Brief Report: Effectiveness of Trichloroacetic Acid vs. Electrocautery Ablation for the Treatment of Anal High-Grade Squamous Intraepithelial Lesion in HIV-Infected Patients.

BACKGROUND: Trichloroacetic acid (TCA) and electrocautery ablation (ECA) are 2 of the main treatment options for anal high-grade squamous intraepithelial lesion (HSIL). Our aim was to compare the efficacy and tolerance of TCA vs. ECA for HSIL. METHODS: Retrospective uncontrolled study of HIV-infected men who have sex with men who had an anal HSIL treated with TCA or ECA. On-treatment effectiveness was evaluated at 6-8 weeks after treatment. A complete response was defined as resolution of HSIL, a partial response as regression to low-grade lesion, and recurrence as biopsy-proven HSIL during follow-up. A propensity-score analysis was used to adjust efficacy to potential confounding. RESULTS: From May 2009 to March 2018, 182 and 56 cases of anal HSIL were treated with ECA and TCA, respectively. Comparing ECA with TCA, a complete response was observed in 33.5% (95% confidence interval: 25.8 to 41.6) vs. 60.7% (50.0 to 74.8) and a partial response in 28.0% (20.3 to 36.0) vs. 23.2% (12.5 to 37.3), respectively (P < 0.001). These differences were maintained in the propensity-score analyses. Side effects were common in both treatment, but tolerance was reported as good in 80.6% (74.2 to 89.2) and 82.6% (73.9 to 93.9) of cases treated with ECA and TCA, respectively, and no serious events were described. Recurrence cumulative incidence for the first 12 months was 14.6% (9.1 to 23.1) for ECA episodes and 27.6% (11.5 to 57.7) for TCA (P = 0.183). CONCLUSIONS: Our study showed a higher efficacy of TCA than ECA with similar rates of side effects. In our opinion, considering the benefits of TCA, it should be considered as a first-line therapy for most anal HSIL management.

The role of oncogenic human papillomavirus determination for diagnosis of high-grade anal intraepithelial neoplasia in HIV-infected MSM.

OBJECTIVE: To assess the oncogenic human papillomavirus (HPV) determination and the cotesting HPV and anal cytology value to detect high-grade anal intraepithelial neoplasia (HGAIN) in a cohort of HIV-MSM. DESIGN AND METHODS: Prospective study of HIV-infected MSM who underwent screening for anal dysplasia. Screening program includes anal cytology, HPV testing, and high-resolution anoscopy (HRA) at each visit. Histological samples were obtained if suspicious lesions were revealed by HRA. Sensitivity and specificity of the different tests were calculated by using histological results of HRA-guided biopsy as the reference test for HGAIN diagnosis. RESULTS: From May 2009 to August 2016, 692 HIV-infected MSM underwent 1827 anal cytologies, 1841 HRA examinations, and 1607 HPV testing. At first screening visit, anal cytology results were abnormal in 418 (60.4%) of 692 patients, and oncogenic HPV genotypes were found in 482 (79.5%) of 606 patients. Anal cytology showed a sensitivity of 89.2% [95% confidence interval (CI); 80.7-94.2] and a specificity of 44.2% (95% CI; 40.2-48.2) to detect HGAIN. Oncogenic HPV testing had 90.4% sensitivity (95% CI; 82-86.8) and 24.4% specificity (95% CI; 20.8-28.3). Cotesting showed a 97.4% sensitivity (95% CI; 91-99.3) and 14% specificity (95% CI; 11.2-17.3). In patients with atypical squamous cells of uncertain significance on cytology, oncogenic HPV testing had 91.3% sensitivity and 28.3% specificity to detect HGAIN. CONCLUSION: Abnormal cytology and oncogenic HPV determination showed similar sensitivity for detecting HGAIN. The two tests used together improved the sensitivity but with lowered specificity. In our opinion, HPV testing does not improve HGAIN detection and should not replace anal cytology as a standard screening test for HIV-infected MSM.

