Clinical implications of stopping nevirapine-based antiretroviral therapy: relative pharmacokinetics and avoidance of drug resistance

: Antiretroviral drug therapy has significantly improved the prognosis and life expectancy of People Living with HIV over the years. But this progress comes with an important caveat that antiretroviral regimens generally require adherence to life-long, daily dosing, to keep viral multiplication under check. Non-adherence to such dosing leads to decreased efficacy and increased drug resistance against antiretroviral drugs. Besides, poor drug penetration to certain tissues like CNS and lymph nodes leads to build-up of viral reservoirs in these sites. To combat some of these challenges and improve patient compliance, long-acting antiretroviral drugs, are a new weapon in the arsenal, in fight against HIV. Few long acting preparations have been approved, and several others are in various clinical and preclinical stages of development. However, longacting formulations also have their share of clinical issues like limited drug distribution, long term adverse drug reactions, drug-drug interactions, and gradual development of drug resistance. Modern technological premises are being tested to mitigate some of these problems. One such promising approach involves nanotechnological methods, which are being used to develop ultra-long acting formulations and drug delivery systems, targeting tissues with residual HIV concentration. LongActing Slow Effective Release Antiretroviral Therapy aka LASER ART, also builds on nanotechnology and prodrug modifications to design preparations with tailor-made favorable pharmacokinetics and wider drug distribution. These recent advances are fueling the progression of antiretroviral therapy towards eliminating the disease.

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Patients Characteristics and Clinical Implications of Suboptimal CD4 T-Cell Gains After 1 Year of Successful Antiretroviral Therapy

Current HIV Research ◽

10.2174/157016208783885038 ◽

2008 ◽

Vol 6 (2) ◽

pp. 100-107 ◽

Cited By ~ 47

Author(s):

Felix Gutierrez ◽

Sergio Padilla ◽

Mar Masia ◽

Jose A. Iribarren ◽

Santiago Moreno ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Cd4 T Cell ◽

Clinical Implications

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HIV Drug Resistance Mutations Detection by Next-Generation Sequencing during Antiretroviral Therapy Interruption in China

Pathogens ◽

10.3390/pathogens10030264 ◽

2021 ◽

Vol 10 (3) ◽

pp. 264

Author(s):

Miaomiao Li ◽

Shujia Liang ◽

Chao Zhou ◽

Min Chen ◽

Shu Liang ◽

...

Keyword(s):

Drug Resistance ◽

Next Generation Sequencing ◽

Antiretroviral Therapy ◽

Detection Threshold ◽

Next Generation ◽

Resistance Mutations ◽

Hiv Drug Resistance ◽

Drug Resistance Mutations ◽

Therapy Interruption ◽

Generation Sequencing

Patients with antiretroviral therapy interruption have a high risk of virological failure when re-initiating antiretroviral therapy (ART), especially those with HIV drug resistance. Next-generation sequencing may provide close scrutiny on their minority drug resistance variant. A cross-sectional study was conducted in patients with ART interruption in five regions in China in 2016. Through Sanger and next-generation sequencing in parallel, HIV drug resistance was genotyped on their plasma samples. Rates of HIV drug resistance were compared by the McNemar tests. In total, 174 patients were included in this study, with a median 12 (interquartile range (IQR), 6–24) months of ART interruption. Most (86.2%) of them had received efavirenz (EFV)/nevirapine (NVP)-based first-line therapy for a median 16 (IQR, 7–26) months before ART interruption. Sixty-one (35.1%) patients had CRF07_BC HIV-1 strains, 58 (33.3%) CRF08_BC and 35 (20.1%) CRF01_AE. Thirty-four (19.5%) of the 174 patients were detected to harbor HIV drug-resistant variants on Sanger sequencing. Thirty-six (20.7%), 37 (21.3%), 42 (24.1%), 79 (45.4%) and 139 (79.9) patients were identified to have HIV drug resistance by next-generation sequencing at 20% (v.s. Sanger, p = 0.317), 10% (v.s. Sanger, p = 0.180), 5% (v.s. Sanger, p = 0.011), 2% (v.s. Sanger, p < 0.001) and 1% (v.s. Sanger, p < 0.001) of detection thresholds, respectively. K65R was the most common minority mutation, of 95.1% (58/61) and 93.1% (54/58) in CRF07_BC and CRF08_BC, respectively, when compared with 5.7% (2/35) in CRF01_AE (p < 0.001). In 49 patients that followed-up a median 10 months later, HIV drug resistance mutations at >20% frequency such as K103N, M184VI and P225H still existed, but with decreased frequencies. The prevalence of HIV drug resistance in ART interruption was higher than 15% in the survey. Next-generation sequencing was able to detect more minority drug resistance variants than Sanger. There was a sharp increase in minority drug resistance variants when the detection threshold was below 5%.

