Search

Background: Over the past decade, antiretroviral therapy (ART) regimens that include integrase strand inhibitors (INSTIs) have become the most commonly used for people with HIV starting ART. Although trials and observational studies have compared virological failure on INSTI-based with other regimens, few data are available on mortality in people with HIV treated with INSTIs in routine care. Therefore, we compared all-cause mortality between different INSTI-based and non-INSTI-based regimens in adults with HIV starting ART from 2013 to 2018. Methods: This cohort study used data on people with HIV in Europe and North America from the Antiretroviral Therapy Cohort Collaboration (ART-CC) and UK Collaborative HIV Cohort (UK CHIC). We studied the most common third antiretroviral drugs (additional to nucleoside reverse transcriptase inhibitor) used from 2013 to 2018: rilpivirine, darunavir, raltegravir, elvitegravir, dolutegravir, efavirenz, and others. Adjusted hazard ratios (aHRs; adjusted for clinical and demographic characteristics, comorbid conditions, and other drugs in the regimen) for mortality were estimated using Cox models stratified by ART start year and cohort, with multiple imputation of missing data. Findings: 62 500 ART-naive people with HIV starting ART (12 422 [19·9%] women; median age 38 [IQR 30-48]) were included in the study. 1243 (2·0%) died during 188 952 person-years of follow-up (median 3·0 years [IQR 1·6-4·4]). There was little evidence that mortality rates differed between regimens with dolutegravir, elvitegravir, rilpivirine, darunavir, or efavirenz as the third drug. However, mortality was higher for raltegravir compared with dolutegravir (aHR 1·49, 95% CI 1·15-1·94), elvitegravir (1·86, 1·43-2·42), rilpivirine (1·99, 1·49-2·66), darunavir (1·62, 1·33-1·98), and efavirenz (2·12, 1·60-2·81) regimens. Results were similar for analyses making different assumptions about missing data and consistent across the time periods 2013-15 and 2016-18. Rates of virological suppression were higher for dolutegravir than other third drugs. Interpretation: This large study of patients starting ART since the introduction of INSTIs found little evidence that mortality rates differed between most first-line ART regimens; however, raltegravir-based regimens were associated with higher mortality. Although unmeasured confounding cannot be excluded as an explanation for our findings, virological benefits of first-line INSTIs-based ART might not translate to differences in mortality. We would like to thank our funders (US National Institute on Alcohol Abuse and Alcoholism and UK Medical Research Council) and all patients and the clinical teams associated with the participating cohort studies. The antiretroviral therapy cohort collaboration is funded by the US National Institute on Alcohol Abuse and Alcoholism (U01-AA026209). UK Collaborative HIV Cohort is funded by the UK Medical Research Council (grant numbers G0000199, G0600337, G0900274, and M004236/1). JACS is funded by National Institute for Health Research Senior Investigator award (NF-SI-0611-10168). AT is funded by the Wellcome Trust under a Sir Henry Wellcome Postdoctoral Fellowship (222770/Z/21/Z). Funding for the individual antiretroviral therapy cohort collaboration cohorts included in this analysis was from Alberta Health, Gilead, National Agency for AIDS Research (France REcherche Nord&Sud Sida-hiv Hépatites), the French Ministry of Health, the Austrian Agency for Health and Food Safety, Stichting HIV Monitoring, the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment, the TP-HIV by the German Centre for Infection Research (NCT02149004), Instituto de Salud Carlos III (through the Red Temática de Investigación Cooperativa en Sida [RD06/006, RD12/0017/0018, and RD16/0002/0006]) as part of the Plan Nacional I + D + i. Other funders of the individual cohorts participating data for this analysis are ISCIII-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional, ViiV Healthcare, Preben og Anna Simonsens Fond, ANRS-Maladies infectieuses émergentes, Institut National de la Santé et de la Recherche Médicale (INSERM), Bristol Myers Squibb, Janssen, Merck, the US National Institute on Alcohol Abuse and Alcoholism (U01-AA026230), the Spanish Ministry of Health, the Swiss National Science Foundation (grant 33CS30_134277), Centers for AIDS Research Network of Integrated Clinical Systems (1R24 AI067039-1, P30-AI-027757), the US Department of Veterans Affairs, the US National Institute on Alcohol Abuse and Alcoholism (U01-AA026224, U01-AA026209, U24-AA020794), the Veterans Health Administration Office of Research and Development, and the US National Institute of Allergy and Infectious Diseases (Tennessee Center for AIDS Research P30 AI110527). Sí

