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Knowledge of Human Polyomavirus (HPyV) infection in the anal area and its association with sexually transmitted infections such as Human Papillomavirus (HPV) and Human Immunodeficiency Virus (HIV) remains limited. Therefore, anal specimens from 150 individuals of both sexes were analyzed for screening purposes. HPV DNA was found in 50.7% of cases, with a predominance of high-risk (HR) genotypes. HPyV DNA was found in 39.3% of samples, with Merkel Cell Polyomavirus (MCPyV) being the most common, with a higher viral load than JCPyV and BKPyV. In addition, MCPyV viral load increased in people living with HIV (PLWH) with HPV infection (p < 0.0001)., (© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.)

The International Anal Neoplasia Society (IANS) developed consensus guidelines to inform anal cancer screening use among various high-risk groups. Anal cancer incidence estimates by age among risk groups provided the basis to identify risk thresholds to recommend screening. Guided by risk thresholds, screening initiation at age 35 years was recommended for men who have sex with men (MSM) and transgender women (TW) with HIV. For other people with HIV and MSM and TW not with HIV, screening initiation at age 45 years was recommended. For solid organ transplant recipients, screening initiation beginning from 10 years post-transplant was recommended. For persons with a history of vulvar precancer or cancer, screening initiation was recommended starting within 1 year of diagnosis of vulvar precancer or cancer. Persons aged ≥45 years with a history of cervical/vaginal HSIL or cancer, perianal warts, persistent (>1 year) cervical HPV16, or autoimmune conditions could be considered for screening with shared decision-making, provided there is adequate capacity to perform diagnostic procedures (high-resolution anoscopy [HRA]). Anal cytology, high-risk (hr) human papillomavirus (HPV) testing (including genotyping for HPV16), and hrHPV-cytology co-testing are different strategies currently used for anal cancer screening that show acceptable performance. Thresholds for referral for HRA or follow-up screening tests are delineated. These recommendations from IANS provide the basis to inform management of abnormal screening results, considering currently available screening tools. These guidelines provide a pivotal foundation to help generate consensus among providers and inform the introduction and implementation of risk-targeted screening for anal cancer prevention., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Purpose: Human Papillomavirus (HPV) in semen represents a controversial topic. Recent evidence suggests a correlation with poor semen quality, but its detection is still unstandardized in this biological fluid. Thus, the aims of this study were to verify the ability of nested PCR to reveal HPV-DNA in semen; to evaluate association of seminal HPV with sperm parameters and risk factors for infection; to investigate the rate of HPV-DNA positivity in patients with and without risk factors; to assess HPV transcriptional activity., Methods: We enrolled sexually active men and collected clinical and anamnestic data during andrological and sexually transmitted infections (STIs) evaluation. For each patient, we performed semen analysis and nested PCR to detect HPV-DNA in semen. In positive semen samples, we proceeded with genotyping and RNA quantification to detect HPV transcriptional activity., Results: We enrolled 185 men (36.0 ± 8.3 years), of which 85 with (Group A) and 100 without HPV risk factors (Group B). Nested PCR was able to reveal HPV-DNA in semen, discovering a prevalence of 8.6% (11.8% in Group A and 6% in Group B, respectively). We observed no correlation between sperm quality and seminal HPV. Genital warts and previous anogenital infection were significantly associated with the risk of HPV positivity in semen. Moreover, no viral transcriptional activity was detected in positive semen samples., Conclusions: Our study suggests that searching for seminal HPV could be important in patients both with and without risk factors, especially in assisted reproduction where the risk of injecting sperm carrying HPV-DNA is possible., (© 2023. The Author(s).)

Human papillomaviruses (HPVs) commonly infect the anogenital mucosa; most infections are transient, but a fraction of those caused by high-risk (HR) types persist and may lead to anogenital cancer. The epidemiology of HPV genotypes in anal infections in groups at different risk for anal cancer has not been well described in Italy. This retrospective study reports the results of HPV DNA testing and complete genotyping performed on anal swabs from 691 female and male patients attending proctology clinics in Rome during 2012-2021; one-third had repeated testing. Cumulative HPV positivity in 1212 anal swabs was approximately 60%, was not age related, and showed an increasing trend over the study period. HPV rates differed significantly by sex and HIV status: HIV-negative women had the lowest (43.6%) and HIV-positive men the highest (83.5%) HPV prevalence. HIV-positive men had more oncogenic HPV genotypes detected, more multiple infections, and the highest frequency of persistent infections. Two-thirds of all infections were vaccine-preventable. This study found that anal HPV infection rates are still elevated and even increasing in groups at low and high risk of developing anal cancer. Prevention programs need to be improved to reduce rates of anal infection in young women and men.

