Sex differences in the effectiveness and tolerability of dolutegravir plus rilpivirine as a switch strategy in people living with HIV.

INTRODUCTION: Dolutegravir + rilpivirine (DTG + RPV) is an effective antiretroviral therapy regimen approved in clinical guidelines as a switch therapy for virologically suppressed people with HIV. Our study aimed to compare the effectiveness and tolerability of DTG + RPV in women and men in real-world clinical practice. METHODS: This was a retrospective analysis of treatment-experienced people with HIV from a large HIV unit who switched to DTG + RPV. We analysed treatment effectiveness, rates of adverse events and discontinuation, and metabolic changes after 48 weeks of treatment. HIV-RNA levels <50 copies/mL were analysed at 48 weeks using both intention-to treat analysis (where missing data were interpreted as failures) and per-protocol analysis (excluding those with missing data or changes due to reasons other than virological failure). Outcomes were compared between women and men based on sex at birth. RESULTS: A total of 307 patients were selected (71 women and 236 men). No transgender people were included. At baseline, women had lived with HIV infection and received antiretroviral therapy for longer than men (23.2 vs 17.4 years and 18.9 vs 14.2 years, respectively). In the intention-to-treat analysis, 74.6% (95% confidence interval [CI] 63.4-83.3%) of women and 83.5% (95% CI 78.2-87.7) of men had HIV-RNA <50 copies/mL. In the per-protocol analysis, 96.4% (95% CI 87.7-99) of women and 99% (95% CI 98.9-99.7) of men had HIV-RNA levels <50 copies/mL. Two women and two men had HIV-RNA >50 copies/mL at 48 weeks. Discontinuation due to adverse events was more frequent in women than in men: 12.7% vs 7.2% (p < 0.02). Neuropsychiatric and gastrointestinal events were the most frequently reported. A median (interquartile range) weight gain of 1.9 kg (0-4.2) in women and 1.2 kg (-1-3.1) in men was reported (median of differences between baseline visit and week 48); the remaining changes in metabolic parameters were neutral. CONCLUSIONS: DTG + RPV exhibited good and similar virological effectiveness in women and men in real-world settings. However, poorer tolerability and more treatment interruptions were observed in women.

Broadly Neutralizing Antibodies for Human Immunodeficiency Virus Treatment: Broad in Theory, Narrow in Reality.

In this viewpoint, we briefly review the status of antiretroviral therapy (ART), its unmet needs, and the role that broadly neutralizing antibodies (bNAbs) might have in the near future for the treatment of human immunodeficiency virus (HIV). We summarize advances in the development of bNAbs as antiretroviral therapy, the results of main clinical trials of bNAbs for HIV treatment and prevention, and its role in cure trials. The limitations of broadly neutralizing antibodies are the current need for primary resistance testing, the still unclear number of antibodies that must be combined, the lack of penetration in anatomical reservoirs, and the role they might play in cure studies. We compare the advantages and disadvantages of "classical ART" and therapy based on broadly neutralizing antibodies. We conclude that broadly neutralizing antibodies still need considerable improvements before they can be considered an alternative to classical ART.

Effectiveness of the BNT162b2 mRNA Covid-19 vaccine in Spanish healthcare workers.

Introduction: Frontline health care workers (HCW) have higher risk than the general population to become infected by SARS.CoV.2, so they were a priority group for Covid-19 vaccine administration. We compared the incidence and prevalence of HCW infected pre-and post-vaccination with the BNT162b2 mRNA COVID-19 vaccine. Material and methods: Prospective observational study carried out between 01/12/20 and 07/03/21 in La Paz University Hospital, Madrid (Spain). SARS.CoV.2 positive cases in HCW after vaccination were collected and compared to those hospitalized COVID-19 patients at the same hospital. Results: Two weeks after finishing the first round of vaccinations daily new cases of HCW infections (symptomatic and asymptomatic) decreased substantially and cumulative cases of infected HCW and hospitalized COVID-19 patients started to diverge. No new positive cases of HCW infection were registered seven days after the second dose of BNT162b2 mRNA COVID-19 vaccine. Conclusions: BNT162b2 mRNA COVID-19 vaccine is highly effective in Spanish HCW.

