Characteristics and rates of infection by HIV in people receiving non-occupational post-exposure prophylaxis (nPEP) against HIV.

INTRODUCTION/OBJECTIVES: The use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary data regarding adherence to this treatment, its effectiveness and tolerance. Our study aims to delve into these factors among individuals who have resorted to nPEP after high-risk sexual encounters. METHODS: We conducted a retrospective observational study of cases administered nPEP for HIV from 1 January 2018 to 31 December 2021 at a tertiary hospital in Madrid. The study included all adults over 18 years who sought care at the emergency department of the Fundación Jiménez Díaz Hospital following a risky sexual encounter and were subsequently recommended HIV nPEP treatment. RESULTS: 878 individuals received nPEP for HIV and underwent initial serological tests. Of these, 621 had comprehensive follow-ups. The prescribed regimen for all was raltegravir (RAL) 1200 mg combined with tenofovir/emtricitabine (TDF/FTC) 245/200 mg daily for 28 days. The study revealed a 1.1% rate (n=10) of previously undetected infection and a 0.16% (n=1) failure rate of nPEP. Regarding regimen tolerability, 5.6% (n=35) experienced symptoms linked to the treatment, yet none necessitated discontinuation of the regimen. On the contrary, six per cent (n=53) reported symptoms consistent with an STI during one of the medical visits; specifically, 4.4% had urethritis, and 1.6% had proctitis. CONCLUSION: nPEP with RAL/TDF/FTC demonstrates high efficacy and safety, contingent on proper adherence. There is an observed increase in STI prevalence in this cohort, with nearly half of the participants not engaging in appropriate follow-up after initiating nPEP.

A specific natural killer cells phenotypic signature associated to long term elite control of HIV infection.

Elite controllers (ECs) are an exceptional group of people living with HIV (PLWH) that control HIV replication without therapy. Among the mechanisms involved in this ability, natural killer (NK)-cells have recently gained much attention. We performed an in-deep phenotypic analysis of NK-cells to search for surrogate markers associated with the long term spontaneous control of HIV. Forty-seven PLWH (22 long-term EC [PLWH-long-term elite controllers (LTECs)], 15 noncontrollers receiving antiretroviral treatment [ART] [PLWH-onART], and 10 noncontrollers cART-naïve [PLWH-offART]), and 20 uninfected controls were included. NK-cells homeostasis was analyzed by spectral flow cytometry using a panel of 15 different markers. Data were analyzed using FCSExpress and R software for unsupervised multidimensional analysis. Six different subsets of NK-cells were defined on the basis of CD16 and CD56 expression, and the multidimensional analysis revealed the existence of 68 different NK-cells clusters based on the expression levels of the 15 different markers. PLWH-offART presented the highest disturbance of NK-cells homeostasis and this was not completely restored by long-term ART. Interestingly, long term spontaneous control of HIV (PLWH-LTEC group) was associated with a specific profile of NK-cells homeostasis disturbance, characterized by an increase of CD16dimCD56dim subset when compared to uninfected controls (UC) group and also to offART and onART groups (p < 0.0001 for the global comparison), an increase of clusters C16 and C26 when compared to UC and onART groups (adjusted p-value < 0.05 for both comparisons), and a decrease of clusters C10 and C20 when compared to all the other groups (adjusted p-value < 0.05 for all comparisons). These findings may provide clues to elucidate markers of innate immunity with a relevant role in the long-term control of HIV.

Efficacy and safety of switching to dolutegravir/lamivudine in virologically suppressed people with HIV-1 aged ≥ 50 years: week 48 pooled results from the TANGO and SALSA studies.

