Influence of dietary supplementation of short-chain fatty acid sodium propionate in people living with HIV (PLHIV).

BACKGROUND: Non-AIDS-associated chronic diseases in HIV+ patients have been on the rise since the advent of antiretroviral therapy. Especially cardiovascular diseases and disruption in the gastrointestinal tract have limited health-related quality of life (QoL). Several of those complications have been associated with chronic systemic inflammation. Short-chain fatty acids (SCFA), with propionate as one of the major compounds, have been described as an important link between gut microbiota and the immune system, defining the pro- and the anti-inflammatory milieu through direct and indirect regulation of T-cell homeostasis. The effects of dietary supplementation of sodium propionate (SP) in people living with HIV (PLHIV) have not yet been investigated prior to this study. OBJECTIVES: To investigate the impact of SP uptake among PLHIV and its relevance to improve QoL, the study aimed to investigate metabolic, immunological, microbiome and patient-reported QoL-related changes post-SP supplementation with follow-up. METHODS: A prospective, non-randomized, controlled, monocentric interventional study was conducted in WIR, Center for Sexual Health and Medicine, in Bochum, Germany. 32 HIV+ patients with unaltered ART-regimen in the last three months were included. Participants were given SP for a duration of 12 weeks in the form of daily oral supplementation and were additionally followed-up for another 12 weeks. RESULTS: The supplementation of SP was well tolerated. We found an improvement in lipid profiles and long-term blood glucose levels. A decrease in pro-inflammatory cytokines and a depletion of effector T cells was observed. Regulatory T cells and IL-10 decreased. Furthermore, changes in taxonomic composition of the microbiome during follow-up were observed and improvement of items of self-reported life-quality assessment. CONCLUSION: Taken together, the beneficial impact of SP in PLHIV reflects its potential in improving metabolic parameters and modulating pro-inflammatory immune responses. Thus, possibly reducing the risk of cardiovascular disorders and facilitating long-term improvement of the gut flora.

Prediction of future cardiovascular events by Framingham, SCORE and asCVD risk scores is less accurate in HIV-positive individuals from the HIV-HEART Study compared with the general population.

OBJECTIVES: Cardiovascular diseases (CVDs) occur more often in people living with HIV (PLWH) than in the general population. It has been reported that CVD risk scores developed for the general population underestimate the CVD risk in PLWH. Performances of the Framingham Risk Score (FRS), the Systematic Coronary Risk Evaluation (SCORE) and the atherosclerotic cardiovascular disease (asCVD) risk score in PLWH were compared with the general population to quantify score-specific differences in risk prediction. METHODS: HIV-positive outpatients from the HIV-HEART (HIVH) study (n = 567) were compared with participants from the population-based Heinz Nixdorf Recall (HNR) study (n ~ 4440) both recruited from the German Ruhr area. During a follow-up time of around 5 years, the associations between the FRS and incident CVD and peripheral artery disease (CVD_pAD), SCORE and coronary heart disease (CHD), and asCVD and incident CVD were examined using logistic regression. Score performances were assessed by comparing the areas under the curve (AUCs). RESULTS: The mean ages were 52.9 ± 6.7 and 59.1 ± 7.7 years in the HIVH and HNR studies, respectively. There were fewer incident CVD events in the HNR study than in the HIVH study (CVD_pAD: 3.9% vs. 12.1%; CHD: 2.1% vs. 7.8%; CVD: 3.5% vs. 9.9%). Age- and sex-adjusted CVD risk was greater with increasing FRS, SCORE and asCVD in both cohorts, but the scores performed more accurately in the HNR than in HIVH study (AUCs FRS: 0.71 vs. 0.65; SCORE: 0.70 vs. 0.62; asCVD: 0.74 vs. 0.62). CONCLUSIONS: Associations between risk scores and future CVD were observed in both cohorts, but the score performances were less reliable in PLWH than in the general population.

Sexual behaviour, STI knowledge and Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) prevalence in an asymptomatic cohort in Ruhr-area, Germany: PreYoungGo study.