Introducción: Los trabajadores sanitarios (TS) de primera línea tienen mayor riesgo de infectarse de SARS-CoV-2 que la población general, por lo que han sido un grupo prioritario para la vacunación frente a COVID-19. Comparamos la incidencia y prevalencia de TS infectados antes y después de la vacunación con BNT162b2 mRNA frente a COVID-19. Material y métodos: Estudio prospectivo observacional realizado entre 01 de diciembre de 2021 en el Hospital Universitario La Paz, Madrid, España. Se registraron los casos positivos para SARS-CoV-2 en TS y se compararon con los hospitalizados por COVID-19. Resultados: Dos semanas tras la primera ronda de vacunación las nuevas infecciones en TS (sintomáticas y asintomáticos) disminuyeron sustancialmente y los casos acumulados de TS infectados y pacientes hospitalizados por COVID-19 empezaron a divergir. No hubo nuevas infecciones en TS vacunados a los siete días de la segunda dosis de la vacuna. Conclusión: La vacuna BNT162b2 mRNA frente a SARS-CoV-2 es altamente eficaz en TS españoles.

[Treatment and prevention of monkeypox]. / Tratamiento y prevención de la viruela del mono.

Monkeypox is a zoonosis that is spread mainly through direct contact with fluids and skin lesions of infected people with vesicles still active. Although the virus was isolated for the first time in 1958 and the first human case was identified in a child in 1970, in the Democratic Republic of the Congo, the disease has progressively increased its incidence in Africa reaching in May 2022 sustained transmission outside this continent. As it is a newly introduced virus in our health system, it is necessary to learn the epidemiological pattern in a different environment from that of traditionally endemic areas and to know the available antiviral treatments, as well as the prophylactic measures that could be considered, knowing that as a virus emerging in our regions, scientific evidence is still limited. There are antivirals that have been shown, in animal models, to effectively combat the disease with very good clinical tolerance. This disease has also forced us to review the characteristics of smallpox vaccines, because they have shown a protective effect against monkeypox. For this reason, it is important to have a document that compiles all the scientific information published in this regard.

New Strategies of ARV: the Road to Simplification.

PURPOSE OF REVIEW: Simplification of antiretroviral therapy is a strategy aiming to reduce pill burden, drug interactions, and toxicity. This review focuses on the most recent and important studies evaluating a reduction on the number of drugs for HIV treatment, both in naive and virologically suppressed patients. RECENT FINDINGS: Interesting studies have been performed in the past years testing dual therapy and monotherapy, with variable rates of virological control. Novel therapeutics like immunotherapy or long-acting antiretrovirals can also be considered for simplification. Reducing the number of drugs for HIV treatment can be an option for selected patients. Current available evidence favors dual therapy over monotherapy. Future research should seek to identify the best candidates for simplification.

[Rabies: Epidemiological update and pre- and post-exposure management]. / Rabia: actualización epidemiológica y abordaje pre y postexposición.

Rabies is a deadly neurotropic viral infection but is preventable through vaccination. Its impact on human and animal health is often devastating. Despite advances in research and control of this disease, along with an effective vaccine, rabies continues to be a lingering threat in many parts of the world. Its high incidence reinforces the constant need to address it with scientific and public health measures. In this review article, we will explore the most important characteristics of the disease, its distribution, symptoms, prevention methods, and the global efforts that have been made to eradicate this deadly disease. The most recent research and advancements in the field of rabies will also be discussed in an effort to understand and combat this deadly disease more effectively.

Imported infectious diseases in migrants from Latin America: A retrospective study from a referral centre for tropical diseases in Spain, 2017-2022.

INTRODUCTION: Detecting imported diseases by migrants and individuals visiting friends and relatives (VFR) is key in the prevention and management of emergent infectious diseases acquired abroad. METHODS: Retrospective descriptive study on migrants and VFR from Central and South America between 2017 and 2022 attended at a National Referral Centre for Tropical Diseases in Madrid, Spain. Demographic characteristics, syndromes and confirmed travel-related diagnoses were obtained from hospital patient medical records. RESULTS: 1654 cases were registered, median age of 42 years, 69.1% were female, and 55.2% were migrants. Most cases came from Bolivia (49.6%), followed by Ecuador (12.9%). Health screening while asymptomatic (31.6%) was the main reason for consultation, followed by Chagas disease follow-up (31%). Of those asymptomatic at screening, 47,2% were finally diagnosed of any disease, mainly Chagas disease (19,7%) and strongyloidiasis (10,2%) CONCLUSION: Our study emphasizes the importance of proactive health screening to detect asymptomatic conditions in migrants and VFR, enabling timely intervention and improved health outcomes. By understanding the unique health profiles of immigrant populations, targeted public health interventions can be devised to safeguard the well-being of these vulnerable groups.

Epidemiological characteristic and prognosis changes in chronic hepatitis B in people living with HIV.

