Broiler chicken distal jejunum microbial communities are more responsive to coccidiosis or necrotic enteritis challenge than dietary anti-interleukin-10 in a model using Salmonella Typhimurium- Eimeria maxima- Clostridium perfringens coinfection.

Dietary anti-interleukin (IL)-10 antibodies may protect broiler performance during coccidiosis by inhibiting Eimeria host-evasion pathways; however, anti-IL-10's effects on microbial communities during coccidiosis and secondary Clostridium perfringens (necrotic enteritis) challenge is unknown. The study objectives were to assess the jejunal microbiota of broilers fed anti-IL-10 during E. maxima ± C. perfringens challenge. Two replicate studies using Ross 308 chicks placed in wire-floor cages (32 cages/ replicate study; 20 chicks/ cage) were conducted, with chicks assigned to diets ± 0.03% anti-IL-10 for 25 d. In both replicate studies, challenge-designated chicks were inoculated with 1 × 108Salmonella Typhimurium colony forming units (CFU) at placement. On d14, S. Typhimurium-inoculated chicks were gavaged with 15,000 sporulated Eimeria maxima M6 oocysts and half the E. maxima-challenged chicks received 1×108C. perfringens CFUs on d 18 and 19. Six chicks/ treatment were euthanized for distal jejunum content collection at baseline (d 14), 7 d post-inoculation (pi) with E. maxima/ 3 dpi with C. perfringens (peak) or 11 dpi with E. maxima/ 7 dpi with C. perfringens (post-peak) for 16S rRNA gene amplicon sequencing. Sequences were quality screened (Mothur V.1.43.0) and clustered into de novo operation taxonomical units (OTU; 99% similarity) using the SILVA reference database (v138). Alpha diversity and log-transformed relative abundance data were analyzed in SAS 9.4 with replicate study, diet, challenge, and timepoint main effects plus associated interactions (P ≤ 0.05). Few baseline changes were observed, but E. maxima ± C. perfringens challenge reduced Romboutsia and Staphylococcus relative abundance 4- to 800-fold in both replicate studies (P ≤ 0.008). At peak challenge with secondary C. perfringens, feeding anti-IL-10 instead of the control diet reduced Clostridium sensu stricto 1 relative abundance 13- and 1,848-fold in both replicate studies (P < 0.0001); however, OTUs identified as C. perfringens were not affected by dietary anti-IL-10. These results indicate that anti-IL-10 does not affect the jejunal microbiota of unchallenged broilers, while coccidiosis or necrotic enteritis challenge generally contributed to greater microbiota alterations than diet.

Sequencing approaches to identify distal jejunum microbial community composition and function in broiler chickens fed anti-interleukin-10 during coccidiosis and necrotic enteritis challenge.

Strategies to counteract interleukin (IL)-10-mediated immune evasion by Eimeria spp. during coccidiosis- like anti-IL-10 antibodies- may protect broiler chicken health and reduce incidence of secondary necrotic enteritis (Clostridium perfringens) via undetermined mechanisms. Objectives were to use sequencing techniques to evaluate jejunal microbial community composition and function in anti-IL-10-fed broilers during coccidiosis and necrotic enteritis. On d0, Ross 308 chicks were placed in 32 cages (15 chicks/ cage) for a 25-d study and randomly assigned to diets ± 0.03% anti-IL-10. Six chicks/ diet were euthanized for distal jejunum content and tissue collection on d 14 (baseline) before inoculating the remainder with saline or 15,000 E. maxima oocysts (M6 strain). Half the chicks challenged with E. maxima were challenged with C. perfringens (1×108 colony forming units) on d 18 and 19. Follow-up samples (6 chicks/treatment) were collected at 7 and 11 d postinoculation (pi) for the E. maxima-only group, or 3 and 7 dpi for the E. maxima + C. perfringens group with 3/7 dpi being designated as peak and 7/11dpi as postpeak challenge. DNA was extracted from digesta for microbiota composition analysis (16S rRNA gene sequencing) while RNA was extracted from tissue to evaluate the metatranscriptome (RNA sequencing). Alpha diversity and genus relative abundances were analyzed using the diet or challenge main effects with associated interactions (SAS 9.4; P ≤ 0.05). No baseline microbial changes were associated with dietary anti-IL-10. At peak challenge, a diet main effect reduced observed species 36.7% in chicks fed anti-IL-10 vs. control; however, the challenge effect reduced observed species and Shannon diversity 51.2-58.3% and 33.0 to 35.5%, respectively, in chicks challenged with E. maxima ± C. perfringens compared to their unchallenged counterparts (P ≤ 0.05). Low sequencing depth limited metatranscriptomic analysis of jejunal microbial function via RNA sequencing. This study demonstrates that challenge impacted the broiler distal jejunum microbiota more than anti-IL-10 while future research to characterize the microbial metatranscriptome may benefit from investigating other intestinal compartments.

