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HIV-2 protease (PR2) is a homodimer targeted by drugs in the treatment of HIV-2 infections. This dimer is often considered symmetric. However, exploration of crystallographic structures showed that the two chains of PR2 exhibit different conformations. This study presents the first analysis of the structural asymmetry of PR2 induced by its intrinsic flexibility. We followed the structural asymmetry of PR2 throughout a molecular dynamics (MD) simulation of 1 microsecond. To do so, we quantified the global and local structural asymmetries of 1001 structures extracted from the MD simulation using the root mean square deviation (RMSD) between the two chains in each structure. We then analyzed the links between global and local asymmetry and PR2 flexibility. Our results showed that the global asymmetry of PR2 evolves over time and that it is not explained by the asymmetry of only one region of PR2. We noted that the most flexible regions of PR2 are the most asymmetric regions, revealing that the structural asymmetry of a region is induced by its intrinsic flexibility. Using multivariate analysis methods, we identified six asymmetric profiles varying from structures exhibiting weak asymmetry to structures with extreme asymmetry in at least eight different regions. The analysis of transitions between the different profiles in the MD simulation showed that two consecutive structures often exhibit similar asymmetric profiles, revealing small deformations. To conclude, this study provides insights which help to better understand PR2’s structure, dynamics, and deformations. Full article

Background: The global push to achieve the 90-90-90 targets designed to end the HIV epidemic has called for the removing of policy barriers to prevention and treatment, and ensuring financial sustainability of HIV programs. Universal health insurance is one tool that can be used to this end. In sub-Saharan Africa, where HIV prevalence and incidence remain high, the use of health insurance to provide comprehensive HIV care is limited. This study looked at the factors that best predict social health insurance enrollment among HIV positive pregnant women using data from the Academic Model Providing Access to Healthcare (AMPATH) in western Kenya. Methods: Cross-sectional clinical encounter data were extracted from the electronic medical records (EMR) at AMPATH. We used univariate and multivariate logistic regressions to estimate the predictors of health insurance enrollment among HIV positive pregnant women. The analysis was further stratified by HIV disease severity (based on CD4 cell count <350 and 350>) to test the possibility of differential enrollment given HIV disease state. Results: Approximately 7% of HIV infected women delivering at a healthcare facility had health insurance. HIV positive pregnant women who deliver at a health facility had twice the odds of enrolling in insurance [2.46 Adjusted Odds Ratio (AOR), Confidence Interval (CI) 1.24–4.87]. They were 10 times more likely to have insurance if they were lost to follow-up to HIV care during pregnancy [9.90 AOR; CI 3.42–28.67], and three times more likely to enroll if they sought care at an urban clinic [2.50 AOR; 95% CI 1.53–4.12]. Being on HIV treatment was negatively associated with health insurance enrollment [0.22 AOR; CI 0.10–0.49]. Stratifying the analysis by HIV disease severity while statistically significant did not change these results. Conclusions: The findings indicated that health insurance enrollment among HIV positive pregnant women was low mirroring national levels. Additionally, structural factors, such as access to institutional delivery and location of healthcare facilities, increased the likelihood of health insurance enrollment within this population. However, behavioral aspects, such as being lost to follow-up to HIV care during pregnancy and being on HIV treatment, had an ambiguous effect on insurance enrollment. This may potentially be because of adverse selection and information asymmetries. Further understanding of the relationship between insurance and HIV is needed if health insurance is to be utilized for HIV treatment and prevention in limited resource settings. Full article

HIV-2 protease (PR2) is a homodimer, which is an important target in the treatment of the HIV-2 infection. In this study, we developed an in silico protocol to analyze and characterize the asymmetry of the unbound PR2 structure using three levels of protein description by comparing the conformation, accessibility, and flexibility of each residue in the two PR2 chains. Our results showed that 65% of PR2 residues have at least one of the three studied asymmetries (structural, accessibility, or flexibility) with 10 positions presenting the three asymmetries in the same time. In addition, we noted that structural and flexibility asymmetries are linked indicating that the structural asymmetry of some positions result from their large flexibility. By comparing the structural asymmetry of the crystallographic and energetically minimized structures of the unbound PR2, we confirmed that the structural asymmetry of unbound PR2 is an intrinsic property of this protein with an important role for the PR2 deformation upon ligand binding. This analysis also allowed locating asymmetries corresponding to crystallization artefacts. This study provides insight that will help to better understand the structural deformations of PR2 and to identify key positions for ligand binding. Full article