Brief Report: Factors Associated With the Selection of Initial Antiretroviral Therapy From 2009 to 2012

Ms, Saag; Ao, Westfall; Colé,; Wc, Mathews; Dr, Drozd; Kh, Mayer; Ga, Burkholder; Kitahata, Mari M.; Em, Maiese

doi:10.1097/qai.0000000000001168

Cited by 8 publications

(6 citation statements)

References 19 publications

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“…Importantly, NMDAR-Ab from different origins (patients versus healthy carriers) do not necessarily share the same molecular impact on the glutamatergic and dopaminergic receptor trafficking. This is consistent with previous finding demonstrating that NMDAR-Ab from healthy carriers or patient with autism spectrum disorder without history of psychosis do not alter NMDAR surface trafficking (12, 25). Our data further highlight that NMDAR-Ab are diverse in their mechanisms of action and call for further investigations to decrypt the alterations on the targeted NMDAR and its membrane partners.…”

Section: Discussionsupporting

confidence: 93%

Human Autoantibodies Against N-Methyl-D-Aspartate Receptor Modestly Alter Dopamine D1 Receptor Surface Dynamics

et al. 2019

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Circulating autoantibodies directed against extracellular domains of the glutamatergic N-methyl-D-aspartate receptors (NMDAR-Ab) elicit psychotic symptoms in humans and behavioral deficits in animal models. Recent advances suggest that NMDAR-Ab exert their pathogenic action by altering the trafficking of NMDAR, which results in a synaptic NMDAR hypofunction consistent with the consensual glutamatergic hypothesis of psychotic disorders. Yet, dysfunction in the dopaminergic signaling is also proposed to be at the core of psychotic disorders. Since NMDAR and dopamine D1 receptors (D1R) form membrane signaling complexes, we investigated whether NMDAR-Ab purified from patients with NMDAR-encephalitis or schizophrenia impaired D1R surface dynamics. As previous data demonstrated that NMDAR-Ab, at least from NMDAR-encephalitis patients, mainly bind to hippocampal NMDAR, we used single nanoparticle imaging to track D1R specifically at the surface of hippocampal neurons that were exposed to either purified G type immunoglobulins (IgGs) from NMDAR-Ab seropositive patients suffering from NMDAR-encephalitis or schizophrenia, or control IgGs from healthy NMDAR-Ab seropositive or seronegative subjects. We report that overnight incubation with NMDAR-Ab from patients, but not from healthy carriers, decreased the surface dynamics of D1R compared with NMDAR-Ab seronegative IgGs. This decrease was abolished, and even reversed, in D1R mutant that cannot physically interact with NMDAR. Overall, our data indicate that NMDAR-Ab from patients with psychotic symptoms alter the trafficking of D1R, likely through the surface crosstalk between NMDAR and D1R.

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Section: Discussionsupporting

confidence: 93%

Human Autoantibodies Against N-Methyl-D-Aspartate Receptor Modestly Alter Dopamine D1 Receptor Surface Dynamics

et al. 2019

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“…The small difference in baseline CD4 + cell counts between treatment groups is likely to reflect the trend in recent years to starting ART at earlier stages of infection, as evidence emerged of improved clinical outcomes and reduced transmission, which coincided with the increased use of INSTIs [ 22 – 24 ]. These findings are similar to those of a US study that analysed the factors associated with the selection of first-line regimens from 2009 to 2012 [ 25 ]. Of 873 patients, 56% had NNRTI, 36% had protease inhibitor and 8% had raltegravir (the only INSTI available at the time).…”

Section: Discussionsupporting

confidence: 88%

First-line HIV treatment outcomes following the introduction of integrase inhibitors in UK guidelines