Summary Background HIV-infected patients with Pneumocystis-pneumonia (PCP) may develop paradoxical immune reconstitution inflammatory syndrome (IRIS), when combination antiretroviral therapy (cART) is started early during the course of PCP-treatment (PCPT). The aim of this study was to identify risk factors and predictors for PCP-IRIS and to improve individualized patient care. Methods An ICD-10 code hospital database query identified all Frankfurt HIV Cohort patients being diagnosed with PCP from January 2010 – June 2016. Patient charts were evaluated retrospectively for demographic, clinical and therapeutic (cART/PCPT) characteristics and incidence of paradoxical IRIS according to French's case definitions. Results IRIS occurred in 12/97 patients that started cART while on PCPT (12.4%). They had a higher rate of re-hospitalization (41.7vs. 4.7%; odds ratio (OR) 14.46; p = 0.009), intensive care treatment (66.7vs. 30.6%; OR = 4.54; p = 0.018), and longer median hospitalization (48 days vs. 23; p 6Log10/ml) before cART initiation was associated with IRIS development (41.6vs. 15.0%; OR 4.05; p = 0.042). Serum immunoglobulin G-levels (IgG) [mg/dl] were lower (894.0 vs. 1446.5; p = 0.023). Conclusion Higher hospitalization rate and morbidity parameters underscore the clinical importance of PCP-related paradoxical IRIS. A baseline viral load of > 6Log10/ml and serum IgG may help to assess individual risks for PCP-IRIS.

The goal of this study was to examine prognostic relationships between cardiac imaging measures and cardiovascular outcome in people living with human immunodeficiency virus (HIV) (PLWH) on highly active antiretroviral therapy (HAART).PLWH have a higher prevalence of cardiovascular disease and heart failure (HF) compared with the noninfected population. The pathophysiological drivers of myocardial dysfunction and worse cardiovascular outcome in HIV remain poorly understood.This prospective observational longitudinal study included consecutive PLWH on long-term HAART undergoing cardiac magnetic resonance (CMR) examination for assessment of myocardial volumes and function, T1 and T2 mapping, perfusion, and scar. Time-to-event analysis was performed from the index CMR examination to the first single event per patient. The primary endpoint was an adjudicated adverse cardiovascular event (cardiovascular mortality, nonfatal acute coronary syndrome, an appropriate device discharge, or a documented HF hospitalization).A total of 156 participants (62% male; age [median, interquartile range]: 50 years [42 to 57 years]) were included. During a median follow-up of 13 months (9 to 19 months), 24 events were observed (4 HF deaths, 1 sudden cardiac death, 2 nonfatal acute myocardial infarction, 1 appropriate device discharge, and 16 HF hospitalizations). Patients with events had higher native T1 (median [interquartile range]: 1,149 ms [1,115 to 1,163 ms] vs. 1,110 ms [1,075 to 1,138 ms]); native T2 (40 ms [38 to 41 ms] vs. 37 ms [36 to 39 ms]); left ventricular (LV) mass index (65 g/mOur findings reveal important prognostic associations of diffuse myocardial fibrosis and LV remodeling in PLWH. These results may support development of personalized approaches to screening and early intervention to reduce the burden of HF in PLWH (International T1 Multicenter Outcome Study; NCT03749343).

