Incidence and risk factors for HIV-tuberculosis coinfection in the Cologne-Bonn region: a retrospective cohort study.

PURPOSE: The risk of developing active tuberculosis (TB) is considerably increased in people living with HIV/AIDS (PLWH). However, incidence of HIV/TB coinfection is difficult to assess as surveillance data are lacking in many countries. Here, we aimed to perform a quantitative analysis of HIV/TB coinfections within the Cologne/Bonn HIV cohort and to determine risk factors for active TB. METHODS: We systematically evaluated data of patients with HIV/TB coinfection between 2006 and 2017. In this retrospective analysis, we compared HIV/TB-coinfected patients with a cohort of HIV-positive patients. The incidence density rate (IDR) was calculated for active TB cases at different time points. RESULTS: During 2006-2017, 60 out of 4673 PLWH were diagnosed with active TB. Overall IDR was 0.181 cases/100 patient-years and ranged from 0.266 in 2006-2009 to 0.133 in 2014-2017. Patients originating from Sub-Saharan Africa had a significantly (p < 0.001) higher IDR (0.694/100 patient-years of observation, 95% CI [0.435-1.050]) in comparison to patients of German origin (0.053/100 patient-years of observation, 95% CI [0.028-0.091]). In terms of TB-free survival, individuals originating from countries with a TB incidence higher than 10/100,000 exhibited a markedly reduced TB-free survival compared to those originating from regions with lower incidence (p < 0.001). In 22 patients, TB and HIV infection were diagnosed simultaneously. CONCLUSION: Overall, we observed a decline in the incidence density rate (IDR) of HIV/TB coinfections between 2006 and 2017. Patients originating from regions with high incidence bear a higher risk of falling ill with active TB. For PLWH born in Germany, the observed risk of active TB appears to be lower compared to other groups within the cohort. These findings should be considered when developing TB containment and screening strategies for PLWH in low-incidence countries.

HIV-Associated Microbial Translocation May Affect Cytokine Production of CD56bright NK Cells via Stimulation of Monocytes.

The mechanisms involved in HIV-associated natural killer (NK) cell impairment are still incompletely understood. We observed HIV infection to be associated with increased plasma levels of IFABP, a marker for gut epithelial barrier dysfunction, and LBP, a marker for microbial translocation. Both IFABP and LBP plasma concentrations were inversely correlated with NK cell interferon-γ production, suggesting microbial translocation to modulate NK cell functions. Accordingly, we found lipopolysaccharide to have an indirect inhibitory effect on NK cells via triggering monocytes' transforming growth factor-ß production. Taken together, our data suggest increased microbial translocation to be involved in HIV-associated NK cell dysfunction.

People living with HIV, HCV and HIV/HCV coinfection in intensive care in a German tertiary referral center 2014-2019.

PURPOSE: The epidemiology of HIV-infected individuals on the Medical Intensive Care Units (MICU) has changed after profound progress in treatment of AIDS-defining illnesses and anti-retroviral therapy (ART). Changes of MICU utilization of Hepatitis C (HCV) patients following roll-out of direct-acting antivirals (DAA) are yet to evaluate. METHODS: We performed a retrospective study on all patients with HIV, HIV/HCV and HCV admitted to the MICU of University Hospital Bonn 2014-2019. We assessed sociodemographic data, available clinical data from HIV patients (CDC stage, CD4 + lymphocyte cell count, HIV-1-RNA, ART) and HCV patients (HCV-RNA, stage of liver cirrhosis, treatment history) and outcome. RESULTS: 237 patients (46 HIV, 22 HIV/HCV, 169 HCV; 168 male, median age 51.3 years) with 325 MICU admissions were included. Admission criteria for HIV patients were infections (39.7% AIDS-associated, 23.8% with controlled HIV-infection) and cardiopulmonary diseases (14.3%). HIV/HCV coinfected patients had infections in controlled/uncontrolled HIV-infection (46.4%), cardiopulmonary diseases and intoxication/drug abuse (17.9% each). Reasons for HCV-mono-infected patients were infections (24.4%), sequelae of liver disease (20.9%), intoxication/drug abuse (18.4%) and cardiopulmonary diseases (15%). 60 patients deceased; most important risk factor was need for mechanical ventilation. The number of HCV-patients admitted to MICU with chronic active disease and sequelae of liver disease decreased while the proportion of patients with completed DAA-treatment increased. CONCLUSION: Infections remain the most important reason for MICU admission in patients with HIV and/or HCV infection while non-AIDS related conditions increased. DAA roll-out has a beneficial effect on liver-associated morbidity in HCV patients admitted to MICU.

