Human immunodeficiency virus type 1 (HIV-1) is a very important global pathogen that preferentially targets CD4+ T cells and causes acquired immunodeficiency syndrome (AIDS) if left untreated. Although antiretroviral treatment efficiently suppresses viremia, markers of immune activation and inflammation remain higher in HIV-1-infected patients than in uninfected individuals. The hypoxia-inducible factor 1α (HIF-1α) is a transcription factor that plays a fundamental role in coordinating cellular metabolism and function. Here we show that HIV-1 infection induces HIF-1α activity and that this transcription factor upholds HIV-1 replication. Moreover, we demonstrate that HIF-1α plays a key role in HIV-1-associated inflammation by promoting the release of extracellular vesicles which, in turn, trigger the secretion of inflammatory mediators by noninfected bystander lymphocytes and macrophages. In summary, we identify that the coordinated actions of HIF-1α and extracellular vesicles promote viral replication and inflammation, thus contributing to HIV-1 pathogenesis.

Inflammation is a hallmark of HIV infection. Among the multiple stimuli that can induce inflammation in untreated infection, ongoing viral replication is a primary driver. After initiation of effective combined antiretroviral therapy (cART), HIV replication is drastically reduced or halted. However, even virologically controlled patients may continue to have abnormal levels of inflammation. A number of factors have been proposed to cause inflammation in HIV infection: among others, residual (low‐level) HIV replication, production of HIV protein or RNA in the absence of replication, microbial translocation from the gut to the circulation, co‐infections, and loss of immunoregulatory responses. Importantly, chronic inflammation in HIV‐infected individuals increases the risk for a number of non‐infectious co‐morbidities, including cancer and cardiovascular disease. Thus, achieving a better understanding of the underlying mechanisms of HIV‐associated inflammation in the presence of cART is of utmost importance. Extracellular vesicles have emerged as novel actors in intercellular communication, involved in a myriad of physiological and pathological processes, including inflammation. In this review, we will discuss the role of extracellular vesicles in the pathogenesis of HIV infection, with particular emphasis on their role as inducers of chronic inflammation.

Summary The massive implementation of the vaccine and antiviral agents against hepatitis B virus (HBV), targeting the envelope and viral polymerase genes, induces a selection pressure that might lead to the emergence of variants that impair the effectiveness of the vaccine, diagnostic methods and antiviral therapy. The aim of this study was to evaluate the prevalence of HBV vaccine escape mutants (VEMs), diagnostic failure mutants (DFMs) and treatment resistance mutants (ARMs) among individuals from Buenos Aires, Argentina. HBV surface antigen and polymerase sequences obtained from serum samples of 530 HBV‐infected individuals were analysed. Samples belonged to genotypes A (28.1%), D (13.6%) and F (58.3%). VEMs, DMFs and ARMs were present in 40 (7.5%), 57 (10.7%) and 27 (5.1%) samples within the studied population. Additionally, eight nonpreviously reported VEMs and nine DFMs were identified. VEMs and DFMs were biased by genotype, being higher in genotype D (33.3% and 33.3%) compared to genotype A (6% and 17.4%) and genotype F (2.3% and 2.3%) (P > 0.001). On the contrary, there was no association between the presence of ARMs and HBV genotype (P = 0.324). VEMs, DFMs and ARMs create public health concerns. The current study provided valuable information about mutants in surface antigen and polymerase in HBV‐infected patients from Argentina where HBV‐F is the most prevalent genotype. Consequently, it constitutes an important reference for Latin American clinicians in order to optimize the management of HBV‐infected patients.