BACKGROUND: As the population of people with HIV ages, concerns over managing age-related comorbidities, polypharmacy, immune recovery, and drug-drug interactions while maintaining viral suppression have arisen. We present pooled TANGO and SALSA efficacy and safety results dichotomized by age (< 50 and ≥ 50 years). METHODS: Week 48 data from the open-label phase 3 TANGO and SALSA trials evaluating switch to once-daily dolutegravir/lamivudine (DTG/3TC) fixed-dose combination vs continuing current antiretroviral regimen (CAR) were pooled. Proportions of participants with HIV-1 RNA ≥ 50 and < 50 copies/mL (Snapshot, intention-to-treat exposed) and safety were analyzed by age category. Adjusted mean change from baseline in CD4 + cell count was assessed using mixed-models repeated-measures analysis. RESULTS: Of 1234 participants, 80% of whom were male, 29% were aged ≥ 50 years. Among those aged ≥ 50 years, 1/177 (< 1%) DTG/3TC participant and 3/187 (2%) CAR participants had HIV-1 RNA ≥ 50 copies/mL at 48 weeks; proportions with HIV-1 RNA < 50 copies/mL were high in both treatment groups (≥ 92%), consistent with overall efficacy and similar to observations in participants aged < 50 years (≥ 93%). Regardless of age category, CD4 + cell count increased or was maintained from baseline with DTG/3TC. Change from baseline in CD4 + /CD8 + ratio was similar across age groups and between treatment groups. One CAR participant aged < 50 years had confirmed virologic withdrawal, but no resistance was detected. In the DTG/3TC group, incidence of adverse events (AEs) was similar across age groups. Proportions of AEs leading to withdrawal were low and comparable between age groups. Although drug-related AEs were generally low, across age groups, drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR. While few serious AEs were observed in both treatment groups, more were reported in participants aged ≥ 50 years vs < 50 years. CONCLUSIONS: Among individuals with HIV-1, switching to DTG/3TC maintained high rates of virologic suppression and demonstrated a favorable safety profile, including in those aged ≥ 50 years despite higher prevalence of concomitant medication use and comorbidities. TRIAL REGISTRATION NUMBER: TANGO, NCT03446573 (February 27, 2018); SALSA, NCT04021290 (July 16, 2019).

Discovery of circulating miRNAs as biomarkers of chronic Chagas heart disease via a small RNA-Seq approach.

Chagas disease affects approximately 7 million people worldwide in Latin America and is a neglected tropical disease. Twenty to thirty percent of chronically infected patients develop chronic Chagas cardiomyopathy decades after acute infection. Identifying biomarkers of Chagas disease progression is necessary to develop better therapeutic and preventive strategies. Circulating microRNAs are increasingly reliable biomarkers of disease and therapeutic targets. To identify new circulating microRNAs for Chagas disease, we performed exploratory small RNA sequencing from the plasma of patients and performed de novo miRNA prediction, identifying potential new microRNAs. The levels of the new microRNAs temporarily named miR-Contig-1519 and miR-Contig-3244 and microRNAs that are biomarkers for nonchagasic cardiomyopathies, such as miR-148a-3p and miR-224-5p, were validated by quantitative reverse transcription. We found a specific circulating microRNA signature defined by low miR-Contig-3244, miR-Contig-1519, and miR-148a-3 levels but high miR-224-5p levels for patients with chronic Chagas disease. Finally, we predicted in silico that these altered circulating microRNAs could affect the expression of target genes involved in different cellular pathways and biological processes, which we will explore in the future.

Increased Prevalence of Symptomatic Human Intestinal Spirochetosis in MSM with High-Risk Sexual Behavior in a Cohort of 165 Individuals.

Human intestinal spirochetosis (HIS) can cause gastrointestinal symptoms, although asymptomatic infections have been described. Individuals from low-income countries, people living with HIV, and men who have sex with men (MSM) show increased risk. A retrospective review of all patients diagnosed with HIS (n = 165) between January 2013 and October 2020 at a tertiary hospital in Madrid, Spain, was performed to assess risk factors for symptomatic HIS, symptoms, and response to treatment. Most patients were male (n = 156; 94.5%), 86.7% were MSM, and 23.5% practiced chemsex, of whom most were symptomatic (p = 0.039). Most patients (78.4%) reported unprotected oral-anal intercourse. A total of 124 (81.1%) were symptomatic; diarrhea was the most common complaint (68.3%). Multivariable regression showed increased odds of symptoms associated with age under 41 (odds ratio 5.44, 95% CI 1.87-15.88; p = 0.002). Colonoscopy was normal in 153 (92.7%). Furthermore, 66.7% presented previous or concomitant sexually transmitted diseases (STDs). Among the patients, 102 underwent testing for other gastrointestinal pathogens, with positive results in 20 (19.6%). All symptomatic patients without concomitant gastrointestinal infection presenting improvement on follow-up (42 of 53) had received either metronidazole or doxycycline (p = 0.049). HIS should be considered as a cause of chronic diarrhea in MSM with high-risk sexual behavior after other causes have been ruled out; treatment with metronidazole is recommended. Coinfection with other STDs is common.