Circulating levels of endotrophin and cross-linked type III collagen reflect liver fibrosis in people with HIV.

BACKGROUND AND AIMS: Liver-associated complications still frequently lead to mortality in people with HIV (PWH), even though combined antiretroviral treatment (cART) has significantly improved overall survival. The quantification of circulating collagen fragments released during collagen formation and degradation correlate with the turnover of extracellular matrix (ECM) in liver disease. Here, we analysed the levels of ECM turnover markers PC3X, PRO-C5, and PRO-C6 in PWH and correlated these with hepatic fibrosis and steatosis. METHODS: This monocentre, retrospective study included 141 PWH. Liver stiffness and liver fat content were determined using transient elastography (Fibroscan) with integrated CAP function. Serum levels of formation of cross-linked type III collagen (PC3X), formation of type V collagen (PRO-C5) and formation type VI collagen (PRO-C6), also known as the hormone endotrophin, were measured with ELISA. RESULTS: Twenty-five (17.7%) of 141 PWH had clinical significant fibrosis with liver stiffness ≥ 7.1 kPa, and 62 PWH (44.0%) had steatosis with a CAP value > 238 dB/m. Study participants with fibrosis were older (p = 0.004) and had higher levels of AST (p = 0.037) and lower number of thrombocytes compared to individuals without fibrosis (p = 0.0001). PC3X and PRO-C6 were markedly elevated in PWH with fibrosis. Multivariable cox regression analysis confirmed PC3X as independently associated with hepatic fibrosis. PRO-C5 was significantly elevated in participants with presence of hepatic steatosis. CONCLUSION: Serological levels of cross-linked type III collagen formation and endotrophin were significantly associated with liver fibrosis in PWH receiving cART and thus may be suitable as a non-invasive evaluation of liver fibrosis in HIV disease.

Mitochondrial Dysfunction Contributes to Impaired Cytokine Production of CD56bright Natural Killer Cells From Human Immunodeficiency Virus-Infected Individuals Under Effective Antiretroviral Therapy.

Human immunodeficiency virus (HIV) infection is associated with impaired natural killer (NK) cell activity, which is only incompletely restored under antiretroviral therapy. Analyzing the bioenergetics profiles of oxygen consumption, we observed that several parameters were significantly reduced in HIV+ NK cells, indicating a mitochondrial defect. Accordingly, we found HIV+ CD56bright NK cells to display a decreased mitochondrial membrane potential and mitochondrial mass. Both parameters were positively correlated with interferon gamma (IFN-γ) production of NK cells. Finally, we demonstrated that stimulation of HIV+ NK cells with MitoTEMPO, a mitochondria-targeting antioxidant, significantly improved IFN-γ production. We identified mitochondrial dysfunction as a mechanism that contributes to impaired NK cell function.

Impact of COVID-19 on HIV late diagnosis in a specialized German centre.

