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Prevalence of Rilpivirine and Etravirine Resistance Mutations in HIV-1 Subtype C-Infected Patients Failing Nevirapine or Efavirenz-Based Combination Antiretroviral Therapy in Botswana

Rilpivirine (RPV) and Etravirine (ETR) are approved second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment. There is a cross-resistance HIV mutation profile between first- and second-generation NNRTI drugs. We determined the prevalence of HIV-1 drug resistance m... Full description

Journal Title: AIDS research and human retroviruses 2018-08-01, Vol.34 (8), p.667-671
Main Author: Diphoko, Thabo
Other Authors: Gaseitsiwe, Simani , Kasvosve, Ishmael , Moyo, Sikhulile , Okatch, Harriet , Musonda, Rosemary , Wainberg, Mark , Makhema, Joseph , Marlink, Richard , Novitsky, Vladimir , Essex, Max
Format: Electronic Article Electronic Article
Language: English
Subjects:
Quelle: Alma/SFX Local Collection
Publisher: Mary Ann Liebert, Inc
ID: ISSN: 0889-2229
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recordid: cdi_maryannliebert_primary_10_1089_aid_2017_0135
title: Prevalence of Rilpivirine and Etravirine Resistance Mutations in HIV-1 Subtype C-Infected Patients Failing Nevirapine or Efavirenz-Based Combination Antiretroviral Therapy in Botswana
format: Article
creator:
  • Diphoko, Thabo
  • Gaseitsiwe, Simani
  • Kasvosve, Ishmael
  • Moyo, Sikhulile
  • Okatch, Harriet
  • Musonda, Rosemary
  • Wainberg, Mark
  • Makhema, Joseph
  • Marlink, Richard
  • Novitsky, Vladimir
  • Essex, Max
subjects:
  • Epidemiology
ispartof: AIDS research and human retroviruses, 2018-08-01, Vol.34 (8), p.667-671
description: Rilpivirine (RPV) and Etravirine (ETR) are approved second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment. There is a cross-resistance HIV mutation profile between first- and second-generation NNRTI drugs. We determined the prevalence of HIV-1 drug resistance mutations (DRMs) to RPV and ETR in Botswana. A total of 168 HIV-1 polymerase gene sequences from participants failing nevirapine (NVP)- or efavirenz (EFV)-containing regimens were analyzed for DRMs using the Stanford University HIV drug resistance database. Forty-one sequences were from an adult antiretroviral therapy (ART) study, the Tshepo study , and 127 from a prevention of mother-to-child transmission (PMTCT) study, the Mashi study , all conducted in Botswana. Prevalence of RPV and ETR highest DRM in the adult ART study ( n  = 41) were K101E (26.2%), E138A (23.8%), and Y181C (26.2%). The PMTCT cohort's ( n  = 127) high prevalence mutations were Y181C (15.7%), E138A (15%), and K101E (11%). A total of 42.9% and 3.2% of patients in the adult ART study and PMTCT study, respectively, had three or more NNRTI mutations at virologic failure. We identified HIV-1 mutations conferring resistance to RPV and ETR even though they have not been used in Botswana. Of concern was the high proportion of sequences from the adult ART study that displayed multiple DRMs; as the number of NNRTI mutations increases, the level of cross-resistance increases. It is plausible that patients displaying such profiles maybe at increased risk of failing second-generation NNRTI drugs, hence, calls for genotyping in patients with prior NVP or efavirenz exposure before prescription of RPV- or ETR-containing cART.
language: eng
source: Alma/SFX Local Collection
identifier: ISSN: 0889-2229
fulltext: fulltext
issn:
  • 0889-2229
  • 1931-8405
url: Link