Diagnosis and Management of Adult Tuberculosis Patients Admitted to a Rural Hospital in Ethiopia.

Background  Ethiopia is one of the countries in the world with the highest rate of tuberculosis (TB). The aim of this study is to describe the characteristics of the patients with TB admitted to a rural hospital in Ethiopia in terms of both diagnosis and clinical management. Methods A retrospective descriptive observational study was conducted. Data were collected from patients older than 13 years who were admitted to the Gambo General Hospital for TB between May 2016 and September 2017. The variables studied were age, sex, symptoms, human immunodeficiency virus (HIV) serology, nutritional status, presence of anemia, chest x-ray or other complementary tests, type of diagnosis (smear microscopy, Xpert MTB-RIF (Cepheid, Sunnyvale, California, USA), or clinical diagnosis), treatment received, outcome, and days of admission. Results One hundred eighty-six patients, aged 13 years and older, were admitted to the TB unit. About 51.6% were female, and the median age was 35 years (interquartile range (IQR) 25-50). Cough was the most frequent symptom on admission (88.7%), and contact with a TB patient was only recognized by 22 patients (11.8%). HIV serology was performed in 148 patients (79.6%); seven were positive (4.7%). About 69.3% met the criteria for malnutrition (body mass index (BMI) <18.5). Most patients, 173 (93%), presented with pulmonary TB and were new cases (94.1%). Patients were diagnosed by clinical parameters in 75% of cases. Smear microscopy was performed in 148 patients, of which 46 (31.1%) were positive, and Xpert MTB-RIF results were only obtained in 16 patients, of which 6 (37.5%) were positive. Chest x-rays were performed in most patients (71%) and were suggestive of TB in 111 (84.1%). The average length of hospital stay was 32 days (confidence interval (CI) 13-50.5). Women tend to be younger than men, have more extrapulmonary TB, and were admitted longer. Nineteen patients died during admission (10.2%). Patients who die were more frequently malnourished (92.9% of those who die were malnourished compared to 67.1% of those who did not die, p = 0.036), tend to be admitted for a shorter time than the survivors and receive more concomitant antibiotic treatment. Conclusions In this rural Ethiopian setting, patients admitted to the hospital for TB are often malnourished (67.1%), the main presentation is pulmonary, mortality is one in 10 admissions and very often receive antibiotics in association with TB treatment (40%).

Limitaciones del ensayo Xpert-MTB/RIF® en el diagnóstico inicial de tuberculosis en el contexto de un hospital rural en Etiopia / Limitations of the Xpert-MTB/RIF® assay in the initial diagnosis of tuberculosis in the context of a rural hospital in Ethiopia

Introducción. Evaluar la implantación del Xpert-MTB/RIF®, como técnica de diagnóstico precoz, en una zona rural de Etiopía. Material y métodos. Se recogieron retrospectivamente los datos de aquellos pacientes mayores de 13 años a los que se solicitó la prueba Xpert MTB/RIF® en un hospital rural situado a 45 km del laboratorio de referencia, durante los 3 primeros años de su implantación (abril 2015-abril 2018). Resultados. Se evaluaron 306 pacientes mayores de 13 años, en 85 (27,8%) hubo un error en el procesamiento de la prueba y no se obtuvo el resultado. De las 221 muestras con resultados, la mediana de tiempo entre la obtención de la muestra y la recepción del resultado fue de 21 días y 42 de ellas fueron positivas (19%, IC 95%: 14,2-24,9%). La muestra de mayor rentabilidad diagnóstica fue la adenopatía (88,8%; [8/9];p<0.001). Conclusiones. Hay más diagnósticos bacteriológicos con Xpert-MTB/RIF®, pero con una tardanza en obtener el resultado y no se logra su principal objetivo que es diagnóstico precoz. (AU)

