Effectiveness of trichloroacetic acid versus electrocautery for the treatment of anal high-grade squamous intraepithelial lesions in persons with HIV.

PURPOSE: This study aimed to compare trichloroacetic acid (TCA) versus electrocautery (ECA) for the treatment of anal high-grade squamous intraepithelial lesions (HSIL). METHODS: This is an observational, single-center study. All subjects with HIV who had anal HSIL treated with TCA or ECA from 2010 to 2022 were included. Effectiveness was evaluated by on-treatment analysis, defining response as the resolution of HSIL and recurrence as a new diagnosis of HSILs during follow-up. A propensity score analysis was used to adjust for confounding factors. RESULTS: In total, 227 and 260 HSIL episodes were treated with ECA and TCA, respectively. Response was observed in 61.7% (95% CI: 55.3-68) of cases treated with ECA and in 73.1% (95% CI: 67.8-78.5) with TCA (p = .004). The effectiveness of TCA was higher in large and multifocal HSILs. Side effects were common with both treatments, but no serious events were described. Tolerability was good in 77.1% and 80.7% of patients treated with ECA and TCA, respectively. At 24 months, recurrent HSIL were observed in 36.3% (95% CI: 27.3-45) and 28% (95% CI: 20.2-35.8) in the ECA and TCA groups (p = .049). A nadir CD4 cell count ≤200 cells/µl was found to be a risk factor for recurrence (OR: 1.77; 95% CI: 1.12-2.78). CONCLUSIONS: In this study, treatment with TCA showed high effectiveness, low recurrence and good tolerability. Considering the benefits of TCA, it could be considered one of the first-line treatments for anal HSIL.

Impact of viral detection in patients with community-acquired pneumonia: An observational cohort study / Impacto de la detección viral en pacientes con neumonía comunitaria: estudio de cohortes observacional

Purpose The presence of a respiratory virus in patients with community-acquired pneumonia (CAP) may have an impact on the bacterial etiology and clinical presentation. In this study we aimed to assess the role of viral infection in the bacterial etiology and outcomes of patients with CAP. Methods We performed a retrospective study of all adults hospitalized with CAP between November 2017 and October 2018. Patients were classified according to the presence of viral infection. An unvaried and a multivaried analysis were performed to identify variables associated with viral infection and clinical outcomes. Results Overall 590 patients were included. A microorganism was documented in 375 cases (63.5%). A viral infection was demonstrated in 118 (20%). The main pathogens were Streptococcus pneumoniae (35.8%), Staphylococcus aureus (2.9%) and influenza virus (10.8%). A trend to a higher rate of S. aureus (p = 0.06) in patients with viral infection was observed. Patients with viral infection had more often bilateral consolidation patterns (17.8% vs 10.8%, p = 0.04), respiratory failure (59.3% vs 42.8%, p = 0.001), ICU admission (17.8% vs 7%, p = 0.001) and invasive mechanical ventilation (9.3% vs 2.8%, p = 0.003). Risk factors for respiratory failure were chronic lung disease, age >65 years, positive blood cultures and viral infection. Influenza, virus but no other respiratory viruses, was associated with respiratory failure (OR, 3.72; 95% CI, 2.06–6.73). Conclusions Our study reinforces the idea that co-viral infection has an impact in the clinical presentation of CAP causing a more severe clinical picture. This impact seems to be mainly due to influenza virus infection (AU)

Objetivos La presencia de virus respiratorios en pacientes con neumonía adquirida en la comunidad (NAC) puede tener un impacto en la etiología bacteriana y en la presentación clínica. El objetivo de este estudio fue evaluar el papel de la infección viral en la etiología bacteriana y la evolución de los pacientes con NAC. Métodos Realizamos un estudio retrospectivo de todos los adultos hospitalizados con diagnóstico de NAC entre noviembre de 2017 y octubre de 2018. Los pacientes fueron clasificados según la presencia de infección viral. Se realizó un análisis univariado y multivariado para identificar variables asociadas con la infección viral y la evolución clínica. Resultados En total se incluyeron 590 pacientes. Se documentó el microorganismo en 375 casos (63,5%). Se demostró una infección viral en 118 (20%). Los principales patógenos fueron S. pneumoniae (35,8%), S. aureus (2,9%) y virus de la influenza (10,8%). Se observó una tendencia a una mayor tasa de S. aureus (p = 0,06) en pacientes con infección viral. Los pacientes con infección viral tenían con mayor frecuencia patrones de consolidación bilateral (17,8% vs 10,8%; p = 0,04), insuficiencia respiratoria (59,3% vs 42,8%; p = 0,001), ingreso en UCI (17,8% vs 7%; p = 0,001) y necesidad de ventilación mecánica invasiva (9,3% vs 2,8%; p = 0,003). Los factores de riesgo para insuficiencia respiratoria fueron enfermedad pulmonar crónica, edad >65 años, hemocultivos positivos e infección viral. El virus de la influenza, pero ningún otro virus respiratorio, se asoció con insuficiencia respiratoria (OR: 3,72; IC 95%: 2,06-6,73). Conclusiones Nuestro estudio refuerza la idea de que la infección viral tiene un impacto en la presentación clínica de la NAC provocando un cuadro clínico más grave. Este impacto parece deberse principalmente a la infección por el virus de la influenza (AU)