BACKGROUND: The ongoing COVID-19 pandemic has been impeding HIV diagnosis and treatment worldwide. Data on the impact of COVID-19 on late diagnosis (LD) in Germany are lacking. Here we present novel data of a single-centre German HIV cohort assessing LD during COVID-19. METHODS: This is a non-interventional, single-centre retrospective cohort assessing the rate of LD comparing HIV diagnoses pre-COVID-19 with those during the COVID-19 pandemic. New diagnoses between 1 January 2019 and 1 February 2020 were classified as pre-COVID-19, and diagnoses between 1 February 2020 and 1 October 2021 were classified as during COVID-19. RESULTS: Between 1 January 2019 and 1 October 2021, 75 patients presented with newly diagnosed HIV infection, 34 pre-COVID-19 and 41 during COVID-19. LD increased to 83% (n = 34/41) during COVID-19 versus 59% (n = 20/34) pre-COVID-19, and CDC stage C3 rose to 44% (n = 18) versus 27%. Hospitalization rate increased to 49% (n = 20) during COVID-19 versus 29% pre-COVID-19, and 12% (n = 5) presented with HIV-associated neurological disease, whereas none were observed in the pre-COVID-19 group. The incidence of LD (p = 0.020), CD4 count < 350 cells/µL (p = 0.037) and < 200 cells/µL (p = 0.022) were statistically significantly associated with the ongoing COVID-pandemic. An association with HIV transmission risk was borderline significant (p = 0.055). CONCLUSIONS: Despite comparable annual rates of new HIV diagnoses, LD has been increasing during the COVID-19 pandemic, resulting in more opportunistic infections and higher hospitalization rates, possibly reflecting pandemic-related shortages in HIV testing and care facilities. Maintaining HIV testing opportunities and access to treatment during a pandemic is crucial so as not to impede WHO elimination goals and so as to prevent an increase in AIDS-related morbidity and mortality.

Implementation of EACS vaccination recommendations among people living with HIV.

OBJECTIVES: With modern combination antiretroviral Treatment (cART) a normal life expectancy among people living with HIV (PLWH) has become reality if started early enough prior to the onset of more pronounced immunodeficiency. Therefore, prevention measures against other infectious diseases among this vulnerable group have gained increased attention. Indeed, the EACS guidelines recommend vaccinations against HAV, HBV, HPV, Influenza, Neisseria meningitidis, Streptococcus pneumoniae and VZV in HIV-infected adults. METHODS: All PLWH under cART attending our ID outpatient clinic between April to June 2018, were assessed during consultation for vaccination status regarding pneumococcus, Hepatitis A and B, influenza, varicella, meningococcus and HPV using a pre-defined questionnaire, vaccination certificates and medical records. In addition, the cohort database was screened for Hepatitis A and B serology and HIV surrogate markers. RESULTS: A total of 305 PLWH (82.3% male, 17.7% female) was included, median age was 48 years (IQR 47-51). Median CD4 + T cell count was 543 (IQR 304-770), and for 297 (97.4%) PLWH CD4 + T cell count was ≥ 200/ul. The viral load was undetectable (< 40 copies/ml) in 289 (94.8%) cases. Highest vaccination rates were observed for HAV (87.4%), Streptococcus pneumoniae (77.4%) and Influenza (76.5%). 64.3% PLWH got vaccinated against HBV, whereas VZV vaccination only played a minor role, in the context of the high rate of cleared infections (99.0%). Lowest vaccination rates were detected for HPV (0%) and Neisseria meningitidis (3.0%). CONCLUSIONS: Our data suggest that vaccination rates among PLWH are higher compared to the general German population. Implementation of EACS guidelines into daily routine though is not fully executed and the need for improving vaccination rates has to be emphasized. Centrally organized vaccination registers as well as electronic medical records could be helpful tools to detect a lack of vaccination coverage and send digital vaccination reminders particularly among risk groups.

[HIV Test in Pregnancy - 100% Not Reached in 2020]. / HIV-Test in der Schwangerschaft ­ 2020 noch nicht bei 100.