Introduction. To evaluate the implementation of Xpert-MTB/RIF®, as an early diagnosis technique, in a rural area of Ethiopia. Material and methods. Data were retrospectively collected from those patients over 13 years of age who were requested to take the Xpert MTB/RIF® test in a rural hospital located 45 km from the reference laboratory, during the first 3 years of its implementation (2015, April -2018, April). Results. A total of 306 patients older than 13 years were evaluated, in 85 (27.8%) there was an error in the processing of the test and the result was not obtained. Of the 221 samples with results, the median time between obtaining the sample and receiving the result was 21 days and 42 of them were positive (19%, 95% CI: 14.2-24.9%). The sample with the highest diagnostic yield was adenopathy (88.8%; [8/9]; p<0.001). Conclusions. There are more bacteriological diagnoses with Xpert-MTB/RIF®, but with a delay in obtaining the result and its main objective, which is early diagnosis, is not achieved. (AU)

48-Week effectiveness and tolerability of dolutegravir (DTG) + lamivudine (3TC) in antiretroviral-naïve adults living with HIV: A multicenter real-life cohort.

BACKGROUND: The main international guidelines indicate DTG/3TC therapy as one of the preferred regimens for people living with HIV (PLWH), due to its observed efficacy in randomized clinical trials. However, information in real-life cohorts is relatively scarce for first-line use. METHODS: A retrospective multicenter study of adult PLWH starting DTG+3TC as a first-line regimen before January 31st, 2020. Virological failure (VF) was defined as 2 consecutive HIV RNA viral load (VL) >50 copies/mL. RESULTS: 135 participants were included. Treatment was started without knowing baseline drug resistance testing (bDRT) results in 71.9% of cases, with baseline resistance mutations being later confirmed in 17 patients (12.6%), two of them with presence of M184V mutation. Effectiveness at week 48 was 85.2% (CI95%: 78.1-90.7%) (ITT missing = failure [M = F]) and 96.6% (CI 95%: 91.6-99.1%) (per-protocol analysis). Six patients (4.4%) discontinued treatment. One developed not confirmed VF after discontinuing treatment due to poor adherence; no resistance-associated mutations emerged. Three discontinued treatments due to central nervous system side effects (2.2%), and two due to a medical decision after determining the M184V mutation in bDRT. Finally, 14 (10.4%) were lost to follow-up, most of them due to the COVID-19 pandemic. CONCLUSIONS: In a real-life multicenter cohort of ART-naïve PLWH, treatment initiation with DTG + 3TC showed high effectiveness and favorable safety results, comparable to those of randomized clinical trials, without treatment-emergent resistance being observed through week 48. Starting treatment before receiving the results of baseline drug resistance testing did not have an impact on the regimen's effectiveness.

Silver Nanoparticles Produced by Laser Ablation and Re-Irradiation Are Effective Preventing Peri-Implantitis Multispecies Biofilm Formation.

Implant-associated infection due to biofilm formation is a growing problem. Given that silver nanoparticles (Ag-NPs) have shown antibacterial effects, our goal is to study their effect against multispecies biofilm involved in the development of peri-implantitis. To this purpose, Ag-NPs were synthesized by laser ablation in de-ionized water using two different lasers, leading to the production of colloidal suspensions. Subsequently, part of each suspension was subjected to irradiation one and three times with the same laser source with which it was obtained. Ag-NPs were immobilized on the surface of titanium discs and the resultant materials were compared with unmodified titanium coupons. Nanoparticles were physico-chemically analysed to determine their shape, crystallinity, chemical composition, and mean diameter. The materials were incubated for 90 min or 48 h, to evaluate bacterial adhesion or biofilm formation respectively with Staphylococcus aureus or oral mixed bacterial flora composed of Streptococcus oralis, Actinomyces naeslundii, Veionella dispar, and Porphyromonas gingivalis. Ag-NPs help prevent the formation of biofilms both by S. aureus and by mixed oral bacterial flora. Nanoparticles re-irradiated three times showed the biggest antimicrobial effects. Modifying dental implants in this way could prevent the development of peri-implantitis.