KLRG1 expression on natural killer cells is associated with HIV persistence, and its targeting promotes the reduction of the viral reservoir.

Human immunodeficiency virus (HIV) infection induces immunological dysfunction, which limits the elimination of HIV-infected cells during treated infection. Identifying and targeting dysfunctional immune cells might help accelerate the purging of the persistent viral reservoir. Here, we show that chronic HIV infection increases natural killer (NK) cell populations expressing the negative immune regulator KLRG1, both in peripheral blood and lymph nodes. Antiretroviral treatment (ART) does not reestablish these functionally impaired NK populations, and the expression of KLRG1 correlates with active HIV transcription. Targeting KLRG1 with specific antibodies significantly restores the capacity of NK cells to kill HIV-infected cells, reactivates latent HIV present in CD4+ T cells co-expressing KLRG1, and reduces the intact HIV genomes in samples from ART-treated individuals. Our data support the potential use of immunotherapy against the KLRG1 receptor to impact the viral reservoir during HIV persistence.

Impact of very early antiretroviral therapy during acute HIV infection on long-term immunovirological outcomes.

OBJECTIVES: We aimed to determine if starting antiretroviral therapy (ART) in the first 30 days after acquiring HIV infection has an impact on immunovirological response. METHODS: Observational, ambispective study including 147 patients with confirmed acute HIV infection (January/1995-August/2022). ART was defined as very early (≤30 days after the estimated date of infection), early (31-180 days), and late (>180 days). We compared time to viral suppression (viral load [VL] <50 copies/ml) and immune recovery (IR) (CD4+/CD8+ ratio ≥1) according to the timing and type of ART using survival analysis. RESULTS: ART was started in 140 (95.2%) patients. ART was very early in 24 (17.1%), early in 77 (55.0%), and late in 39 (27.9%) cases. Integrase strand transfer inhibitor (INSTI)-based regimens were the most used in both the overall population (65%) and the very early ART group (23/24, 95.8%). Median HIV VL and CD4+/CD8+ ratio pre-ART were higher in the very early ART group (P <0.05). Patients in the very early and early ART groups and treated with INSTI-based regimens achieved IR earlier (P <0.05). Factors associated with faster IR were the CD4+/CD8+ ratio pre-ART (hazard ratio: 9.3, 95% CI: 3.1-27.8, P <0.001) and INSTI-based regimens (hazard ratio: 2.4, 95% CI: 1.3-4.2, P = 0.003). CONCLUSIONS: The strongest predictors of IR in patients who start ART during AHI are the CD4+/CD8+ ratio pre-ART and INSTI-based ART regimens.

Oral fosfomycin for treatment of acute bacterial prostatitis caused by multidrug-resistant Enterobacterales.

