HIV-1 drug-resistance patterns among patients on failing treatment in a large number of European countries

Background: Information about patterns of HIV-1 drug resistance among treatment-exposed patients is crucial for the development of novel effective drugs. Currently no system exists that monitors patterns of resistance in patients failing therapy. Methods: The study included 1,988 HIV-1 sequences from patients experiencing therapy failure collected between 2000 and 2004 in 15 European countries. Genotypic resistance was interpreted using the ANRS algorithm. Phenotypic resistance was predicted using the Virco geno- to phenotype system. Results: 80.7% of the sequences included at least one drug-resistance mutation. Mutations were found for NRTIs (73.5%), NNRTIs (48.5%), and protease inhibitors (35.8%). Ninety percent of sequences with genotypic resistance harbored M184V, M41L, K103N, D67N, and/or T215Y. Among NRTIs, resistance was most frequently predicted for lamivudine. About half of all sequences had reduced susceptibility for NNRTIs. Resistance to most boosted protease inhibitors was found in &lt; 25%. No sequence had resistance to all currently available drugs. Conclusion: Levels of resistance among patients with therapy failure were high. The patterns of resistance reflect resistance to drugs available for a longer time. Fully suppressive regimens can be designed even for the most mutated HIV because boosted protease inhibitors have remained active against most circulating viruses and new drug classes have become available.</p

Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

Background: Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. Methods and Findings: LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95-0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19-20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55-12.43). Conclusions: LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP

The Role of Platelet-Activating Factor in Chronic Inflammation, Immune Activation, and Comorbidities Associated with HIV Infection.

With the advent of highly effective antiretroviral therapy, cardiovascular disease has become an important cause of morbidity and mortality among people with treated HIV-1, but the pathogenesis is unclear. Platelet-activating factor is a potent lipid mediator of inflammation that has immunomodulatory effects and a pivotal role in the pathogenesis of inflammatory disorders and cardiovascular disease. Limited scientific evidence suggests that the platelet-activating factor pathway may be a mechanistic link between HIV-1 infection, systemic inflammation, and immune activation that contribute to pathogenesis of chronic HIV-related comorbidities, including cardiovascular disease and HIV-associated neurocognitive disorders. In this review, we examine the mechanisms by which the cross-talk between HIV-1, immune dysregulation, inflammation, and perturbations in the platelet-activating factor pathway may directly affect HIV-1 immunopathogenesis. Understanding the role of platelet-activating factor in HIV-1 infection may pave the way for further studies to explore therapeutic interventions, such as diet, that can modify platelet-activating factor activity and use of platelet-activating factor inhibitors that might improve the prognosis of HIV-1 infected patients

Successful Treatment of Immune Reconstitution Inflammatory Syndrome-Related Hemophagocytic Syndrome in an HIV Patient with Primary Effusion Lymphoma

Although the connection of [secondary hemophagocytic syndrome (sHS)] with HIV has been well documented, optimal treatment regimen is not well established. This is due not only to the rarity of the syndrome, but also to the heterogeneity of the involved population. Most cases are related to opportunistic infections or malignancies in advanced stage, but many cases are also related to seroconversion, in the primary infection setting. Moreover, in the [antiretroviral treatment (ART)] era, rare cases of ART-related sHS have been reported. In these, often fatal cases, an [immune reconstitution inflammatory syndrome (IRIS)] process is involved, posing a serious challenge to the treating physician. We hereby report a case of successful treatment of an HIV patient with primary effusion lymphoma who experienced sHS shortly after ART onset. Our patient, treated with high dose dexamethasone and gamma globulin, achieved complete remission. This case might hint possible therapeutic insights in the treatment of IRIS-related sHS

The Role of Macrolides for the Management of Community-Acquired Pneumonia and Pneumonia by the Novel Coronavirus SARS-CoV-2 (COVID-19): A Position Paper by Four Medical Societies from Greece

In light of the accumulating evidence for survival benefit coming from the use of macrolides for community-acquired pneumonia (CAP), a group of experts from the field of internal medicine and infectious diseases frame a position statement on the use of macrolides for the management of bacterial CAP and for infection by the novel coronavirus (COVID-19). The statement is framed taking into consideration existing publications and own research experience. The main content of this statement is that the combination of one beta-lactam and a macrolide should be the first treatment of choice for patients with severe bacterial CAP. Severity is assessed as scoring 2 or more points on the CURB65 scoring system of severity or as pneumonia severity index III to V or C-reactive protein more than 150 mg/l; the suggested macrolide is either azithromycin or clarithromycin. The experts also suggest that in COVID-19 pneumonia, the combination of one beta-lactam and a macrolide should be reserved only when there is strong suspicion of bacterial co-infection

The European Non Occupational Post-Exposure Prophylaxis (NONOPEP) Registry :Demand and use of antiretrovirals (ARV) to prevent HIV Infection

info:eu-repo/semantics/nonPublishe