Functional and structural damage of the intestinal mucosal barrier significantly contribute to translocation of gut microbial products into the bloodstream and are largely involved in HIV-1 associated chronic immune activation. This microbial translocation is largely due to a progressive exhaustion of intestinal macrophage phagocytic function, which leads to extracellular accumulation of microbial derived components and results in HIV-1 disease progression. This study aims to better understand whether the modulation of gut microbiota promotes an intestinal immune restoration in people living with HIV (PLWH). Long-term virologically suppressed PLWH underwent blood, colonic, and fecal sampling before (T0) and after 6 months (T6) of oral bacteriotherapy. Age- and gender-matched uninfected controls (UC) were also included. 16S rRNA gene sequencing was applied to all participants' fecal microbiota. Apoptosis machinery, mitochondria, and apical junctional complex (AJC) morphology and physiological functions were analyzed in gut biopsies. At T0, PLWH showed a different pattern of gut microbial flora composition, lower levels of occludin (p = 0.002) and zonulin (p = 0.01), higher claudin-2 levels (p = 0.002), a reduction of mitochondria number (p = 0.002), and diameter (p = 0.002), as well as increased levels of lipopolysaccharide (LPS) (p = 0.018) and cCK18 (p = 0.011), compared to UC. At T6, an increase in size (p = 0.005) and number (p = 0.008) of mitochondria, as well as amelioration in AJC structures (p < 0.0001) were observed. Restoration of bacterial richness (Simpson index) and biodiversity (Shannon index) was observed in all PLWH receiving oral bacteriotherapy (p < 0.05). Increased mitochondria size (p = 0.005) and number (p = 0.008) and amelioration of AJC structure (p < 0.0001) were found at T6 compared to T0. Moreover, increased occludin and zonulin concentration were observed in PLWH intestinal tracts and decreased levels of claudin-2, LPS, and cCK18 were found after oral bacteriotherapy (T0 vs. T6, p < 0.05 for all these measures). Oral bacteriotherapy supplementation might restore the balance of intestinal flora and support the structural and functional recovery of the gut mucosa in antiretroviral therapy treated PLWH., (© 2022 Wiley Periodicals LLC.)

Objective: To assess evidence on the efficacy of adjuvant human papillomavirus (HPV) vaccination in patients treated for HPV-related disease across different susceptible organ sites., Methods: A systematic review was conducted to identify studies addressing the efficacy of adjuvant HPV vaccination on reducing the risk of recurrence of HPV-related preinvasive diseases. Results were reported as mean differences or pooled odds ratios (OR) with 95% confidence intervals (95% CI)., Results: Sixteen studies were identified for the final analysis. Overall, 21,472 patients with cervical dysplasia were included: 4132 (19.2%) received the peri-operative HPV vaccine, while 17,340 (80.8%) underwent surgical treatment alone. The recurrences of CIN 1+ (OR 0.45, 95% CI 0.27 to 0.73; p = 0.001), CIN 2+ (OR 0.33, 95% CI 0.20 to 0.52; p < 0.0001), and CIN 3 (OR 0.28, 95% CI 0.13 to 0.59; p = 0.0009) were lower in the vaccinated than in unvaccinated group. Similarly, adjuvant vaccination reduced the risk of developing anal intraepithelial neoplasia ( p = 0.005) and recurrent respiratory papillomatosis ( p = 0.004). No differences in anogenital warts and vulvar intraepithelial neoplasia recurrence rate were observed comparing vaccinated and unvaccinated individuals., Conclusions: Adjuvant HPV vaccination is associated with a reduced risk of CIN recurrence, although there are limited data regarding its role in other HPV-related diseases. Further research is warranted to shed more light on the role of HPV vaccination as adjuvant therapy after primary treatment.

Bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) is a recommended once-daily single tablet regimen for the treatment of people living with HIV-1 (PLWH). We aimed to assess efficacy, safety and tolerability of BIC/FTC/TAF among PLWH, with a specific focus on people older than 55 years. Thus, we recruited an observational retrospective real-life cohort including all PLWH who underwent a therapeutic switch to BIC/FTC/TAF, independently from the provenience treatment regimen. After 48 weeks of follow-up, 147 PLWH were included and 93 were older than 55 years. PLWH with HIV-RNA < 37 copies/mL increased from 140 to 146 ( p < 0.033). Among the overall population, we observed an increase in CD4 + T cells count by 30.1% ( p -value < 0.001), in CD8 + T cells count by 7.1% ( p -value = 0.004) and in CD4 + /CD8 + ratio by 21.5% ( p -value < 0.001). Lipidic profile was characterized by decreasing total cholesterol/HDL ratio by 8% ( p -value < 0.001) and LDL by 6.8% ( p -value = 0.007). Total body weight increased by 1.8% ( p -value = 0.014) and BMI by 4.2% ( p -value < 0.001), even remaining within the healthy range. Hepatic and renal profile were not altered by the switch, nor were adverse events and/or discontinuations events detected. In conclusion, BIC/FTC/TAF is effective, safe and well tolerated in real life and among PLWH older than 55.

Background: Anal HPV infection, anal dysplasia and, ultimately, anal cancer are particularly common in HIV-infected men who have sex with men. Treatment of anal dysplasia, aiming to prevent evolution to squamous cell carcinoma of the anus, is currently limited to direct ablation and/or application of topical therapy. The aim of the present study is to investigate the effect of oral bacteriotherapy (Vivomixx® in EU, Visbiome® in USA) on anal HPV infection and HPV-related dysplasia of the anal canal in HIV-infected men who have sex with men., Methods: In this randomized, placebo-controlled, quadruple-blinded trial (NCT04099433), HIV-positive men who have sex with men with anal HPV infection and HPV-related dysplasia were randomized to receive oral bacteriotherapy or placebo for 6 months. Anal HPV test, anal cytology and high resolution anoscopy with biopsies of anal lesions were performed at baseline and at the end of the study. Safety and tolerability of oral bacteriotherapy were also evaluated. Interim analysis results were presented., Results: 20 participants concluded the study procedures to date. No serious adverse events were reported. In respect to participants randomized to placebo, individuals in the experimental arm showed higher rate of anal dysplasia regression ( p = 0.002), lower rate of onset of new anal dysplasia ( p = 0.023) and lower rates of worsening of persistent lesions ( p = 0.004). Clearance of anal HPV infection was more frequently observed in the bacteriotherapy group ( p = 0.067)., Conclusion: Being an interim analysis, we limit ourselves to report the preliminary results of the current study. We refer the conclusions relating to the possible effectiveness of the intervention to the analysis of the definitive data.

