acceso a las intervenciones que se ha demostrado que funcionan pero que no han llegado a una gran parte de las personas que podrían beneficiarse de ellas. Los investigadores identifican los problemas prácticos a los que se enfrentan los programas de salud pública y tratan de encontrar soluciones que mejoren los resultados sanitarios. En las investigaciones operativas, se utilizan datos de programas recopilados rutinariamente para descubrir formas de ofrecer una atención sanitaria más efectiva, eficiente y equitativa. Puesto que una investigación sobre la ejecución puede abordar muchos tipos de cuestiones, pueden ser apropiados muchos diseños de investigación. Las directrices existentes sobre la presentación de informes cubren parcialmente los métodos utilizados en las investigaciones operativas y sobre la ejecución, por lo que se llevó a cabo una consulta a través de la Organización Mundial de la Salud (OMS), la Alianza para la Investigación en Políticas y Sistemas de Salud (Alianza IPSS) y el Programa Especial de Investigaciones y Enseñanzas sobre Enfermedades Tropicales (TDR) y se desarrollaron directrices para facilitar la financiación, realización, revisión y publicación de dichos estudios. El objetivo es proporcionar una referencia práctica para financiadores, investigadores, responsables de la formulación de políticas, implementadores, revisores y editores que trabajen con investigaciones operativas y sobre la ejecución. Se trata de un área en evolución, por lo que prevemos supervisar el uso de estas directrices y desarrollar versiones futuras si fuera necesario.

HIV-2 viral tropism influences CD4+ T cell count regardless of viral load.

BACKGROUND: HIV-2 infection is characterized by low plasma viraemia and slower progression to AIDS in comparison with HIV-1 infection. However, antiretroviral therapy in patients with HIV-2 is less effective and often fails to provide optimal CD4 recovery. METHODS: We examined viral tropism in persons with HIV-2 infection enrolled in the HIV-2 Spanish cohort. Viral tropism was estimated based on V3 sequences obtained from plasma RNA and/or proviral DNA. RESULTS: From a total of 279 individuals with HIV-2 infection recorded in the Spanish national register, 58 V3 sequences belonging to 42 individuals were evaluated. X4 viruses were recognized in 14 patients (33%). Patients with X4 viruses had lower median CD4+ cell counts than patients with R5 viruses [130 (17-210) versus 359 (180-470) cells/mm(3); P = 0.007]. This was true even considering only the subset of 19 patients on antiretroviral therapy [94 (16-147) versus 184 (43-368) cells/mm(3); P = 0.041]. In multivariate analysis, significant differences in CD4+ cell counts between patients with X4 and R5 viruses remained after adjusting for age, gender, antiretroviral therapy and viral load. CONCLUSIONS: The presence of X4-tropic viruses in HIV-2 infection is associated with low CD4+ cell counts, regardless of antiretroviral treatment. Along with CD4+ cell counts, viral tropism testing may assist decisions about when to initiate antiretroviral therapy in HIV-2-infected individuals.

Prospects for Controlling Hepatitis B Globally.

Infection with the hepatitis B virus (HBV) is highly prevalent globally. Over 250 million people suffer from chronic hepatitis B, and more than 800,000 patients die each year due to hepatitis B complications, including liver cancer. Although protective HBV vaccines are recommended for all newborns, global coverage is suboptimal. In adults, sexual transmission is by far the most frequent route of contagion. The WHO estimates that 1.5 million new HBV infections occur annually. Oral nucleos(t)ide analogues entecavir and tenofovir are the most frequent antivirals prescribed as HBV therapy. Almost all patients adherent to the medication achieve undetectable plasma viremia beyond 6 months of monotherapy. However, less than 5% achieve anti-HBs seroconversion, and viral rebound occurs following drug discontinuation. Therefore, nucleos(t)ide analogues need to be lifelong. New long-acting formulations of tenofovir and entecavir are being developed that will maximize treatment benefit and overcome adherence barriers. Furthermore, new antiviral agents are in development, including entry inhibitors, capside assembly modulators, and RNA interference molecules. The use of combination therapy pursues a functional HBV cure, meaning it is negative for both circulating HBV-DNA and HBsAg. Even when this goal is achieved, the cccDNA reservoir within infected hepatocytes remains a signal of past infection, and HBV can reactivate under immune suppression. Therefore, new gene therapies, including gene editing, are eagerly being pursued to silence or definitively disrupt HBV genomes within infected hepatocytes and, in this way, ultimately cure hepatitis B. At this time, three actions can be taken to push HBV eradication globally: (1) expand universal newborn HBV vaccination; (2) perform once-in-life testing of all adults to identify susceptible HBV persons that could be vaccinated (or re-vaccinated) and unveil asymptomatic carriers that could benefit from treatment; and (3) provide earlier antiviral therapy to chronic HBV carriers, as being aviremic reduces the risk of both clinical progression and transmission.