INTRODUCTION: Due to hepatitis B virus (HBV) treatment and vaccination during the last decades in Spain, epidemiological and prognosis of chronic hepatitis B (CHB) may have changed. METHODS: Retrospective review of CHB-HIV coinfected patients in a single reference center in Madrid until year 2019. We compared incidence, epidemiological and clinical characteristics according diagnosis period (before 2000, 2000-2004, 2005-2009, 2010-2014, 2015-2019). A retrospective longitudinal study was done to assess mortality, related risk factors and hepatic decompensation. RESULTS: Out of 5452 PLHIV, 160 had CHB (prevalence 2.92%; 95%CI 2.5-3.4), 85.6% were men, median age 32.1 (27-37.2). Incidence rate did not change over the years (2.4/100 patients-year). PLHIV with CHB diagnosed before year 2000 (n = 87) compared with those diagnosed between 2015 and 2019 (n = 11) were more often native-Spanish (90.8% vs. 18.2%), had infected using intravenous drugs (55.2% vs. 0), were coinfected with hepatitis C (40% vs. 9.1%) or hepatitis delta virus (30.4% vs. 0) and had more severe liver disease (cirrhosis 24.1% vs. 0). After a median follow-up of 20.4 years, 23 patients died (7.1/1000 patients-year) and 19 had liver decompensation (4.9/1000 patients-year). All deaths and liver decompensation occurred in patients diagnosed before year 2010. Mortality was associated with higher liver fibrosis in Fibroscan® (HR 1.06, 95% CI 1.03-1.09). CONCLUSION: The epidemiology of CHB in PLHIV in our cohort is changing with less native Spanish, more sexually transmitted cases and less coinfection with other hepatotropic virus. Patients diagnosed before 2010 have worst prognosis related to higher grades of liver fibrosis.

Effectiveness of the BNT162b2 mRNA Covid-19 vaccine in Spanish healthcare workers.

INTRODUCTION: Frontline health care workers (HCW) have higher risk than the general population to become infected by SARS.CoV.2, so they were a priority group for Covid-19 vaccine administration. We compared the incidence and prevalence of HCW infected pre-and post-vaccination with the BNT162b2 mRNA COVID-19 vaccine. MATERIAL AND METHODS: Prospective observational study carried out between 01/12/20 and 07/03/21 in La Paz University Hospital, Madrid (Spain). SARS.CoV.2 positive cases in HCW after vaccination were collected and compared to those hospitalized COVID-19 patients at the same hospital. RESULTS: Two weeks after finishing the first round of vaccinations daily new cases of HCW infections (symptomatic and asymptomatic) decreased substantially and cumulative cases of infected HCW and hospitalized COVID-19 patients started to diverge. No new positive cases of HCW infection were registered seven days after the second dose of BNT162b2 mRNA COVID-19 vaccine. CONCLUSIONS: BNT162b2 mRNA COVID-19 vaccine is highly effective in Spanish HCW.

Coronavirus-19 disease risk and protective factors associated with HLA/KIR polymorphisms in Ecuadorian patients residing in Madrid.

BACKGROUND: Immigrants represented 21.8% of cases in a Spanish cohort of hospitalised patients with COVID-19, a proportion exceeding the percentage of immigrants in that area's total population. Among the ethnic-related genetic risk factors for COVID-19, human leukocyte antigen (HLA) genotypes in diverse populations might bias the response to SARS-CoV-2 infection and/or progression. Similarly, genetic differences in natural killer-activating and inhibitory receptors could play a role in the immune system's response to the viral infection. METHODS: We characterised HLA alleles and KIR genes in 52 Ecuadorian patients hospitalised for moderate and severe COVID-19 and 87 Ecuadorian controls from the general population living in the same area. RESULTS: There was a significantly increased frequency of the HLA-B*39 antigen and the activating KIR2DS4 receptor in the presence of its HLA-C*04 ligand in the COVID-19 group when compared with the control group. In contrast, there was a significant reduction in the frequency of carriers of KIR2DL1 and of the KIR3DL1/Bw4 receptor/ligand combination among COVID-19 group. On the other hand, HLA-A*24:02 and HLA-DRB1*09:01 alleles showed significantly lower frequencies specifically in the severe COVID-19 group. CONCLUSION: HLA-B*39 alleles might be genetic risk factors for developing COVID-19 in Ecuadorian individuals. In the presence of its ligand C*04, the natural killer-activating receptor KIR2DS4 might also increase the risk of developing COVID-19, while, in the presence of HLA-Bw4 alleles, the inhibitory receptor KIR3DL1 might play a protective role. Patients with COVID-19 who carry HLA-A*24:02 and HLA-DRB1*09:01 alleles might be protected against more severe forms of COVID-19.

