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Rajneesh K Joshi - One of the best experts on this subject based on the ideXlab platform.

  • antiretroviral resistance following Immunological Monitoring in a resource limited setting of western india a cross sectional study
    PLOS ONE, 2017
    Co-Authors: Santosh Karade, Smita Kulkarni, Manisha Ghate, Ajit Patil, Rajkumar Londhe, Sonali Salvi, Dileep Kadam, Rajneesh K Joshi
    Abstract:

    Background The free antiretroviral therapy (ART) program in India still relies on the clinico-Immunological Monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following Immunological Monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART. Methods and findings This cross-sectional study was performed at a state-sponsored ART clinic of Pune city in western India between January and June 2016. Consecutive adults receiving first-line ART with Immunological failure (IF) were recruited for plasma viral load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL underwent HIV drug resistance genotyping. Of these, 75 plasma sample were successfully genotyped. The median CD4 count and duration of ART at the time of failure were 98 (IQR: 61.60–153.50) cells/μL and 4.62 (IQR: 3.17–6.15) years, respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first-line failure, sequences from 56.67% of individuals indicated low- to high-level resistance to all available NRTI. The proportion of sequences with ≥2 thymidine analogue mutations (TAMs) and ≥3 TAMs were 62.12% and 39.39%, respectively. An average of 1.98 TAMs per sequence were observed following IF as compared to 0.37 TAMs per sequence following targeted PVL Monitoring at 12 months of ART from a prior study; this difference was significant (p<0.001). Conclusion The option of cycling of NRTI analogues between first- and second-line regimens would no longer be effective if individuals are followed-up by Immunological Monitoring due to accumulation of mutations. Introduction of routine PVL Monitoring is a priority for the long-term sustainability of free ART program in India.

  • Antiretroviral resistance following Immunological Monitoring in a resource-limited setting of western India: A cross-sectional study.
    PLOS ONE, 2017
    Co-Authors: Santosh Karade, Smita Kulkarni, Manisha Ghate, Rajkumar Londhe, Sonali Salvi, Dileep Kadam, Rajneesh K Joshi, Ajit A. Patil, Bharat B. Rewari, Raman R. Gangakhedkar
    Abstract:

    Background The free antiretroviral therapy (ART) program in India still relies on the clinico-Immunological Monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following Immunological Monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART. Methods and findings This cross-sectional study was performed at a state-sponsored ART clinic of Pune city in western India between January and June 2016. Consecutive adults receiving first-line ART with Immunological failure (IF) were recruited for plasma viral load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL underwent HIV drug resistance genotyping. Of these, 75 plasma sample were successfully genotyped. The median CD4 count and duration of ART at the time of failure were 98 (IQR: 61.60–153.50) cells/μL and 4.62 (IQR: 3.17–6.15) years, respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first-line failure, sequences from 56.67% of individuals indicated low- to high-level resistance to all available NRTI. The proportion of sequences with ≥2 thymidine analogue mutations (TAMs) and ≥3 TAMs were 62.12% and 39.39%, respectively. An average of 1.98 TAMs per sequence were observed following IF as compared to 0.37 TAMs per sequence following targeted PVL Monitoring at 12 months of ART from a prior study; this difference was significant (p

Santosh Karade - One of the best experts on this subject based on the ideXlab platform.

  • antiretroviral resistance following Immunological Monitoring in a resource limited setting of western india a cross sectional study
    PLOS ONE, 2017
    Co-Authors: Santosh Karade, Smita Kulkarni, Manisha Ghate, Ajit Patil, Rajkumar Londhe, Sonali Salvi, Dileep Kadam, Rajneesh K Joshi
    Abstract:

    Background The free antiretroviral therapy (ART) program in India still relies on the clinico-Immunological Monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following Immunological Monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART. Methods and findings This cross-sectional study was performed at a state-sponsored ART clinic of Pune city in western India between January and June 2016. Consecutive adults receiving first-line ART with Immunological failure (IF) were recruited for plasma viral load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL underwent HIV drug resistance genotyping. Of these, 75 plasma sample were successfully genotyped. The median CD4 count and duration of ART at the time of failure were 98 (IQR: 61.60–153.50) cells/μL and 4.62 (IQR: 3.17–6.15) years, respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first-line failure, sequences from 56.67% of individuals indicated low- to high-level resistance to all available NRTI. The proportion of sequences with ≥2 thymidine analogue mutations (TAMs) and ≥3 TAMs were 62.12% and 39.39%, respectively. An average of 1.98 TAMs per sequence were observed following IF as compared to 0.37 TAMs per sequence following targeted PVL Monitoring at 12 months of ART from a prior study; this difference was significant (p<0.001). Conclusion The option of cycling of NRTI analogues between first- and second-line regimens would no longer be effective if individuals are followed-up by Immunological Monitoring due to accumulation of mutations. Introduction of routine PVL Monitoring is a priority for the long-term sustainability of free ART program in India.

  • Antiretroviral resistance following Immunological Monitoring in a resource-limited setting of western India: A cross-sectional study.
    PLOS ONE, 2017
    Co-Authors: Santosh Karade, Smita Kulkarni, Manisha Ghate, Rajkumar Londhe, Sonali Salvi, Dileep Kadam, Rajneesh K Joshi, Ajit A. Patil, Bharat B. Rewari, Raman R. Gangakhedkar
    Abstract:

    Background The free antiretroviral therapy (ART) program in India still relies on the clinico-Immunological Monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following Immunological Monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART. Methods and findings This cross-sectional study was performed at a state-sponsored ART clinic of Pune city in western India between January and June 2016. Consecutive adults receiving first-line ART with Immunological failure (IF) were recruited for plasma viral load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL underwent HIV drug resistance genotyping. Of these, 75 plasma sample were successfully genotyped. The median CD4 count and duration of ART at the time of failure were 98 (IQR: 61.60–153.50) cells/μL and 4.62 (IQR: 3.17–6.15) years, respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first-line failure, sequences from 56.67% of individuals indicated low- to high-level resistance to all available NRTI. The proportion of sequences with ≥2 thymidine analogue mutations (TAMs) and ≥3 TAMs were 62.12% and 39.39%, respectively. An average of 1.98 TAMs per sequence were observed following IF as compared to 0.37 TAMs per sequence following targeted PVL Monitoring at 12 months of ART from a prior study; this difference was significant (p

Jane E Carter - One of the best experts on this subject based on the ideXlab platform.

  • misclassification of first line antiretroviral treatment failure based on Immunological Monitoring of hiv infection in resource limited settings
    Clinical Infectious Diseases, 2009
    Co-Authors: Rami Kantor, Lameck Diero, Allison Delong, Lydia Kamle, Sarah Muyonga, Fidelis Mambo, Eunice Walumbe, Wilfred Emonyi, Philip A Chan, Jane E Carter
    Abstract:

    BACKGROUND: The Monitoring of patients with human immunodeficiency virus (HIV) infection who are treated with antiretroviral medications in resource-limited settings is typically performed by use of clinical and Immunological criteria. The early identification of first-line antiretroviral treatment failure is critical to prevent morbidity mortality and drug resistance. Misclassification of failure may result in premature switching to second-line therapy. METHODS: Adult patients in western Kenya had their viral loads (VLs) determined if they had adhered to first-line therapy for >6 months and were suspected of experiencing Immunological failure (ie their CD4 cell count decreased by 25% in 6 months). Misclassification of treatment failure was defined as a 25% decrease in CD4 cell count with a VL of <400 copies/mL. Logistic and tree regressions examined relationships between VL and 4 variables: CD4 T cell count (hereafter CD4 cell count) percentage of T cells expressing CD4 (hereafter CD4 cell percentage) percentage decrease in the CD4 T cell count (hereafter CD4 cell count percent decrease) and percentage decrease in the percentage of T cells expressing CD4 (hereafter CD4% percent decrease). RESULTS: There were 149 patients who were treated for 23 months; they were identified as having a 25% decrease in CD4 cell count (from 375 to 216 cells/microL) and a CD4% percent decrease (from 19% to 15%); of these 149 patients 86 (58%) were misclassified as having experienced treatment failure. Of 42 patients who had a 50% decrease in CD4 cell count 18 (43%) were misclassified. In multivariate logistic regression misclassification odds were associated with a higher CD4 cell count a shorter duration of therapy and a smaller CD4% percent decrease. By combining these variables we may be able to improve our ability to predict treatment failure. CONCLUSIONS: Immunological Monitoring as a sole indicator of virological failure would lead to a premature switch to valuable second-line regimens for 58% of patients who experience a 25% decrease in CD4 cell count and for 43% patients who experience a 50% decrease in CD4 cell count and therefore this type of Monitoring should be reevaluated. Selective virological Monitoring and the addition of indicators like trends CD4% percent decrease and duration of therapy may systematically improve the identification of treatment failure. VL testing is now mandatory for patients suspected of experiencing first-line treatment failure within the Academic Model Providing Access to Healthcare (AMPATH) in western Kenya and should be considered in all resource-limited settings.