Given human immunodeficiency virus-1 (HIV-1)-infected patients have alterations in the type I interferon (IFN-I) pathway and are also at elevated risk of atherosclerosis, we evaluated IFN-I response and subclinical cardiovascular disease (CVD) association in HIV-1-infected patients. Transcript levels of IFN-α/β and IFN-stimulated gene 56 (ISG56) were evaluated by RT/real-time PCR in peripheral blood mononuclear cells collected from asymptomatic HIV-1-positive male patients at high risk of developing CVD (n = 34) and healthy subjects (n = 21). Stenosis degree (≥ or <50%), calcium volume score, calcium Agatston score, and myocardial extracellular volume were examined by coronary computerized tomography scan. Carotid intima-media thickness (cIMT), Framingham risk score, atherosclerotic cardiovascular disease (ASCVD) score, and risk score developed by data collection on adverse effects of anti-HIV drugs (D:A:D) were also measured. Increased IFN-α, IFN-β, and ISG56 levels were observed in all HIV-1-infected males compared to healthy controls (p < .001 for all genes analyzed). HIV-1-infected patients with a stenosis degree ≥50% showed a higher Framingham risk score (p = .019), which was correlated with IFN-β and ISG56 levels. HIV-1-infected males with enhanced IFN-I levels and stenosis displayed a higher ASCVD calculated risk (p = .011) and D:A:D score (p = .004). Also, there was a trend toward higher IFN-α and ISG56 mRNA levels in HIV-1-positive patients with an increased cIMT (p > .05). Dysregulation of IFN-I response might participate in the pathogenesis of HIV-1-associated CVD., (© 2021 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Background: Mounting evidence suggests SARS-CoV-2 may impact on host microbiota and gut inflammation, infecting intestinal epithelial cells. This possible link and its implications can be investigated by observing the effects of modulation of the microbial flora in patients with COVID-19. The aim of this study was to compare the rate of mortality, the need of ICU hospitalization and the length of hospitalization in patients with severe COVID-19 pneumonia who received the best available therapy (BAT) vs. patients treated with BAT and supplemented with oral bacteriotherapy. Methods: This retrospective, observational cohort study included 200 adults with severe COVID-19 pneumonia. All patients received therapeutic regimens including low molecular weight heparin plus one or more between hydroxychloroquine, azithromycin, antivirals, and Tocilizumab. Oral bacteriotherapy was used as complementary treatment. Results: Out of the 200 patients, 112 received BAT without oral bacteriotherapy, and 88 BAT with oral bacteriotherapy. Crude mortality was 22%. Eleven percent died in the group of patients treated with BAT plus oral bacteriotherapy vs. 30% subjects in the group of patients managed only with BAT ( p < 0.001). By multivariate analysis, the age >65 years, CRP >41.8 mg/L, Platelets <150.000 mmc, and cardiovascular events were associated with the increased risk of mortality. Oral bacteriotherapy was an independent variable associated with a reduced risk for death. Despite large prospective trials are needed, this study highlights a possible role for oral bacteriotherapy in the management of patients hospitalized for COVID-19 pneumonia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ceccarelli, Borrazzo, Pinacchio, Santinelli, Innocenti, Cavallari, Celani, Marazzato, Alessandri, Ruberto, Pugliese, Venditti, Mastroianni and d'Ettorre.)

To investigate the effects of oral bacteriotherapy on intestinal phenylalanine and tyrosine metabolism, in this longitudinal, double-arm trial, 15 virally suppressed HIV+ individuals underwent blood and fecal sample collection at baseline and after 6 months of oral bacteriotherapy. A baseline fecal sample was collected from 15 healthy individuals and served as control group for the baseline levels of fecal phenylalanine and tyrosine. CD4 and CD8 immune activation (CD38 + ) was evaluated by flow cytometry. Amino acid evaluation on fecal samples was conducted by Proton Nuclear Magnetic Resonance. Results showed that HIV+ participants displayed higher baseline phenylalanine/tyrosine ratio values than healthy volunteers. A significand reduction in phenylalanine/tyrosine ratio and peripheral CD4 + CD38 + activation was observed at the end of oral bacteriotherapy. In conclusion, probiotics beneficially affect the immune activation of HIV+ individuals. Therefore, the restoration of intestinal amino acid metabolism could represent the mechanisms through which probiotics exert these desirable effects.