Disseminated gonococcal disease in pediatrics: Case report and review of the literature.

Hematogenous spread of Neisseria gonorrhoeae, a sexually transmitted pathogen, results in disseminated gonococcal disease (DGD), also known as arthritis-dermatitis syndrome, due to the development of skin lesions, tenosynovitis, and arthritis. The most frequently affected population is young adults. We describe the case of an adolescent female who acutely developed skin lesions, arthritis, tenosynovitis, and constitutional symptoms. The causal agent was identified by a culture of vaginal secretion and treated with ceftriaxone for 7 days with complete recovery. It is important to differentiate this clinical picture from other types of arthritis developed in adolescence.

Bulevirtide in the Treatment of Hepatitis Delta: Drug Discovery, Clinical Development and Place in Therapy.

It has been ten years since the identification of NTCP as the cell surface receptor for HBV and HDV entry into hepatocytes. The search for molecules interfering with the binding of NTCP and HBV/HDV led to design bulevirtide (BLV). This large polypeptide mimics a region of the pre-S1 HBsAg and blocks viral entry by inhibitory competition. BLV was initially tested in cell cultures, animal models and more recently in Phase I-III human trials (called 'MYRS'). As monotherapy or in combination with peginterferon, BLV is well tolerated and exhibits potent antiviral activity. Plasma viremia significantly declines and/or becomes undetectable in more than 75% of patients treated for >24 weeks. However, serum HBsAg concentrations remain unchanged. No selection of BLV resistance in HBV/HDV has been reported in vivo to date. BLV is administered subcutaneously once daily at doses between 2 and 10 mg. BLV received conditional approval in Europe in 2020 to treat chronic hepatitis delta. The advent of peginterferon lambda or new specific anti-HDV antivirals (lonafarnib, etc.) will open the door for combination therapies with BLV. Since there is no stable reservoir for HDV-RNA within infected hepatocytes, viral clearance might be achieved using antivirals for a minimum timeframe. This is what happens in hepatitis C combining several antivirals, curing nearly all patients treated for 3 months. Clearance of HDV-RNA genomes may occur despite HBV persistence as cccDNA or chromosome integrated HBV-DNA within hepatocytes. This is supported by cases of HDV elimination using BLV despite persistence of serum HBsAg. Another path for HDV cure will derive from achieving HBsAg clearance, the goal of new promising anti-HBV gene therapies (bepirovirsen, etc.). In summary, the advent of BLV has triggered a renovated interest for antiviral therapy in hepatitis delta. We envision combination therapies that will lead to HDV cure in the near future.

Impact of the COVID-19 pandemic on hospital admissions due to viral hepatitis in Spain.

BACKGROUND: Before the advent of COVID-19 vaccines, hospitalizations due to SARS-CoV-2 infection during 2020 collapsed most medical centers worldwide. Disruptions in health care for clinical conditions other than COVID-19 were not uniform. Herein, we report the impact of COVID-19 on hospitalizations due to viral hepatitis in Spain. METHODS: Retrospective study of all hospitalizations in Spain during 10 months before (pre-pandemic period) and after (pandemic period) March 1st 2020. Admissions with a diagnosis of hepatitis B, C and/or delta were retrieved and compared using the Spanish National Registry of Hospital Discharges. RESULTS: Nationwide hospitalizations declined 14.6% during the pandemic period, from 3,144,164 to 2,684,845. This reduction was significantly more pronounced for admissions due to viral hepatitis (18.1% drop), falling from 46,521 to 38,115. During the pandemic period, patients admitted with viral hepatitis died significantly more frequently than during the pre-pandemic period (7.2% vs 6.1%; p < 0.001). Liver transplants significantly declined during the pandemic period. COVID-19 was diagnosed in 10.3% of patients hospitalized with viral hepatitis during the pandemic period. This subset of patients was older and died 2.4-fold more frequently than the rest, despite having advanced liver disease less frequently. CONCLUSION: Hospitalizations due to viral hepatitis significantly declined in Spain during the COVID-19 pandemic. Patients admitted with viral hepatitis experienced a greater mortality during the pandemic period. Deaths were more pronounced when coinfected with SARS-CoV-2 despite having advanced liver disease less frequently.

