DYNAMICS BEHAVIOR OF MUTATION DURING REPRODUCTION ON HIV-1 DRUG RESISTANCE

2013 ◽  
Vol 06 (03) ◽  
pp. 1350018 ◽  
Author(s):  
GUANGYU HUANG ◽  
AIJUN FAN ◽  
KAIFA WANG
Keyword(s):  
Mathematical Model ◽  
Drug Resistance ◽  
Highly Active Antiretroviral Therapy ◽  
Transmission Dynamics ◽  
Transition Dynamics ◽  
Highly Active ◽  
Neutral Mutation ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1

To study the transition dynamics of resistant-type human immunodeficiency virus 1 (HIV-1) in highly active antiretroviral therapy (HAART) and the affect of neutral mutation in the evolution of HIV-1, a mathematical model is proposed when mutation occurs mainly during reproduction. The derived results show that the resistant-type will certainly colonize in patients once mutation occurs. Furthermore, a neutral mutation is closely related to the colonized pattern of resistant-type HIV-1 quasispecies and there are some changes in the pattern of transmission dynamics when mutation occurs mainly during reproduction or in the absence of reproduction, which may lead to significant strategies for predicting or checking HIV-1 drug resistance in HAART.

scholarly journals HIV-1 gp41 genetic diversity and enfuvirtide resistance-associated mutations among enfuvirtide-naïve patients in southern China

2020 ◽  
Author(s):  
Le Chang ◽  
Junpeng Zhao ◽  
Lu Zhang ◽  
Huimin Ji ◽  
Xinyi Jiang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Highly Active Antiretroviral Therapy ◽  
Molecular Diversity ◽  
Southern China ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Resistance Patterns ◽  
Treatment Naïve ◽  
Resistant Mutants ◽  
Hiv 1

Abstract Background: Human immunodeficiency virus (HIV) increasing molecular diversity and emergence of drug resistant mutants remain a major concern in Southern China, enfuvirtide (ENF/T-20) is the first entry inhibitor used in patients failing highly active antiretroviral therapy (HAART). However, data on HIV-1 gp41genetic diversity and primary ENF resistance-associated mutations among treatment-naïve patients in southern China is limited. The objective was to identify molecular diversity and ENF resistance patterns of HIV-1 in southern China, using envelop (env) gp41 sequences and bioinformatics tools, which may help optimize ART. Methods: From December 2018 to January 2019, 439 blood plasma samples from ENF-naïve HIV-1 patients were collected from Shenzhen, Wuhan and Chongqing, of which, 396 HIV env regions were sequenced and subtyped, and were performed the analysis of drug resistance-associated mutations (DRMs). Results: The main subtypes were circulating recombinant form (CRF) 01_AE (30.6%) and CRF07_BC (48.7%), CRF55_01B had been the fourth subtype in our work, many rare CRFs were observed. Notably, CRF02_AG and CRF_BF strains typically found in Africa and US respectively were identified amongst Chinese HIV-1 patients. Known DRMs were detected in 27.5% (109/396) of ENF treatment-naïve patients. One major DRM (L44M), many secondary DRMs including (N126K, E137K, S138A) and lots of polymorphisms were found in the study, which have been proved to elevate resistance to ENF. Conclusion: HIV-1 molecular diversity among people in southern China observed in the work indicates that HIV-1 variability is becoming increasingly complex in the south of China. A diverse set of primary DRMs discovered in this study described the serious threat to ART, which remind us the urgent need of timely surveillance of HIV-1 viral diversity and drug resistance in China.

scholarly journals Malignancies, Particularly B-Cell Lymphomas, Are a Frequent Cause of Mortality in Human Immunodeficiency Virus-1 Patients Despite Highly Active Antiretroviral Therapy

2015 ◽  
Vol 2 (4) ◽  
Author(s):  
Daniel O. Griffin ◽  
Michael Metzger ◽  
Kaitlin Poeth ◽  
Kathy Deng ◽  
Arif Dharsee ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
B Cell ◽  
Highly Active Antiretroviral Therapy ◽  
B Cell Lymphomas ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Human Immunodeficiency Virus 1 ◽  
Hiv Negative