To assess the feasibility of oral fosfomycin-tromethamine (FT) for the management of acute bacterial prostatitis (ABP) caused by multidrug-resistant (MDR) Enterobacterales. An observational study of adult patients diagnosed with ABP from Vall d'Hebron University Hospital (Barcelona, Spain), treated with oral FT. The primary outcome was clinical cure defined as symptom relief at the control visit, 2-4 weeks post-end of treatment. Secondary outcomes included microbiological cure, relapse, and adverse events related to the treatment. Eighteen patients with ABP caused by Enterobacterales (15 Escherichia coli and three Klebsiella pneumoniae) were included. Microorganisms were MDR bacteria [14 extended-spectrum beta-lactamase (ESBL) producers and two carbapenemase producing K. pneumoniae]. Patients received treatment with FT 3 g/48 hours during a median of 14 days (Q25-Q75, 12-17.75). Fifteen patients received a lead-in phase of intravenous suitable antimicrobial during a median of 7 days (Q25-Q75, 3.75-8). No patient had to stop treatment due to adverse events, and the only side effect reported in two patients was diarrhea. Clinical cure was achieved in all (18/18) patients and microbiological cure in 11/12 patients. After a median of follow-up of 5 months (Q25-Q75, 2-11), 2/18 patients relapsed with an orchitis and a new episode of ABP. FT is an attractive step-down therapy for ABP in patients with resistance or side effects to first-line drugs. The availability of oral treatment could reduce the use of the carbapenems, with a benefit in the quality of life of the patient, health costs, and an ecological impact. IMPORTANCE We present a brief but largest and interesting experience in which we use fosfomycin-tromethamine (FT) for the treatment of acute bacterial prostatitis (ABP) due to multiresistant bacteria. Our study provides new data that help to consider FT as a plausible alternative for treating ABP in patients with resistance or side effects to first-line drugs. The availability of an alternative oral treatment to avoid the use of the carbapenems could have important benefits in terms of quality of life of the patient, health costs, and an ecological impact.

Impact of viral detection in patients with community-acquired pneumonia: An observational cohort study.

PURPOSE: The presence of a respiratory virus in patients with community-acquired pneumonia (CAP) may have an impact on the bacterial etiology and clinical presentation. In this study we aimed to assess the role of viral infection in the bacterial etiology and outcomes of patients with CAP. METHODS: We performed a retrospective study of all adults hospitalized with CAP between November 2017 and October 2018. Patients were classified according to the presence of viral infection. An unvaried and a multivaried analysis were performed to identify variables associated with viral infection and clinical outcomes. RESULTS: Overall 590 patients were included. A microorganism was documented in 375 cases (63.5%). A viral infection was demonstrated in 118 (20%). The main pathogens were Streptococcus pneumoniae (35.8%), Staphylococcus aureus (2.9%) and influenza virus (10.8%). A trend to a higher rate of S. aureus (p=0.06) in patients with viral infection was observed. Patients with viral infection had more often bilateral consolidation patterns (17.8% vs 10.8%, p=0.04), respiratory failure (59.3% vs 42.8%, p=0.001), ICU admission (17.8% vs 7%, p=0.001) and invasive mechanical ventilation (9.3% vs 2.8%, p=0.003). Risk factors for respiratory failure were chronic lung disease, age >65 years, positive blood cultures and viral infection. Influenza, virus but no other respiratory viruses, was associated with respiratory failure (OR, 3.72; 95% CI, 2.06-6.73). CONCLUSIONS: Our study reinforces the idea that co-viral infection has an impact in the clinical presentation of CAP causing a more severe clinical picture. This impact seems to be mainly due to influenza virus infection.

Cardiovascular events in delayed presentation of HIV: the prospective PISCIS cohort study.

Objectives: People with HIV (PWH) have a higher cardiovascular risk than the general population. It remains unclear, however, whether the risk of cardiovascular disease (CVD) is higher in late HIV presenters (LP; CD4 ≤ 350 cells/µL at HIV diagnosis) compared to PWH diagnosed early. We aimed to assess the rates of incident cardiovascular events (CVEs) following ART initiation among LP compared to non-LP. Methods: From the prospective, multicentre PISCIS cohort, we included all adult people with HIV (PWH) initiating antiretroviral therapy (ART) between 2005 and 2019 without prior CVE. Additional data were extracted from public health registries. The primary outcome was the incidence of first CVE (ischemic heart disease, congestive heart failure, cerebrovascular, or peripheral vascular disease). The secondary outcome was all-cause mortality after the first CVE. We used Poisson regression. Results: We included 3,317 PWH [26 589.1 person/years (PY)]: 1761 LP and 1556 non-LP. Overall, 163 (4.9%) experienced a CVE [IR 6.1/1000PY (95%CI: 5.3-7.1)]: 105 (6.0%) LP vs. 58 (3.7%) non-LP. No differences were observed in the multivariate analysis adjusting for age, transmission mode, comorbidities, and calendar time, regardless of CD4 at ART initiation [aIRR 0.92 (0.62-1.36) and 0.84 (0.56-1.26) in LP with CD4 count <200 and 200- ≤ 350 cells/µL, respectively, compared to non-LP]. Overall mortality was 8.5% in LP versus 2.3% in non-LP (p < 0.001). Mortality after the CVE was 31/163 (19.0%), with no differences between groups [aMRR 1.24 (0.45-3.44)]. Women vs. MSM and individuals with chronic lung and liver disease experienced particularly high mortality after the CVE [aMRR 5.89 (1.35-25.60), 5.06 (1.61-15.91), and 3.49 (1.08-11.26), respectively]. Sensitivity analyses including only PWH surviving the first 2 years yielded similar results. Conclusion: CVD remains a common cause of morbidity and mortality among PWH. LP without prior CVD did not exhibit an increased long-term risk of CVE compared with non-LP. Identifying traditional cardiovascular risk factors is essential for CVD risk reduction in this population.