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titlePrevalence of Rilpivirine and Etravirine Resistance Mutations in HIV-1 Subtype C-Infected Patients Failing Nevirapine or Efavirenz-Based Combination Antiretroviral Therapy in Botswana
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creatorDiphoko, Thabo ; Gaseitsiwe, Simani ; Kasvosve, Ishmael ; Moyo, Sikhulile ; Okatch, Harriet ; Musonda, Rosemary ; Wainberg, Mark ; Makhema, Joseph ; Marlink, Richard ; Novitsky, Vladimir ; Essex, Max
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descriptionRilpivirine (RPV) and Etravirine (ETR) are approved second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment. There is a cross-resistance HIV mutation profile between first- and second-generation NNRTI drugs. We determined the prevalence of HIV-1 drug resistance mutations (DRMs) to RPV and ETR in Botswana. A total of 168 HIV-1 polymerase gene sequences from participants failing nevirapine (NVP)- or efavirenz (EFV)-containing regimens were analyzed for DRMs using the Stanford University HIV drug resistance database. Forty-one sequences were from an adult antiretroviral therapy (ART) study, the Tshepo study , and 127 from a prevention of mother-to-child transmission (PMTCT) study, the Mashi study , all conducted in Botswana. Prevalence of RPV and ETR highest DRM in the adult ART study ( n  = 41) were K101E (26.2%), E138A (23.8%), and Y181C (26.2%). The PMTCT cohort's ( n  = 127) high prevalence mutations were Y181C (15.7%), E138A (15%), and K101E (11%). A total of 42.9% and 3.2% of patients in the adult ART study and PMTCT study, respectively, had three or more NNRTI mutations at virologic failure. We identified HIV-1 mutations conferring resistance to RPV and ETR even though they have not been used in Botswana. Of concern was the high proportion of sequences from the adult ART study that displayed multiple DRMs; as the number of NNRTI mutations increases, the level of cross-resistance increases. It is plausible that patients displaying such profiles maybe at increased risk of failing second-generation NNRTI drugs, hence, calls for genotyping in patients with prior NVP or efavirenz exposure before prescription of RPV- or ETR-containing cART.
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descriptionRilpivirine (RPV) and Etravirine (ETR) are approved second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment. There is a cross-resistance HIV mutation profile between first- and second-generation NNRTI drugs. We determined the prevalence of HIV-1 drug resistance mutations (DRMs) to RPV and ETR in Botswana. A total of 168 HIV-1 polymerase gene sequences from participants failing nevirapine (NVP)- or efavirenz (EFV)-containing regimens were analyzed for DRMs using the Stanford University HIV drug resistance database. Forty-one sequences were from an adult antiretroviral therapy (ART) study, the Tshepo study , and 127 from a prevention of mother-to-child transmission (PMTCT) study, the Mashi study , all conducted in Botswana. Prevalence of RPV and ETR highest DRM in the adult ART study ( n  = 41) were K101E (26.2%), E138A (23.8%), and Y181C (26.2%). The PMTCT cohort's ( n  = 127) high prevalence mutations were Y181C (15.7%), E138A (15%), and K101E (11%). A total of 42.9% and 3.2% of patients in the adult ART study and PMTCT study, respectively, had three or more NNRTI mutations at virologic failure. We identified HIV-1 mutations conferring resistance to RPV and ETR even though they have not been used in Botswana. Of concern was the high proportion of sequences from the adult ART study that displayed multiple DRMs; as the number of NNRTI mutations increases, the level of cross-resistance increases. It is plausible that patients displaying such profiles maybe at increased risk of failing second-generation NNRTI drugs, hence, calls for genotyping in patients with prior NVP or efavirenz exposure before prescription of RPV- or ETR-containing cART.
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abstractRilpivirine (RPV) and Etravirine (ETR) are approved second-generation non-nucleoside reverse transcriptase inhibitors (NNRTIs) for HIV treatment. There is a cross-resistance HIV mutation profile between first- and second-generation NNRTI drugs. We determined the prevalence of HIV-1 drug resistance mutations (DRMs) to RPV and ETR in Botswana. A total of 168 HIV-1 polymerase gene sequences from participants failing nevirapine (NVP)- or efavirenz (EFV)-containing regimens were analyzed for DRMs using the Stanford University HIV drug resistance database. Forty-one sequences were from an adult antiretroviral therapy (ART) study, the Tshepo study , and 127 from a prevention of mother-to-child transmission (PMTCT) study, the Mashi study , all conducted in Botswana. Prevalence of RPV and ETR highest DRM in the adult ART study ( n  = 41) were K101E (26.2%), E138A (23.8%), and Y181C (26.2%). The PMTCT cohort's ( n  = 127) high prevalence mutations were Y181C (15.7%), E138A (15%), and K101E (11%). A total of 42.9% and 3.2% of patients in the adult ART study and PMTCT study, respectively, had three or more NNRTI mutations at virologic failure. We identified HIV-1 mutations conferring resistance to RPV and ETR even though they have not been used in Botswana. Of concern was the high proportion of sequences from the adult ART study that displayed multiple DRMs; as the number of NNRTI mutations increases, the level of cross-resistance increases. It is plausible that patients displaying such profiles maybe at increased risk of failing second-generation NNRTI drugs, hence, calls for genotyping in patients with prior NVP or efavirenz exposure before prescription of RPV- or ETR-containing cART.
pubMary Ann Liebert, Inc
doi10.1089/aid.2017.0135