Introduction: In Mexico, HIV genotyping is performed in people living with HIV (PLWH) failing their first-line antiretroviral (ARV) regimen; it is not routinely done for all treatment-naive PLWH before ARV initiation. The first nationally representative survey published in 2016 reported that the prevalence of pretreatment drug mutations in treatment-naive Mexican PLWH was 15.5% to any antiretroviral drug and 10.6% to non-nucleoside reverse transcriptase inhibitors (NNRTIs) using conventional Sanger sequencing. Most reports in Mexico focus on HIV pol gene and nucleoside and non-nucleoside reverse transcriptase inhibitor (NRTI and NNRTI) drug resistance mutations (DRMs) prevalence, using Sanger sequencing, next-generation sequencing (NGS) or both. To our knowledge, NGS has not be used to detect pretreatment drug resistance mutations (DRMs) in the HIV protease (PR) gene and its substrate the Gag polyprotein. Methods: Treatment-naive adult Mexican PLWH were recruited between 2016 and 2019. HIV Gag and protease sequences were obtained by NGS and DRMs were identified using the WHO surveillance drug resistance mutation (SDRM) list. Results: One hundred PLWH attending a public national reference hospital were included. The median age was 28 years-old, and most were male. The median HIV viral load was 4.99 [4.39–5.40] log copies/mL and median CD4 cell count was 150 [68.0–355.78] cells/mm³. As expected, most sequences clustered with HIV-1 subtype B (97.9%). Major PI resistance mutations were detected: 8 (8.3%) of 96 patients at a detection threshold of 1% and 3 (3.1%) at a detection threshold of 20%. A total of 1184 mutations in Gag were detected, of which 51 have been associated with resistance to PI, most of them were detected at a threshold of 20%. Follow-up clinical data was available for 79 PLWH at 6 months post-ART initiation, seven PLWH failed their first ART regimen; however no major PI mutations were identified in these individuals at baseline. Conclusions: The frequency of DRM in the HIV protease was 7.3% at a detection threshold of 1% and 3.1% at a detection threshold of 20%. NGS-based HIV drug resistance genotyping provide improved detection of DRMs. Viral load was used to monitor ARV response and treatment failure was 8.9%.

Orthoflavivirus, a genus of positive-sense, single-stranded RNA viruses belonging to the family Flaviviridae, infects vertebrates and is transmitted by arthropods (arboviruses). These include pathogens such as dengue, yellow fever, Zika, and Japanese encephalitis viruses. These are clinically relevant viruses that can cause symptoms ranging from mild to severe forms, with hemorrhagic and neurological involvement, posing significant threats to human health worldwide. The immune response to Orthoflavivirus involves a complex interaction between innate and adaptive immunity, with T cells and neutralizing antibodies playing key roles. Cross-reactivity between serotypes can lead to ineffective viral control and complicate both immunopathology and vaccine development. It should be noted that there are still no approved antiviral treatments against Orthoflavivirus. ‑Therefore, strategies have been implemented to control these infections, such as vector management and vaccines. Some have already been approved and have been instrumental in significantly reducing these infections, as was the case with yellow fever, whose vaccine served as the basis for the development of current vaccines. Despite these achievements, vaccine efficacy remains variable. This chapter will focus on providing a comprehensive understanding of the advances related to Orthoflavivirus, including their immunological characteristics, immune responses, vaccination strategies, and current challenges.

This chapter examines the interaction between dengue virus infection and mucosal involvement. It describes the innate and adaptive immune responses that occur on these surfaces, including the role of epithelial barriers, immune cells, cytokines, and antibody-mediated immunity. Additionally, it reviews the main signaling pathways activated during dengue infection, including their contribution to both the control of viral replication and inflammatory and pathogenic processes. Particular attention is given to the mechanisms through which the immune response can control viral infection, while an excessive or dysregulated response may contibute to tissue damage and disease porgession. Findings from in vitro studies are presented, and clinical cases are analyzed, reporting the clinical manifestations observed in the oral, nasal, conjunctival, and genital mucosa, with special emphasis on identifying warning signs in patients with dengue infection. These manifestations are discussed in relation to the systemic effects of dengue and their potential clinical relevance. Furthermore, a comparison is made with other infections caused by arboviruses, such as Zika and Chikungunya viruses, to identify similarities and differences in mucosal involvement and facilitate differential diagnosis. This comparison also provides a broader understanding of the clinical manifestations associated with arboviral infections and their importance in patient evaluation.Finally, potential therapeutic strategies aimed at modulating the immune response and mitigating disease progression are discussed. This chapter emphasizes continued research into pharmacological treatments and therapeutic strategies to reduce inflammation, control viral replication, and prevent tissue damage, while recognizing dengue is mucosal effects and clinical features to enable early diagnosis and timely tretament.