Effectiveness of topical cidofovir for treatment of refractory anal high-grade squamous intraepithelial lesion.

OBJECTIVES: Ablative electrocautery is effective treating anal high-grade squamous intraepithelial lesions (HSILs). However, persistence or recurrence of the HSIL despite ablative sessions is not uncommon. The aim of this study is to assess the feasibility of topical cidofovir as salvage therapy for the management of refractory HSIL. DESIGN: A prospective uncontrolled unicenter study of men and transgender people who have sex with men with HIV who had a refractory intra-anal HSIL after ablative treatments and who received topical cidofovir (ointment at 1%, auto-applicated, three times a week, a total of 8 weeks) as salvage therapy. Effectiveness was evaluated on-treatment defining response as resolution or regression to low-grade lesion of HSIL in the biopsy posttreatment. Tolerance and recurrences were recorded. RESULTS: From 2017 to 2022, 23 patients with refractory intra-anal HSIL (78.3% persistent lesions, 39% affecting > 50% of circumference, and a median of six previous ablative sessions) were treated with topical cidofovir. A response was observed in 16 of 23 patients [69.5% (95% confidence interval (95% CI) 50.8-88.4)]. Local tolerance was reported as regular or bad in 13 patients (52.2%), requiring modification of the treatment in eight patients (three early discontinuation and five dose reduction). Non-serious side effects were reported. After a median follow-up of 30.3 months, two of the 16 patients with a response developed recurrent HSIL [recurrence rate, 25.4% at 12 months (95% CI, 0-35)]. CONCLUSION: Topical cidofovir could be a good option in the management of anal HSIL due to its good effectiveness, low recurrence rate, and acceptable tolerance even in difficult-to-treat lesions.

Prevalence of non-alcoholic fatty liver disease in a multicentre cohort of people living with HIV in Spain.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is one of the most important liver comorbidities in people living with HIV (PLWH). Factors that could lead to a higher prevalence of NAFLD or ease the onset of fibrosis are unclear. METHODS: Cohort study of the Spanish HIV Research Network, which comprehends 46 hospitals and more than 15,000 PLWH. Primary objectives were to assess NAFLD prevalence and liver fibrosis according to hepatic steatosis index (HSI) and NAFLD fibrosis score, respectively. Factors associated with both were analysed. RESULTS: A total of 4798 PLWH were included of whom 1461 (30.5%) showed an HSI>36; these patients had higher risk for significant fibrosis (OR 1.91; 95%CI 1.11-3.28). Factors associated with NAFLD were body mass index (OR 2.05; 95%CI 1.94-2.16) and diabetes (OR 4.68; 95%CI 2.17-10.08), while exposure to integrase strand transfer inhibitors showed a lower risk (OR 0.78; 95%CI 0.62-0.97). In patients with HSI>36, being female (OR 7.33; 95%CI 1.34-40), age (OR 1.22; 95%CI 1.11-1.34), body mass index (OR 1.35; 95%CI 1.18-1.54) and exposure to thymidine analogues (OR 75.4, 95%CI 6.9-823.5) were associated with a higher risk of significant fibrosis. However, exposure to non-nucleoside reverse transcriptase inhibitors (OR 0.12, 95%CI 0.02-0.89) and time of exposure to protease inhibitors (OR 0.97, 95%CI 0.95-1) showed a lower risk. CONCLUSION: NAFLD prevalence was high in our cohort. Patients exposed to INSTI showed a lower risk of NAFLD. In patients with hepatic steatosis, exposure to thymidine analogues had 75-fold more risk of significant fibrosis while exposure to NNRTIs reduced this risk.

Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies.

BACKGROUND: Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized. METHODS: We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants. RESULTS: Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection. CONCLUSIONS: This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.

Sexual behavior and drug use impact in gay, bisexual, and other men who have sex with men

Background: The emergence of chemsex has raised several concerns about gay, bisexual, and other men who have sex with men's (GBMSM) health. In this study we aim to analyze illicit drugs and chemsex use, sexual behavior and sexually transmitted infections (STI) in GBMSM who attended to a sexual health clinic and to explore any potential association between drug use and STI.MethodsWe conducted an observational study between January and June 2019 among GBMSM population attending to a STI clinic in Barcelona, Spain. An anonymous self-administered questionnaire was given consecutively to all participants older than 18 years who accepted to participate.ResultsA total of 514 GBMSM (median age of 34 years-old) were included. The median number of sexual partners in the last year was 20. Seventy-one percent did not use condoms consistently for receptive anal intercourse. Drug abuse prevalence in the preceding year was 64.2%, and 26.5% of the individuals practiced chemsex. Gamma-hydroxibutyrate/gammabutyrolactone, poppers and methamphetamine were the most common drugs in chemsex. Chemsex was associated to group sex (OR 9.8 [95 CI: 4–24]), HIV infection (OR 2.5 [95 CI: 1.1–5.8]), taking pre-exposure prophylaxis (OR 3.2 [95 CI: 1.5–7.1]), developing gonorrhea (OR 3.7 [95 CI: 1.5–8.8]) or syphilis (OR 6.7 [95 CI: 2.4–18.7]).ConclusionsThe prevalence of drug use and chemsex was high among GBMSM in Barcelona. Chemsex was associated with group sex, taking PrEP, and contracting syphilis, gonorrhea, and HIV. (AU)

Antecedentes: El chemsex genera preocupaciones sobre la salud de gays, bisexuales y otros hombres que tienen sexo con hombres (GBHSH). En este estudio analizamos el uso de sustancias recreativas, chemsex, comportamiento sexual e infecciones de transmisión sexual (ITS) en GBHSH y exploramos cualquier asociación potencial entre el uso de drogas e ITS.MétodosEstudio observacional entre enero y junio de 2019 entre GBHSH atendidos en una clínica de ITS de Barcelona, España. Se entregó un cuestionario autoadministrado anónimo de forma consecutiva a todos los adultos que aceptaron participar.ResultadosSe incluyeron 514 GBHSH (edad mediana 34 años). La mediana del número de parejas sexuales en el último año fue de 20. El 71% no usó preservativo de manera consistente para el coito anal receptivo. La prevalencia de uso de drogas el año previo fue del 64,2% y el 26,5% de las personas practicó chemsex. Gamma-hidroxibutirato/gammabutirolactona, poppers y metanfetamina fueron las drogas más comunes en chemsex. El chemsex estuvo asociado a practicar sexo en grupo (OR 9,8 [IC 95%: 4-24]), infección por VIH (OR 2,5 [IC 95% 1,1-5,8]), profilaxis preexposición de VIH (PrEP) (OR 3,2 [IC 95% 1,5-7,1]), gonorrea (OR 3,7 [IC 95%: 1,5-8,8]) y sífilis (OR 6,7 [IC 95%: 2,4 - 18,7]).ConclusionesLa prevalencia de consumo de drogas y chemsex fue alta entre GBHSH en Barcelona. El chemsex se asoció con sexo en grupo, toma de PrEP e infección por sífilis, gonorrea y VIH. (AU)

Community-acquired pneumonia in hospitalised patients: changes in aetiology, clinical presentation, and severity outcomes in a 10-year period.