Risk factors of high-grade anal intraepithelial neoplasia recurrence in HIV-infected MSM.

OBJECTIVE: To assess risk factors of high-grade anal intraepithelial neoplasia (HGAIN) recurrence in a cohort of HIV-infected MSM. DESIGN AND METHODS: Consecutive HIV-infected 100 MSM with a history of successfully treated intra-anal HGAIN with electrocautery were followed with anal cytology, human papillomavirus (HPV) determination, and high-resolution anoscopy (HRA) at 3-6-month intervals. HGAIN recurrence was analyzed using Kaplan-Meier analysis. Risk factors of recurrence were assessed using Cox proportional hazards regression. The value of different tests for detecting recurrence was also assessed. RESULTS: After a mean follow-up of 17.6 months, 39 of the 100 patients [39%, 95% confidence interval (CI): 29-49] developed recurrent HGAIN, 24 at the previously treated site, and 15 at a different site. The probability of recurrence was 23.5% at 12 months (95% CI: 13.9-33.1) and 53.3% at 24 months (95% CI: 34.3-72.7). Risk factors of recurrence were presence of hepatitis C antibodies (hazard ratio 2.79; 95% CI: 1.04-7.53), nadir CD4 cell count less than 200 cells/µl (hazard ratio 2.61; 95% CI: 1.06-6.44), and HGAIN lesions affecting at least two octants of anal circumference (hazard ratio 8.27; 95% CI: 1.1-62). Infection by at least two HPV oncogenic strains increased the risk of recurrence (hazard ratio 2.3; 95% CI: 0.98-5.42). HRA, anal cytology, and oncogenic HPV determination test showed a sensitivity of 100, 79.4, and 86.7%, and a specificity of 57.7, 36.6, and 34.7%, respectively, for detecting HGAIN recurrence. CONCLUSION: The risk of HGAIN recurrence in HIV-infected MSM is high. Regular posttreatment follow-up of these patients is mandatory, and performing direct HRA appears to be the best strategy.

Cerebrospinal fluid and plasma lopinavir concentrations and viral response in virologically suppressed patients switching to lopinavir/ritonavir monotherapy once daily.

BACKGROUND: Lopinavir/ritonavir (LPV/r) monotherapy is used in selected virologically suppressed HIV-infected patients. Some would prefer a once-daily (OD) dose instead of the usual twice-daily dose to favour adherence. However, trough concentrations of the drug in blood and particularly in cerebrospinal fluid (CSF) may not be adequate to maintain viral suppression. METHODS: Prospective, open-label pilot study to evaluate the efficacy and safety of LPV/r monotherapy OD. HIV-1-infected patients, virologically suppressed for at least 6 months were enrolled. HIV viral load (VL) was determined at baseline and at weeks 4, 8, 12, 16, 24, 36 and 48. Lumbar puncture was performed in a subgroup of patients to evaluate CSF VL and CSF LPV concentrations. RESULTS: A total of 21 patients were included. At week 48, 85.7% (n=18) showed viral suppression (VL<40 copies/ml). Two patients had viral failure (9.5%) and a third was withdrawn from the study because of gastrointestinal symptoms. Nine patients were enrolled in the substudy. CSF VL was <40 copies/ml in all cases. Median (range) LPV concentration was 9.78 ng/ml (1.93-78.3) in CSF and 1,970 (154-16,700) ng/ml in plasma; the CSF/plasma ratio was 0.004 (0.001-0.186). CONCLUSIONS: In this small pilot study, LPV/r monotherapy OD maintained plasma HIV RNA suppression at 48 weeks in most patients, with no cases of CSF viral escape. However, CSF LPV concentrations were close to the 50% inhibitory concentration threshold in several patients; hence, this intervention should be avoided in patients with advanced immune suppression and/or those individuals presenting with significant comorbidities such as hepatitis C coinfection.