BACKGROUND AND OBJECTIVES: STIs present a significant threat to individual and public health, disproportionately affecting youth. The study aimed to evaluate (a) the prevalence of asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections among youth using a rapid assay platform, (b) the participants' sexual behaviour and STI knowledge, (c) the utility of the rapid assay in reducing diagnosis-to-treatment time. METHODS: In this study, 272 subjects (14-31 years) were included between 12/2016 and 7/2018. A questionnaire was used to collect sociodemographic data, sexual behaviour and STI knowledge. Prevalence of CT and NG infections were tested from oral, vaginal and anal swabs for women and oral, anal swabs and urine for men, using the Cepheid Xpert® CT/NG assay. Time intervals between (i) test to the time the patient were informed of the result (turn around time - TAT) and (ii) test to therapy initiation was documented. RESULTS: Of the 272 subjects (48.9% female, 48.9% male, undisclosed 2.2%), 56.6 % reported university education. 46.6% were men who have sex with men (MSM), and 47.4% of women and 63.1% of men had anal intercourse. 59.9% had previously been tested for HIV, while only 39.7% had for CT, 20.6% for NG. Among these asymptomatic youth 7.7% were positive for CT and 5.5% for NG. The localization of CT were 3.7% genital, 5.5% anal and 2.2% oral, while the corresponding localization of NG were 0.4%, 2.9%, 4.4% respectively. 91.8% of the participants were informed of a positive result within 24 h with a median TAT of 03:09 h. 73.3% initiated therapy within 24 h, with a median time from testing to therapy initiation being 06:50 h. CONCLUSION: Asypmtomatic CT and NG infections are common and often not tested in persons at risk. The Cepheid Xpert® CT/NG assay is an effective strategy as it reduces STI diagnosis-to-treatment time to less than a day.

[Diagnostic workup and treatment of sexually transmitted infections]. / Diagnostik und Therapie von sexuell übertragbaren Infektionen.

There are a number of reasons to exclude sexual transmitted infections (STI). In addition to testing patients presenting with symptoms like discharge, burning when urinating or genitals ulcers, risk-adapted STI tests should be offered. Medical history taking should include sexual orientation and practices, symptoms also of sex partners and symptom-free intervals, previous STI and other medical conditions (especially allergies against antibiotics), previous treatment, vaccination status, contraceptive methods and condom use. Clinical examination depends on anatomy, sexual practices and symptoms. It should always include the inspection of the genital and anal region, the throat and the skin. The goal is to also diagnose oral and anal STI and to provide guideline-based treatment including monitoring of outcome.

[Profile of Kaposi sarcoma patients in the competence network HIV/AIDS]. / Profil der Kaposi-Sarkom-Patienten im Kompetenznetz HIV/AIDS.

BACKGROUND: Kaposi's sarcoma (KS) represents the most common AIDS-defining neoplasm. Only very few studies regarding the course and treatment of human immunodeficiency virus (HIV)-associated KS have been carried out in Germany. OBJECTIVE: In this study the course of HIV-associated KS was observed in patients from the cohort database of the competence network for HIV/AIDS. MATERIAL AND METHODS: Data from HIV-associated KS patients from 9 German core centers from 1987 to 2011 were retrospectively collected. Kaplan-Meier curves for the recurrence and survival probability were calculated. RESULTS: In 222 patients KS was diagnosed at a median age of 38.5 ± 10.1 years. Men were almost exclusively affected (97.7%). The HIV viral load at the time of diagnosis was in 7.4% <50 copies/ml. Of the patients 55.5% developed KS with a CD4 cell count of <200 cells/µl and 9.5% with >500 cells/µl. In 68 patients KS therapy consisted exclusively of the optimization or initiation of antiretroviral therapy (ART). In addition, 71 patients were treated with pegylated liposomal doxorubicin. During the median follow-up period of 8.9 ± 4.9 years, 80.2% of the patients were free of KS recurrence. Survival rates after 5 and 10 years were 96.8% and 91.3%, respectively. CONCLUSION: Even with a good immune status HIV-associated KS occurred. An effective ART was the most important mainstay of therapy. With appropriate therapy, HIV-positive patients with KS showed a good survival rate.

MicroRNA-155 is a biomarker of T-cell activation and immune dysfunction in HIV-1-infected patients.