INTRODUCTION: In 2019 38 million people were living with HIV worldwide, more than half of them girls and women. Knowledge about maternal HIV status enables HIV transmission prophylaxis, reducing mother-to-child transmission<1%. We aimed to investigate the implementation of the mandatory documentation of counseling and optional HIV testing in the maternity records as recommended in the German maternity guidelines. METHODS: In the Obstetric Department of the University Hospital Bonn, maternity records were reviewed from June to October 2020, and pregnant women were interviewed regarding the patients' recall of counseling and HIV testing as well as their attitude towards a universal screening strategy using an anonymous questionnaire. RESULTS: Documentation was incomplete in 11% of maternal records: in 8% there was neither documentation of counseling nor of HIV testing, in 3% documentation of counseling only. In 291 questionnaires 47% of pregnant women could not recall counselling. 90% of pregnant women were in favor of universal HIV testing in pregnancy, 9% were undecided, and 1% opposed it. 55% would support change from an "opt-in" to an "opt-out" screening policy in pregnancy. SUMMARY: Documentation of counseling and HIV testing was incomplete in 11% of cases, and nearly half of the women could not recall counselling. New strategies from midwives and obstetricians need to be developed to achieve universal HIV testing in pregnant women leading to zero HIV mother-to-child transmissions.

SARS-CoV-2 seroconversions and chains of infection in healthcare professionals in a German maximum care provider (The CoSHeP study).

INTRODUCTION: The CoSHeP study provides novel data on SARS-CoV-2 seroconversion rates in healthcare professionals (HP) at risk at the University Hospital Bonn, a maximum healthcare provider in a region of 900.000 inhabitants. METHODS: Single-center, longitudinal observational study investigating rate of SARS-CoV-2 IgG seroconversion in HP at 2 time-points. SARS-CoV-2 IgG was measured with Roche Elecsys Anti-SARS-CoV-2 assay. RESULTS: Overall, 150 HP were included. Median age was 35 (range: 19-68). Main operational areas were intensive care unit (53%, n = 80), emergency room (31%, n = 46), and infectious disease department (16%, n = 24). SARS-CoV-2-IgG was detected in 5 participants (3%) at inclusion in May/June 2020, and in another 11 participants at follow-up (December 2020/ January 2021). Of the 16 seropositive participants, 14 had already known their SARS-CoV-2 infection because they had performed a PCR-test previously triggered by symptoms. Trailing chains of infection by self-assessment, 31% (n = 5) of infections were acquired through private contacts, 25% (n = 4) most likely through semi-private contacts during work. 13% (n = 2) were assumed to result through contact with contagious patients, further trailing was unsuccessful in 31% (n = 5). All five participants positive for SARS-CoV-2 IgG at inclusion remained positive with a median of 7 months after infection. DISCUSSION: Frontline HP caring for hospitalized patients with COVID-19 are at higher risk of SARS-CoV-2 infections. Noteworthy, based upon identified chains of infection most of the infections were acquired in private environment and semi-private contacts during work. The low rate of infection through infectious patients reveals that professional hygiene standards are effective in preventing SARS-CoV-2 infections in HP. Persisting SARS-CoV-2-IgG might indicate longer lasting immunity supporting prioritization of negative HP for vaccination.

Hepatitis C reinfection with protease inhibitor-resistant hepatitis C virus in an HIV-coinfected MSM.

There is an ongoing global hepatitis C virus (HCV) epidemic mainly related to high-risk behaviour in persons who inject drugs (PWID) and in HIV-infected men who have sex with men (MSM) which continues to fuel the HCV epidemic. Treatment of HCV infection with direct antiviral therapy (DAA) has been very successful in the last decade. Main obstacles for HCV elimination are HCV reinfections observed in PWID and HIV-infected MSM. We present here an HIV-infected MSM patient who has been reinfected thrice with HCV. The virus which was investigated from his last reinfection episode reveals transmission of a newly acquired HCV protease inhibitor (PI) resistance, despite not having been exposed to HCV-PIs during his last DAA therapy.

Obstacles to HBV functional cure: Late presentation in HIV and its impact on HBV seroconversion in HIV/HBV coinfection.