Gut-Microbiota-Metabolite Axis in Early Renal Function Decline.

INTRODUCTION: Several circulating metabolites derived from bacterial protein fermentation have been found to be inversely associated with renal function but the timing and disease severity is unclear. The aim of this study is to explore the relationship between indoxyl-sulfate, p-cresyl-sulfate, phenylacetylglutamine and gut-microbial profiles in early renal function decline. RESULTS: Indoxyl-sulfate (Beta(SE) = -2.74(0.24); P = 8.8x10-29), p-cresyl-sulfate (-1.99(0.24), P = 4.6x10-16), and phenylacetylglutamine(-2.73 (0.25), P = 1.2x10-25) were inversely associated with eGFR in a large population base cohort (TwinsUK, n = 4439) with minimal renal function decline. In a sub-sample of 855 individuals, we analysed metabolite associations with 16S gut microbiome profiles (909 profiles, QIIME 1.7.0). Three Operational Taxonomic Units (OTUs) were significantly associated with indoxyl-sulfate and 52 with phenylacetylglutamine after multiple testing; while one OTU was nominally associated with p-cresyl sulfate. All 56 microbial members belong to the order Clostridiales and are represented by anaerobic Gram-positive families Christensenellaceae, Ruminococcaceae and Lachnospiraceae. Within these, three microbes were also associated with eGFR. CONCLUSIONS: Our data suggest that indoxyl-sulfate, p-cresyl-sulfate and phenylacetylglutamine are early markers of renal function decline. Changes in the intestinal flora associated with these metabolites are detectable in early kidney disease. Future efforts should dissect this relationship to improve early diagnostics and therapeutics strategies.

Risk of progression to high-grade anal intraepithelial neoplasia in HIV-infected MSM.

OBJECTIVE: To assess the value of several factors to predict the risk of progression to high-grade anal intraepithelial neoplasia (HGAIN) in a cohort of HIV-infected MSM. DESIGN: Longitudinal study of 556 HIV-infected MSM who underwent screening for anal dysplasia (include anal cytology and high-resolution anoscopy at each visit). METHODS: Progression rate to HGAIN was estimated by Kaplan-Meier analysis. Predictors of progression were assessed by Cox-proportional hazards regression. RESULTS: Sixty-eight incidents HGAIN cases over 649 person-years of follow-up were diagnosed, resulting in a progression rate of 10.5 cases/100 person-years [95% confidence interval (CI), 8.1-13.3). The cumulative incidence of HGAIN was 7.2% at 12 months (95% CI, 4.3-10.1) and 16.2% at 24 months (95% CI, 11.7-20.7). Independent risk factors for progression were as follows: abnormal cytology [hazard ratio (HR), 2.5 (95% CI, 1.2-4.9) if low-grade squamous intraepithelial lesion, HR 2.76 (95% CI, 1.4-5.3) if atypical squamous cells of uncertain significance and HR 7.73 (95% CI, 2.3-25.4) if high-grade squamous intraepithelial lesion], abnormal high-resolution anoscopy (HR 3.57; 95% CI, 2-6.4) and infection by 16 or 18 human papillomavirus (HR 1.63; 95% CI, 1-2.6). To be receiving HAART (HR 0.4; 95% CI, 0.2-0.7) and have stable sexual couple (HR 0.62; 95% CI, 0.4-0.9) were protective factors. Patients with favorable predictors had an incident rate of 2.86 cases/100 person-years (95% CI, 3.5-10.3). CONCLUSION: The rate of progression to HGAIN varies according to different predictors that should be considered when assessing the particular risk of each patient. Patients with low risk of progression could be screened at longer intervals. BRIEF SUMMARY: We describe the risk of progression to HGAIN in a cohort of 556 HIV-infected MSM. The incidence rate of HGAIN varies widely according to different predictors. These factors should be considered when assessing the particular risk of each patient.