High frequency of CD8 escape mutations in elite controllers as new obstacle for HIV cure.

Accumulation of mutations in epitopes of cytolytic-T-lymphocytes immune response (CTL) in HIV-reservoir seems to be one of the reasons for shock-and-kill strategy failure. Ten non-controller patients on successful cART (TX) and seven elite controllers (EC) were included. HIV-Gag gene from purified resting memory CD4+ T-cells was sequenced by Next-Generation-Sequencing. HLA class-I alleles were typed to predict optimal HIV-Gag CTL epitopes. For each subject, the frequency of mutated epitopes in the HIV-Gag gene, the proportion of them considered as CTL-escape variants as well as their effect on antigen recognition by HLA were assessed. The proportion (%) of mutated HIV-Gag CTL epitopes in the reservoir was high and similar in EC and TX (86%[50-100] and 57%[48-82] respectively, p=0.315). Many of them were predicted to negatively impact antigen recognition. Moreover, the proportion of mutated epitopes considered to be CTL-escape variants was also similar in TX and EC (77%[49-92] vs. 50%[33-75] respectively, p=0.117). Thus, the most relevant finding of our study was the high and similar proportions of HIV-Gag CTL-escape mutations in the reservoir of both HIV-noncontroller patients with cART (TX) and patients with spontaneous HIV-control (EC). Our findings suggest that escape mutations of CTL-response may be another obstacle to eliminate the HIV reservoir and constitute a proof of concept that challenges HIV cure strategies focused on the reactivation of reservoirs. Due to the small sample size that could impact the robustness of the study, further studies with larger cohorts of elite controller patients are needed to confirm these results.

El código postal como “código de barras” de las resistencias antimicrobianas / The postal code as a “bar code” of antimicrobial resistance

Introducción. La necesidad de integrar en la práctica clínica las resistencias locales es cada vez más urgente, especialmente en Atención Primaria, donde el tratamiento empírico es frecuente. Material y métodos. Se desarrolló un estudio retrospectivo observacional en el área de salud de Alcalá de Henares de los aislados microbiológicos positivos de Neisseria gonorrhoeae de cualquier localización (uretral, cervical, faríngea, rectal u orina). Se analizaron características sociodemográficas y resistencias a cefalosporinas, azitromicina, penicilina y quinolonas. Se relacionó cada aislado con su código postal de procedencia. Resultados. Se analizaron 256 muestras microbiológicas de N. gonorrhoeae, la mayoría pertenecientes a hombres (92,9%) con edad media de 33 años. La mitad de las muestras (49,8%) fueron resistentes a ciprofloxacino. La evolución temporo-espacial de las resistencias antimicrobianas se integró en mapas de calor con los códigos postales con más resistencias. Conclusión. Conocer las resistencias locales puede ayudar a pautar tratamientos empíricos más adecuados, especialmente en Atención Primaria, evitando la utilización de antibióticos inadecuados y disminuyendo las tasas de resistencias. (AU)

Introduction. The need to integrate local resistances into clinical practice is increasingly urgent, especially in Primary Care where empirical treatment is frequent. Methods. A retrospective observational study of positive microbiological isolates of Neisseria gonorrhoeae from any location (urethral, cervical, pharyngeal, rectal or urine) was carried out in the health area of Alcalá de Henares. Sociodemographic characteristics and resistance to cephalosporins, azithromycin, penicillin and quinolones were analyzed. Each isolate was related to its postal code of origin. Results. We analyzed 256 microbiological samples of N.gonorrhoeae, most of them male (92.9%) with a mean age of 33 years. Half of the samples (49.8%) were resistant to ciprofloxacin. Temporal and spatial evolution of antimicrobial resistance was integrated in heat maps. Conclusion. Knowing local resistances can help to prescribe more adequate empirical treatments, especially in Primary Care, avoiding inadequate antibiotics and decreasing resistance rates. (AU)

Changes in Quality of Sleep, Mood, and Other Neuropsychiatric Symptoms After Switching Dolutegravir/Lamivudine/Abacavir to Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in a Randomized Study of People With Human Immunodeficiency Virus With Poor Sleep Quality: GESIDA 10418.