The choice of an optimal antiretroviral therapy (ART) in naive patients presenting late for initial therapy with advanced HIV infection, that is, with a CD4 cell count

After pre-exposure prophylaxis (PrEP) was introduced, rates of sexually transmitted infections (STIs) increased among PrEP users. However, data on STI trends in people living with HIV since then are limited. Since September 2019, PrEP has been covered by statutory German health insurance (SHI) in vulnerable groups. This study aimed to determine whether this coverage of PrEP costs affected STI rates in people living with HIV (specifically, men who have sex with men).All patients of the HIVCENTER Frankfurt diagnosed with at least one STI within the observation period were retrospectively enrolled in the study. STIs included infection with Treponema pallidum, Chlamydia trachomatis, Neisseria gonorrhoeae, and/or Trichomonas vaginalis. The observation period covered 1 year before and 1 year after the coverage of PrEP costs by German SHI. Data were collected from outpatient clinic records.In total, 143 patients were enrolled in the study. The observation period was September 2018 to August 2019 for group 1 (n = 73) and September 2019 to August 2020 for group 2 (n = 70). The most frequent STIs were syphilis and infections due to chlamydia, gonococci, and trichomonads, in descending order. Infections with T. pallidum occurred more often in group 2 than in group 1 (60.0% vs. 50.7%; p = 0.253) as did chlamydia (37.1% vs. 28.8%; p = 0.286).A tendency for an increased ratio of STIs in people living with HIV was observed after the introduction of PrEP coverage by German SHI. STIs should be discussed intensively with people living with HIV, since the communities of PrEP users and people living with HIV overlap, and changes in risk behaviour might influence both groups.

Funding Acknowledgements Type of funding sources: None. Background/Introduction People living with human immunodeficiency virus (HIV, PLWH) are at increased risk of cardiovascular disease (CVD). HIV infection and accelerated traditional risk factors due to highly-active antiretroviral therapy (HAART) are proposed mechanisms for increased rate of heart failure (HF). The pathophysiological drivers of myocardial dysfunction and worse cardiovascular outcome in HIV remain poorly understood. Purpose To examine prognostic relationships of cardiac imaging measures with cardiovascular outcome in PLWH on HAART. Methods This is a prospective observational longitudinal study using cardiac magnetic resonance (CMR) imaging in consecutive PLHWH on long-term HAART who were screened for underlying CVD and followed up clinically for adjudicated adverse cardiovascular events (cardiovascular mortality, non-fatal acute coronary syndrome, an appropriate device discharge, or a documented HF hospitalization). Imaging protocol included routine assessment of cardiac volumes and function, scar by late gadolinium enhancement, myocardial perfusion and native T1 /T2 mapping. Time-to-event analysis was performed from the index CMR exam to the first single event per patient Systematic risk scores for CVD (Framingham risk score (FRS), Data Collection on Adverse effects of anti-HIV Drugs score, D:A:D and MAGGIC integer score) were calculated using original online calculators. Results 156 participants (males 62%, 50 [42-57] years of age) were included. 24 events were observed (4 HF deaths, 1 sudden cardiac death, 2 non-fatal acute myocardial infarction, 1 appropriate device discharge and 16 HF hospitalizations) during a median follow-up of 13 [9-19] months. Patients with events had higher native T1 (ms, 1149 [1115-1163] ms vs. 1110 [1075-1138] ms), native T2 (ms, 40 [38-41] vs. 37 [36-39]), LV mass index (g/m², 65 [49-77] vs. 57 [49-64]) p Conclusions Native myocardial T1 and LV mass by CMR, as opposed to traditional cardiovascular risk scores, predict cardiovascular outcome in PLWH, together reflecting the pathological myocardial remodeling of myocardial fibrosis and inflammation that potentially explain higher rates of HF in PLWH as compared to the non-infected population. These findings may inform personalized approaches to screening and early intervention to reduce the burden of HF.