Prevalence and Factors Associated with Vitamin D Deficiency and Hyperparathyroidism in HIV-Infected Patients Treated in Barcelona.

Vitamin D deficiency is an important problem in patients with chronic conditions including those with human immunodeficiency virus (HIV) infection. The aim of this cross-sectional study was to identify the prevalence and factors associated with vitamin D deficiency and hyperparathyroidism in HIV patients attended in Barcelona. Cholecalciferol (25OH vitamin D3) and PTH levels were measured. Vitamin D insufficiency was defined as 25(OH) D < 20 ng/mL and deficiency as <12 ng/mL. Hyperparathyroidism was defined as PTH levels >65 pg/mL. Cases with chronic kidney failure, liver disease, treatments or conditions potentially affecting bone metabolism were excluded. Among the 566 patients included, 56.4% were exposed to tenofovir. Vitamin D insufficiency was found in 71.2% and 39.6% of those had deficiency. PTH was measured in 228 subjects, and 86 of them (37.7%) showed high levels. Adjusted predictors of vitamin D deficiency were nonwhite race and psychiatric comorbidity, while lipoatrophy was a protective factor. Independent risk factors of hyperparathyroidism were vitamin D < 12 ng/mL (OR: 2.14, CI 95%: 1.19-3.82, P: 0.01) and tenofovir exposure (OR: 3.55, CI 95%: 1.62-7.7, P: 0.002). High prevalence of vitamin deficiency and hyperparathyroidism was found in an area with high annual solar exposure.

Enfermedades infecciosas cutáneas importadas / No disponible

La inmigración y los viajes a países tropicales,suponen un aumento en la incidencia de enfermedadesimportadas, llamadas así por ser contraídasen otros países, especialmente los situados en unalatitud tropical.Los problemas de salud más comunes al regreso del trópicoson la diarrea (70%), seguida del síndrome febril (11-19%) y en tercer lugar los problemas cutáneos (15%).Las dermatopatías importadas pueden estar en elcontexto de una enfermedad sistémica o constituirpor si misma un problema único y localizado.Los problemas dermatológicos importados más comunesson picaduras de insecto, larva migrans cutánea,reacciones alérgicas, infecciones bacterianas (heridasinfectadas y abscesos), dermatitis por artrópodos,miasis, tungiasis, urticaria, fiebre, exantema, leishmaniasiscutáneas y quemaduras. Se considera quehasta un 3% de las personas procedentes de latitudestropicales presentarán dermatopatías y la mayoría decasos (61%) aparecen estando aún en aquel país.El tratamiento de las parasitosis será específico(mebendazol, ivermectina o albendazol), el de lasinfecciones bacterianas, los antimicrobianos deprimera elección en infecciones cutáneas (amoxicilina-clavulánico, clindamicina) administrados porvía oral o tratamiento local según la entidad de laclínica. Los procesos alérgicos e inflamatorios setratarán sintomáticamente(AU)

Inmigration and travels to tropical countrys, are thecause of incidence growing of skin imported infectiousdiseases, usually fron tropical countrys.The most common clinical problems returningfrom tropical latitudes are diarrhoea (70%), fever(11-19%), and in thirth place skin lesions.Importedskin diseases can be in the context of sistemicdiseases or to be an unic and localized problem.The imported skin lesions mor common are insectbites, cutaneous larva migrans, allergys and bacterialinfections, arthropod-reactive dermatitis,myasis, tungiasis, urticaria, fever, rush, cutaneusleishmaniasis and burns. About 3% of the peoplecomming from tropical countrys will present skinlesiond and the mayority of cases (61%) to appearbefore to come back.The parasitosis treatment will be specific (mebendazol,ivermectine, albendazol), skin infections withthe antibiotics of first choice (amoxicilin-clavulanic,clindamicin) per os o local treatment dependingof the clinical problem. Allergys and inflamatoryproblems will be symptomatic treated(AU)