Impact of potent nucleos(t)ide therapy on hepatitis B hospitalisations in Spain.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is a major cause of decompensated cirrhosis and liver cancer worldwide. Newborn HBV vaccination was implemented in Spain two decades ago, and potent oral antivirals entecavir and tenofovir were introduced around 2007. AIM: To assess the clinical benefits of these interventions nationwide. METHODS: Including HBV as a diagnosis, we performed a retrospective study of all hospitalisations in Spain the Spanish National Registry of Hospital Discharges. Information was retrieved from 1997 to 2017. RESULTS: From 73,939,642 nationwide hospital admissions during the study period, 129,634 (0.17%) included HBV as diagnosis. Their number doubled from 2007 to 2017 and the median age increased from 44 to 58 years. Most HBV admissions recorded chronic hepatitis B. In-hospital death occurred in 6.4%. Co-infection with HIV or hepatitis C virus occurred in 11.9% and 23.3%, respectively. Patients with HIV-HBV co-infection had significantly greater mortality than individuals with HBV mono-infection. The rate of HBV hospitalisations significantly increased over time with a transient drop around 2007, coincident with the arrival of new potent oral antivirals. Although the proportion of HBV hepatic decompensation events has declined, the rate of liver cancer continues to rise. The small subset of patients with hepatitis delta superinfection increasingly and disproportionately accounts for hepatic decompensation events and liver cancer. CONCLUSION: Hospital admissions of individuals with HBV infection are increasing in Spain. While hepatic decompensation events declined following the introduction of potent oral nucleos(t)ide therapy, HBV-related liver cancer is rising. No benefit of oral antiviral therapies is seen on hepatitis delta.

Safety considerations in the management of hepatitis C and HIV co-infection.

INTRODUCTION: Both HCV and HIV are highly prevalent infections with current estimates of 57 and 38 million people infected worldwide, respectively. Oral antivirals can be curative for HCV and rescue HIV patients from disease progression. Dual therapy in coinfected patients requires expertise. AREAS COVERED: Four major issues challenge dual HCV and HIV treatment, including overlapping drug-related side effects, hepatitis B reactivation, immune reconstitution inflammatory syndromes (IRIS), and drug-drug interactions (DDI). A search was conducted in PubMed from January 2010 to March 2023. EXPERT OPINION: The advent of second-generation direct-acting antivirals (DDA) that depict higher antiviral potency, fewer side effects, pangenotypic activity and are co-formulated has expanded the indication of HCV therapy and particularly in HIV-coinfected individuals. Sequential initiation of antiretrovirals (ARV) followed by DAA is generally preferred to start dual treatment concomitantly. Close monitoring of rare episodes of HBV reactivation and IRIS is warranted. The most frequent DDI between DAA and ARV affect drug metabolism by CYP450 induction/inhibition, leading to abnormal drug exposures. Throughout this mechanism interact most HCV and HIV protease inhibitors and non-nucleoside polymerase inhibitors. Exposure to some HIV and HCV nucleos(t)ide analogues (e.g. tenofovir and sofosbuvir, respectively) is subject to induction/inhibition of drug transporters and requires special attention in patients with renal insufficiency.

Increased incidence of giant cell arteritis and associated stroke during the COVID-19 pandemic in Spain: A nation-wide population study.

