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.

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.

Latency reversal agents affect differently the latent reservoir present in distinct CD4+ T subpopulations.

Latency reversal agents (LRAs) have proven to induce HIV-1 transcription in vivo but are ineffective at decreasing the size of the latent reservoir in antiretroviral treated patients. The capacity of the LRAs to perturb the viral reservoir present in distinct subpopulations of cells is currently unknown. Here, using a new RNA FISH/flow ex vivo viral reactivation assay, we performed a comprehensive assessment of the viral reactivation capacity of different families of LRAs, and their combinations, in different CD4+ T cell subsets. We observed that a median of 16.28% of the whole HIV-reservoir induced HIV-1 transcripts after viral reactivation, but only 10.10% of these HIV-1 RNA+ cells produced the viral protein p24. Moreover, none of the LRAs were powerful enough to reactivate HIV-1 transcription in all CD4+ T cell subpopulations. For instance, the combination of Romidepsin and Ingenol was identified as the best combination of drugs at increasing the proportion of HIV-1 RNA+ cells, in most, but not all, CD4+ T cell subsets. Importantly, memory stem cells were identified as highly resistant to HIV-1 reactivation, and only the combination of Panobinostat and Bryostatin-1 significantly increased the number of cells transcribing HIV within this subset. Overall, our results validate the use of the RNA FISH/flow technique to assess the potency of LRAs among different CD4+ T cell subsets, manifest the intrinsic differences between cells that encompass the latent HIV reservoir, and highlight the difficulty to significantly impact the latent infection with the currently available drugs. Thus, our results have important implications for the rational design of therapies aimed at reversing HIV latency from diverse cellular reservoirs.

Screening for asymptomatic STIs in HIV-infected men who have sex with men.

We aimed to study the prevalence, characteristics and risk factors of asymptomatic sexually transmitted infections (STIs) in HIV-infected men who have sex with men (MSM). We conducted a prospective cross-sectional study, including asymptomatic HIV-infected MSM attending regular visits between December 2014 and December 2017. Of the 301 patients included, 60 patients (19.9%) presented at least one STI. The most common STI was syphilis (33 of 69 STIs), followed by chlamydia (19 of 69), gonorrhoea (10 of 69), hepatitis C virus (4 of 69) and lymphogranuloma venereum (3 of 69). Illicit drug use during sex was the only variable significantly associated with the presence of an STI on multivariate analysis (OR 2.13; 95% CI 1.17-3.89). We were unable to identify a subgroup of patients where we could potentially avoid STI screening. Our findings support current guidelines that recommend routine screening for all HIV-infected MSM regardless of their self-reported sexual history.

Response to direct-acting antivirals for hepatitis C treatment in vertically HIV/HCV co-infected patients.

Direct-acting antivirals (DAAs) for HCV treatment have improved tolerance and efficacy among adults, but experience in vertical transmission is scarce. In our vertically HIV/HCV co-infected youth cohort of 58 patients, DAA achieved excellent rates of cure among naïve and pretreated individuals. Treating vertically infected seems important as 29.6% displayed advanced fibrosis at treatment initiation.

A case report of long treatment with Itraconazole in a patient with chronic Chagas disease.

BACKGROUND: Current available treatments (benznidazole and nifurtimox) for Chagas disease (CD) show limited efficacy in chronic phase and frequent undesirable effects. Ergosterol synthesis inhibitors (ESI) had been considered as promising drugs for CD treatment and despite its recent poor results in several clinical trials, different strategies have been proposed to optimize its role in this infection. CASE PRESENTATION: We present a case of chronic Chagas disease in patient diagnosed with HIV who received treatment for histoplasmosis with itraconazol during twelve months. Even though T. cruzi rt-PCR was persistently negative during treatment, when itraconazol was stopped she presented with a positive blood rt-PCR. CONCLUSION: Several studies using different ESI had been published for CD treatment. Either in vitro or in vivo assays demonstrated activity against T. cruzi of the different triazole derivatives so different clinical trials had been carried out to evaluate its efficacy and safety. Despite contradictory evidence in the animal model, longer treatments along with other treatment strategies previously proposed suggests that ESI failure rates in positive peripheral blood rt-PCR are higher than that obtained with the current treatments of choice.