BACKGROUND AND OBJECTIVE: Community-acquired pneumonia (CAP) is a frequent cause of hospitalisation. Several factors, such as pandemics, vaccines and globalisation may lead to changes in epidemiology, clinical presentation, and outcomes of CAP, which oblige to a constant actualisation. We performed this study to analyse how these factors have evolved over a 10-year period. MATERIALS AND METHODS: Patients diagnosed with CAP for two 1-year periods that were 10 years apart (2007-2008 and 2017-2018) were included. We compared microbiological information, clinical data and evolutive outcomes in the two periods. A mortality analysis was performed. RESULTS: 1043 patients were included: 452 during the first period (2007- 2008), and 591 during the second period (2017-2018). Bacterial aetiology did not change during the 10-year period, besides a slight increase in Staphylococcus aureus (0.9% vs 2.9%, p = 0.026). There was a decline in the proportion of bacteraemia in the second period (14.8% vs 9.6%, p = 0.012). The incidence of complicated pleural effusion and septic shock declined too (6.4% vs 3.6%, p = 0.04 and 15.5% vs 6.3%, p < 0.001). Respiratory failure and Intensive care unit (ICU) admission were similar in both periods. Variables independently associated with mortality were age and septic shock. Influenza vaccine was a protective factor against mortality in the second period. CONCLUSIONS: We have not found relevant differences in the bacterial aetiology of CAP over this 10-year period. There has been a decline in septic complications of CAP such as septic shock, bacteraemia, and complicated pleural effusion. Influenza vaccination is an important tool to reduce mortality.KEY MESSAGESThere were no differences in the bacterial pathogens causing CAP among the 10-year study period. There has been a decline in septic complications of CAP such as septic shock, bacteraemia, and complicated pleural effusion.

Mortality and immunovirological outcomes in patients with advanced HIV disease on their first antiretroviral treatment: differential impact of antiretroviral regimens.

OBJECTIVES: To assess the clinical and immunovirological outcomes among naive patients with advanced HIV presentation starting an antiretroviral regimen in real-life settings. METHODS: This was a multicentre, prospective cohort study. We included all treatment-naive adults with advanced HIV disease (CD4+ T cell count < 200 cells/mm3or presence of an AIDS-defining illness) who started therapy between 2010 and 2020. The main outcomes were mortality, virological effectiveness (percentage of patients with viral load of ≤50 copies/mL) and immune restoration (percentage of patients with CD4+ T cell count above 350 cells/mm3). Competing risk analysis and Cox proportional models were performed. A propensity score-matching procedure was applied to assess the impact of the antiretroviral regimen. RESULTS: We included 1594 patients with advanced HIV disease [median CD4+T cell count of 81 cells/mm3and 371 (23.3%) with AIDS-defining illness] and with a median follow-up of 4.44 years. The most common ART used was an integrase strand transfer inhibitor (InSTI) regimen (46.9%), followed by PI (35.7%) and NNRTI (17.4%), with adjusted mortality rates at 3 years of 3.1% (95% CI 1.8%-4.3%), 4.7% (95% CI 2.2%-7.1%) and 7.6% (95% CI 5.4%-9.7%) (P = 0.001), respectively. Factors associated with increased mortality included older age and history of injection drug use, whilst treatment with an InSTI regimen was a protective factor [HR 0.5 (95% CI 0.3-0.9)]. A sensitivity analysis with propensity score procedure confirms these results. Patients who started an InSTI achieved viral suppression and CD4+ T cell count above 350 cells/mm3significantly earlier. CONCLUSIONS: In this large real-life prospective cohort study, a significant lower mortality, earlier viral suppression and earlier immune reconstitution were observed among patients with advanced HIV disease treated with InSTIs.

Exploratory study of an oral screening dysplasia program for HIV-infected men who have sex with men.

BACKGROUND: HIV-infected men who have sex with men (MSM) are at high risk to develop human papilloma virus (HPV)-related oropharyngeal cancer. The aim of our study was to assess the usefulness of a pilot oral dysplasia screening program and its correlation with an anal dysplasia screening program. METHODS: This was a prospective study with HIV-infected MSM. Oral and anal screenings were performed based on HPV determination, liquid cytology, direct and microscopy oral examinations, high-resolution anoscopy and biopsies, if necessary. RESULTS: A total of 103 patients were included. The mean age of the patients was 44.6 years, 55.3% were smokers, and 57.3% had a history of previous anal high-grade squamous intraepithelial lesions (HSILs). The prevalence of oral HPV infections was 14% (9% HPV-high risk), the prevalence of abnormal cytology was 25.2%, and in 4.8% of the patients, oral examinations showed suspicious HSILs. Oral microscopy did not detect additional lesions that visual inspection. Five oral biopsies were performed and the results were normal. No risk factors for oral HPV infections were identified. The prevalence of anal HPV infections was 88.3% (76.7% HPV-high risk), 52.9% of the patients had altered cytology, and in 45.6% anoscopy showed changes suggestive of HSILs. Seventy-two anal biopsies were performed, detecting 25 cases of HSILs (24.3%).A poor correlation was observed between oral and anal HPV infections (κ = 0.037). CONCLUSIONS: The prevalence of oral HPV infections, abnormal cytology and lesions in HIV-infected MSM was low, and their correlation with anal HPV-related lesions was slight. These results confirm the current barriers to oral dysplasia screening techniques.