INTRODUCTION: SARS-CoV-2 infection and COVID-19 vaccines might have increased the incidence of giant-cell arteritis (GCA) and the risk of associated stroke in Spain. METHODS: Retrospective nation-wide observational analysis of all adults hospitalized with GCA in Spain during 5 years (Jan-2016 and Dec-2021). The incidence and proportion of admissions with or because of GCA and GCA-associated stroke were compared between pre-pandemic (2016-2019) and pandemic (2020 and 2021) years. Sensitivity analyses were conducted for the different COVID-19 waves and vaccine timing schedules. RESULTS: A total of 17,268 hospital admissions in patients diagnosed with GCA were identified. During 2020 there were 79.3 and 8.1 per 100,000 admissions of GCA and GCA-associated stroke, respectively. During 2021 these figures were 80.8 and 7.7 per 100,00 admissions, respectively. As comparison, yearly admissions due to GCA and GCA-associated stroke were 72.4 and 5.7 per 100,00, respectively, during the pre-pandemic period (p < 0.05). Coincident with the third wave of COVID-19 (and first vaccine dosing), the rate of GCA-associated stroke admissions increased significantly (from 6.7 to 12%; p < 0.001). Likewise, there was an increase in GCA-associated stroke (6.6% vs 4.1%, p = 0.016) coincident with the third dose vaccination (booster) in patients older than 70 at the end of 2021. In multivariate analysis, only patients admitted during the third COVID-19 wave (and first vaccine dosing) (OR = 1.89, 95% CI 1.22-2.93), and during the third vaccination dosing in patients older than 70 (booster) (OR = 1.66, CI 1.11-2.49), presented a higher GCA-associated stroke risk than the same months of previous years after adjustment by age, sex, classical cardiovascular risk factors and COVID-19 diagnosis. CONCLUSIONS: The COVID-19 pandemic led to an increased incidence of GCA during 2020 and 2021. Moreover, the risk of associated stroke significantly risen accompanying times of COVID-19 vaccine dosing, hypothetically linked to an increased thrombotic risk of mRNA-SARS-CoV-2 vaccines. Hence, forthcoming vaccine policies and indications must weigh the risk of severe COVID-19 with the risk of flare or stroke in patients with GCA.

Pre-exposure prophylaxis of non-HIV viral infections and the role of long-acting antivirals.

Viruses cause a large burden of human infectious diseases. During the past 50 years, antivirals have been developed to treat many pathogenic viruses, including herpesviruses, retroviruses, hepatitis viruses, and influenza. Besides being used as treatment, antivirals have shown efficacy for preventing certain viral infections. Following the success in the HIV field, a renewed interest has emerged on the use of antivirals as prophylaxis for other viruses. The development of formulations with extended half-life has pushed further this consideration in persons at risk for a wide range of viral infections. In this way, long-acting antivirals might behave as "chemovaccines" when classical vaccines do not exist, cannot be recommended, immune responses are suboptimal, escape mutants emerge, and/or immunity wanes. Five main caveats would temper its use, namely, selection of drug resistance, drug interactions, short- and long-term side effects, potential teratogenicity in women of child-bearing age, and high cost. Herein, we discuss the prospects for long-acting antivirals as prophylaxis of human viral infections other than HIV.

Design of a Rheumatology Transition Clinic for a Resource-Constrained Setting.

OBJECTIVES: To describe the design process of a medical care program for adolescents with pediatric onset rheumatic diseases (PRD) during the transition from pediatric to adult care in a resource-constrained hospital. METHODS: The model of attention was developed in three steps: 1) the selection of a multidisciplinary team, 2) the evaluation of the state of readiness of patients and caregivers for the transition, and 3) the design of a strategy of attention according to local needs. The results of the first two steps were used in order to develop the strategy of attention. RESULTS: The transition process was structured in three stages: pretransition (at pediatric rheumatology clinic), Transition Clinic for Adolescents with Rheumatic Diseases (TCARD, the main intervention), and post-transition (at adult rheumatology clinic). Each stage was divided, in turn, into a variable number of phases (8 in total), which included activities and goals that patients and caregivers were to accomplish during the process. A multidisciplinary approach was planned by pediatric and adult rheumatologists, nutritionists, physiatrists, psychiatrist, psychologist, nurse, and social worker. During TCARD, counseling, education, nutritional, physical, and mental health interventions were considered. CONCLUSIONS: The proposed transition model for patients with rheumatic diseases can be a useful tool in developing countries.

Development of tropical spastic paraparesis in human T-lymphotropic virus type 1 carriers is influenced by interleukin 28B gene polymorphisms.

Interleukin 28B (IL28B) rs12979860 polymorphisms were examined in 41 individuals with human T-lymphotrophic virus type 1 (HTLV-1). The alleles CT/TT were more frequent in 12 individuals with HTLV-1-associated myelopathy/tropical spastic paraparesis than in 29 asymptomatic carriers (80% vs 20%; P = .03), and median HTLV-1 proviral load was greater in CT/TT than CC carriers (P = .01). Thus, IL28B testing and closer follow-up of HTLV-1 asymptomatic CT/TT carriers is warranted.