Dietary peptide-specific antibodies against interleukin-4 differentially alter systemic immune cell responses during Eimeria challenge with minimal impacts on the cecal microbiota.

Eimeria spp. induce host interleukin (IL)-4 production, a potent immune regulator, during coccidiosis to evade immune responses. Dietary anti-IL-4 may preserve bird performance during challenge; however, specific mechanisms have not been investigated. Study objectives were to develop peptide-specific anti-IL-4 antibodies and evaluate immune cell profiles and the cecal microbiota during Eimeria challenge. Four candidate IL-4 peptides were selected based on antigenicity and location. Hens were injected with conjugated peptide or carrier-only control (3/injection), eggs were collected post-vaccination and yolks were pooled by peptide before freeze-drying. On d 0, 300 Ross 708 broilers were placed in floor pens (10/pen) and assigned to 5 diets consisting of basal diet + 2% egg yolk powder containing antibodies against 1 of 4 target peptides or carrier-only control for 14-d starter and grower periods (28 d total). Baseline blood and cecal contents were collected on d 14 (6 birds/diet) before half the remainder were inoculated with 10X Coccivac-B52 (Merck Animal Health, Kenilworth, NJ). Body weight (BW) and feed intake (FI) were recorded weekly and blood and cecal samples were collected at 3, 7, and 14 d post-inoculation (pi; 3/treatment). Immune cell profiles in peripheral blood mononuclear cells (PBMC) were evaluated flow cytometrically and cecal microbial communities determined by 16S/18S rRNA gene amplicon sequencing. Data were log-transformed when necessary and analyzed with diet, Eimeria, and timepoint fixed effects plus associated interactions (SAS 9.4; P ≤ 0.05). Anti-IL-4 did not alter baseline performance but generally increased PBMC Bu-1+ B cells 38.0 to 55.4% (P < 0.0001). Eimeria challenge reduced FI and BWG 16.1 and 30.3%, respectively, regardless of diet (P < 0.0001) with only birds fed peptide 4 antibodies not recovering feed conversion by d 28. Minimal diet-associated cecal microbiota changes were observed, indicating that anti-IL-4 effects were likely host-specific. Eimeria-challenged birds fed peptide 3 antibodies displayed minimal immune cell fluctuations compared to unchallenged counterparts, suggesting these antibodies potentially modulated intestinal immune responses to minimize systemic requirements, making them good candidates for further research.

Dietary alfalfa hay or lipid-soluble alfalfa extract may improve broiler growth, but fiber presence may be detrimental during Eimeria vaccine challenge.