OBJECTIVES The aim of the study was to investigate the efficacy and safety of first-line antiretroviral therapy (ART) with integrase inhibitor (INI) or protease inhibitor (PI)-based regimens in patients with low CD4 cell counts and/or an AIDS-defining disease. METHODS We conducted a retrospective, multicentre analysis to investigate discontinuation proportions and virological response in patients with CD4 cell counts

BACKGROUND To assess the association between HLA-B57.01 (Human leukocyte antigen) and clinical parameters of chronic periodontitis in people living with HIV (PLWHIV). METHODS All patients were recruited from the HIVCENTER at the University Hospital Frankfurt during April 2014 and July 2015. Periodontal examination included Periodontal Screening Index (PSI), Gingivalindex (GI), Bleeding on Probing Index (BOP), Periodontal Probing Depth (PD), Clinical Attachment Level (CAL) and DMF-T Score (decayed, missing, filled teeth). Associations among periodontitis, HLA-system and additional risk factors in PLWHIV were evaluated in multivariate analyses. RESULTS One hundred PLWHIV were enrolled. Forty-five patients were naive, meaning that these patients never took antiretroviral (ARV) drugs before, 55 patients treated with combined antiretroviral therapy (cART). Nineteen patients presented a positive HLA-B 57.01 status. PLWHIV who were carriers of HLA-B 57.01 had significantly lower PSI-scores (Grade 3 or higher; 0/19 [0%] versus 16/41 [39%] versus 17/40 [42%]; p =

We describe a strain of Lassa virus representing a putative new lineage that was isolated from a cluster of human infections with an epidemiologic link to Togo. This finding extends the known range of Lassa virus to Togo.

Two patients with Lassa fever are described who are the first human cases treated with a combination of ribavirin and favipiravir. Both patients survived but developed transaminitis and had prolonged detectable virus RNA in blood and semen, suggesting that the possibility of sexual transmission of Lassa virus should be considered.

This investigation was carried out with already available point-of-care testing (POCT) systems for coagulation parameters to evaluate the qualitative and semiquantitative determination of the time- and concentration-dependent anticoagulant effects of the direct oral anticoagulants rivaroxaban and dabigatran.The whole blood prothrombin time (PT), activated partial thromboplastin time (aPTT), and activated clotting time (ACT) were determined using the GEM PCL Plus coagulation system. Whole blood PT was also measured on the CoaguCheck XS instrument. In addition, PT and aPTT values were obtained in citrated plasma using the PT reagent Neoplastin Plus and the STA APTT reagent. Drug concentrations of rivaroxaban and dabigatran were determined with a chromogenic anti-Xa assay and the hemoclot assay, which are reported to have good agreement with liquid chromatography coupled with tandem mass spectrometry measurements. POCT was performed in 27 consecutive patients who received rivaroxaban 10, 15, or 20 mg once daily and in 15 patients receiving dabigatran 110 or 150 mg twice daily. Blood samples were collected predose and 2 hours after observed drug intake at steady state.Two hours after observed rivaroxaban administration, the whole blood PT measured on the GEM PCL Plus was prolonged by an average of 64.5% in comparison with predose levels. Less differentiation was observed for rivaroxaban when the PT was measured on the CoaguCheck XS instrument or in plasma (prolongation of 24.1% and 36.8%, respectively). After 2 hours observed dabigatran administration, the whole blood aPTT was comparable with plasma values and was prolonged by 23.5% in comparison with trough values. Significant concentration-dependent prolongations of the activated clotting time were observed to different extents for both direct anticoagulants.Direct oral anticoagulants display variable ex vivo effects on different POCT-assays. POCT for aPTT is sensitive to increased concentrations of dabigatran, whereas the PT-POCT assessed with test systems such as the GEM PCL Plus may be helpful to measure the pharmacodynamic anticoagulant effects of rivaroxaban in emergency clinical situations.