Several cohorts have shown that long-term tenofovir-containing combination antiretroviral therapy (cART) leads to higher HBsAg seroclearance rates in HIV/HBV coinfected patients vs HBV-monoinfected patients under tenofovir disoproxil fumarate (TDF)-based therapy. We have analysed data on determinants of HBsAg loss in a retrospective multicentric cohort of 359 HIV/HBV coinfected patients. Median CD4 T-cell count at baseline was 359/ul (321-404), CDC stage was C in 20% (n = 70). Most patients (68%) were ART-naïve when TDF- or tenofovir alafenamide (TAF)-containing cART was initiated (baseline). After a median follow-up of 11 years HBsAg loss had occurred in 66/359 (18%) patients. However, patients with stage CDC C (P ≤ .001), lower CD4 gain (P = .043) and not receiving TDF/FTC (P = .008) were less likely to lose HBsAg. Long-term TDF-containing cART appears to achieve higher rates of HBsAg seroclearance compared to published data for HBV monoinfected subjects. However, late presentation for HIV and poor immune recovery significantly impair HBV seroconversion rates.

Treatment modification after starting cART in people living with HIV: retrospective analysis of the German ClinSurv HIV Cohort 2005-2017.

OBJECTIVE: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving. METHODS: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan-Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data. RESULTS: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59-66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39-0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011-2017), being on a multi-tablet regimen (MTR). CONCLUSIONS: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.

HPV-associated anal lesions in HIV+ patients: long-term results regarding quality of life.

PURPOSE: HIV infection and concomitant HPV-associated anal lesions may significantly impact on patients' quality of life (QoL), as they are predicted to have negative effects on health, psyche, and sexuality. MATERIAL AND METHODS: Fifty-two HIV+ patients with HPV-associated anal lesions were enrolled in a survey approach after undergoing routine proctologic assessment and therapy for HPV-associated anal lesions if indicated over a time span of 11 years (11/2004-11/2015). Therapy consisted of surgical ablation and topic treatment. QoL was analyzed using the SF-36 and the CECA questionnaires. RESULTS: Fifty-two of 67 patients (77.6%) were successfully contacted and 29/52 provided full information. The mean age was 43.8 ± 12.8 years. The median follow-up from treatment to answering of the questionnaire was 34 months. Twenty-one percent (6/29) of the patients reported suffering from recurrence of condyloma acuminata, three patients from anal dysplasia (10.3%). In the SF-36, HIV+ patients did not rate their QoL as significantly different over all items after successful treatment of HPV-associated anal lesions. In the CECA questionnaire, patients with persisting HPV-associated anal lesions reported significantly higher emotional stress levels and disturbance of everyday life compared to patients who had successful treatment (71.9/100 ± 18.7 vs. 40.00/100 ± 27.4, p = 0.004). Importantly, the sexuality of patients with anal lesions was significantly impaired (59.8/100 ± 30.8 vs. 27.5/100 ± 12.2, p = 0.032). CONCLUSION: HPV-associated anal lesions impact significantly negative on QoL in HIV+ patients. Successful treatment of HPV-associated anal lesions in HIV+ patients improved QoL. Specific questionnaires, such as CECA, seem to be more adequate than the SF-36 in this setting.

Compartment-specific distribution of human intestinal innate lymphoid cells is altered in HIV patients under effective therapy.