Lipid-soluble components in late-cutting alfalfa are linked to beneficial immune and microbiota responses in mouse challenge models; therefore, responses in a comparative poultry Eimeria challenge model were investigated. The study objective was to evaluate performance, immunity, and the cecal microbiota in broilers fed ground hay or lipid-soluble extract from late (fifth) cutting alfalfa during Eimeria challenge. At hatch, 432 Ross 708 broilers were placed in 24 floor pens (18 birds/pen) and assigned to 3 isocaloric/isonitrogenous dietary treatments consisting of control, 5% ground hay, or 0.25% lipid-soluble extract for a 42-d trial divided into 14 d starter, grower, and finisher periods. On d 14, 4 birds/treatment were euthanized to collect blood and cecal contents before half the remainder were inoculated with 10X Merck Coccivac-B52 (Kenilworth, NJ). Tissue samples were collected at 3, 7, 14, and 28 d postinoculation (pi; 4 birds/diet × Eimeria group) with body weight (BW) and feed intake (FI) recorded weekly. Immune populations within peripheral blood mononuclear cells were characterized by flow cytometry while cecal microbial communities were profiled by 16S rRNA gene amplicon sequencing. Data were normalized when appropriate and analyzed to evaluate the effects of diet, Eimeria challenge, and timepoint (SAS 9.4; P ≤ 0.05). Before challenge, dietary alfalfa hay or extract increased FI 6.9 to 8.0% and increased CD3+ T cells 19.3 to 24.9% compared to control-fed birds (P ≤ 0.007). Alfalfa did not significantly affect post-Eimeria performance, but Eimeria-challenged birds fed hay showed the greatest numeric reduction in final BW compared to their unchallenged counterparts (0.17 kg) vs. control and extract-fed birds (0.02-0.04 kg). Immune cell changes did not indicate recruitment from peripheral blood to local infection sites; however, alfalfa hay may have accelerated Bu-1+ B cell development by 7 d in unchallenged birds (P < 0.0001). During Eimeria-challenge, dietary alfalfa extract preserved alpha diversity measures related to species richness (P ≤ 0.007). Collectively, these results indicate potential benefits of feeding lipid-soluble extract from late cutting alfalfa to broilers during Eimeria challenge.

Characterization of the eukaryotic microbial communities in the chicken ileum in cage-free and conventional commercial housing systems.

The current shift from conventional cage (CC) hen housing facilities towards cage-free (CF) hen housing in the egg industry has left many questions regarding how level of fecal exposure and exposure to other hens may influence the hen intestinal microbiota. In a previous publication we reported differences in the bacterial ileal communities and ileal morphology between hens in CC and CF production environments at a single commercial site. Here, we present the first 18S rRNA gene amplicon sequencing-based characterization of the eukaryotic ileal microbiota of adult layer hens, and their associations with intestinal health parameters and the bacterial microbiota. DNA was extracted from the ileal digesta of hens (n = 32 CC, n = 48 CF) using the Qiagen Powerlyzer Powersoil kit, followed by amplification of the V9 region of the 18S rRNA gene. Paired end sequencing was performed with the Illumina MiSeq platform, and the resulting reads were processed according to the Mothur MiSeq protocol in Mothur v1.43.0. De novo operational taxonomic unit (OTU) clustering was performed in mothur with a 99% similarity threshold, and OTUs were taxonomically classified with the SILVA SSU v138 reference database. OTUs classified as vertebrate, plant, or arthropod were removed, resulting in 3,136,400 high quality reads and 1,370 OTUs. Associations between OTUs and intestinal parameters were calculated using PROC GLIMMIX. PERMANOVA over Bray-Curtis distances revealed differences between CC and CF eukaryotic ileal microbiota at the whole community level, but no OTUs were differentially abundant after correcting for false discovery (P > 0.05; q > 0.1). Kazachstania and Saccharomyces, closely related genera of yeast, represented 77.1% and 9.7% of sequences respectively. Two Kazachstania OTUs and 1 Saccharomycetaceae OTU were positively correlated with intestinal permeability (r2 ≥ 0.35). Eimeria accounted for 7.6% of sequences across all samples. Intriguingly, 15 OTUs classified as Eimeria were inversely associated with intestinal permeability (r2 ≤ -0.35), suggesting Eimeria may play a more complex role in the microbiota of healthy birds than has been observed in disease challenges.

