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Drug susceptibility to etravirine and darunavir among Human Immunodeficiency Virus Type 1-derived pseudoviruses in treatment-experienced patients with HIV/AIDS in South Korea.

Kwon OK, Kim SS, Rhee JE, Kee MK, Park M, Oh HR, Choi JY - Virol. J. (2015)

Bottom Line: The 50% inhibitory concentration (IC50) values were calculated and drug susceptibility was compared.Drug susceptibility was generally higher for etravirine and darunavir compared with efavirenz, amprenavir, and indinavir in pseudoviruses derived from treatment-experienced patients.This study may help to find a more effective HAART in the case of HIV-1 infected patients that have difficulty being treated.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Pathology, Division of AIDS, Korea National Institute of Health, Osong, Republic of Korea. jh5246@korea.kr.

ABSTRACT

Background: In South Korea, about 20 types of antiretroviral drugs are used in the treatment of patients with human immunodeficiency virus/acquired immune deficiency syndrome. Since 2010, raltegravir, etravirine, and darunavir have been spotlighted as new drugs for highly active antiretroviral therapy (HAART)-experienced adults with resistant HIV-1 in South Korea. In this study, we investigated potential susceptibility of pseudoviruses derived from treatment-experienced Korean patients to etravirine vs efavirenz and to darunavir vs amprenavir and indinavir using a modified single-round assay.

Methods: Pseudoviruses derived from nine treatment-experienced patients infected with HIV-1 were investigated by comparison with the wild-type strain pNL4-3. The 50% inhibitory concentration (IC50) values were calculated and drug susceptibility was compared. The intensity of genotypic drug resistance was classified based on the 'SIR' interpretation of the Stanford data base.

Results: Drug susceptibility was generally higher for etravirine and darunavir compared with efavirenz, amprenavir, and indinavir in pseudoviruses derived from treatment-experienced patients. Pseudoviruses derived from patients KRB4025 and KRB8014, who exhibited long-term use of protease inhibitors, showed an outside of tested drug concentration, especially for amprenavir and indinavir. However, they exhibited a lower fold-change in resistance to darunavir.

Conclusions: Etravirine and darunavir have been used in HAART since 2010 in South Korea. Therefore, these antiretroviral drugs together with other newly introduced antiretroviral drugs are interesting for the optimal treatment of patients with treatment failure. This study may help to find a more effective HAART in the case of HIV-1 infected patients that have difficulty being treated.

No MeSH data available.


Related in: MedlinePlus

Comparison of IC50against three PIs (amprenavir, indinavir, and darunavir) and two NNRTIs (etravirine and efavirenz) for nine treatment-experienced patient-derived recombinant pseudoviruses based on simultaneous measurement of drug susceptibility. Each color indicates the following antiretroviral drugs: blue (amprenavir), green (indinavir), brown (darunavir), gray (efavirenz), and orange (etravirine). Each experiment was repeated three times. (a) pNL4-3, WT; (b) KRB8067; (c) KRC2065; (d) KRB5018; (e) KRC2092; (f) KRB4025; (g) KRB8014; (h) KRC3221; (i) KRC0064; (j) KRC4543.
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Fig1: Comparison of IC50against three PIs (amprenavir, indinavir, and darunavir) and two NNRTIs (etravirine and efavirenz) for nine treatment-experienced patient-derived recombinant pseudoviruses based on simultaneous measurement of drug susceptibility. Each color indicates the following antiretroviral drugs: blue (amprenavir), green (indinavir), brown (darunavir), gray (efavirenz), and orange (etravirine). Each experiment was repeated three times. (a) pNL4-3, WT; (b) KRB8067; (c) KRC2065; (d) KRB5018; (e) KRC2092; (f) KRB4025; (g) KRB8014; (h) KRC3221; (i) KRC0064; (j) KRC4543.

Mentions: The IC50 for five antiretroviral drugs was analyzed using WT-derived pseudoviruses to establish a standard level using XLfit (IDBS). The following antiretroviral drugs were tested in parallel: efavirenz and etravirine, amprenavir, indinavir, and darunavir. Figure 1 shows a sigmoidal dose–response curve between serially diluted drugs and infectivity. For each antiretroviral drug, the IC50 was as follows (in descending order for each drug category): efavirenz (4.40E–02 nM) and etravirine (1.34E–02 nM) among NNRTIs; and indinavir (13.5 nM), amprenavir (7.17 nM), and darunavir (6.80E–01 nM) among PIs. The FC in drug resistance was compared with the IC50 value of the WT against each antiretroviral drug (Figure 1).Figure 1


Drug susceptibility to etravirine and darunavir among Human Immunodeficiency Virus Type 1-derived pseudoviruses in treatment-experienced patients with HIV/AIDS in South Korea.