Usefulness of Sofia Pneumococcal FIA® test in comparison with BinaxNOW® Pneumococcal test in urine samples for the diagnosis of pneumococcal pneumonia.

The Sofia Pneumococcal FIA® test is a recently introduced immunofluorescent assay automatically read aimed to detect Streptococcus pneumoniae antigen in urine. The aim of this study was to evaluate the usefulness of SofiaFIA® urinary antigen test (UAT) in comparison with classical immunochromatographic BinaxNOW® test for the diagnosis of pneumococcal pneumonia (PP). Observational study was conducted in the Hospital Universitari Vall d'Hebron from December 2015 to August 2016. Consecutive adult patients diagnosed of pneumonia and admitted to the emergency department in whom UAT was requested were prospectively enrolled. Paired pneumococcal UAT was performed (BinaxNOW® and SofiaFIA®) in urine samples. To assess the performance of both tests, patients were categorized into proven PP (isolation of S. pneumoniae in sterile fluid) or probable PP (isolation of S. pneumoniae in respiratory secretion). Sensitivity, specificity, and concordance were calculated. A total of 219 patients with pneumonia were enrolled, of whom 14% had a proven or probable PP, 22% a non-pneumococcal etiology, and 64% an unidentified pathogen. Concordance between tests was good (κ = 0.81). Sensitivity of SofiaFIA® and BinaxNOW® UAT was 78.6 and 50% for proven PP (p = 0.124), and 74.2 and 58% for proven/probable PP (p = 0.063). Specificity for both tests was 83.3 and 85.5% for proven and proven/probable PP. In patients without an identified pathogen, SofiaFIA® test was positive in 33 (23.6%) cases and BinaxNOW® in 25 (17.8%), so Sofia Pneumococcal FIA® detected 32.6% more cases than BinaxNOW® (p = 0.001). Sofia Pneumococcal FIA® test showed an improved sensitivity over visual reading of BinaxNOW® test without a noticeable loss of specificity.

Withdrawing inactive NRTIs in HIV-1 subjects with suppressed viraemia: a randomized trial.

BACKGROUND: Extensively pretreated subjects with virological failure (VF) may receive salvage regimens containing NRTIs with only residual or no activity. Once virological suppression is achieved, their contribution remains elusive. METHODS: This was a multicentre, randomized, prospective study. Subjects with at least one prior VF, HIV-1 RNA <50 copies/mL for ≥6 months and receiving a regimen with at least two active drugs (one of them a boosted PI) were randomized 1:1 to stop (experimental arm) or maintain (control arm) NRTIs. EudraCT: 2012-000198-21. RESULTS: Ninety subjects were randomized (experimental, n = 45; and control, n = 45). The mean age was 50 years, 80% were male, the mean CD4+ cell count was 542 cells/mm(3) and the median number of prior VFs was 3. Seventy-four subjects (82%) harboured the mutation M184V/I and the median number of thymidine-associated mutations was 3 (IQR: 0-4). In the experimental arm, thirty-two (71%) subjects removed one NRTI and 13 (29%) subjects removed two. Twenty-two of 45 (49%) discontinued tenofovir disoproxil fumarate. Forty-one of 45 (91.1%, experimental arm) and 44 of 45 (97.8%, control arm) had HIV-1 RNA <50 copies/mL at 48 weeks (difference: -6.7%; 95% CI: -17.4, 4.1). In a post-hoc analysis allowing NRTI reintroduction, efficacy rates were 95.6% and 97.8%, respectively (difference: -2.2%; 95% CI: -7.2, 2.7). Rates of discontinuation at 48 weeks were 2% in both arms. One subject developed a late VF with resistance selection. CONCLUSIONS: In patients receiving a successful multidrug salvage regimen with at least two active drugs (one a boosted PI), the withdrawal of inactive NRTIs was safe, rates of VF were low and drug resistance was uncommon at 48 weeks in this small study. This strategy could potentially prevent long-term toxicities, reduce the number of drugs and reduce costs if non-inferiority was met in a fully powered trial.

