Antiretroviral therapies (ART) are strongly associated with weight gain and metabolic syndrome (MetS) development in HIV-infected patients. Few studies have evaluated the association between gut microbiota and integrase strand transfer inhibitor (INSTI)-based and protease inhibitor (PI)-based regimens in HIV-infected patients with MetS. To assess this, fecal samples were obtained from HIV-infected patients treated with different regimens (16 PI + MetS or 30 INSTI + MetS) and 18 healthy controls (HCs). The microbial composition was characterized using 16S rRNA amplicon sequencing. The INSTI-based and PI-based regimens were associated with a significant decrease in α-diversity compared to HCs. The INSTI + MetS group showed the lowest α-diversity between both regimens. A significant increase in the abundance of short-chain fatty acid (SCFA)-producing genera (Roseburia, Dorea, Ruminococcus torques, and Coprococcus) was observed in the PI + MetS group, while Prevotella, Fusobacterium, and Succinivibrio were significantly increased in the INSTI + MetS group. Moreover, the Proteobacteria/Firmicutes ratio was overrepresented, and functional pathways related to the biosynthesis of LPS components were increased in the INSTI + MetS group. The gut microbiota of patients receiving INSTIs showed a more pronounced dysbiosis orchestrated by decreased bacterial richness and diversity, with an almost complete absence of SCFA-producing bacteria and alterations in gut microbiota functional pathways. These findings have not been previously observed.

HIV infection results in marked alterations in the gut microbiota (GM), such as the loss of microbial diversity and different taxonomic and metabolic profiles. Despite antiretroviral therapy (ART) partially ablating gastrointestinal alterations, the taxonomic profile after successful new ART has shown wide variations. Our objective was to determine the GM composition and functions in people living with HIV (PLWHIV) under ART in comparison to seronegative controls (SC). Fecal samples from 21 subjects (treated with integrase strand-transfer inhibitors, INSTIs) and 18 SC were included. We employed 16S rRNA amplicon sequencing, coupled with PICRUSt2 and fecal short-chain fatty acid (SCFA) quantification by gas chromatography. The INSTI group showed a decreased α-diversity (p < 0.001) compared to the SC group, at the expense of increased amounts of Pseudomonadota (Proteobacteria), Segatella copri, Lactobacillus, and Gram-negative bacteria. Concurrently, we observed an enrichment in Megasphaera and Butyricicoccus, both SCFA-producing bacteria, and significant elevations in fecal butyrate in this group (p < 0.001). Interestingly, gut dysbiosis in PLWHIV was characterized by a proinflammatory environment orchestrated by Pseudomonadota and elevated levels of butyrate associated with bacterial metabolic pathways, as well as the evident presence of butyrogenic bacteria. The role of this unique GM in PLWHIV should be evaluated, as well as the use of butyrate-based supplements and ART regimens that contain succinate, such as tenofovir disoproxil succinate. This mixed profile is described for the first time in PLWHIV from Mexico.

Non-alcoholic fatty liver disease (NAFLD) is closely associated with other metabolic disease and cardiovascular disease. Regular exercise reduces hepatic fat content and could be the first-line treatment in the management of NAFLD. This review aims to summarize the current evidence of the beneficial effects of exercise training and identify the molecular pathways involved in the response to exercise to define their role in the resolution of NAFLD both in animal and human studies. According to the inclusion criteria, 43 animal studies and 14 RCTs were included in this systematic review. Several exercise modalities were demonstrated to have a positive effect on liver function. Physical activity showed a strong association with improvement in inflammation, and reduction in steatohepatitis and fibrosis in experimental models. Furthermore, both aerobic and resistance exercise in human studies were demonstrated to reduce liver fat, and to improve insulin resistance and blood lipids, regardless of weight loss, although aerobic exercises may be more effective. Resistance exercise is more feasible for patients with NAFLD with poor cardiorespiratory fitness. More effort and awareness should be dedicated to encouraging NAFLD patients to adopt an active lifestyle and benefit from it its effects in order to reduce this growing public health problem.

Background: Methamphetamine (MA) use in people living with HIV (PLWH) has been linked to neurocognitive and behavioral dysregulation. We hypothesized that PLWH with active MA use (MAHIV) would show poorer cognitive performance, greater emotional and sleep burden, higher behavioral risk, and alterations in circulating biomarkers of immune activation and neuronal injury, relative to PLWH without MA use and HIV-negative Controls. Methods: Cross-sectional analytic study of 121 adults: PLWH with MA use (MAHIV, n = 40), PLWH without use (n = 42), and HIV-negative Controls (n = 39). Outcomes were ART discontinuation, physical activity, neurocognition (MoCA), depression (BDI), anxiety (GAD-7), sleep (PSQI), and substance use (ASSIST). Circulating biomarkers measured by ELISA: sCD14, neuron-specific enolase (NSE), S100B, and neurofilament light chain (NfL). Results: MAHIV participants had more frequent ART discontinuation than PLWH and the lowest physical activity. Chemsex with polysubstance use, condomless sex, and multiple partners were most prevalent in MAHIV. This group showed the highest anxiety and depressive burdens, and the greatest sleep disturbances. Global cognition (MoCA) was lowest in MAHIV, with significant deficits in executive function, memory, attention, and language; 82.5% had at least mild cognitive impairment. sCD14 was significantly higher in MAHIV than in PLWH and Controls, and NSE was elevated in both MAHIV and PLWH versus Controls. sCD14 correlated inversely with MoCA and positively with GAD-7 and BDI-II. Conclusions: Among PLWH, MA use is associated with greater ART nonadherence, syndemic mental-health and sleep disturbances, broader neurocognitive deficits, and elevations in circulating sCD14 and NSE. The sCD14–cognition and sCD14–mood relationships highlight chronic immune activation as a candidate pathway for neurocognitive and affective impairment and support sCD14 and NSE as potential stratification and monitoring biomarkers in MA-using PLWH.

Background: Vasculonecrotic reactions in leprosy are typically associated with type 2 reactions. Differentiating between necrotizing erythema nodosum leprosum (nENL) and Lucio’s phenomenon (LP) can be difficult, as overlapping clinical and histopathological features have been reported. Mycobacterium lepromatosis, a recently identified species causing leprosy, has been sporadically linked to LP. While type 1 reactions are more commonly observed in HIV-coinfected individuals, reports of LP or ENL occurring outside the context of immune reconstitution inflammatory syndrome (IRIS) remain rare. Methods: We report a case of a vasculonecrotic leprosy reaction due to M. lepromatosis in an antiretroviral-naive patient with advanced HIV infection. Results: The patient presented with a two-month history of papules and nodules that progressed to painful necrotic ulcers, accompanied by systemic symptoms. Clinically, the presentation was consistent with nENL; however, histopathological analysis supported a diagnosis of LP. The patient rapidly deteriorated, developing septic shock and dying shortly thereafter. To our knowledge, this is the first reported case of a leprosy-associated vasculonecrotic reaction caused by M. lepromatosis in an HIV-infected individual not associated with IRIS. Conclusions: Vasculonecrotic reactions in leprosy are life-threatening emergencies due to their potential for rapid clinical deterioration and sepsis. In individuals with advanced HIV infection, recognition of these reactions may be challenging, as they can mimic other opportunistic infections, including fungal diseases, malignant syphilis, and disseminated mycobacterial infections. Early identification and prompt treatment are critical to improving outcomes.