Objectives: Gender-specific studies remain a neglected area of biomedical research. Recent reports have emphasized that sex-related biological factors may affect disease progression during HIV-1 infection. The aim of this study was to investigate the influence of sex on the levels of immune activation in the gut and in peripheral blood of individuals with HIV treated with fully suppressive antiretroviral therapy (ART)., Methods: Thirty individuals with HIV undergoing long-term fully suppressive ART were enrolled in this study. Lamina propria lymphocytes (LPL) and peripheral blood mononuclear cells (PBMCs) were isolated from gut biopsies collected by pancolonoscopy and peripheral blood samples. The expression of markers of immune activation was evaluated by multi-parametric flow cytometry. This is a sub analysis of ClinicalTrials.gov Identifier: NCT02276326 RESULTS: We observed differences in the levels of immune activation in the gut and in PBMCs, with values higher in the gut compartment compared to PBMCs. In addition, we found that the mean value of the levels of immune activation was higher in the women than in the men. Finally, we measured the markers of immune activation by mean relative difference (MRD) and confirmed the higher value in the women., Conclusion: A significant sex-related difference in the level of immune activation was observed in a population of individuals with HIV on long-term ART. A more complete characterization of these differences may support the introduction of sex-specific approaches in the clinical management of individuals with HIV.

Several studies evidenced that a sedentary lifestyle is related with higher levels of systemic inflammation and highlighted that physical activity can trigger anti-inflammatory effects. To evaluate the impact of self-prescribed physical activity on fitness status, metabolism, inflammation and immune-activation in people living with HIV, an interim analysis of the results of the clinical trial PRIMO (NCT03392805) was performed. Patients enrolled were divided in 2 groups on the basis of self-prescribed physical activity: a physically active group (self-prescribed physical activity) and a sedentary group. Physical fitness was evaluated by sport medicine specialists and related to nutritional status, anthropometric variables, adipokines levels (adiponectin, leptin, resistin), peripheral immune-activation (CD38, HLA-DR on CD4 and CD8), and plasma inflammatory markers (IL-6 and TNF-α). The physically active group had a better profile in anthropometric measures and aerobic fitness but did not show lower levels of immune-activation compared to sedentary group. Also serum IL-6, TNF-α, and adipokines levels showed no statistical differences. On the basis of these data, a regular self-organized physical activity seems useful to improve cardio-respiratory fitness, but unable to control HIV-related immune-activation.

Objective: To investigate whether a probiotic supplementation to cART patients modifies the cerebrospinal fluid (CSF) proteome and improves neurocognitive impairment., Methods: 26 CSF samples from 13 HIV-positive patients [six patients living with HIV (PLHIV) and seven patients with a history of AIDS (PHAIDS)] were analyzed. All patients underwent to neurocognitive evaluation and blood sampling at baseline and after 6 months of oral bacteriotherapy. Immune phenotyping and activation markers (CD38 and HLA-DR) were evaluated on peripheral blood mononuclear cells (PBMC). Plasma levels of IL-6, sCD14, and MIP-1β were detected, by enzyme-linked immunosorbent assay (ELISA). Functional proteomic analysis of CSF sample was conducted by two-dimensional electrophoresis; a multivariate analysis was performed by principal component analysis (PCA) and data were enriched by STRING software., Results: Oral bacteriotherapy leads to an improvement on several cognitive test and neurocognitive performance in both groups of HIV-positive subjects. A reduction in the percentage of CD4 + CD38 + HLA-DR + T cells was also observed at peripheral level after the probiotic intake (p = 0.008). In addition, the probiotic supplementation to cART significantly modifies protein species composition and abundance at the CSF level, especially those related to inflammation (β2-microglobulin p = 0.03; haptoglobin p = 0.06; albumin p = 0.003; hemoglobin p = 0.003; immunoglobulin heavy chains constant region p = 0.02, transthyretin p = 0.02) in PLHIV and PHAIDS., Conclusions: Our results suggest that oral bacteriotherapy as a supplement to cART could exert a role in the amelioration of inflammation state at peripheral and CNS level.

Background: A wide debate is ongoing regarding the role of cutaneous dysbiosis in the pathogenesis and evolution of difficult-to-treat chronic wounds. Nowadays, probiotic treatment considered as an useful tool to counteract dysbiosis but the evidence in regard to their therapeutic use in the setting of difficult-to-treat cutaneous ulcers is still poor., Aim: CLINICAL REPORT: An 83-year-old woman suffering a critical limb ischemia and an infected difficult-to-treat ulcerated cutaneous lesion of the right leg, was complementary treated with local application of a mixture of probiotic bacteria., Methods: Microbiological and metabolomic analysis were conducted on wound swabs obtained before and after bacteriotherapy., Results: During the treatment course, a progressive healing of the lesion was observed with microbiological resolution of the polymicrobial infection of the wound. Metabolomic analysis showed a significant difference in the local concentration of propionate, 2-hydroxyisovalerate, 2-oxoisocaproate, 2,3-butanediol, putrescine, thymine, and trimethylamine before and after bacteriotherapy., Conclusion: The microbiological and metabolomic results seem to confirm the usefulness of complementary probiotic treatment in difficult-to-treat infected wounds. Further investigations are needed to confirm these preliminary findings.

