Objectives: To describe the prevalence of baseline drug‐resistance mutations, resistance to antiretroviral drugs, and the subsequent virological response to therapy in treatment‐naïve patients from Mexico with established HIV‐1 infection.Methods: Resistance testing was performed on plasma samples from antiretroviral‐naïve patients. Data on mutations associated with antiretroviral drug resistance were obtained using Stanford software (http://hivdb.stanford.edu).Results: Ninety‐six treatment‐naïve individuals were enrolled in the study during 2002–2003. Of these, 83 patients (86%) had at least one resistance mutation and 15 (16%) had drug resistance. At baseline, the mean plasma viral load was 299 834 HIV‐1 RNA copies/mL, and at follow‐up it was 37 620 copies/mL (P<0.0001). Primary mutations in the reverse transcriptase region were observed in 15% of patients. For nucleoside inhibitors, mutations T215Y/C and F77L (3%) and D67N/S, T69N and M184V (2%), were detected. For nonnucleoside inhibitors, mutations K103N/R (6%), Y181C (3%) and G190A (2%) were detected. Overall, 6% of patients showed resistance to delavirdine and nevirapine, 4% to efavirenz, and 2% to lamivudine and nelfinavir. Twelve patients showed no response to treatment and three of these patients had antiretroviral drug resistance.Conclusions: The prevalence of baseline drug‐resistance mutations found in this study was similar to that found in previous reports for newly HIV‐infected individuals, although access to and management of antiretrovirals in Mexico are different.

The circadian rhythms generated by the master biological clock located in the brain’s hypothalamus influence central physiological processes. At the molecular level, a core set of clock genes interact to form transcription–translation feedback loops that provide the molecular basis of the circadian rhythm. In animal models of disease, a desynchronization of clock genes in peripheral tissues with the central master clock has been detected. Interestingly, patients with vascular dementia have sleep disorders and irregular sleep patterns. These alterations in circadian rhythms impact hormonal levels, cardiovascular health (including blood pressure regulation and blood vessel function), and the pattern of expression and activity of antioxidant enzymes. Additionally, oxidative stress in vascular dementia can arise from ischemia-reperfusion injury, amyloid-beta production, the abnormal phosphorylation of tau protein, and alterations in neurotransmitters, among others. Several signaling pathways are involved in the pathogenesis of vascular dementia. While the precise mechanisms linking circadian rhythms and vascular dementia are still being studied, there is evidence to suggest that maintaining healthy sleep patterns and supporting proper circadian rhythm function may be important for reducing the risk of vascular dementia. Here, we reviewed the main mechanisms of action of molecular targets related to the circadian cycle and oxidative stress in vascular dementia.

The serine incorporator 5 (SERINC5) is a recently discovered restriction factor that inhibits viral infectivity by preventing fusion. Retroviruses have developed strategies to counteract the action of SERINC5, such as the expression of proteins like negative regulatory factor (Nef), S2, and glycosylated Gag (glycoGag). These accessory proteins downregulate SERINC5 from the plasma membrane for subsequent degradation in the lysosomes. The observed variability in the action of SERINC5 suggests the participation of other elements like the envelope glycoprotein (Env) that modulates susceptibility of the virus towards SERINC5. The exact mechanism by which SERINC5 inhibits viral fusion has not yet been determined, although it has been proposed that it increases the sensitivity of the Env by exposing regions which are recognized by neutralizing antibodies. More studies are needed to understand the role of SERINC5 and to assess its utility as a therapeutic strategy.

MicroRNAs (miRNAs/miRs) may serve as therapeutic agents or targets in diseases in which the expression of proteins plays an important role. The aim of the present study was to compare the expression levels of specific miRNAs, as well as their correlation with markers of response to antiretroviral (ARV) therapy, in patients with human immunodeficiency virus type 1 (HIV-1) infection with and without resistance to highly active antiretroviral therapy (HAART). Methods: miRNA assays were performed on plasma samples obtained from 20 HIV-1-positive patients. A total of ten patients were divided into two groups: HAART-responsive and HAART-resistant (n=5 per group). Commercial arrays were subsequently used to identify 84 miRNAs. A total of three differentially expressed miRNAs were selected and analyzed by quantitative PCR (qPCR). Five other patients were subsequently added to each group for a new relative expression analysis. The absolute expression level of the two miRNAs was obtained and compared using the Student’s t test. Receiver operating characteristic (ROC) curves were used to identify patients with antiretroviral therapy (ART) resistance. Results: The array analysis revealed that miR-15b-5p, miR-16-5p, miR-20a-5p, miR-26a-5p, miR-126-3p and miR-150-5p were down-regulated in patients with HAART-resistance comparing with HAART-responsive. The expression levels of miR-16-5p, miR-26a-5p and miR-150-5p were confirmed using qPCR. The area under the ROC curve was 1.0 for the three miRNAs. Conclusions: The lower expression levels of miR-16-5p and miR-26a-5p in patients with HAART-resistance suggested that these may serve as potential biomarkers for the identification of HAART-responsive patients.