AIDS research and human retroviruses最新文献

Accompanied with the appearance and prevalence of the new K₂₈E₃₂ variant among men who have sex with men, HIV-1 circulating recombinant form 07_BC (CRF07_BC) was becoming the most predominant subtype circulating in China. The K₂₈E₃₂ variant with five specific mutations in reverse transcriptase coding region appears to have significantly higher in vitro HIV-1 replication ability than the wild-type strain. In this study, we characterized the special mutations/substitutions in the K₂₈E₃₂ variant at the genomic level. Ten specific mutations that rarely appeared in other six main HIV-1 subtypes/CRFs (A-D, CRF01_AE, and CRF02_AG) were identified in the coding genes/regions of the K₂₈E₃₂ variant, including S77L and a novel seven-amino acid detection (32DKELYPL38) (p6Δ7) in p6, I135L in integrase, T189S in Vif, H/Y15L/F in Vpr, I264V/A and LV/LI328-329VG in gp41, and H82C and S97P in Rev. The special locations of the novel p6Δ7, and gp41 mutations I264V/A and LV/LI328-329VG in crucial protein functional domains suggest that these mutations might be functionally important to the K₂₈E₃₂ variant. Furthermore, eight specific substitutions were identified in Rev responsive element (RRE) of the K₂₈E₃₂ variant, and were revealed to increase the stability of RRE structure with a lower minimum free energy. Whether these mutations/substitutions contribute to improved transmissibility of the CRF07_BC K₂₈E₃₂ variant needs to be further confirmed.

Compared to young heterosexual men, young sexual and gender minorities (YSGM) have elevated systemic inflammation and unique intestinal microbial profiles, influenced by HIV infection and substance use. However, links between cannabis use and microbial dysbiosis in this population have not been well described. In this pilot study, we aimed to characterize the complex interrelationships between cannabis use and microbial community structure in YSGM in relationship to HIV status. Cannabis use was assessed by self-administered Cannabis Use Disorder Identification Test (CUDIT) questionnaires and rectal microbial community alpha-diversity metrics were assessed via 16S ribosomal ribonucleic acid (rRNA) sequencing in a subset of YSGM (n = 42) in the RADAR cohort (aged 16-29) in Chicago. Multivariable regression models were used to assess the relationship between cannabis use and microbiome alpha-diversity metrics, adjusting for HIV status and other risk characteristics, including inflammation, which was evaluated by plasma levels of C-reactive protein (CRP). Problematic cannabis use, but not general use, was significantly inversely associated with microbial community richness (Adj. Beta = -8.13; 95% confidence interval [CI]: -15.68 to -0.59) and Shannon diversity (Adj. Beta = -0.04; 95% CI: -0.07 to 0.009). No significant association was observed between CUDIT score and community evenness, nor was any significant moderation observed by HIV status. We observed that problematic cannabis use was associated with reduced microbial community richness and Shannon diversity, adjusting for within population differences in inflammation and HIV status. Future research should aim to assess how cannabis use contributes to microbiome-related health factors among YSGM and if decreasing cannabis use can restore gut microbial community structure.

HIV-1 subtype C is associated with more than half of infections in southern Brazil and has been increasing in other regions of the country. In a previous study carried out in northeastern Brazil, we found a prevalence of 4.1% of subtype C. This work investigates the origin of subtype C in the state of Bahia based on five new viral sequences. The phylogenetic analysis showed that subtype C viruses found in Bahia descend from the main lineage that circulates in other Brazilian regions.

The concept of vulnerability in bioethics was first referenced in 1979, when the Belmont Report highlighted the need for special consideration of certain populations in the application of its general principles of respect for persons, beneficence, and justice in research with human participants. Since then, a body of literature has emerged regarding the content, status, and scope, as well as ethical and practical implications of vulnerability in biomedical research. The social history of HIV treatment development has at various points reflected and actively influenced bioethics' debate on vulnerability. In the late 1980s and early 1990s, people with AIDS activist groups drafted landmark patient empowerment manifestos like The Denver Principles, fighting to have greater involvement in the design and oversight of clinical trials related to HIV treatment, and in doing so, pushed against research ethics protocols created with the intention of protecting vulnerable populations. The determination of appropriate benefit/risk profiles in clinical trials was no longer limited to the purview of clinicians and scientists, but began to include the perspectives of people with HIV (PWH) and affected communities. In contemporary HIV cure-related research, where participants often risk health for no personal clinical benefit, the community's voiced motivations and objectives for participation continue to challenge population-based accounts of vulnerability. While the development of a framework for discussion and the establishment of clear regulatory requirements are necessary to support the practical and ethical conduct of research, they risk distraction from the fundamental value of voluntary participation and potentially overlook the unique history and perspectives of PWH in their participation in the quest toward an HIV cure.

More than 40 years after the first reported cases of what then became known as acquired immunodeficiency syndrome (AIDS), tremendous progress has been achieved in transforming the disease from almost universally fatal to a chronic manageable condition. Nonetheless, the efforts to find a preventative vaccine or a cure for the underlying infection with Human Immunodeficiency Virus (HIV) remain largely unsuccessful. Many challenges intrinsic to the virus characteristics and host response need to be overcome for either goal to be achieved. This article will review the obstacles to an effective HIV cure, specifically the steps involved in the generation of HIV latency, focusing on the role of the gut-associated lymphoid tissue, which has received less attention compared with the peripheral blood, despite being the largest repository of lymphoid tissue in the human body, and a large site for HIV persistence.

HIV infection has been linked to selenium deficiency and chronic inflammation. Both selenium deficiency and inflammation have been associated with poor health outcomes among individuals with HIV. However, the role of serum selenium levels in inflammation has not been studied among individuals with HIV. We assessed the relationship of serum selenium levels to C-reactive protein (CRP), a marker of inflammation, in individuals with HIV in Kathmandu, Nepal. In this cross-sectional study, we measured the normal serum CRP and selenium levels of 233 individuals with HIV (109 women and 124 men) using the latex agglutination turbidimetric and atomic absorption methods, respectively. We used multiple linear regression analysis in examining the association of serum selenium levels with CRP adjusting for sociodemographic and clinical parameters, including antiretroviral therapy, CD4⁺ T cell count, chronic diseases, and body mass index. The geometric means of CRP and selenium levels were 1.43 mg/liter and 9.65 μg/dL, respectively. Overall, serum selenium levels were inversely associated with CRP levels (β for one unit change in log selenium; β = -1.01, p = .06). Mean CRP levels significantly decreased with increasing selenium across selenium tertiles (p for trend = .019). The mean serum CRP levels were 40.8% lower in the highest selenium tertile than in the lowest. Our study suggests that high serum selenium levels may reduce serum CRP levels in individuals with HIV, although a longitudinal study is warranted to establish causality.