Treatment and prevention of monkeypox.

Monkeypox is a zoonosis that is spread mainly through direct contact with fluids and skin lesions of infected people with vesicles still active. Although the virus was isolated for the first time in 1958 and the first human case was identified in a child in 1970, in the Democratic Republic of the Congo, the disease has progressively increased its incidence in Africa reaching in May 2022 sustained transmission outside this continent. As it is a newly introduced virus in our health system, it is necessary to learn the epidemiological pattern in a different environment from that of traditionally endemic areas and to know the available antiviral treatments, as well as the prophylactic measures that could be considered, knowing that as a virus emerging in our regions, scientific evidence is still limited. There are antivirals that have been shown, in animal models, to effectively combat the disease with very good clinical tolerance. This disease has also forced us to review the characteristics of smallpox vaccines, because they have shown a protective effect against monkeypox. For this reason, it is important to have a document that compiles all the scientific information published in this regard.

No changes in hemostasis after COVID-19-heterologous vaccination schedule: A subanalysis of the phase 2 CombiVacS study.

Background: Several cases of unusual thrombotic events and thrombocytopenia were described after vaccination with recombinant adenoviral vectors encoding the spike protein antigen of SARS-CoV-2. Objectives: The objective of this study was to elucidate the impact of a COVID-19 heterologous vaccination schedule, including priming with adenovirus vaccine, on hemostasis profiles. Methods: The present study is a subanalysis of the CombiVacS clinical trial initiated in April 2021 that included adult participants previously vaccinated with a single dose of ChAdOx1-S. Between 8 and 12 weeks after vaccination, they were randomly assigned (2:1) to receive either BNT162b2 vaccine (intervention group, n = 99) or continue observation (control group, n = 50). Samples drawn before and 28 days after a vaccination with BNT162b2 were analyzed for platelet count and markers of hemostasis (D-dimer, anti-PF4 antibodies, cfDNA, PAI-1, thrombin generation, and serum capacity to activate platelets). Results: Platelet count from all participants after receiving BNT162b2 was within the normal range. Anti-PF4 antibodies were present in 26% and 18% of the subjects from the control and intervention groups, respectively, at day 28. In most cases, the levels of anti-PF4 antibodies were high before receiving BNT162b2. Serum from these participants did not activate platelets from healthy controls. There were no differences between the groups in PAI-1 and cfDNA plasma levels. According to the D-dimer plasma concentration, the thrombin generation test showed that none of the participants had a procoagulant profile. Conclusion: Our data suggest that the heterologous vaccination against COVID-19 with ChAdOx1-S and a second dose with BNT162b2 might be safe in terms of haemostasis.

Dengue outbreak amongst travellers returning from Cuba-GeoSentinel surveillance network, January-September 2022.

Increasing numbers of travellers returning from Cuba with dengue virus infection were reported to the GeoSentinel Network from June to September 2022, reflecting an ongoing local outbreak. This report demonstrates the importance of travellers as sentinels of arboviral outbreaks and highlights the need for early identification of travel-related dengue.

Virologic Response to Dolutegravir Plus Lamivudine in People With Suppressed Human Immunodeficiency Virus Type 1 and Historical M184V/I: A Systematic Literature Review and Meta-analysis.

Background: To investigate the impact of the M184V/I mutation on virologic response to dolutegravir plus lamivudine (DTG + 3TC) in suppressed-switch populations, a meta-analysis was performed using virologic outcomes from people with human immunodeficiency virus type 1 (PWH) with and without M184V/I before DTG + 3TC switch in real-world studies identified via systematic literature review. Sensitivity analyses were performed using data from PWH with M184V/I in interventional studies identified via targeted literature review. Methods: Single-arm meta-analyses using common- and random-effects models were used to estimate proportions of PWH with virologic failure (VF) among real-world populations with and without M184V/I and interventional study participants with M184V/I at 24, 48, and 96 weeks. Results: Literature reviews identified 5 real-world studies from 3907 publications and 51 abstracts meeting inclusion criteria and 5 interventional studies from 1789 publications and 3 abstracts. All time points had low VF incidence in PWH with M184V/I (real-world: 1.43%-3.81%; interventional: 0.00%) and without (real-world: 0.73%-2.37%). Meta-analysis-estimated proportions (95% confidence interval) with VF were low at weeks 24, 48, and 96, respectively, for PWH with M184V/I (real-world: 0.01 [.00-.04], 0.03 [.01-.06], and 0.04 [.01-.07]; interventional: 0.00 [.00-.02], 0.00 [.00-.01], and 0.00 [.00-.03]) and without (real-world: 0.00 [.00-.02], 0.02 [.01-.04], and 0.02 [.00-.05]). One real-world study (n = 712) reported treatment-emergent M184V at VF in 1 of 652 (0.15%) PWH without prior M184V/I. Conclusions: Results suggest that prior M184V/I has minimal impact on virologic suppression after switching to DTG + 3TC and provide reassurance when considering switching regimens in virologically suppressed PWH with incomplete treatment history or limited treatment options.