The life cycle-dependent transcriptional profile of the obligate intracellular amoeba symbiont Amoebophilus asiaticus.

Free-living amoebae often harbor obligate intracellular bacterial symbionts. Amoebophilus (A.) asiaticus is a representative of a lineage of amoeba symbionts in the phylum Bacteroidota. Here, we analyse the transcriptome of A. asiaticus strain 5a2 at four time points during its infection cycle and replication within the Acanthamoeba host using RNA sequencing. Our results reveal a dynamic transcriptional landscape throughout different A. asiaticus life cycle stages. Many intracellular bacteria and pathogens utilize eukaryotic-like proteins (ELPs) for host cell interaction and the A. asiaticus 5a2 genome shows a particularly high abundance of ELPs. We show the expression of all genes encoding ELPs and found many ELPs to be differentially expressed. At the replicative stage of A. asiaticus, ankyrin repeat proteins and tetratricopeptide/Sel1-like repeat proteins were upregulated. At the later time points, high expression levels of a type 6 secretion system that likely prepares for a new infection cycle after lysing its host, were found. This study reveals comprehensive insights into the intracellular lifestyle of A. asiaticus and highlights candidate genes for host cell interaction. The results from this study have implications for other intracellular bacteria such as other amoeba-associated bacteria and the arthropod symbionts Cardinium forming the sister lineage of A. asiaticus.

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.

High prevalence of recreational and illicit drug use in German people living with HIV with a potential for drug-drug interactions with antiretroviral therapy.

Recreational drug use is higher in people living with HIV (PLHIV) than in the general population in Europe. This use increases the risk for drug-drug interactions (DDIs) and adverse events. We assessed the prevalence and clinical consequences of substance abuse among PLHIV. BESIDE was a cross-sectional, multi-center study in 2016/18, evaluating comorbidities, polypharmacy and recreational/illicit drug use in PLHIV on antiretroviral therapy (ART) in Germany. Legal and illicit drug use was recorded using two anonymous patient questionnaires one year apart (Q1 and Q2). The BESIDE study population consisted of 453 PLHIV (22% female, median age 46 years). Recreational drug use was reported by the majority (Q1: ever used 73%, within previous 6 months 56%): nitrite inhalants ("poppers"), cannabis and PDE-5 inhibitors were common across all age groups; ecstasy, (meth-)amphetamine and gamma-hydroxybutyrate/gamma-butyrolactone were predominantly reported by younger PLHIV. Based on Q2, two-thirds of PLHIV (67%) had been informed about potential risks of drug abuse by their doctors, whereas one-third (33%) had talked to their doctors on their own initiative with only 7% considering drug use in combination with ART a problem. Strikingly, 44% and 42% had undergone medical treatment or had been hospitalized due to drug use. These data emphasize the high clinical relevance of recreational drug use in PLHIV and the need for treating physicians to pro-actively communicate the potential risks.

Eosinophilic pustular folliculitis (EPF) in a patient with HIV infection.

Eosinophilic pustular folliculitis is a chronic, recurrent dermatosis, of unknown etiology, which is histologically characterized by folliculotropic inflammatory infiltrates with admixed eosinophils in the dermis. It has often presented with immunosuppression and especially with HIV-Infection. In the HAART-era, eosinophilic pustular folliculitis has become a rarity. It is often being misdiagnosed as acne vulgaris, rosacea, bacterial folliculitis, dermatomycosis and seborrheic dermatitis. The treatment of this disease may be difficult.

Host immunity and the colon microbiota of mice infected with Citrobacter rodentium are beneficially modulated by lipid-soluble extract from late-cutting alfalfa in the early stages of infection.