Innate lymphocyte cells (ILCs), a novel family of innate immune cells are considered to function as key orchestrators of immune defences at mucosal surfaces and to be crucial for maintaining an intact intestinal barrier. Accordingly, first data suggest depletion of ILCs to be involved in human immunodeficiency virus (HIV)-associated damage of the intestinal mucosa and subsequent microbial translocation. However, although ILCs are preferentially localized at mucosal surfaces, only little is known regarding distribution and function of ILCs in the human gastrointestinal tract. Here, we show that in HIV(-) individuals composition and functional capacity of intestinal ILCs is compartment-specific with group 1 ILCs representing the major fraction in the upper gastrointestinal (GI) tract, whereas ILC3 are the predominant population in ileum and colon, respectively. In addition, we present first data indicating that local cytokine concentrations, especially that of IL-7, might modulate composition of gut ILCs. Distribution of intestinal ILCs was significantly altered in HIV patients, who displayed decreased frequency of total ILCs in ileum and colon owing to reduced numbers of both CD127(+)ILC1 and ILC3. Of note, frequency of colonic ILC3 was inversely correlated with serum levels of I-FABP and sCD14, surrogate markers for loss of gut barrier integrity and microbial translocation, respectively. Both expression of the IL-7 receptor CD127 on ILCs as well as mucosal IL-7 mRNA levels were decreased in HIV(+) patients, especially in those parts of the GI tract with reduced ILC frequencies, suggesting that impaired IL-7 responses of ILCs might contribute to incomplete reconstitution of ILCs under effective anti-retroviral therapy. This is the first report comparing distribution and function of ILCs along the intestinal mucosa of the entire human gastrointestinal tract in HIV(+) and HIV(-) individuals.

Fibroblast growth factor 21 is independently associated with severe hepatic steatosis in non-obese HIV-infected patients.

BACKGROUND: Severe hepatic steatosis shows a high prevalence and contributes to morbidity and mortality in human immunodeficiency virus (HIV) infected patients. Known risk factors include obesity, dyslipidaemia and features of metabolic syndrome. Fibroblast growth factor 21 (FGF-21) is involved with hepatic glucose and lipid metabolism. This study aimed to evaluate FGF-21 as a biomarker for severe hepatic steatosis in non-obese HIV-infected patients. METHODS: This is a prospective, cross-sectional, monocentric study including HIV-infected out-patients. Hepatic steatosis was measured via controlled attenuation parameter (CAP) using FibroScan 502 touch (ECHOSENS, France). Severe hepatic steatosis was defined at CAP ≥ 253 dB/m. Peripheral blood samples were collected and plasma was analysed for FGF-21. Demographic and clinical characteristics were collected from patient's health records. RESULTS: In total, 73 non-obese HIV-monoinfected patients were included in this study. Prevalence of severe hepatic steatosis was 41%. Patients with severe hepatic steatosis showed significantly higher levels of FGF-21. Univariate analysis revealed FGF-21, BMI, hyperlipidaemia, ALT levels and arterial hypertension as significant, while multivariate analysis showed only FGF-21, arterial hypertension and ALT levels as significant independent risk factors for severe hepatic steatosis. CONCLUSION: This study presents FGF-21 as an independent and stronger predictor of severe hepatic steatosis than blood lipids in HIV-infected patients. Moreover, arterial hypertension and ALT levels predict severe steatosis even in non-obese HIV-monoinfected patients. Furthermore, this study supports existing metabolic risk factors and expands them to non-obese HIV-infected patients.

[Treatment of HPV-associated Anal Lesions in HIV-positive Patients - Comparison of Surgical Treatment and Topical Therapy with Imiquimod]. / Behandlung HPV-assoziierter analer Läsionen bei HIV-positiven Patienten ­ chirurgische Abtragung vs. topische Therapie mit Imiquimod.