Kwon OK, Kim SS, Rhee JE, Kee MK, Park M, Oh HR, Choi JY - Virol. J. (2015)

Comparison of IC50against three PIs (amprenavir, indinavir, and darunavir) and two NNRTIs (etravirine and efavirenz) for nine treatment-experienced patient-derived recombinant pseudoviruses based on simultaneous measurement of drug susceptibility. Each color indicates the following antiretroviral drugs: blue (amprenavir), green (indinavir), brown (darunavir), gray (efavirenz), and orange (etravirine). Each experiment was repeated three times. (a) pNL4-3, WT; (b) KRB8067; (c) KRC2065; (d) KRB5018; (e) KRC2092; (f) KRB4025; (g) KRB8014; (h) KRC3221; (i) KRC0064; (j) KRC4543.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4404133&req=5

Fig1: Comparison of IC50against three PIs (amprenavir, indinavir, and darunavir) and two NNRTIs (etravirine and efavirenz) for nine treatment-experienced patient-derived recombinant pseudoviruses based on simultaneous measurement of drug susceptibility. Each color indicates the following antiretroviral drugs: blue (amprenavir), green (indinavir), brown (darunavir), gray (efavirenz), and orange (etravirine). Each experiment was repeated three times. (a) pNL4-3, WT; (b) KRB8067; (c) KRC2065; (d) KRB5018; (e) KRC2092; (f) KRB4025; (g) KRB8014; (h) KRC3221; (i) KRC0064; (j) KRC4543.
Mentions: The IC50 for five antiretroviral drugs was analyzed using WT-derived pseudoviruses to establish a standard level using XLfit (IDBS). The following antiretroviral drugs were tested in parallel: efavirenz and etravirine, amprenavir, indinavir, and darunavir. Figure 1 shows a sigmoidal dose–response curve between serially diluted drugs and infectivity. For each antiretroviral drug, the IC50 was as follows (in descending order for each drug category): efavirenz (4.40E–02 nM) and etravirine (1.34E–02 nM) among NNRTIs; and indinavir (13.5 nM), amprenavir (7.17 nM), and darunavir (6.80E–01 nM) among PIs. The FC in drug resistance was compared with the IC50 value of the WT against each antiretroviral drug (Figure 1).Figure 1

Bottom Line: The 50% inhibitory concentration (IC50) values were calculated and drug susceptibility was compared.Drug susceptibility was generally higher for etravirine and darunavir compared with efavirenz, amprenavir, and indinavir in pseudoviruses derived from treatment-experienced patients.This study may help to find a more effective HAART in the case of HIV-1 infected patients that have difficulty being treated.

View Article: PubMed Central - PubMed

Affiliation: Department of Immunology and Pathology, Division of AIDS, Korea National Institute of Health, Osong, Republic of Korea. jh5246@korea.kr.

ABSTRACT

Background: In South Korea, about 20 types of antiretroviral drugs are used in the treatment of patients with human immunodeficiency virus/acquired immune deficiency syndrome. Since 2010, raltegravir, etravirine, and darunavir have been spotlighted as new drugs for highly active antiretroviral therapy (HAART)-experienced adults with resistant HIV-1 in South Korea. In this study, we investigated potential susceptibility of pseudoviruses derived from treatment-experienced Korean patients to etravirine vs efavirenz and to darunavir vs amprenavir and indinavir using a modified single-round assay.

Methods: Pseudoviruses derived from nine treatment-experienced patients infected with HIV-1 were investigated by comparison with the wild-type strain pNL4-3. The 50% inhibitory concentration (IC50) values were calculated and drug susceptibility was compared. The intensity of genotypic drug resistance was classified based on the 'SIR' interpretation of the Stanford data base.

Results: Drug susceptibility was generally higher for etravirine and darunavir compared with efavirenz, amprenavir, and indinavir in pseudoviruses derived from treatment-experienced patients. Pseudoviruses derived from patients KRB4025 and KRB8014, who exhibited long-term use of protease inhibitors, showed an outside of tested drug concentration, especially for amprenavir and indinavir. However, they exhibited a lower fold-change in resistance to darunavir.

Conclusions: Etravirine and darunavir have been used in HAART since 2010 in South Korea. Therefore, these antiretroviral drugs together with other newly introduced antiretroviral drugs are interesting for the optimal treatment of patients with treatment failure. This study may help to find a more effective HAART in the case of HIV-1 infected patients that have difficulty being treated.

No MeSH data available.


Related in: MedlinePlus