Alfalfa is a forage legume commonly associated with ruminant livestock production that may be a potential source of health-promoting phytochemicals. Anecdotal evidence from producers suggests that later cuttings of alfalfa may be more beneficial to non-ruminants; however, published literature varies greatly in measured outcomes, supplement form, and cutting. The objective of this study was to measure body weight, average daily feed intake, host immunity, and the colon microbiota composition in mice fed hay, aqueous, and chloroform extracts of early (1st) and late (5th) cutting alfalfa before and after challenge with Citrobacter rodentium. Prior to inoculation, alfalfa supplementation did not have a significant impact on body weight or feed intake, but 5th cutting alfalfa was shown to improve body weight at 5- and 6-days post-infection compared to 1st cutting alfalfa (P = 0.02 and 0.01). Combined with the observation that both chloroform extracts improved mouse body weight compared to control diets in later stages of C. rodentium infection led to detailed analyses of the immune system and colon microbiota in mice fed 1st and 5th cutting chloroform extracts. Immediately following inoculation, 5th cutting chloroform extracts significantly reduced the relative abundance of C. rodentium (P = 0.02) and did not display the early lymphocyte recruitment observed in 1st cutting extract. In later timepoints, both chloroform extracts maintained lower splenic B-cell and macrophage populations while increasing the relative abundance of potentially beneficially genera such as Turicibacter (P = 0.02). At 21dpi, only 5th cutting chloroform extracts increased the relative abundance of beneficial Akkermansia compared to the control diet (P = 0.02). These results suggest that lipid soluble compounds enriched in late-cutting alfalfa modulate pathogen colonization and early immune responses to Citrobacter rodentium, contributing to protective effects on body weight.

Beginning to offer drinking water at birth increases the species richness and the abundance of Faecalibacterium and Bifidobacterium in the gut of preweaned dairy calves.

We previously demonstrated that dairy calves having access to drinking water since birth (W0) achieved greater body weight, fiber digestibility, and feed efficiency than those that first received drinking water at 17 d of age (W17). Since gut microbiota composition could be linked to growth and development of animals, the objective of this study was to examine the effect of offering drinking water to newborn calves on composition of bacteria in the gut using a fecal microbiota analysis. Fresh feces were collected directly from the rectum of calves in W0 (n = 14) and W17 (n = 15) at 2, 6, and 10 wk of age. All of the calves were fed pasteurized waste milk, weaned at 7 wk of age, and offered tap water according to the treatment. The DNA was sequenced using 16S rRNA gene-amplicon sequencing on an Illumina MiSeq system (Illumina Inc., San Diego, CA). The sequences were clustered into operational taxonomic units (OTU) with a 99% similarity threshold. Treatment effects on α-diversity indices and relative abundance of the 10 most abundant genera were analyzed using GLIMMIX procedure of SAS (SAS Institute Inc., Cary, NC). Statistical significance (q-value) of treatment effects on the 50 most abundant OTU was determined with a false discovery rate analysis. At 2 wk of age, W0 had a greater number of observed OTU (5,908 vs. 4,698) and species richness (Chao 1 index) than W17. The number of OTU and richness indices increased from wk 2 to 6, but the increment of W17 was greater than that of W0. The Shannon and inverse-Simpson indices increased linearly with age, but no difference was observed between W0 and W17 at any time point. The Firmicutes to Bacteroidetes ratios were also similar at every time point but decreased markedly when calves were weaned. The relative abundance of genera Faecalibacterium and Bacteroides was greater in W0 than W17 at 2 wk of age. The genus Faecalibacterium continued to be more abundant in W0 than W17 at 6 wk of age but had similar abundance 3 wk after weaning (10 wk of age). The abundance of Faecalibacterium at wk 6 was positively correlated with apparent total-tract digestibility of acid detergent fiber at 10 wk of age. Calves receiving water since birth had greater abundance of OTU related to Faecalibacterium prausnitzii, and Bifidobacterium breve at 6 wk of age (q < 0.085). These species are known to improve growth in preweaned calves. The abundance of none of the genera and OTU was different between W0 at W17 at 10 wk of age (q > 0.100). Overall, beginning to offer drinking water at birth has a potential to modulate gut microbiota composition and thereby positively affect performance of young dairy heifer calves (≤10 wk of age).