Background: Although switching antiretroviral therapy (ART) in people with human immunodeficiency virus experiencing insomnia due to dolutegravir-related neurotoxicity is well founded upon evidence, there is a lack of proof in regard to the outcome of stopping dolutegravir-based ART in people without insomnia but reporting poor sleep quality. Methods: This is a randomized, multicenter, open-label study to evaluate the reversibility of patient-reported sleep disturbances in patients on dolutegravir/lamivudine/abacavir without insomnia after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants were randomized to switch ART at baseline or at week 4 and then completed 8 weeks of darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Our primary objective was to compare changes in sleep quality between arms at week 4. Secondary objectives were to compare changes in mood and neuropsychiatric symptoms (NS) at week 4 and 4 and 8 weeks after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. The participants completed a survey, including the Pittsburgh Sleep Quality Index (PSQI), the Hospital Anxiety and Depression scale (HADS), and specific questions to explore NS, at each visit to assess those objectives. Results: We included 72 participants. The results show that study arms were similar at baseline; however, at week 4, PSQI scores remained unchanged with dolutegravir/lamivudine/abacavir, whereas patients improved significantly after switching to darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Similar differences between arms were also observed in HADS and NS changes. At weeks 4 and 8 after all participants switched to darunavir/cobicistat/emtricitabine/tenofovir alafenamide, we have observed significant improvements in PSQI and HAD scores and in NS. Conclusions: In patients reporting subclinical sleep disturbances without insomnia, switching from dolutegravir/lamivudine/abacavir to darunavir/cobicistat/emtricitabine/tenofovir alafenamide was associated with better sleep quality and improvements in mood and NS.

Impact of Xpert MTB/RIF in the Diagnosis of Childhood Tuberculosis in Rural Ethiopia.

BACKGROUND: This study assesses the impact of the Xpert MTB/RIF in the diagnosis of childhood tuberculosis (TB) in a rural hospital in a resource-constrained setting. METHODS: Retrospective cross-sectional study in children evaluated for presumptive TB from 1 June 2016 to 31 May 2017 at the Gambo General Hospital in rural Southern Ethiopia. Children were evaluated according to a defined protocol based on national guidelines. Samples were submitted for Xpert MTB/RIF assay to the nearest reference laboratory. RESULTS: Of the 201 children assessed for presumptive TB, 46.3% (93/201) were diagnosed with TB. Of these, 49.5% (46/93) were microbiologically confirmed, mostly by Xpert MTB/RIF (only one patient was diagnosed by smear alone). The rest were clinically diagnosed. Microbiologically confirmed patients had a higher mean age, longer duration of fever and cough and lymphadenopathy more frequently than those clinically diagnosed. Gastric aspirates were Xpert MTB/RIF-positive in 18.2% of the samples (26/143); none were smear-positive (0/140). Sputum samples were Xpert MTB/RIF-positive in 27.1% (13/35) of the samples and smear-positive in 8.6% (3/35). There were no HIV-positive patients and just one case of rifampicin-resistant TB. A long delay (median 15 days) was detected in returning the results. CONCLUSION: Xpert MTB/RIF serves as an important adjunctive test for diagnosing childhood TB in rural settings, with microbiological confirmation in up to half the TB cases. Processes need to be optimized to achieve an early diagnosis. The diagnosis of childhood TB in high-burden countries such as Ethiopia still relies largely upon diagnostic algorithms and the clinician's skills.Lay summaryWorld Health Organization recommends the use of Xpert MTB/RIF to improve the microbiological diagnosis of childhood tuberculosis (TB) since 2014, but the impact of this test under real conditions in rural areas of low-income countries is not clear. We conducted a cross-sectional study in children evaluated for presumptive TB from 1 June 2016 to 31 May 2017 at the Gambo General Hospital in rural Southern Ethiopia. Children were evaluated according to a clinical protocol based on national guidelines and samples were submitted for Xpert MTB/RIF assay to the nearest reference laboratory.Of the 201 children assessed, 46.3% (93/201) were diagnosed with tuberculosis. Of these, 48.4% (45/93) were microbiologically confirmed by Xpert MTB/RIF [smear microscopy only diagnosed the 5.4% (5/93)]. Patients with microbiologically confirmed tuberculosis had a higher mean age, longer duration of fever and cough and had lymphadenopathy more frequently than those clinically diagnosed. A long delay in returning the results (median 15 days) was detected. Xpert MTB/RIF serves as an important test for diagnosing childhood TB in rural settings, with microbiological confirmation in up to half the cases. Processes need to be optimized to achieve an early diagnosis. The diagnosis of childhood TB in high-burden countries still relies largely upon diagnostic algorithms and the clinician's skills.