Darunavir and ritonavir total and unbound plasmatic concentrations in HIV-HCV-coinfected patients with hepatic cirrhosis compared to those in HIV-monoinfected patients.

Our objective was to describe the pharmacokinetic (PK) parameters of total and unbound darunavir and ritonavir concentrations in HIV-hepatitis C virus (HCV)-coinfected patients with cirrhosis, as ritonavir-boosted darunavir is mainly metabolized in the liver, and hepatic cirrhosis might modify darunavir-ritonavir concentrations. This was a prospective, case-control, and unicenter study. HIV-HCV-coinfected patients with compensated cirrhosis (cases) and HIV-monoinfected patients with normal liver function (controls) were included. Darunavir-ritonavir was given at 800/100 mg once daily. Patients were followed for 24 weeks to assess safety and efficacy. A steady-state 12-h PK study was performed. Total and unbound concentrations were determined by liquid chromatography-tandem mass spectrometry. The unbound fraction was obtained by ultrafiltration. The plasma area under the concentration-time curve (AUC) and oral clearance (CL/F) were assessed by noncompartmental models. Thirty patients (20 cases and 10 controls) were included. Among cirrhotic patients, the Child-Pugh score was C in 4 cases, B in 1 case, and A in 15 cases; the median (interquartile range) transient elastography values were 20 kPa (14 to 26 kPa), and 5 patients had prior clinical decompensations. There were no significant differences in the darunavir PK parameters between cases and controls except for longer time to maximum plasma concentrations (Tmax) and half-lives in the cirrhotic patients. There were no significant differences in ritonavir total concentrations, but the unbound concentrations were higher in cirrhotic patients. There were significant correlations between the darunavir total and unbound concentrations in both cirrhotic patients and controls. There were no differences in PK parameters based on Child-Pugh score, liver elasticity, gender, or use of concomitant medications. In conclusion, in HIV-HCV-coinfected patients with clinically compensated cirrhosis receiving darunavir-ritonavir at 800/100 mg once daily, the darunavir total and unbound concentrations are similar to those observed in noncirrhotic patients, and dose adjustments are not necessary.

Risk factors for respiratory failure in pneumococcal pneumonia: the importance of pneumococcal serotypes.

Pneumococcal serotypes are one of the main determinants of pneumococcal disease severity; however, data about their implication in respiratory failure are scarce. We conducted an observational study of adults hospitalised with invasive pneumococcal pneumonia to describe the host- and pathogen-related factors associated with respiratory failure. Of 1258 adults with invasive pneumococcal disease, 615 (48.9%) had respiratory failure at presentation. Patients with respiratory failure were older (62.1 years versus 55.4 years, p<0.001) and had a greater proportion of comorbid conditions. They also had a greater proportion of septic shock (41.7% versus 6.1%, p<0.001), required admission to the intensive care unit more often (38.4% versus 4.2%, p<0.001) and had a higher mortality (25.5% versus 3.5%, p<0.001). After adjustment, independent risk factors for respiratory failure were: age >50 years (OR 1.63, 95% CI 1.15-2.3), chronic lung disease (OR 1.54, 95% CI 1.1-2.15), chronic heart disease (OR 1.49, 95% CI 1.01-2.22) and infection caused by serotypes 3 (OR 1.97, 95% CI 1.23-3.16), 19A (OR 2.34, 95% CI 1.14-4.42) and 19F (OR 3.55, 95% CI 1.22-10.28). In conclusion, respiratory failure is a frequent complication of pneumococcal pneumonia and causes high morbidity and mortality. Pneumococcal serotypes 3, 19A and 19F are the main risk factors for this complication.

Impact of the 2009 influenza A H1N1 pandemic on invasive pneumococcal disease in adults.