[Classical sexually transmitted diseases in the anorectal region]. / Klassische sexuell übertragbare Infektionen im Analbereich.

BACKGROUND: Sexually transmitted infections (STIs) in the anorectal region are disproportionally detected in risk populations such as men who have sex with men (MSM). However, due to changes in sexual behaviour they are increasingly diagnosed in heterosexual individuals. Due to the recent implementation of oral HIV pre-exposure prophylaxis together with lack of condom use, a further rise in STIs is expected. OBJECTIVES: This review addresses epidemiology, clinical picture, diagnostic pitfalls and current therapy guidelines of "classical" bacterial STIs involving the anorectum. CONCLUSIONS: STI manifestations in the anal region are frequently nonspecific or asymptomatic so that the diagnosis may be missed. In an endoscopic examination of the rectum, they can even mimic inflammatory bowel disease or malignancy. Therefore, knowledge of possible symptoms of bacterial STIs in this area is helpful for early diagnosis. Coinfections with other STIs are common and should prompt a search of other pathogens including HIV and hepatitis B/C.

Vaginal microbiota diverges in sows with low and high reproductive performance after porcine reproductive and respiratory syndrome vaccination.

Previous studies have demonstrated evidence for a relationship between the vaginal microbiome and reproductive performance, suggesting the vaginal microbiota may serve as a tool to predict farrowing outcomes in commercial pigs. In this study, we compared the vaginal microbiome in sows with low and high farrowing performance and used it to classify animals with contrasting reproductive outcomes in commercial sows following immune challenge with porcine respiratory and reproductive syndrome (PRRS) vaccination. Eighteen microbes were differentially abundant (q-value < 0.05) between the Low and High farrowing performance groups. Among them, Campylobacter, Bacteroides, Porphyromonas, Lachnospiraceae unclassified, Prevotella, and Phascolarctobacterium were also selected in the discriminant and linear regression analyses, and could be used as potential biomarkers for reproductive outcomes. The correct classification rate in the two groups was 100%. In conclusion, this study demonstrates that vaginal microbiota collected after PRRS vaccination could be potentially used to classify sows into having low or high farrowing performance in commercial herds.

Determinants of blood telomere length in antiretroviral treatment-naïve HIV-positive participants enrolled in the NEAT 001/ANRS 143 clinical trial.

OBJECTIVES: Our aim was to investigate factors associated with baseline blood telomere length in participants enrolled in NEAT 001/ANRS 143, a randomized, open-label trial comparing ritonavir-boosted darunavir (DRV/r) plus raltegravir (RAL) with DRV/r plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in antiretroviral therapy (ART)-naïve HIV-positive adults. METHODS: A cross-sectional study of 201 randomly selected participants who had stored samples available was carried out. We measured telomere length (i.e. the relative telomere length, calculated as the telomere to single copy gene ratio) at baseline with monochrome quantitative multiplex polymerase chain reaction (PCR). We used multivariable predictive linear regression to calculate mean differences and 95% confidence intervals (CIs) for the association between baseline telomere length and baseline characteristics. RESULTS: The baseline characteristics of the 201 participants did not differ from those of the 805 participants in the parent trial population: 89% were male, the mean age was 39 years, 83.6% were Caucasian, 93% acquired HIV infection via sexual transmission, the mean estimated time since HIV diagnosis was 2.1 years, the mean HIV-1 RNA load was 4.7 log10 HIV-1 RNA copies/mL, the mean nadir and baseline CD4 counts were 301 and 324 cells/µL, respectively, and the mean CD4:CD8 ratio was 0.4. In the univariate analysis, shorter telomere length was associated with older age (per 10 years) (P < 0.001), HIV-1 RNA ≥ 100 000 copies/mL (P = 0.001), CD4 count < 200 cells/µL (P = 0.037), lower CD4:CD8 ratio (P = 0.018), statin treatment (P = 0.004), and current alcohol consumption (P = 0.035). In the multivariable analysis, older age (P < 0.001) and HIV RNA ≥ 100 000 copies/mL (P = 0.054) were independently associated with shorter telomere length. CONCLUSIONS: Both age and HIV RNA viral load correlated with shorter blood telomere length in untreated persons living with HIV. These results suggest that HIV infection and age have synergistic and independent impacts upon immunosenescence.