Introduction : Asymptomatic neurosyphilis (ANS) is a disease that is difficult to diagnose in people living with HIV (PLWH). The European Guidelines on the management of syphilis suggest that ANS should be suspected and thus the lumbar puncture (LP) should be performed in cases of (1) late syphilis (acquired >2 years previously), (2) CD4 + cells ≤ 350/mm 3 and/or a serum Venereal Disease Research Laboratory/Rapid Plasma Reagin (VDRL/RPR) title > 1:32, (3) "serological failure" after syphilis therapy, and (4) the use of alternative treatment for syphilis. In the present study, we aimed to verify the accuracy of the guideline's criteria for the indication of LP in the suspicion of ANS in a cohort of PLWH. Methods : This retrospective study was carried out in a cohort of PLWH referred at a single medical center of a large academic hospital in Italy. Clinical and laboratory data of patients diagnosed with late syphilis were extracted from the cohort and analyzed. The European Guidelines of syphilis were adopted for patient management. Results : Out of a cohort of 713 PLWH, only 51 (7%) had a diagnosis of late syphilis and were therefore included in the study. Thirty-one subjects (61%) met one or more diagnostic criteria to perform LP: 39% (12/31) of patients undergoing LP had a diagnosis of ANS. The accuracy of predictive criteria for ANS, suggested by the guidelines, was 62% for RPR > 1:32 and 74% for CD4 + ≤ 350 cc/µL. The simultaneous occurrence of both criteria (RPR > 1:32 plus CD4 + ≤ 350 cc/µL) achieved a diagnostic accuracy of 59%. Interestingly, only 17% of patients who underwent LP for serological failure were eventually diagnosed positive for ANS. Conclusion : Asymptomatic neurosyphilis represents a challenging, but not uncommon, diagnosis. Therefore, it requires a careful investigation. Low CD4 + cell count and RPR > 1:32 remain excellent predictors of neurosyphilis, but have become the only acceptable predictors of ANS in PLWH. "Serologic failure" should be regarded with caution as a criterion to perform LP in order to investigate possible ANS in HIV-syphilis coinfected patients asymptomatic for neurological disorders. The retrospective nature of this single-site study may represent a limit to the interpretation of the data. Thus, larger clinical studies on the topic are warranted.

Introduction : Recent insights show that gut-mucosal immunity and intestinal microbiota play a key role in the pathogenesis of HIV infection. Alterations in the composition of intestinal flora (dysbiosis) could be associated with an impaired intestinal epithelium barrier activity and an impaired mucosal immunity function, significantly contributing to microbial translocation which is considered a major driver of chronic immune activation. Areas covered : This article provides an overview on the novel trends in probiotic therapy application. A particular emphasis is addressed to the importance of probiotics as a novel strategy to attenuate or prevent gastrointestinal involvement and to improve gut-mucosal immunity in HIV-infected subjects. Therefore, opportunities, limits and methodological criticalities of supplementation with probiotic therapy are considered and analyzed. Expert opinion : Use of probiotics is emerging as a novel strategy to manage dysbiosis and gut-mucosal impairment, to reduce immune activation and to limit a number of non-AIDS-related disorders. However, despite the growing use of probiotic therapy, mechanisms by which oral bacteria intake exhibits its effects are strain-related and disease-specific, hence clinicians need to take these two factors into consideration when suggesting probiotic supplementation to HIV-infected patients.

Background: Candida albicans ' ability to evade host immune responses represents a serious threat for vulnerable patients., Objectives: To investigate if (1) feces from healthy subjects exert anti- Candida activity; (2) fecal anti- Candida activity is modified by probiotic administration and (3) different probiotic differently modulate anti- Candida activity., Patients and Methods: Feces from healthy donors were analyzed before and after seven days of dietary supplementation with two different probiotic formulations (VSL#3 ® ; Vivomixx ® ). Candida albicans was cultured with decreasing concentrations of diluted feces, obtained before and after the treatment period. The relationship between anti- Candida activity of feces, interferon-α, anti-interferon-α antibodies and the expression of MxA, ISG15 and IFNAR1 was also evaluated., Results: Feces obtained prior to probiotic intake and feces collected after supplementation with VSL#3 ® did not affect Candida albicans growth. On the contrary, a 3log 10 inhibition of Candida development was observed after Vivomixx ® intake. Interferon-α played a role in the inhibition of Candida growth., Conclusion: Fecal anti- Candida activity was not observed prior to probiotic supplementation. Seven days of administration of Vivomixx ® increased fecal anti- Candida activity, the same effect was not observed after intake of VSL#3 ® . The probiotic-induced anti- Candida activity seems to be related to an increased local production and release of interferon-α. Clinical trials are needed to determine if a short pretreatment with specific probiotic formulations may increase anti- Candida defenses in patients at risk.