Sexual behavior and drug use impact in gay, bisexual, and other men who have sex with men.

BACKGROUND: The emergence of chemsex has raised several concerns about gay, bisexual, and other men who have sex with men's (GBMSM) health. In this study we aim to analyze illicit drugs and chemsex use, sexual behavior and sexually transmitted infections (STI) in GBMSM who attended to a sexual health clinic and to explore any potential association between drug use and STI. METHODS: We conducted an observational study between January and June 2019 among GBMSM population attending to a STI clinic in Barcelona, Spain. An anonymous self-administered questionnaire was given consecutively to all participants older than 18 years who accepted to participate. RESULTS: A total of 514 GBMSM (median age of 34 years-old) were included. The median number of sexual partners in the last year was 20. Seventy-one percent did not use condoms consistently for receptive anal intercourse. Drug abuse prevalence in the preceding year was 64.2%, and 26.5% of the individuals practiced chemsex. Gamma-hydroxibutyrate/gammabutyrolactone, poppers and methamphetamine were the most common drugs in chemsex. Chemsex was associated to group sex (OR 9.8 [95 CI: 4-24]), HIV infection (OR 2.5 [95 CI: 1.1-5.8]), taking pre-exposure prophylaxis (OR 3.2 [95 CI: 1.5-7.1]), developing gonorrhea (OR 3.7 [95 CI: 1.5-8.8]) or syphilis (OR 6.7 [95 CI: 2.4-18.7]). CONCLUSIONS: The prevalence of drug use and chemsex was high among GBMSM in Barcelona. Chemsex was associated with group sex, taking PrEP, and contracting syphilis, gonorrhea, and HIV.

Pharmacotherapeutic interventions for the treatment of bacterial prostatitis.

INTRODUCTION: Bacterial prostatitis, acute or chronic, is one of the most prevalent urogenital infections in men. Its diagnosis requires the application of a careful methodology. Gram-negative bacilli are the most frequent causative agents, and in recent years, an increase in the frequency of multiresistant bacteria has been detected. The choice of the optimal antimicrobial treatment requires the selection of drugs with proven in vitro activity associated with good penetration into the prostatic tissue, especially in chronic forms of infection. AREAS COVERED: The aim of this article is to summarize the current evidence regarding the pathogenesis, etiology, empirical and definitive antimicrobial therapy, and new pharmacotherapeutic interventions to improve the prognosis of bacterial acute or chronic prostatitis. EXPERT OPINION: Bacterial prostatitis requires the application of an accurate diagnostic protocol to identify the causative agent and establish the optimal antimicrobial treatment. The structural and biochemical characteristics of prostatic tissue result in poor penetration of antimicrobials; therefore, in the choice of treatment, it is essential to select agents with proven antimicrobial activity and pharmacokinetic characteristics that ensure good and sustained concentrations in this area. Patients with chronic forms of infection require prolonged treatment, and relapses of the infectious process are frequent.

Identification of HIV-reservoir cells with reduced susceptibility to antibody-dependent immune response.

Human immunodeficiency virus (HIV) establishes a persistent infection in heterogeneous cell reservoirs, which can be maintained by different mechanisms including cellular proliferation, and represent the main obstacle to curing the infection. The expression of the Fcγ receptor CD32 has been identified as a marker of the active cell reservoirs in people on antiretroviral therapy (ART), but if its expression has any role in conferring advantage for viral persistence is unknown. Here, we report that HIV-infected cells expressing CD32 have reduced susceptibility to natural killer (NK) antibody-dependent cell cytotoxicity (ADCC) by a mechanism compatible with the suboptimal binding of HIV-specific antibodies. Infected CD32 cells have increased proliferative capacity in the presence of immune complexes, and are more resistant to strategies directed to potentiate NK function. Remarkably, reactivation of the latent reservoir from antiretroviral-treated people living with HIV increases the pool of infected CD32 cells, which are largely resistant to the ADCC immune mechanism. Thus, we report the existence of reservoir cells that evade part of the NK immune response through the expression of CD32.