Bouzidi

José

Phillips

et al. 2020

Aids

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on behalf of the UK CHIC StudyObjective: To investigate the characteristics and outcomes of people who initiated different antiretroviral therapy (ART) regimens during the era of integrase strand transfer inhibitors (INSTIs).Design: UK-based observational cohort study.Methods: UK Collaborative HIV Cohort study participants were included if they had started ART between 1 January 2012 and 30 June 2017. Virological failure was defined as the first of two consecutive plasma HIV RNA more than 50 copies/ml, at least 6 months after starting ART. Follow-up was censored at ART discontinuation, class switch or death. The risk of virological failure among those on INSTI, protease inhibitor or nonnucleoside reverse transcriptase inhibitor (NNRTI) regimens was compared using Kaplan-Meier and Cox regression methods.Results: Of 12 585 participants, 45.6% started a NNRTI, 29.0% a protease inhibitor and 25.4% an INSTI regimen. Over a median follow-up of 20.3 months (interquartile range 7.9-38.9), 7.5% of participants experienced virological failure. Compared with those starting an NNRTI regimen, people receiving INSTIs or protease inhibitors were more likely to experience virological failure: INSTI group adjusted hazard ratio 1.52, 95% confidence interval 1.19-1.95, P ¼ 0.0009; protease inhibitor group adjusted hazard ratio 2.70, 95% confidence interval 2.27-3.21, P less than 0.0001, likelihood ratio test P less than 0.0001. Conclusion:First-line INSTI regimens were associated with a lower risk of virological failure than protease inhibitor regimens but both groups were more likely to experience virological failure than those initiating treatment with a NNRTI. There is likely to be residual channelling bias resulting from selected use of INSTIs and protease inhibitors in specific clinical contexts, including in those with a perceived risk of poor adherence.

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“…worse physical status which is consistent with previous studies in the UK and US [11,22]. This preference may be due to increasing evidence supporting superior immunological and virological responses with INSTI-containing regimens from clinical trials [3,7].…”

Section: Discussionsupporting

confidence: 88%

Effectiveness of integrase strand transfer inhibitors among treatment-naive HIV-infected patients in China: A retrospective real-world study

Chen,

Liu,

Xie

et al. 2023

Preprint

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Background Integrase strand transfer inhibitors (INSTIs) in anti-retroviral therapy (ART) have been recommended by the World Health Organization for their higher efficacy, favorable safety and tolerability. However, the clinical evidence supporting switching to INSTI-containing regimes in low-and-middle-income countries is limited, as few patients have access to these regimes. We aimed to assess the effectiveness of INSTI-containing regimens in real-world settings in China compared to government-provided free ART. Method We compared the short-term and long-term effectiveness between INSTI-containing regimens and free ART drugs provided by the Chinese government in four dimensions: viral suppression status, immune response, liver and kidney function, and AIDS-related diseases. To control baseline confounders, we used propensity score matching, calculated using logistic regression including sociodemographic and baseline factors. Results Among 12,836 patients initiating ART from 2012 to 2019, 673 (5.2%) used INSTI-containing regimens. Compared with patients initiating ART with free drugs, patients initiating ART with INSTI-containing regimens were more likely to be older (43.26±14.87 vs. 36.43±12.19; p<0.001), not single (66.6% vs. 51.0%; p<0.001), infected with HIV through sexual behavior with an opposite-sex partner (50.7% vs. 42.2%; p<0.001), had a lower baseline CD4 cell count (50 cells/μL vs. 239 cells/μL; p<0.001), present more AIDS-related diseases and abnormal results of liver and kidney function, and had more TB infection. For short-term effectiveness, patients initiating INSTI-containing regimens were more likely to achieve viral suppression (81.4% vs. 52.0%; p<0.001). The differences in immune response, liver and kidney function and AIDS-related diseases were not significant between the two groups. For long-term effectiveness, viral suppression rates were similar (87.96% vs. 84.59%; p=0.135), with no significant differences in immune response, liver and kidney function, or AIDS-related diseases. Conclusions Our study suggests that patients initiating ART with INSTI-containing regimens have worse physical status at baseline than patients starting with free ART drugs. Furthermore, we found better virological performances of INSTI-containing regimens in the short-term but not in the long-term due to a high rate of drug changes. Our findings have clinical implications and provide new evidence regarding the effectiveness of INSTI-containing regimes in LMICs.

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Brief Report: Factors Associated With the Selection of Initial Antiretroviral Therapy From 2009 to 2012

Cited by 8 publications

References 19 publications

Human Autoantibodies Against N-Methyl-D-Aspartate Receptor Modestly Alter Dopamine D1 Receptor Surface Dynamics

Human Autoantibodies Against N-Methyl-D-Aspartate Receptor Modestly Alter Dopamine D1 Receptor Surface Dynamics

First-line HIV treatment outcomes following the introduction of integrase inhibitors in UK guidelines

Effectiveness of integrase strand transfer inhibitors among treatment-naive HIV-infected patients in China: A retrospective real-world study

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