Pacemaker pocket infection by Nocardia carnea. First case description and literature review.

Acid-fast gram-positive bacilli are a seldom causal agent of cardiac implantable electronic devices (CIED) infections. A pacemaker pocket infection by Nocardia carnea is presented. The objective of this review is to know the incidence of pacemaker pocket infection by Nocardia and to collect information to contribute to the management of this infection. We describe both our case and those found in the literature. Only three cases were found. Two of the patients were older than 70 years without immunosuppression, presenting erythema at the pacemaker implantation site as main symptom. Bloodstream infection was registered in one of them. Three microorganisms were sensitive to cotrimoxazole. The minimum time of antibiotic therapy was 6 weeks. An incomplete device removal was done in one case, resulting in an unfavorable clinical course. The incidence of pacemaker pocket infection by these microorganisms is low, resolved in most cases with antibiotic treatment and device removal.

Long-term Evaluation of Residual Viremia in a Clinical Trial of Dolutegravir Plus Lamivudine as Maintenance Treatment for Participants With and Without Prior Lamivudine Resistance.

In this pilot clinical trial, we evaluated rates of residual replication in persons without lamivudine resistance-associated mutations in proviral DNA population sequencing who switched to dolutegravir plus lamivudine. After 144 weeks, there was no signal of changes in residual viremia based on qualitative detection methods, irrespective of past lamivudine resistance. Clinical Trials Registration. NCT03539224.

Risks and benefits of reducing the number of drugs to treat HIV-1 infection.

Introduction: Despite the efficacy and safety of antiretroviral therapy, new treatment options are needed to address the concerns of patients and physicians regarding long-term toxicities, costs, and convenience of lifelong antiretroviral therapy. To achieve this goal, one strategy is to reduce the number of drugs in the antiretroviral regimen.Areas covered: We review the recent evidence on the efficacy and safety of reduced drug regimens and their potential risks and benefits. There is currently strong evidence showing that some two-drug regimens have a comparable efficacy and short-term safety compared to standard three-drug regimens. The fixed-dose combination of dolutegravir/lamivudine is already an alternative for many treatment-naïve and virologically suppressed HIV-1 infected adults supported by large randomized clinical trials. The co-formulation dolutegravir plus rilpivirine is also a switch strategy for maintenance therapy. Long-acting injectable cabotegravir plus rilpivirine has already regulatory approval, and islatravir plus doravirine is an expected option in the near future. Some two-drug regimens have not been as successful.Expert opinion: Long-term safety issues of these two-drug regimens remain to be determined, but with the overwhelming evidence available in virological control and short-term safety, the potential benefits of some of these two-drug regimens appear to outweigh the risks.

Effectiveness of the BNT162b2 mRNA Covid-19 vaccine in Spanish healthcare workers.

INTRODUCTION: Frontline health care workers (HCW) have higher risk than the general population to become infected by SARS.CoV.2, so they were a priority group for Covid-19 vaccine administration. We compared the incidence and prevalence of HCW infected pre-and post-vaccination with the BNT162b2 mRNA COVID-19 vaccine. MATERIAL AND METHODS: Prospective observational study carried out between 01/12/20 and 07/03/21 in La Paz University Hospital, Madrid (Spain). SARS.CoV.2 positive cases in HCW after vaccination were collected and compared to those hospitalized COVID-19 patients at the same hospital. RESULTS: Two weeks after finishing the first round of vaccinations daily new cases of HCW infections (symptomatic and asymptomatic) decreased substantially and cumulative cases of infected HCW and hospitalized COVID-19 patients started to diverge. No new positive cases of HCW infection were registered seven days after the second dose of BNT162b2 mRNA COVID-19 vaccine. CONCLUSIONS: BNT162b2 mRNA COVID-19 vaccine is highly effective in Spanish HCW.