OBJECTIVES: In HIV+-patients, routine proctological assessment is warranted due to the high incidence of human papilloma virus (HPV) infection-related anogenital lesions, such as Condylomata acuminata (C. ac.), anal intraepithelial dysplasia (AIN) and anal cancer. For C. ac. and AIN, surgical resection and topical therapy with imiquimod have been discussed as treatment options. BACKGROUND: In this study, we contrasted surgical resection and topical imiquimod therapy of HPV-associated anal lesions in HIV+-patients, with a focus on healing rates and clinical outcome. We also analysed whether a synergistic treatment effect was detectable. METHODS: This was a retrospective analysis of 97 HIV+ patients who underwent proctological evaluation and treatment over a 10-year period (11/2004 - 11/2015) at our centre. Initial success of surgical treatment, topical imiquimod therapy and the combination of the two strategies were compared. RESULTS: In 53/97 patients (54%), HPV-associated anal disease was diagnosed upon the first visit. In approx. 50% of the patients, the HIV infection was adequately controlled (52 patients with viral load < 40 copies [53.6%]) under cART. The mean age was 41.0 ± 11.6 years. In 7/53 patients with macroscopic C. ac., low-grade and in 18/53 patients high-grade AIN were additionally confirmed. Success rates of surgical resection, imiquimod treatment and the combination of the two were compared. Complete remission of C. ac. and AIN four weeks after treatment was considered a therapeutic success. For C. ac., success rates with imiquimod were 5/25 (20.0%) vs. surgery* 30/57 (52.6%, Mann-Whitney U test p < 0.05) vs. surgery+imiquimod 7/15 (46.7%). For AIN, success rates with imiquimod were 4/24 (16.7%) vs. surgery* 47/83 (56.7%, Mann-Whitney U test p < 0.05) vs. surgery+imiquimod 9/21 (42.8%). In 7/92 (13%) of surgical treatments, complications were reported: four minor and two significant bleeding episodes and one perianal thrombosis. No side effects of imiquimod were documented besides skin irritation. CONCLUSION: Surgery is more effective than topical imiquimod as initial therapy of HPV-related anogenital disease in HIV+-patients. A synergistic effect could not be demonstrated. On this basis, we recommend surgical treatment of C. ac. and AIN in HIV+-patients as first line treatment.

[Treatment of HIV in Pregnancy - Progress Over One Decade]. / Behandlung von HIV in der Schwangerschaft ­ Entwicklung über eine Dekade.

INTRODUCTION: Worldwide, 37 million people are infected with HIV; more than 50% are women. Currently, MTCT (mother-to-child transmission) can be reduced to<1%. The intention of the present study was to analyze the development of (1) the course of pregnancy of HIV-infected women, (2) the mode of delivery and (3) the post-exposure prophylaxis of the newborn over the last decade. METHODOLOGY: In this retrospective study, data from HIV-infected women who between 2005 and 2016 received care at the HIV outpatient department and gave birth at the Department of Obstetrics at University Hospital Bonn was analyzed. Furthermore, neonatal data was collected and HIV-MTCT was evaluated. RESULTS: In the 2005-2016 study period, 87 pregnancies in 61 women were identified. Seventy babies were born alive at the Department of Obstetrics, University Hospital Bonn. 53% of these women were of African origin. The median of CD4+ cell count was 510 cells/ml (IQR 444); however, 32 women (52%) had more than 500 cells/ml. During the antenatal period, the HI viral load had been suppressed completely in 77% of women (<50 HIV-1-RNA copies/ml) and was<400 HIV-1-RNA copies/ml in 92% of women. The elective cesarean section rate fell significantly from 77% in the years 2005-2011 to 58% in 2012-2016. The proportion of deliveries after 37 weeks of gestation increased markedly from 60% to 69% after 2012. Additionally, while between 2005-2011 the birth weight of 78% of the newborns was between the 10th and 90th percentile, this proportion increased to 92% after 2012. Fifty-four of 70 newborns (77%) were classified as having low to normal HIV transmission risk. A vertical HIV transmission from mother to child did not occur (0/70). CONCLUSIONS: Between 2005 and 2016 no vertical HIV transmission from mother to child occurred (0/70). Due to the change in treatment strategy, the elective cesarean section rate fell significantly as well the rate of premature births. An optimal interdisciplinary collaboration builds the basis for successful treatment of HIV in pregnancy.

Moderate endurance training (marathon-training) - effects on immunologic and metabolic parameters in HIV-infected patients: the 42 KM cologne project.