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Major drug resistance mutations to HIV-1 protease inhibitors (PI) among patients exposed to PI class failing antiretroviral therapy in São Paulo State, Brazil

PLoS ONE ◽

10.1371/journal.pone.0223210 ◽

2019 ◽

Vol 14 (10) ◽

pp. e0223210

Author(s):

Giselle de Faria Romero Soldi ◽

Isadora Coutinho Ribeiro ◽

Cintia Mayumi Ahagon ◽

Luana Portes Ozório Coelho ◽

Gabriela Bastos Cabral ◽

...

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

Protease Inhibitors ◽

Sao Paulo ◽

Resistance Mutations ◽

Paulo State ◽

Drug Resistance Mutations ◽

São Paulo State ◽

Major Drug ◽

Hiv 1

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Editorial (Thematic Issue: Adherence to Antiretroviral Therapy, Retention in Care and HIV Drug resistance in Nigeria)

Current HIV Research ◽

10.2174/1570162x1304150615193456 ◽

2015 ◽

Vol 13 (4) ◽

pp. 260-261 ◽

Cited By ~ 2

Author(s):

Nicaise Ndembi

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

Retention In Care ◽

Thematic Issue ◽

Hiv Drug Resistance ◽

Therapy Retention

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HIV-1 transmitted drug resistance mutations among antiretroviral therapy-Naïve individuals in Surabaya, Indonesia

AIDS Research and Therapy ◽

10.1186/s12981-015-0046-y ◽

2015 ◽

Vol 12 (1) ◽

Cited By ~ 14

Author(s):

Tomohiro Kotaki ◽

Siti Qamariyah Khairunisa ◽

Adiana Mutamsari Witaningrum ◽

Muhammad Qushai Yunifiar M ◽

Septhia Dwi Sukartiningrum ◽

...

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

Transmitted Drug Resistance ◽

Resistance Mutations ◽

Drug Resistance Mutations ◽

Hiv 1

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Dynamics Analysis and Simulation of a Modified HIV Infection Model with a Saturated Infection Rate

Computational and Mathematical Methods in Medicine ◽

10.1155/2014/145162 ◽

2014 ◽

Vol 2014 ◽

pp. 1-14 ◽

Cited By ~ 8

Author(s):

Qilin Sun ◽

Lequan Min

Keyword(s):

Drug Resistance ◽

Antiretroviral Therapy ◽

Hiv Infection ◽

Equilibrium Point ◽

Infection Rate ◽

Reproductive Number ◽

Infection Model ◽

Asymptotically Stable ◽

Globally Asymptotically Stable ◽

Hiv Rna

This paper studies a modified human immunodeficiency virus (HIV) infection differential equation model with a saturated infection rate. It is proved that if the basic virus reproductive numberR0of the model is less than one, then the infection-free equilibrium point of the model is globally asymptotically stable; ifR0of the model is more than one, then the endemic infection equilibrium point of the model is globally asymptotically stable. Based on the clinical data from HIV drug resistance database of Stanford University, using the proposed model simulates the dynamics of the two groups of patients’ anti-HIV infection treatment. The numerical simulation results are in agreement with the evolutions of the patients’ HIV RNA levels. It can be assumed that if an HIV infected individual’s basic virus reproductive numberR0<1then this person will recover automatically; if an antiretroviral therapy makes an HIV infected individual’sR0<1, this person will be cured eventually; if an antiretroviral therapy fails to suppress an HIV infected individual’s HIV RNA load to be of unpredictable level, the time that the patient’s HIV RNA level has achieved the minimum value may be the starting time that drug resistance has appeared.

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