Introduction : HIV infection is accompanied by a variety of neurological disorders. Depression of cell-mediated immunity is followed by the development of central nervous system opportunistic infections/tumours, and frequently by the occurrence of the AIDS dementia complex (ADC). However, the pathophysiology of the emergence of neuro-AIDS is still unknown. Despite the development of cognitive impairments, the early diagnosis, objectification and quantification of the existence and extent of this impairment during infection are difficult to recognize in each individual case. To support the early diagnosis of ADC, there is a need for additional, non-invasive diagnostic methods. In this study, it is of interest to answer the clinically relevant question of whether magnetic resonance spectroscopy can detect changes in the cerebral metabolism of asymptomatic HIV-positive patients and is possibly suitable for the early diagnosis and prevention of HIV encephalopathy. Methods : A group of 13 asymptomatic, HIV-positive patients with combined antiretroviral therapy (cART) and 13 healthy controls were examined with 2D 1H-MRS and 3D 31P-MRS at 3T. The patients were treated with cART for at least 12 months. Changes in the absolute concentrations of phosphorylated metabolites (ATP), N-acetyl-aspartate, creatine, myo-Isonitol, glutamate/glutamine and choline-containing compounds were compared with that of control subjects. Results : Asymptomatic HIV-positive patients had significantly lower N-acetyl-aspartate in the white matter in a frontal and parietal target region. The other evaluated metabolites in the 1H MRS showed no significant difference between the HIV-positive patients and healthy controls. The 31P-MRS detected significant elevated values regarding the choline-containing compounds PEth, GPE and PCho. Conclusions : This spectroscopic study revealed a significantly lower N-acetyl-aspartate in the white matter in a frontal and parietal cerebral target region in asymptomatic, HIV-positive patients as an early sign of neuronal disintegration. The 31P-MRS detected significant elevated values regarding the choline-containing compounds PEth, GPE and PCho as an early sign of gliosis. Furthermore we could show that with the use of 1H-MRS and 31P-MRS cerebral metabolites can be reliably detected and measured in HIV-positive patients. The 1H-MRS and 31P-MRS is therefore suited as a diagnostic tool for early cerebral metabolic changes in HIV-positive patients. (Published: 2 November 2014) Citation : Abstracts of the HIV Drug Therapy Glasgow Congress 2014 Schuettfort G et al. Journal of the International AIDS Society 2014, 17(Suppl 3) :19577 http://www.jiasociety.org/index.php/jias/article/view/19577 | http://dx.doi.org/10.7448/IAS.17.4.19577

Inferior vena cava thrombosis (IVCT) is a rare event, and studies detailing its underlying aetiologies are scarce.One hundred and forty-one IVCT patients (57% females, median age 47 years) were analysed with a focus on malignancy-related thrombosis and compared with 141 age- and sex-matched control patients with isolated lower-extremity deep vein thrombosis.Malignancies were more prevalent among IVCT patients compared with the control group (39% vs. 7.8%; P0.001). Malignancy-related IVCT more frequently involved the suprarenal and hepatic segments of the IVC and extended more often to the right atrium than IVCT did in non-cancer patients. Among IVCT patients with malignancies, renal cell carcinoma (38%) and other malignancies of the genitourinary tract (25%) were the most common tumours. Analysis of the underlying pathological mechanisms of malignancy-related thrombosis identified external compression of the IVC by tumour masses in 9 cases (16%), and progression of malignancy into the IVC (so-called "tumour thrombosis") in 24 cases (44%). The remaining 22 cases (40%) were attributed to malignancy-related hypercoagulability and the presence of additional venous thromboembolism risk factors, such as previous surgery, immobilisation, or chemotherapy.Malignancies substantially contribute to the risk of thrombosis involving the IVC. Tumour invasion, especially in cases of renal cell cancer and malignancy-related hypercoagulability are major triggering factors for thrombogenesis.