Objective: The influence of sex on gut mucosal T-cell response in HIV-1 infection remains largely unknown. We explored whether the frequencies of interferon-γ and/or IL-17 producing naive, T central memory and T effector memory (TEM) CD4+ (Th1, Th17) and CD8+ T (Tc1, Tc17) cells measured in gut and peripheral districts differed between female and male HIV-1-infected patients., Methods: Thirty long-term-treated HIV-1-infected individuals were enrolled. The frequencies of Th1, Th17, Tc1, Tc17-cell subsets (single and double) were evaluated by multiparametric flow cytometry in lamina propria lymphocytes and peripheral blood mononuclear cells (PBMC)., Results: A sex-based pattern was recorded in the differences of Th1, Th17, Tc1, Tc17-cell subset (single and double) frequencies between gut and peripheral blood. Female patients had stronger alterations in the gut mucosal T-cell repertoire, especially increased Th1, Th17, and Th1/Th17-cell subset frequencies, compared with the blood district than their male counterparts. Higher naive Tc1, Tc17, Tc1/Tc17, TEM Tc17, and TEM Tc1/Tc17 levels were also recorded in the gut mucosa than in the PBMC of HIV-1-infected women. Males and females also differed in their gut T-cell response, with women being characterized by higher Th1, Th17, Tc1, Tc17, and Th1/Th17 cells subset levels than men. By contrast, only TEM Th1/Th17 and TEM Tc17 in PBMC differed between males and females., Conclusion: Sex-based differences observed in the gut T-cell response of HIV-1-infected patients might contribute to the disease dimorphism.

Objectives: The aim of the study was to investigate if the supplementation with multistrain probiotics may be able to modulate T cell response in HIV-1 infected patients and to evaluate the anti-HIV activity of probiotic by studying fecal water (FW) samples., Methods: Three HIV-1-positive patients (Pt1, Pt2 and Pt3) on long-term suppressive combined antiretroviral therapy (cART) received a specific multi-strain probiotic supplementation (Vivomixx ®), for six months (T6). Levels of T cell subsets were evaluated by flow cytometry. Anti- HIV activity of FW samples was evaluated in vitro., Results: CD4+ T cells levels increased in all HIV-1 infected patients whereas activation markers (CD38 and HLA-DR) were decreased both on CD4+ and CD8+ T cells. FW samples presented an increased inhibitory activity against HIV-1 compared to T0 (FW-Pt1: T0 =40%, T6 = 65% of reduction; FW Pt2: T0 = 26%, T6 = 46% of reduction; FW Pt3: T0 = 47%, T6 = 94% of reduction)., Discussion: Our data suggest that the administration of the specific probiotic formulation improves the antiviral status of people living with HIV-1 under cART, also modulating T cell response., Conclusion: Anti-HIV activity of FW may have several public health and social implications for sexually transmitted diseases that need to be further explored., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: Chronic immune activation and poor T-cell immune response are strongly associated with disease progression and pathogenesis of both hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-1 infections. Little is known about the impact of anti-HCV Interferon (IFN)-free direct-acting antiviral (DAA) therapy on the systemic T-cells activation and patterns of peripheral T-cells producing pro-inflammatory cytokines., Patients and Methods: Forty-five subjects including 18 HCV mono-infected, 17 HCV/HIV-1 co-infected patients under antiretroviral therapy (ART), and 10 healthy controls (HCs) were recruited. Blood samples were collected at baseline (T0) and 12 weeks after the end of DAA therapy (T1). Cell phenotypes (CD3, CD4, CD8), activation markers (CD38 and HLA-DR), and frequency of IFN-γ, interleukin (IL)-17, and IL-22 producing CD4+ and CD8+ T-cells were measured by flow cytometry. Plasma levels of related cytokines were also measured by enzyme-linked immunosorbent assay (ELISA)., Results: Both HCV, and HCV/HIV-1 patients before and after therapy, showed significant higher percentages of any T-cell subset expressing CD38 and/or HLA-DR compared to HCs. No differences were observed in T-cells activation at T1 compared to T0 in patient groups, and when HCV patients were compared to HCV/HIV-1 group (P>0.05). After therapy, the potential of total circulating T helper (Th) and T cytotoxic (Tc) cells producing IFN-γ, IL-17, and IL-22 were increased. Plasma level of IFN-γ at baseline was showed difference compared to HCs, and significantly reduced after therapy (P<0.05)., Conclusion: Total T-cells immune response enhances after therapy, however, the state of immune activation may remain elevated for a longtime after the end of treatment and contribute to post-Sustained Virologic Response (SVR) consequences., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Introduction: Here we present the case of a 56-year-old human immunodeficiency virus (HIV)-infected man with multiple anal condylomas and positivity for human papilloma virus (HPV) 18 on anal brushing. Biopsies of the anal mucosa led to the diagnosis of Bowen's disease and a subsequent pelvic magnetic resonance imaging (MRI) scan evidenced multiple reactive lymphoadenopathies and large intra-anal condylomas. The patient was treated with a complete excision of Bowen's lesion and with a 4 months course of supplementation with a high concentration multistrain probiotic formulation administered orally and by rectal instillation with the purpose to reduce local inflammation and to enhance local mucosal immunity., Conclusion: An MRI performed at the end of the supplementation period evidenced the clearance of the anal condylomas previously described and no evidence of residual lymphadenopathies. Trials are therefore required to confirm this therapeutic possibility and for a better understanding of the mechanisms by which this specific probiotic formulation interacts with local epithelium when administered by the anal route.