Abstract Human immunodeficiency virus (HIV)-1-infected individuals are affected by diseases at rates above those of their HIV-negative peers despite the increased life expectancy of the highly active antiretroviral therapy era. We followed a cohort of approximately 2000 HIV-1-infected patients for 5 years. The most frequent cause of death in this HIV-1-infected cohort was malignancy, with 39% of all classified deaths due to cancer. Among the cancer deaths, B-cell lymphomas were the most commonly seen malignancy, representing 34% of all cancer deaths. These lymphomas were very aggressive with a median survival of <2 months from time of diagnosis.

scholarly journals Darunavir-Resistant HIV-1 Protease Constructs Uphold a Conformational Selection Hypothesis for Drug Resistance

Viruses ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1275
Author(s):  
Zhanglong Liu ◽  
Trang T. Tran ◽  
Linh Pham ◽  
Lingna Hu ◽  
Kyle Bentz ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Highly Active Antiretroviral Therapy ◽  
Double Resonance ◽  
Resonance Spectroscopy ◽  
Distance Measurements ◽  
Paramagnetic Resonance ◽  
Highly Active ◽  
Open Conformation ◽  
Potent Protease Inhibitor ◽  
Hiv 1

Multidrug resistance continues to be a barrier to the effectiveness of highly active antiretroviral therapy in the treatment of human immunodeficiency virus 1 (HIV-1) infection. Darunavir (DRV) is a highly potent protease inhibitor (PI) that is oftentimes effective when drug resistance has emerged against first-generation inhibitors. Resistance to darunavir does evolve and requires 10–20 amino acid substitutions. The conformational landscapes of six highly characterized HIV-1 protease (PR) constructs that harbor up to 19 DRV-associated mutations were characterized by distance measurements with pulsed electron double resonance (PELDOR) paramagnetic resonance spectroscopy, namely double electron–electron resonance (DEER). The results show that the accumulated substitutions alter the conformational landscape compared to PI-naïve protease where the semi-open conformation is destabilized as the dominant population with open-like states becoming prevalent in many cases. A linear correlation is found between values of the DRV inhibition parameter Ki and the open-like to closed-state population ratio determined from DEER. The nearly 50% decrease in occupancy of the semi-open conformation is associated with reduced enzymatic activity, characterized previously in the literature.

Management of HIV-1 Infection in Adults and Adolescents

2000 ◽  
Vol 13 (6) ◽  
pp. 426-441 ◽  
Author(s):  
Kenneth R. Eugenio ◽  
Caroline S. Zeind
Keyword(s):  
Highly Active Antiretroviral Therapy ◽  
Patient Adherence ◽  
Social Barriers ◽  
Highly Active ◽  
Immunodeficiency Virus ◽  
Improve Patient Adherence ◽  
Substantial Decline ◽  
Improve Patient ◽  
Hiv 1 ◽  
New Strategies

The management of Human Immunodeficiency Virus-1 (HIV-1) infection has undergone dramatic change since its initial identification. Advances have occurred in drug development, viral pathology understanding, laboratory monitoring and genetic analysis. With the advent of highly active antiretroviral therapy (HAART), there has been a substantial decline in HIV-1-related morbidity and mortality. Today, HIV-1 infection is treated as a chronic disease that requires strict patient adherence to HAART. Pharmacists provide pharmaceutical care to patients with HIV disease in a variety of ways, and they can improve patient adherence rates. Current therapeutic strategies have not resulted in eradication of HIV-1 infection. Present and future therapeutic challenges include viral resistance, reservoirs of virus and drug toxicities. Globally, the spread of HIV-1 infection continues at an alarming rate, and economic and social barriers may limit access and success of HAART. New strategies and novel approaches in managing HIV-1 infection continue to be developed in an effort to cure and eradicate this disease.

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