Planning HIV therapy to prevent future comorbidities: patient years for tenofovir alafenamide.

Since the introduction of suppressive antiretroviral therapy (ART), HIV has become a chronic disease, with infected people in high-income countries approaching similar life expectancy to the general population. As this population ages, an increasing number of people with HIV are living with age-, treatment-, and disease-related comorbidities. Lifestyle factors such as smoking, alcohol abuse, and substance misuse have a role in age-related comorbidity. Some degree of immune dysfunction is suggested by the presence of markers of immune activation/inflammation despite effective suppression of HIV replication. Cumulative exposure to some antiretroviral drugs contributes to HIV-associated comorbidities, with risk increasing with age. Specifically, tenofovir disoproxil fumarate (TDF), ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir are associated with renal impairment, and TDF is known to cause loss of bone mineral density. Tenofovir alafenamide (TAF) was developed to improve on the safety profile of TDF, while maintaining its efficacy. TAF has better stability in plasma, and higher intracellular accumulation of tenofovir diphosphate in target cells, which has resulted in improved antiviral activity at lower doses with improved renal and bone safety. TAF has been studied extensively in randomized clinical trials and real-world studies. TAF-based regimens are recommended over TDF-containing regimens for the improved safety profile.

[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.

Pilot-study on the feasibility of sentinel node navigation surgery in combination with thoracolaparoscopic lymphadenectomy without esophagectomy in early esophageal adenocarcinoma patients.

High-risk submucosal esophageal adenocarcinoma's might be treated curatively by means of radical endoscopic resection, followed by thoracolaparoscopic lymphadenectomy without concomitant esophagectomy. A preclinical study has shown the feasibility and safety of this approach; however, no studies are performed in a clinical setting. In addition, sentinel node navigation surgery could be valuable in tailoring the extent of the lymphadenectomy. This study aimed to evaluate the feasibility and safety of thoracolaparoscopic lymphadenectomy without esophagectomy (phase I) and sentinel node navigation surgery (phase II) in patients with early esophageal adenocarcinoma. Patients with T1N0M0 early esophageal adenocarcinoma scheduled for esophagectomy without neoadjuvant therapy were included. Phase I: Two-field, esophagus preserving, thoracolaparoscopic lymphadenectomy was performed, followed by esophagectomy in the same session. Primary outcome parameters were the number of lymph nodes resected, and number of retained lymph nodes in the esophagectomy specimen. Phase II: A radioactive tracer was injected endoscopically the day before surgery. Static imaging was performed 15 and 120 minutes after injection. The day of surgery, sentinel node navigation surgery followed by esophagectomy was performed. Primary outcome parameters were the percentage of patients with a detectable sentinel node, and the concordance between static imaging and probe-based detection of sentinel node. Phase I: Five patients were included, and a median of 30 (IQR: 25-46) lymph nodes was resected. A median of 6 (IQR: 2-9) retained lymph nodes was found in the esophagectomy specimen. No acute adverse events occurred, but near the end of lymphadenectomy esophageal discoloration was observed, possibly indicating ischemia. Phase II: In all five included patients sentinel nodes could be visualized and resected, at a median of 3 (IQR: 2-5) locations. There was a high concordance between imaging and probe-based detection of sentinel nodes. In conclusion, sentinel node navigation surgery followed by lymphadenectomy without concomitant esophagectomy seems feasible in patients with high-risk submucosal early esophageal adenocarcinoma. More evidence is however needed before applying this technique in clinical practice.