OBJECTIVES: MicroRNA-155 (miR-155) regulates T-cell differentiation and activation. It has also been associated with HIV infection. However, it remains unclear whether miR-155 is related to the T-cell response in HIV-infected individuals (e.g. T-cell activation and exhaustion). METHODS: We performed a cross-sectional study involving 121 HIV-1-infected patients on highly active antiretroviral therapy (HAART) and 43 HAART-naïve patients. MiR-155 levels in the peripheral blood were determined by quantitative reverse transcription-polymerase chain reaction (PCR). T-cell immune activation, exhaustion, and homeostasis were measured by determining the expression of CD38, programmed death 1 (PD-1) and CD127 via flow cytometry. RESULTS: The levels of miR-155 in total peripheral blood mononuclear cells, CD4 T cells and CD8 T cells from HIV-1-infected patients were increased (P < 0.01). Nonresponders and HAART-naïve patients also exhibited a higher percentage of CD8+ CD38+ T cells and a lower percentage of CD4+ CD127+ and CD8+ CD127+ T cells (P < 0.05). We also found higher levels of PD-1 expression on the CD4+ and CD8+ T cells of HIV-1-infected patients (P < 0.05). CONCLUSIONS: Our findings suggest that miR-155 levels in the peripheral blood of HIV-1-infected patients are increased and associated with T-cell activation. Therefore, miR-155 is a potential biomarker of the immune response following HIV-1 infection.

Reference curves for CD4 T-cell count response to combination antiretroviral therapy in HIV-1-infected treatment-naïve patients.

OBJECTIVES: The aim of this work was to provide a reference for the CD4 T-cell count response in the early months after the initiation of combination antiretroviral therapy (cART) in HIV-1-infected patients. METHODS: All patients in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) cohort who were aged ≥ 18 years and started cART for the first time between 1 January 2005 and 1 January 2010 and who had at least one available measurement of CD4 count and a viral load ≤ 50 HIV-1 RNA copies/mL at 6 months (± 3 months) after cART initiation were included in the study. Unadjusted and adjusted references curves and predictions were obtained using quantile regressions. RESULTS: A total of 28 992 patients were included in the study. The median CD4 T-cell count at treatment initiation was 249 [interquartile range (IQR) 150, 336] cells/µL. The median observed CD4 counts at 6, 9 and 12 months were 382 (IQR 256, 515), 402 (IQR 274, 543) and 420 (IQR 293, 565) cells/µL. The two main factors explaining the variation of CD4 count at 6 months were AIDS stage and CD4 count at cART initiation. A CD4 count increase of ≥ 100 cells/mL is generally required in order that patients stay 'on track' (i.e. with a CD4 count at the same percentile as when they started), with slightly higher gains required for those starting with CD4 counts in the higher percentiles. Individual predictions adjusted for factors influencing CD4 count were more precise. CONCLUSIONS: Reference curves aid the evaluation of the immune response early after antiretroviral therapy initiation that leads to viral control.

Higher rates of triple-class virological failure in perinatally HIV-infected teenagers compared with heterosexually infected young adults in Europe.

OBJECTIVES: The aim of the study was to determine the time to, and risk factors for, triple-class virological failure (TCVF) across age groups for children and adolescents with perinatally acquired HIV infection and older adolescents and adults with heterosexually acquired HIV infection. METHODS: We analysed individual patient data from cohorts in the Collaboration of Observational HIV Epidemiological Research Europe (COHERE). A total of 5972 participants starting antiretroviral therapy (ART) from 1998, aged < 20 years at the start of ART for those with perinatal infection and 15-29 years for those with heterosexual infection, with ART containing at least two nucleoside reverse transcriptase inhibitors (NRTIs) and a nonnucleoside reverse transcriptase inhibitor (NNRTI) or a boosted protease inhibitor (bPI), were followed from ART initiation until the most recent viral load (VL) measurement. Virological failure of a drug was defined as VL > 500 HIV-1 RNA copies/mL despite ≥ 4 months of use. TCVF was defined as cumulative failure of two NRTIs, an NNRTI and a bPI. RESULTS: The median number of weeks between diagnosis and the start of ART was higher in participants with perinatal HIV infection compared with participants with heterosexually acquired HIV infection overall [17 (interquartile range (IQR) 4-111) vs. 8 (IQR 2-38) weeks, respectively], and highest in perinatally infected participants aged 10-14 years [49 (IQR 9-267) weeks]. The cumulative proportion with TCVF 5 years after starting ART was 9.6% [95% confidence interval (CI) 7.0-12.3%] in participants with perinatally acquired infection and 4.7% (95% CI 3.9-5.5%) in participants with heterosexually acquired infection, and highest in perinatally infected participants aged 10-14 years when starting ART (27.7%; 95% CI 13.2-42.1%). Across all participants, significant predictors of TCVF were those with perinatal HIV aged 10-14 years, African origin, pre-ART AIDS, NNRTI-based initial regimens, higher pre-ART viral load and lower pre-ART CD4. CONCLUSIONS: The results suggest a beneficial effect of starting ART before adolescence, and starting young people on boosted PIs, to maximize treatment response during this transitional stage of development.