BACKGROUND: The incidence of invasive pneumococcal disease (IPD) appears to be associated with influenza. The objectives of this study were to evaluate the changes in IPD incidence and clinical data as well as the trends in Streptococcus pneumoniae serotype distribution in adults during the peak period of the 2009 influenza A H1N1 pandemic (IAP). METHODS: We performed a prospective multicentre study on IPD from week 42 to 48, 2009 in an area of Barcelona (Catalonia, Spain) covering 1,483,781 adult inhabitants. Serotyping was done by Quellung reaction. The data from 2009 were compared to those from the same periods in 2008 and 2010. RESULTS: Two hundred and three cases of IPD were detected during 2009, compared with 182 in 2008 and 139 in 2010. The incidence of IPD during the 7-week study period in 2009 (2.89) was statistically higher than that observed in 2008 (1.96) and 2010 (1.46). IAP was confirmed in 3/30 patients during the 2009 study period. Patients with IPD in 2009 were significantly healthier and younger than those in the other years, although the mortality was higher than in 2008 (p = 0.05) and 2010 (p > 0.05). Eleven (10 non-PCV-7) serotypes not present in 2008 appeared in 2009. CONCLUSIONS: During weeks 42 to 48, in which the 2009 IAP peaked in Catalonia, the incidence of IPD was statistically higher than that observed in the same time period in 2008 and 2010, with some differences in the epidemiological data, showing a close relationship between S. pneumoniae and influenza.

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.

Risk stratification for CNS infection: A potential tool to avoid unwarranted lumbar punctures - An observational study.

OBJECTIVE: Central nervous system (CNS) infection poses a diagnostic challenge especially in elderly patients who frequently exhibit atypical symptoms. Our study aimed to identify patients with a low risk of CNS infection, in whom lumbar puncture (LP) could be avoided. METHODS: Observational study of consecutive adult patients who underwent a LP in the emergency room (ER) of Hospital Universitari Vall d'Hebron between January 2017 and December 2021. We performed a univariate and multivariate analysis to identify factors associated with non-CNS infection. These factors were used to create a combined variable, and its diagnostic positive predictive value and specificity to detect patients without CNS infections were calculated. RESULTS: We included 489 patients of which 77 (15.7%) were diagnosed with CNS infection. Median age was 62 years (IQR 41-78) and 240 (49.1%) were male. In the multivariate analysis, variables associated with non-CNS infection were female sex (OR 1.89; 95% CI 1.12-3.20), age older than 80 years (OR 3.14; 95% CI 1.20-8.19), previous cognitive impairment (OR 3.91; 95% CI 1.18-13.01), and clinical presentation without meningitis triad (fever, headache and neck stiffness) (OR 4.12; 95% CI 1.72-9.85). A composite variable encompassing age older than 80, cognitive impairment, and the absence of the meningitis triad was used as a diagnostic tool to identify patients with non-CNS infection, exhibiting a 98% positive predictive value and 99% specificity. CONCLUSIONS: This study identifies factors associated with a low risk of CNS infection. Thus, a more precise clinical approach could help clinicians to detect patients who would not benefit from a LP.

NKG2C and NKG2A coexpression defines a highly functional antiviral NK population in spontaneous HIV control.

Elite controllers (ECs), a unique group of people with HIV (PWH), exhibit remarkable control of viral replication in the absence of antiretroviral therapy. In this study, we comprehensively characterized the NK cell repertoire in ECs after long-term viral control. Phenotypic profiling of NK cells revealed profound differences compared with other PWH, but marked similarities to uninfected individuals, with a distinctive prevalence of NKG2C+CD57+ memory-like NK cells. Functional analyses indicated that ECs had limited production of functional molecules upon NK stimulation and consequently reduced natural cytotoxicity against non-HIV target cells. Importantly, ECs showed an exceptional ability to kill primary HIV-infected cells by the antibody-dependent cell cytotoxicity adaptive mechanism, which was achieved by a specific memory-like NK population expressing CD16, NKG2A, NKG2C, CD57, and CXCR3. In-depth single-cell RNA-seq unveiled a unique transcriptional signature in these NK cells linked to increased cell metabolism, migration, chemotaxis, effector functions, cytokine secretion, and antiviral response. Our findings underscore a pivotal role of NK cells in the immune control of HIV and identify specific NK cells as emerging targets for immunotherapies.