BACKGROUND: Improved treatment options of HIV have resulted in regular physical activities of many HIV-infected patients. However, data on effects of sports in HIV-patients are scarce. METHODS: 21 HIV-infected persons were monitored prospectively while preparing for a marathon run. Multiple parameters with regard to immunology, quality of life and metabolism were measured at 4 time points (at baseline 1 year before the marathon run, 3 and 6 months after beginning of training, and immediately before marathon). RESULTS: 13 out of 21 participants completed the marathon (12 male, 1 female; median age 42 years [27-50]; CD4 = 620/µl [146-1268]; 11 were on ART since 3.5 years [1-7]). 8 participants ceased training early. All reasons for stopping (besides one pre-existing metatarsal fracture) were not regarded as training-related (e.g. time limitation n = 3; newly diagnosed anal cancer n = 1; personal reasons/unknown n = 3). We observed a significant increase in absolute CD4-T-cells (620/µl [146-1268] vs. 745 [207-1647]; p = 0.001) with simultaneous decrease of CD4-T-cell apoptosis (53% [47-64] vs. 32% [14-42]); p < 0.01). No effects on viral load independent of ART occurred. Systolic blood pressure and cholesterol improved significantly, although moderate and normal at baseline (cholesterol 185 mg/dl [98-250] vs. 167 [106-222], p = 0.02; RRsys 125 mmHg [100-145] vs. 120 [100-140], p = 0.01). Blood count, liver enzymes, creatinine and CK remained unchanged. CONCLUSIONS: The results of this pilot study indicated improved metabolic and immunologic parameters in HIV-infected patients undergoing moderate endurance training. Although training effects or ART cannot be ultimately separated as underlying mechanisms, we conclude that marathon training is safe for HIV-infected patients and potentially improves general health. TRIAL REGISTRATION: DRKS00011592 (retrospectively registered on February 9th 2017).

Circulating microRNAs as a marker for liver injury in human immunodeficiency virus patients.

UNLABELLED: Human immunodeficiency virus (HIV) and hepatitis virus coinfection amplify and accelerate hepatic injury. MicroRNAs (miRNAs) are small regulatory RNAs suggested as biomarkers for liver injury. We analyzed the circulating levels of miRNAs in HIV patients with regard to the extent and etiology of liver injury. Total RNA was extracted from 335 serum samples of HIV patients and 22 healthy control participants using Qiazol. Comprehensive polymerase chain reaction (PCR) array analyses (768 miRNA) were performed in serum samples of eight HIV, eight HIV/HCV (hepatitis C virus), six HCV patients, and three healthy controls. Reverse transcription (RT)-PCR measured levels of miRNA-122, miRNA-22, and miRNA-34a in serum samples of 335 patients and 19 healthy control participants. Liver injury and fibrosis in these patients were defined using aspartate aminotransferase (AST) levels, fibrosis-4 (FIB-4) index and AST-to-platelet ratio index (APRI) score. The miRNA pattern of HIV/HCV samples showed altered expression of 57 and 33 miRNA compared to HCV and HIV infection, respectively. miRNA-122, miRNA-22, and miRNA-34a were highly up-regulated in HIV/HCV patients. Analyzing the entire cohort, these miRNAs were correlated with liver function tests and were independent predictors of liver injury (AST >2 × ULN). miRNA-122 and miRNA-22 were associated with relevant fibrosis (FIB-4 >1.45; APRI >1). Circulating levels of miRNA-122 were independent predictors for relevant fibrosis in HIV patients. Interestingly, miRNA-122 and miRNA-34a levels were higher in HIV/HCV patients, miRNA-22 levels were highest in HIV/HBV patients, and circulating levels of miRNA-34a correlated positively with illicit drug use and ethanol consumption. CONCLUSION: Circulating miRNA-122, miRNA-22, and miRNA-34a correlates with the etiology of liver injury in HIV patients. These biomarkers not only mirror different mechanisms of hepatic injury, but also are independent predictors of liver injury in HIV patients.