Asymptomatic anal sexually transmitted infections in HIV-positive men attending anal cancer screening.

BACKGROUND: HIV-positive men who have sex with men (HIV+MSM) have an increased risk for anal dysplasia and for sexually transmitted infections (STIs). OBJECTIVES: We determined the positivity rates of Chlamydia trachomatis (CT), Neisseria gonorrhoea (NG), Mycoplasma genitalium (MG) and syphilis in HIV+MSM participating in an anal cancer screening programme. METHODS: In total, 852 intra-anal swabs were collected from 503 HIV+MSM between 2012 and 2014. Anal cytology and polymerase chain reaction assays for human papillomavirus (HPV), CT, NG and MG detection were performed. The syphilis status was determined serologically. Risk factors for STIs were explored by multiple logistic regression analysis. RESULTS: In total 20·7% (104 of 503) of the patients had an STI other than HPV within the study period. The most common was CT, found in 10·9%, followed by NG (8·9%) and MG (4·2%). Early syphilis was detected in 4·6% and past syphilis in 44·5% of the HIV+MSM. Eighteen patients (3·6%) had more than one STI episode, and 90·6% of the 127 cases of STIs were asymptomatic. Age, anal HPV infection, abnormal anal cytology and previous syphilis were risk factors for STI. CONCLUSIONS: Anal STIs are frequent and mostly asymptomatic in HIV+MSM participating in anal cancer screening. STI screening should be incorporated into anal cancer screening programmes for HIV+MSM.

Viral load strategy: impact on risk behaviour and serocommunication of men who have sex with men in specialized care.

BACKGROUND: Incidence and prevalence of HIV are continuously high in German men, who have sex with men (MSM). Different transmission risk minimizing strategies have been observed. The viral load strategy rates patients unlikely to be sexually infectious if their viral load under effective therapy is stably suppressed during 6 months and no other sexually transmitted infections are present. OBJECTIVES: We aim to objectify the current popularity of the viral load strategy, the adherence to basic conditions and its impact on risk behaviour and serocommunication. Until now, no data on a German sample of HIV-positive MSM in regular specialized outpatient care are available. METHODS: Cross-sectional study with group comparisons between user group and non-user-group of the viral load strategy. Self-report questionnaires were conducted with 269 sexually active German HIV+MSM under effective treatment in specialized outpatient care. Structured interviews gathered additional information about approach to and realization of definite action levels concerning sexual risk behaviour and transmission risk minimizing strategies. RESULTS: Twenty-seven of 269 participants (10%) affirmed knowledge of having an undetectable viral load and stated this to be criteria for unprotected sexual behaviour. This subgroup reported more unprotected insertive (P = 0.018) and receptive anal intercourse (P = 0.042), more anonymous sex partners (P = 0.008) and less consistent safer sex. Analysing serocommunication, less addressing HIV/AIDS in general (P = 0.043) and less disclosing to sex partners (P = 0.023) was found, especially in anonymous settings. Differentiating serocommunication characteristics, a focus on seroguessing was depicted. CONCLUSIONS: The user group of the viral load strategy is small. But a less frequent, more reactive and assumptive serocommunication leads to an imprecise information exchange paired with higher frequency of risky behaviour, especially in anonymous settings, where frank serocommunication is often avoided. The targeted group of the viral load strategy diverges greatly from the user group.