Intraepithelial CD15 infiltration identifies high-grade anal dysplasia in people with HIV.

Men who have sex with men (MSM) with HIV are at high risk for squamous intraepithelial lesion (SIL) and anal cancer. Identifying local immunological mechanisms involved in the development of anal dysplasia could aid treatment and diagnostics. Here, we studied 111 anal biopsies obtained from 101 MSM with HIV, who participated in an anal screening program. We first assessed multiple immune subsets by flow cytometry, in addition to histological examination, in a discovery cohort. Selected molecules were further evaluated by immunohistochemistry in a validation cohort. Pathological samples were characterized by the presence of resident memory T cells with low expression of CD103 and by changes in natural killer cell subsets, affecting residency and activation. Furthermore, potentially immunosuppressive subsets, including CD15+CD16+ mature neutrophils, gradually increased as the anal lesion progressed. Immunohistochemistry verified the association between the presence of CD15 in the epithelium and SIL diagnosis for the correlation with high-grade SIL. A complex immunological environment with imbalanced proportions of resident effectors and immune-suppressive subsets characterized pathological samples. Neutrophil infiltration, determined by CD15 staining, may represent a valuable pathological marker associated with the grade of dysplasia.

Effects of immunocompromise and comorbidities on pneumococcal serotypes causing invasive respiratory infection in adults: implications for vaccine strategies.

BACKGROUND: The 13-valent pneumococcal conjugate vaccine (PCV13) has recently been approved for use in immunocompromised adults. However, it is unclear whether there is an association between specific underlying conditions and infection by individual serotypes. The objective was to determine the prevalence of serotypes covered by PCV13 in a cohort of patients with invasive pneumococcal disease of respiratory origin and to determine whether there are specific risk factors for each serotype. METHODS: An observational study of adults hospitalized with invasive pneumococcal disease in 2 Spanish hospitals was conducted during the period 1996-2011. A multinomial regression analysis was performed to identify conditions associated with infection by specific serotypes (grouped according their formulation in vaccines and individually). RESULTS: A total of 1094 patients were enrolled; the infecting serotype was determined in 993. In immunocompromised patients, 64% of infecting serotypes were covered by PCV13. After adjusting for age, smoking, alcohol abuse, and nonimmunocompromising comorbidities, the group of serotypes not included in either PCV13 or PPV23 were more frequently isolated in patients with immunocompromising conditions and cardiopulmonary comorbidities. Regarding individual serotypes, 6A, 23F, 11A, and 33F were isolated more frequently in patients with immunocompromise and specifically in some of their subgroups. The subgroup analysis showed that serotype10A was also associated with HIV infection. CONCLUSIONS: Specific factors related to immunocompromise seem to determine the appearance of invasive infection by specific pneumococcal serotypes. Although the coverage of serotypes in the 13-valent conjugate pneumococcal vaccine (PCV13) was high, some non-PCV13-emergent serotypes are more prevalent in immunocompromised patients.

The increasing incidence of empyema.

PURPOSE OF REVIEW: The aim of this review is to highlight recent changes concerning the incidence of empyema. In this article we have focused on community-acquired empyema RECENT FINDINGS: The incidence of empyema seems to have been increasing both in children and adults worldwide in the past decades, mainly in healthy young adults and in older patients. The bacteriology of pleural infection is changing as well. In children, the most common microorganism that causes empyema continues to be Streptococcus pneumoniae. Interestingly, the widespread use of the seven valent conjugate vaccine has produced a replacement phenomenon with the emergence of some pneumococcal serotypes such as serotypes 1, 3 and 19A, which have a higher propensity to cause empyema. Moreover increases in the incidence of empyema due to Staphylococcus aureus have also been observed. In adults, increases in the rate of empyema due to Streptococcus milleri group and S. aureus have been reported. SUMMARY: Continued surveillance in the epidemiology of empyema is needed. Progress in new strategies of prevention, such as a new generation of conjugate pneumococcal vaccines and protein-based vaccines, could become an important step in the control of this important complication.

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.

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.

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.