Past and future of HIV infection. A document based on expert opinion / Pasado y futuro de la infección por VIH. Un documento basado en la opinión de expertos

HIV infection is now almost 40 years old. In this time, along with the catastrophe and tragedy that it has entailed, it has also represented the capacity of modern society to take on a challenge of this magnitude and to transform an almost uniformly lethal disease into a chronic illness, compatible with a practically normal personal and relationship life. This anniversary seemed an ideal moment to pause and reflect on the future of HIV infection, the challenges that remain to be addressed and the prospects for the immediate future. This reflection has to go beyond merely technical approaches, by specialized professionals, to also address social and ethical aspects. For this reason, the Health Sciences Foundation convened a group of experts in different aspects of this disease to discuss a series of questions that seemed pertinent to all those present. Each question was presented by one of the participants and discussed by the group. The document we offer is the result of this reflection. (AU)

La infección por VIH cumple ahora casi 40 años de existencia. En este tiempo, junto a la catástrofe y la tragedia que ha supuesto, ha representado también la capacidad de la sociedad moderna de asumir un reto de esta magnitud y de transformar, gracias al tratamiento antirretroviral, una enfermedad mayoritariamente letal en una enfermedad crónica, compatible con una vida personal y de relación prácticamente normales. Este aniversario parecía un momento idóneo para pararse a reflexionar sobre el futuro de la infección VIH, los retos que todavía quedan por abordar y las perspectivas para el inmediato futuro. Esa reflexión tiene que ir más allá de planteamientos meramente técnicos, de profesionales especializados, para abordar aspectos sociales y éticos. Por este motivo, la Fundación de Ciencias de la Salud convocó a un grupo de expertos en distintos aspectos de esta infección para discutir una serie de preguntas que parecieron pertinentes a todos los convocados. Cada pregunta era expuesta por uno de los participantes y discutida por el grupo. El documento que ofrecemos es el resultado de esa reflexión. (AU)

Initiation of antiretroviral therapy in treatment-naive adults with HIV infection at the first specialist appointment.

BACKGROUND: Fast initiation of ART has been associated with higher rates of retention in HIV care and viral suppression at 48 weeks and with lower mortality rates. However, scarce evidence exists in our setting, where diagnosis and treatment are carried out in different contexts. METHODS: An observational retrospective study evaluating efficacy and safety of ART prescribed at the first specialist appointment, without baseline laboratory data, in a tertiary hospital in downtown Madrid. Individuals with a new diagnosis of HIV infection who initiated treatment at their first appointment with an infectious diseases specialist before receiving baseline laboratory results were included, irrespective of the ART regimen chosen. RESULTS: One hundred and eight participants were included. The majority (99.1%) were MSM who had acquired infection during sexual intercourse. The efficacy of ART, without baseline laboratory results at the time of initiation, was 85.2% (92/108) in the ITT analysis and 91.7% (99/108) in the treatment-related discontinuation equals failure analysis. All but nine patients presented an undetectable viral load (<50 copies/mL) at 48 weeks from starting ART. No serious adverse effects associated with the strategy were observed. In total, 101 participants continued care at 48 weeks with retention in HIV care rate of 93.5% (101/108). CONCLUSIONS: Initiating ART at the first available opportunity without baseline laboratory data does not reduce efficacy or safety of ART and achieves rapid virological control with high rates of retention in HIV care.

HIV-reservoir size is not affected either by HCV coinfection or by direct acting antivirals (DAAs) therapy.