The male ScreenING Study: prevalence of HPV-related genital and anal lesions in an urban cohort of HIV-positive men in Germany.

BACKGROUND: Human papillomaviruses (HPV) induce condylomata, anogenital cancers and their precursor lesions as anal or penile intraepithelial neoplasia (AIN/PIN). HIV-positive individuals have an increased risk for the development of anogenital HPV-induced lesions. OBJECTIVE: Estimation of the prevalence of HPV-related anogenital benign and malignant lesions in HIV-infected men attending a screening programme. METHODS: Four hundred HIV-positive men [98% men who have sex with men (MSM)] were enrolled in this prospective study from 2008 to 2011. All patients received an inspection of the anogenital region, digital rectal examination, high-resolution anoscopy (HRA), anal cytology, anal/penile histology if required, and HPV-typing of anal and penile swabs. RESULTS: At baseline, 75% (n = 302) of the men had abnormal anal cytological/histological results. 41% presented with low-grade (n = 164), 24% with high-grade anal dysplasia (n = 95) and two men with invasive anal cancer. 2.3% had PIN (n = 9) and one patient had penile cancer at baseline. Throughout the study period, 75% had anal dysplasia (low-grade n = 177, high-grade n = 125), 3.3% (n = 13) had PIN and two further patients developed anal cancer. Within the study period, 52.8% (n = 211) had condylomata (49% anal, 15% penile, 11% anal plus penile condylomata). At baseline, 88.5% of anal and 39.3% of penile swabs were HPV-DNA positive, and 77.8% of anal and 26.5% of penile swabs carried high-risk HPV-types. HPV16 was the most frequent HPV-type. CONCLUSION: HIV-positive MSM have a high risk for HPV-induced condylomata, (pre)malignant anogenital lesions and anogenital cancers. Screening for HPV-induced dysplasia is crucial to avoid progression to invasive carcinomas. Additionally, HPV-vaccination recommendations should be extended to high-risk populations.

[Modern diagnosis of sexually transmitted diseases]. / Moderne Diagnostik sexuell übertragbarer Infektionen.

Diagnosis of sexually transmitted diseases (STD) has significantly improved in recent years by the application of nucleic acid amplification tests (NAAT). In addition to detection of infectious agents, molecular methods were also used for characterization of pathogens (typing, genotypic resistance testing). In contrast to conventional Sanger sequencing of amplicons, new sequencing technologies (next generation sequencing) are able to identify resistant variants that represent only small minorities in a heterogeneous population. NAATs are also available as fully automated closed systems that can be run independently of centralized laboratories and will become increasingly important for point-of-care testing.

[Local health study : Outreach medical services for female sex workers in Bochum]. / Local Health Study : Aufsuchende medizinische Angebote für Sexarbeiterinnen in Bochum.

BACKGROUND: Inadequate access to prevention and medical treatment for female sex workers (SW) represents a challenge for the German health system. Accessibility and care for SW in Bochum (Germany) through a cooperation between the Interdisciplinary Immunology Outpatient Clinic, Center for Sexual Health and Medicine of St. Josef's Hospital, the Bochum health department and the Madonna e.V. was the focus of this work. PATIENTS AND METHODS: Medical outreach services were provided for the diagnosis of sexually transmitted infections (STI) in SW in brothels in Bochum between August 2013 and January 2014. After clarification and verbal consent from the SW, free HIV, syphilis, chlamydia, gonorrhea and trichomoniasis tests were offered and carried out using pseudonyms for the SW. RESULTS: A total of 112 SW were reached (up to 55.4 % within the framework of the STI Outreach Study). Of the SW, 94.6 % had an immigrant background. The majority (61.3 %) of SW were between 20 und 29 years old. Only 19.0 % of the collective had health insurance. The following STIs were diagnosed: 12.5 % chlamydia, 6.2 % syphilis, 3.6 % gonorrhea, 3.6 % trichomoniasis, and 0.9 % HIV. These results were compared with results from STI studies in SW in Germany. Treatment was performed in accordance with the standards of the German STI Society. CONCLUSION: The offer improved the accessibility and the utilization of medical services by SW in Bochum. A further improvement of services is urgently needed.