Background: Gut microbiota has metabolic activity which influences mucosal homeostasis, local and systemic immune responses, and other anatomical systems (i.e., brain). The effects of dysbiosis are still poorly studied in Human Immunodeficiency Virus-1 (HIV-1) positive subjects and insufficient data are available on the impairment of the gut-brain axis, despite neurocognitive disorders being commonly diagnosed in these patients. This study evaluated the impact of a probiotic supplementation strategy on intrathecal immune activation and cognitive performance in combined antiretroviral therapy (cART) treated HIV-1 infected subjects., Methods: Thirty-five HIV-1 infected individuals were included in this study. At baseline (T0) a battery of tests was administered, to evaluate neurocognitive function and a lumbar puncture was performed to determine neopterin concentration in cerebrospinal fluid (CSF), as a marker of Central Nervous System (CNS) immune activation. Subsequently, a subgroup of participants underwent a 6-month course of multi-strain probiotics supplementation; this intervention group was evaluated, after probiotic treatment, with a second lumbar puncture and with repeated neurocognitive tests., Results: At T0, all participants showed impaired results in at least one neurocognitive test and elevated neopterin concentrations in CSF. After supplementation with probiotics (T6), the interventional group presented a significant decrease in neopterin concentration and a significant improvement in several neurocognitive tests. In contrast, no significant modifications were observed in the neurocognitive performance of controls between T0 and T6. The CNS Penetration Effectiveness Score of antiretroviral therapy did not show an influence from any of the investigated variables., Conclusions: Multi-strain probiotic supplementation seems to exert a positive effect on neuroinflammation and neurocognitive impairment in HIV-1 infected subjects, but large trials are needed to support the concept that modulation of the gut microbiota can provide specific neurological benefits in these patients.

Background: To date, no data are available regarding the effects of probiotics on the pathway of tryptophan/serotonin metabolism among human immunodeficiency virus (HIV) 1-infected individuals. Because a condition of dysbiosis might be responsible for the altered use of tryptophan described in this population, the aim of this study was to investigate the link between probiotic supplementation and serotonin levels in combined antiretroviral therapy-treated patients and the subsistence of an interplay with inflammation., Methods: We conducted a pilot study that included 8 HIV-positive subjects. We collected blood and fecal samples before and after 6 months of probiotic supplementation, to measure the level of serotonin in serum and tryptophan in stool, the expression of CD38 and HLA-DR on peripheral CD4+ T lymphocytes (as immune activation markers), the expression of indoleamine 2,3-dioxygenase 1 messenger RNA (mRNA) and IFN-γ mRNA (as markers of tryptophan metabolism and systemic inflammation)., Results: After probiotic supplementation, we observed a significant increase in concentration of serum serotonin ( P = .008) and a decreased level of tryptophan in plasma. Moreover, a significant reduction in CD38 and HLA-DR expression on the surface of peripheral CD4+ T cells ( P = .008) and a reduced expression of indoleamine 2,3-dioxygenase 1 mRNA on peripheral blood mononuclear cells ( P = .04) were observed., Conclusions: Considering that this probiotic (Vivomixx® in EU; Visbiome® in USA) has an influence on tryptophan metabolism, larger studies on this topic are needed., Competing Interests: DECLARATION OF CONFLICTING INTERESTS: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Type I IFNs are pleiotropic cytokines that exert concerted activities in the development of antiviral responses. Regulatory T cells represent a physiologic checkpoint in the balance between immunity and tolerance, requiring fine and rapid controls. Here, we show that human regulatory T cells are particularly sensitive to the sequential effects of IFN-α. First, IFN-α exerts a rapid, antiproliferative and proapoptotic effect in vitro and in vivo, as early as after 2 d of pegylated IFN/ribavirin therapy in patients with chronic hepatitis C. Such activities result in the decline, at d 2, in circulating regulatory T cell frequency and specifically of the activated regulatory T cell subset. Later, IFN-based therapy restrains the fraction of regulatory T cells that can be polarized into IFN-γ-producing Th1-like regulatory T cells known to contribute to chronic immune activation in type 1 inflammation. Indeed, Th1-like regulatory T cell frequency significantly declines after 30 d of therapy in vivo in relation to the persistent decline of relevant IL-12 sources, namely, myeloid and 6-sulfo LacNAc-expressing dendritic cells. This event is recapitulated by experiments in vitro, providing evidence that it may be attributable to the inhibitory effect of IFN-α on IL-12-induced, Th1-like regulatory T cell polarization. In summary, our results suggest that IFN-α-driven, early regulatory T cell depletion contributes to the development of antiviral immunity, ultimately resulting in the resolution of type 1 inflammation., (© Society for Leukocyte Biology.)

HIV infection may enhance immune-activation, while little is known regarding the role of HCV infection. This study investigates the impact of HCV in HIV coinfected patients with undetectable viraemia under HAART on the levels of peripheral T cell's immune-activation. We determined T lymphocytes subsets to characterize immune-activation defined as CD38 and/or HLA-DR expression in chronic monoinfected HCV, HIV, and HIV/HCV coinfected subjects. One hundred and fifty six patients were divided into three groups: (i) 77 HIV+ patients; (ii) 50 HCV+ patients; and (iii) 29 coinfected HIV/HCV patients. The level of CD4(+) was significantly higher in HCV+ than in HIV+ or in coinfected HIV/HCV subjects. The frequencies of CD4(+) CD38(+) /HLA-DR(-) , CD4(+) CD38(-) /HLA-DR(+) and CD4(+) CD38(+) /HLA-DR(+) in HIV+ patients were comparable to those measured in coinfected patients, but statistically higher than those observed in HCV+ subjects. The percentage of CD8(+) was comparable in HIV-1+ patients and coinfected HIV/HCV but the results obtained in both groups were significantly higher compared to the results obtained in HCV patients. The level of CD8(+) CD38(+) /HLA-DR(-) showed values lower in HIV+ patients than in that monoinfected HCV and coinfected HIV/HCV patients. The frequencies of CD8(+) CD38(-) /HLA-DR(+) were higher in HIV+ patients compared to HCV+ and coinfected HIV/HCV patients. HIV/HCV coinfected group showed highest levels of CD8(+) CD38(+) /HLA-DR(+) . HIV plays a pivotal role to determine the immune activation in the host. The role of HCV needs of further investigations but our data show that HCV mainly influences the immune-activation of the pool of CD8, but also probably plays a supporting additive effect on CD4 immune-activation. J. Med. Virol. 88:1347-1356, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