The role of HCV on the HIV reservoir is controversial since the reduction on HIV-DNA levels after HCV eradication with IFNα/RBV treatment seems to be the result of drugs instead of HCV clearance. We assessed whether HCV eradication can decrease HIV-DNA content in HIV/HCV-coinfected patients treated with direct-acting antivirals, DAAs (IFNα/RBV-free regimens). Cell-associated HIV-DNA was measured by ddPCR in 25 HIV-monoinfected and 25 HIV/HCV-coinfected patients. There were no differences in HIV-DNA levels between groups neither at baseline nor at 12 weeks after DAAs treatment completion. Our results indicate that HCV does not appear to influence the HIV reservoir size and suggest the lack of an anti-HIV action for DAAs.

Epidemiologic and Economic Analysis of Rapid Antiretroviral Therapy Initiation with Bictegravir/Emtricitabine/Tenofovir Alafenamide in Spain.

OBJECTIVE: This study aimed to assess the potential epidemiological and economic impact of rapid initiation of human immunodeficiency virus (HIV) treatment with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) on HIV transmission compared with the current initiation observed in clinical practice in Spain. METHODS: A transmission model was adapted to estimate the cumulative HIV infection incidence and potential cost savings based on the number of HIV infections prevented among men who have sex with men, heterosexual males and females, and people who inject drugs (PWID) over a 20-year time horizon. The analysis compared rapid antiretroviral therapy (ART) initiation with B/F/TAF (9 days from diagnosis until treatment initiation) versus current ART initiation practice (with an average of 35 days from diagnosis to treatment). People living with HIV were distributed according to their treatment status. Risk for transmission was assigned to undiagnosed, diagnosed in care and not receiving ART, and receiving ART but virally unsuppressed, which was estimated by sexual contact, needles and syringes shared among PWID, state of HIV infection, and ART use. RESULTS: In the base-case analysis, rapid ART initiation with B/F/TAF is expected to prevent 992 new HIV infections over the next 20 years compared with current ART initiation practices. Considering the lifetime costs of treating HIV infection, the reduction in HIV incidence could result in potential cost savings of €323 million. CONCLUSIONS: These results suggest that rapid ART initiation with B/F/TAF in newly diagnosed patients with HIV is a high-value strategy for the Spanish National Health System and society, reducing HIV incidence and thereby reducing future related direct and indirect costs of care.

Un paciente con mal de Pott / A patient with Pott’s disease

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Bone Deleterious Effects of Different NRTIs in Treatment-naïve HIV Patients After 12 and 48 Weeks of Treatment.

BACKGROUND: Bone alterations have been observed in the course of HIV infection, characterized by a marked decrease in bone mineral density (BMD) and an increase in the frequency of fractures as a result of fragility. We aim to evaluate early changes in bone metabolic profile and the possible association with tenofovir and other nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs) in treatment-naïve HIV patients. METHODS: We conducted a prospective study in naïve HIV-infected adults (under 50 years), separated into three groups according to NRTI therapy: tenofovir disoproxil fumarate (TDF); tenofovir alafenamide (TAF) and abacavir (ABC). BMD and epidemiological, immunological and metabolic bone parameters were evaluated. Bone markers were analyzed in plasma at baseline, 12 and 48 weeks after initiating treatment. RESULTS: Average age of patients was 34.8 years (± 9.6). 92.4% of them with CD4 count > 200 cel/µL. At week 12 after starting treatment, both TDF [increase in PN1P (31.7%, p = 0.004), TRAP (11.1%, p = 0.003), OPN (19.3%, p = 0.045) and OC (38.6%, p = 0.001); decrease in OPG (-23.4%, p = 0.003)] and TAF [increase in 42.6% for CTX (p = 0.011), 27.3% for OC (p = 0.001) and 21% for TRAP (p = 0.008); decrease in OPG (-28.8%, p = 0.049)] presented a deep resorption profile compared to ABC, these differences in bone molecular markers, a tendency to equalize at week 48, where no significant differences were observed. Patients treated with TDF showed the greatest decrease in Z-score in both lumbar spine (LS) and femoral neck (FN) at week 48 without statistically significant differences. CONCLUSION: Treatment-naïve HIV patients have a high prevalence of low bone density. Treatment with TDF is associated with greater bone deterioration at 12 and 48 weeks. TAF seems to present similar early bone deterioration at 12 weeks which disappears at 48 weeks.