Therapy and prophylaxis of opportunistic infections in HIV-infected patients: a guideline by the German and Austrian AIDS societies (DAIG/ÖAG) (AWMF 055/066).

INTRODUCTION: There was a growing need for practical guidelines for the most common OIs in Germany and Austria under consideration of the local epidemiological conditions. MATERIALS AND METHODS: The German and Austrian AIDS societies developed these guidelines between March 2010 and November 2011. A structured Medline research was performed for 12 diseases, namely Immune reconstitution inflammatory syndrome, Pneumocystis jiroveci pneumonia, cerebral toxoplasmosis, cytomegalovirus manifestations, candidiasis, herpes simplex virus infections, varizella zoster virus infections, progressive multifocal leucencephalopathy, cryptosporidiosis, cryptococcosis, nontuberculosis mycobacteria infections and tuberculosis. Due to the lack of evidence by randomized controlled trials, part of the guidelines reflects expert opinions. The German version was accepted by the German and Austrian AIDS Societies and was previously published by the Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF; German Association of the Scientific Medical Societies). CONCLUSION: The review presented here is a translation of a short version of the German-Austrian Guidelines of opportunistic infections in HIV patients. These guidelines are well-accepted in a clinical setting in both Germany and Austria. They lead to a similar treatment of a heterogeneous group of patients in these countries.

[Off-label use and G-BA. Legal framework for off-label use]. / Off-label-Use und G-BA. Rechtliche Rahmenbedingungen für Off-label-Use.

Off-label use of medicinal products, i.e. beyond their submitted, tested and approved indications, lies between 30 and 90%--depending on the indication. In dermatology, off-label use is of special importance, for even guideline-endorsed standard therapeutic approaches for common dermatological diseases like atopic eczema, psoriasis, or malignant melanoma are to some extent not licensed for these indications. In addition, many of the approximately 5000 dermatological diseases have a low prevalence. For many such orphan diseases, there are no approved drugs, and it is not feasible that licensing studies will be performed for these indications within a foreseeable time. A reliable legal framework for the reimbursement of medicinal products that are used off-label is essential both for patients and to allow physicians to choose the most adequate therapy. Therefore, off-label use expert groups have been convened by the Federal Ministry of Health (BMG) in order to improve patient care. So far this new and innovative approach has not provided any reasonable improvement for many patients with dermatological diseases whose treatment can only be off-label since a comprehensive evaluation of all off-label indications is not possible. The following statement of the former Federal Minister of Health, U. Schmidt, is particularly true for dermatological therapy: "Good oncologic care also requires a good drug treatment--especially in the outpatient setting. The use of drugs which are not or not yet approved for this indication is often required here". Federal Minister of Health, Ulla Schmidt, 25th German Cancer Congress, 10 March 2002, Berlin.

Substance use and sexual risk behaviour among HIV-positive men who have sex with men in specialized out-patient clinics.

OBJECTIVES: Unprotected sexual intercourse between men who have sex with men (MSM) is the most common route of HIV infection in Germany. Approximately 70% of newly infected people are MSM. Substance use is a determinant of sexual risk behaviour in the general population, but also in the MSM subpopulation. There are only a few studies, from the USA, on the correlation between substance use and sexual risk behaviour in HIV-infected MSM in specialized care. METHODS: In a German sample of 445 HIV-infected MSM treated in specialized out-patient clinics, the influence of substance use on sexual risk behaviour was investigated. Information was obtained from subjects using self-report questionnaires and a structured interview. RESULTS: Recreational drug use was common. The prevalences of cannabis addiction (4.5%), harmful use of cannabis (4.3%) and harmful use of dissociative anaesthetics (0.4%) were higher than in the general German male population. A substantial proportion of patients reported unprotected insertive (32.9%) and receptive (34.6%) anal intercourse during the last 12 months. Use of cannabis, amyl nitrite, dissociative anaesthetics, cocaine, amphetamines and erectile dysfunction medication was significantly correlated with unprotected sexual contacts. Substance use in the context of sexual activity significantly increased sexual risk behaviour. CONCLUSIONS: Substance use, especially in the context of sexual activity, should be taken into account when developing new prevention and intervention programmes aimed at reducing sexual risk behaviour in HIV-infected MSM currently in specialized care.