Objective
Nevirapine is widely prescribed for HIV-1 infection. We characterized relationships between nevirapine-associated cutaneous and hepatic adverse events and genetic variants among HIV-infected adults.
Design
We retrospectively identified cases and controls. Cases experienced symptomatic nevirapine-associated severe (grade III/IV) cutaneous and/or hepatic adverse events within 8 weeks of initiating nevirapine. Controls did not experience adverse events during more than 18 weeks of nevirapine therapy.
Methods
Cases and controls were matched 1 : 2 on baseline CD4 T-cell count, sex, and race. Individuals with 150 or less CD4 T cells/μl at baseline were excluded. We characterized 123 human leukocyte antigen (HLA) alleles and 2744 single-nucleotide polymorphisms in major histocompatibility complex (MHC) and drug metabolism and transport genes.
Results
We studied 276 evaluable cases (175 cutaneous adverse events, 101 hepatic adverse events) and 587 controls. Cutaneous adverse events were associated with CYP2B6 516G→T (OR 1.66, all), HLA-Cw*04 (OR 2.51, all), and HLA-B*35 (OR 3.47, Asians; 5.65, Thais). Risk for cutaneous adverse events was particularly high among Blacks with CYP2B6 516TT and HLA-Cw*04 (OR 18.90) and Asians with HLA-B*35 and HLA-Cw*04 (OR 18.34). Hepatic adverse events were associated with HLA-DRB*01 (OR 3.02, Whites), but not CYP2B6 genotypes. Associations differed by population, at least in part reflecting allele frequencies.
Conclusion
Among patients with at least 150 CD4 T cells/μl, polymorphisms in drug metabolism and immune response pathways were associated with greater likelihood of risk for nevirapine-related adverse events. Results suggest fundamentally different mechanisms of adverse events: cutaneous, most likely MHC class I-mediated, influenced by nevirapine CYP2B6 metabolism; hepatic, most likely MHC class II-mediated and unaffected by such metabolism. These risk variants are insensitive for routine clinical screening.
The paper presents the results of a study that attempts to investigate the impact of foreign direct investment (FDI) on environmental performance (EP) by constructing a panel quantile regression model. Based on panel data from 1990 to 2014, this study contributes to evaluate the EP of each of the 40 countries using a directional slack-based model considering undesirable output. Our findings reveal several key conclusions: first, FDI has an insignificant influence on EP for the full sample. Second, the impact of FDI on EP between developed and developing countries exists heterogeneity. Furthermore, there is heterogeneity regarding the effect of FDI on EP at different quantiles of EP in developed countries. Specifically, in the developed countries, the effect is statistically insignificant at the lower quantile of EP, then it turns significantly positive at the middle and high quantile, and the positive effect rises with the increase of quantiles of EP. Finally, based on the conclusions of quantitative analysis, some important policy recommendations are proposed: different governments ought to enact different strategies for the introduction of FDI, according to different development situations of different countries.
The paper presents the results of a study that attempts to investigate the impact of foreign direct investment (FDI) on energy intensity by constructing panel regression model and panel smooth transition regression (PSTR) model. Based on panel data from 1990 to 2014, this study contributes to conduct the impact of FDI on energy intensity from the perspective of emerging country, including BRICS and non-BRICS countries, and investigates the channels of influence of FDI on energy intensity. Besides that, we intend to employ the PSTR model to reveal the nonlinear mechanism of FDI on energy intensity. Our findings reveal several key conclusions: first, FDI exerts insignificant impact on energy intensity in the emerging countries. Second, the impact of FDI on energy intensity is heterogeneous between BRICS and non-BRICS countries. Third, innovation capacity plays various moderating effects on the relationship of FDI and energy intensity among different types of emerging countries. Furthermore, the nonlinear mechanism of FDI on energy intensity is realized with industrial structure as the transition variable, which plays a different effect on the impact of FDI on energy intensity between different samples.
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