CD8(+) T cells specific to caspase-cleaved antigens derived from apoptotic T cells represent a principal player in chronic immune activation. Here, we found that both apoptotic epitope-specific and hepatitis C virus (HCV)-specific CD8(+) T cells were mostly confined within the effector memory (EM) or terminally differentiated EM CD45RA(+) cell subsets expressing a dysfunctional T-helper 1-like signature program in chronic HCV infection. However, apoptotic epitope-specific CD8(+) T cells produced tumor necrosis factor α and interleukin 2 at the intrahepatic level significantly more than HCV-specific CD8(+) T cells, despite both populations expressing high levels of programmed death 1 receptor. Contextually, only apoptotic epitope-specific CD8(+) T cells correlated with both interferon-stimulated gene levels in T cells and hepatic fibrosis score. Together, these data suggest that, compared with HCV-specific CD8(+) T cells, apoptotic epitope-specific CD8(+) T cells can better sustain chronic immune activation, owing to their capacity to produce tumor necrosis factor α, and exhibit greater resistance to inhibitory signals during chronic HCV infection., (© The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Background: Recently published studies have highlighted the importance of phylogenetic and phylodynamic analyses in supporting epidemiological investigations to reconstruct the transmission network of human immunodeficiency virus. Here, we report a case of sexual transmission of human immunodeficiency virus type 1 between a man and a woman that marks once more the importance of a tightened collaboration between phylogeny and epidemiology., Case Presentation: We describe a case of human immunodeficiency virus type 1 subtype B transmission in a stable Caucasian heterosexual couple. The man was 30 years old and the woman was 21 years old at the time of their presentation to the Department of Public Health and Infectious Diseases of the University of Rome "Sapienza". The couple reported a history of drug abuse., Conclusion: Phylogenetic analysis is a powerful technique that if properly used can prove valuable in research investigations. In the case presented here, a phylogenetic analysis alongside epidemiological evidence allowed us to determine the most probable source of the human immunodeficiency virus infection. The dated tree allowed us to date the transmission event, the time point, and the direction of transmission based on the phylogeny, which agreed with the presumptive time of infection determined from clinical history-taking.

Introduction: During HIV infection the severe depletion of intestinal CD4+ T-cells is associated with microbial translocation, systemic immune activation, and disease progression. This study examined intestinal and peripheral CD4+ T-cell subsets reconstitution under combined antiretroviral therapy (cART), and systemic immune activation markers., Methods: This longitudinal single-arm pilot study evaluates CD4+ T cells, including Th1 and Th17, in gut and blood and soluble markers for inflammation in HIV-infected individuals before (M0) and after eight (M8) months of cART. From January 2010 to December 2011, 10 HIV-1 naïve patients were screened and 9 enrolled. Blood and gut CD4+ T-cells subsets and cellular immune activation were determined by flow-cytometry and plasma soluble CD14 by ELISA. CD4+ Th17 cells were detected in gut biopsies by immunohistochemistry. Microbial translocation was measured by limulus-amebocyte-lysate assay to detect bacterial lipopolysaccharide (LPS) and PCR Real Time to detect plasma bacterial 16S rDNA., Results: Eight months of cART increased intestinal CD4+ and Th17 cells and reduced levels of T-cell activation and proliferation. The magnitude of intestinal CD4+ T-cell reconstitution correlated with the reduction of plasma LPS. Importantly, the magnitude of Th17 cells reconstitution correlated directly with blood CD4+ T-cell recovery., Conclusion: Short-term antiretroviral therapy resulted in a significant increase in the levels of total and Th17 CD4+ T-cells in the gut mucosa and in decline of T-cell activation. The observation that pre-treatment levels of CD4+ and of CD8+ T-cell activation are predictors of the magnitude of Th17 cell reconstitution following cART provides further rationale for an early initiation of cART in HIV-infected individuals., Trial Registration: ClinicalTrials.gov NCT02097381.

HIV-1-associated Guillan-Barre syndrome (hGBS) is an ascendant progressive polyradiculoneuropathy described throughout the course of the viral disease, mainly associated with the acute retroviral syndrome. HGBS is occasionally described in severely immunocompromised subjects in the context of the immune reconstitution inflammatory syndrome. The case described occurred soon after the start of a combined antiretroviral treatment in an HIV-1 infected patient with ulcerative colitis in the absence of severe immunosuppression. This manifestation may be interpreted as an uncommon appearance of an immune reconstitution syndrome in the presence of a predisposing autoimmune pathology.