Morphine Increases Lamivudine- and Nevirapine-Induced Human Immunodeficiency Virus-1 Drug-Resistant Mutations<i>In Vitro</i>

Liang, Bingyu; Jiang, Junjun; Pan, Peijiang; Chen, Rongfeng; Zhuang, Daomin; Zhao, Fangning; Chen, Hui; Huang, Jiegang; Su, Qi-jian; Cao, Cunwei; Li, Jingyun; Liang, Hao; Li, Ye

doi:10.1089/mdr.2015.0347

Cited by 11 publications

(5 citation statements)

References 49 publications

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Section: Discussionmentioning

confidence: 99%

“…Although a higher HIV-1 prevalence among IDUs was observed in a number of epidemiological studies, as well as in vitro laboratory evidence supporting that morphine could enhance the susceptibility of immune cells to HIV infection as well as HIV replication in cells [22-27], abused drugs do not increase the TDR rate at the population level. This result is consistent with in vitro evidence from our previous study, which shows that morphine treatment alone could not induce any DRMs in the absence of the antiretroviral drugs lamivudine or nevirapine [27]. The result is also consistent with the finding of a recent meta-analysis on antiretroviral resistance rates between IDUs and non-IDUs, which included 12 studies with different results and indicated that the risk of development of antiretroviral resistance did not differ significantly between IDUs and non-IDUs [19].…”

Section: Discussionmentioning

confidence: 99%

“…However, overwhelming in vitro laboratory evidence has confirmed that morphine, the active metabolite of heroin, enhances the susceptibility of immune cells to HIV infection as well as HIV replication in cells [22-26]. Furthermore, our recent findings show that morphine treatment could increase anti-HIV drug-induced HIV-1 drug-resistant mutations in vitro [27] under the selective pressure of antiretroviral drugs. When considering the results of epidemiological and laboratory studies, an interesting issue arises – whether or not drug abuse, mainly heroin, increases TDR occurrence among IDUs without ART.…”

Section: Introductionmentioning

confidence: 98%

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No Difference in Prevalence of Transmitted Drug Resistance between Injection Drug Users and Non-Injection Drug Users: A Cross-Sectional Study among Antiretroviral Treatment-Naïve HIV Patients

et al. 2018

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Objectives: The epidemiological evidence is inconsistent about whether HIV-positive injection drug users (IDUs) are at higher risk of developing antiretroviral resistance than any other HIV-positive populations. This study aims to investigate and compare transmitted drug resistance (TDR) between IDUs and non-IDUs in Lingshan County, an HIV-hit region in Guangxi, China, where IDU and heterosexual transmission were the two dominant transmission routes and roughly equally contributed to the local HIV transmission. Methods: A cross-sectional study was conducted among newly diagnosed and antiretroviral-treatment (ART)-naïve HIV-1 patients from Lingshan County. The pol gene of HIV-1 from the individuals was sequenced followed by genotyping and TDR analysis. Results: Two dominant transmission routes, heterosexual contact and IDU, accounted for 49.2 and 45.9% of 183 HIV-1 infection cases, respectively. Three genotypes, including CRF08_BC (70.6%), CRF01_AE (24.4%), and CRF07_BC (5.0%), and three unique recombinant forms (1.6%), were identified. There was a significant difference in genotype distribution among the different transmission routes (F = 21.814, p < 0.001). The overall TDR prevalence was 5.5%. There were no significant differences in TDR prevalence among the different transmission routes (F = 1.420, p = 0.439). Conclusions: Injection drug use has little impact on TDR prevalence compared with other routes of transmission.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

No Difference in Prevalence of Transmitted Drug Resistance between Injection Drug Users and Non-Injection Drug Users: A Cross-Sectional Study among Antiretroviral Treatment-Naïve HIV Patients

et al. 2018

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“…Notably, HIV proteins also synergize with morphine to increase the expression of opioid receptors, alter cell cycle regulation, and exacerbate neurotoxicity and neuroinflammation [54][55][56][57][58][59][60]. Using an in vitro HIV-CD4+ T cell system, Liang et al showed that morphine treatment induced more drug-resistant mutations under selective pressure from antiretroviral drugs and shortened the generation time for such mutations compared to controls treated with only antiretroviral drugs [61]. The inhibitory effects of antiretroviral therapies on HIV replication in primary astrocytes in vitro were also attenuated by morphine [62].…”

Section: Opioids and Hivmentioning

confidence: 99%

Drugs of Abuse and Their Impact on Viral Pathogenesis

Blackard

Sherman

2021

Viruses

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Commonly misused substances such as alcohol, cocaine, heroin, methamphetamine, and opioids suppress immune responses and may impact viral pathogenesis. In recent years, illicit use of opioids has fueled outbreaks of several viral pathogens, including the human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV). This review focuses on the myriad of mechanisms by which drugs of abuse impact viral replication and disease progression. Virus–drug interactions can accelerate viral disease progression and lead to increased risk of virus transmission.

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“…As a commonly used NNRTI for HIV-1 treatment, NVP can combine with HIV-1 RT and destroy the catalytic site of RT, thus blocking the activity of DNA polymerase and HIV replication [ 11 , 12 ]. However, continuous usage of nevirapine (NVP) induces drug-resistant mutations in HIV-1 virus and further failure of NNRTI treatment [ 13 , 14 , 15 ]. Y188C mutant HIV-1 reverse transcriptase (Y188CM-RT) is an important mutation that leads to NVP resistance in vivo [ 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Me-Better Drug Design Based on Nevirapine and Mechanism of Molecular Interactions with Y188C Mutant HIV-1 Reverse Transcriptase

Wang

et al. 2022

Molecules

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In this paper, the Y188C mutant HIV-1 reverse transcriptase (Y188CM-RT) target protein was constructed by homology modeling, and new ligands based on nevirapine (NVP) skeleton were designed by means of fragment growth. The binding activity of new ligands to Y188CM-RT was evaluated by structural analysis, ADMET prediction, molecular docking, energy calculation and molecular dynamics. Results show that 10 new ligands had good absorbability, and their binding energies to Y188CM-RT were significantly higher than those of wild-type HIV-1 reverse transcriptase(wt). The binding mode explained that fragment growth contributed to larger ligands, leading to improved suitability at the docking pocket. In the way of fragment growth, the larger side chain with extensive contact at terminal is obviously better than substituted benzene ring. The enhancement of docking activity is mainly due to the new fragments such as alkyl chains and rings with amino groups at NVP terminal, resulting in a large increase in hydrophobic bonding and the new addition of hydrogen bonding or salt bonding. This study is expected to provide reference for the research on non-nucleoside reverse transcriptase inhibitors resistance and AIDS treatment.

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Morphine Increases Lamivudine- and Nevirapine-Induced Human Immunodeficiency Virus-1 Drug-Resistant MutationsIn Vitro

Cited by 11 publications

References 49 publications

No Difference in Prevalence of Transmitted Drug Resistance between Injection Drug Users and Non-Injection Drug Users: A Cross-Sectional Study among Antiretroviral Treatment-Naïve HIV Patients

No Difference in Prevalence of Transmitted Drug Resistance between Injection Drug Users and Non-Injection Drug Users: A Cross-Sectional Study among Antiretroviral Treatment-Naïve HIV Patients

Drugs of Abuse and Their Impact on Viral Pathogenesis

Me-Better Drug Design Based on Nevirapine and Mechanism of Molecular Interactions with Y188C Mutant HIV-1 Reverse Transcriptase

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