Rami Kantor - One of the best experts on this subject based on the ideXlab platform.

  • misclassification of first line antiretroviral treatment failure based on Immunological Monitoring of hiv infection in resource limited settings
    Clinical Infectious Diseases, 2009
    Co-Authors: Rami Kantor, Lameck Diero, Allison Delong, Lydia Kamle, Sarah Muyonga, Fidelis Mambo, Eunice Walumbe, Wilfred Emonyi, Philip A Chan, Jane E Carter
    Abstract:

    BACKGROUND: The Monitoring of patients with human immunodeficiency virus (HIV) infection who are treated with antiretroviral medications in resource-limited settings is typically performed by use of clinical and Immunological criteria. The early identification of first-line antiretroviral treatment failure is critical to prevent morbidity mortality and drug resistance. Misclassification of failure may result in premature switching to second-line therapy. METHODS: Adult patients in western Kenya had their viral loads (VLs) determined if they had adhered to first-line therapy for >6 months and were suspected of experiencing Immunological failure (ie their CD4 cell count decreased by 25% in 6 months). Misclassification of treatment failure was defined as a 25% decrease in CD4 cell count with a VL of <400 copies/mL. Logistic and tree regressions examined relationships between VL and 4 variables: CD4 T cell count (hereafter CD4 cell count) percentage of T cells expressing CD4 (hereafter CD4 cell percentage) percentage decrease in the CD4 T cell count (hereafter CD4 cell count percent decrease) and percentage decrease in the percentage of T cells expressing CD4 (hereafter CD4% percent decrease). RESULTS: There were 149 patients who were treated for 23 months; they were identified as having a 25% decrease in CD4 cell count (from 375 to 216 cells/microL) and a CD4% percent decrease (from 19% to 15%); of these 149 patients 86 (58%) were misclassified as having experienced treatment failure. Of 42 patients who had a 50% decrease in CD4 cell count 18 (43%) were misclassified. In multivariate logistic regression misclassification odds were associated with a higher CD4 cell count a shorter duration of therapy and a smaller CD4% percent decrease. By combining these variables we may be able to improve our ability to predict treatment failure. CONCLUSIONS: Immunological Monitoring as a sole indicator of virological failure would lead to a premature switch to valuable second-line regimens for 58% of patients who experience a 25% decrease in CD4 cell count and for 43% patients who experience a 50% decrease in CD4 cell count and therefore this type of Monitoring should be reevaluated. Selective virological Monitoring and the addition of indicators like trends CD4% percent decrease and duration of therapy may systematically improve the identification of treatment failure. VL testing is now mandatory for patients suspected of experiencing first-line treatment failure within the Academic Model Providing Access to Healthcare (AMPATH) in western Kenya and should be considered in all resource-limited settings.

  • Misclassification of First-Line Antiretroviral Treatment Failure Based on Immunological Monitoring of HIV Infection in Resource-Limited Settings
    Clinical Infectious Diseases, 2009
    Co-Authors: Rami Kantor, Lameck Diero, Allison Delong, Lydia Kamle, Sarah Muyonga, Fidelis Mambo, Eunice Walumbe, Wilfred Emonyi, Philip A Chan, E. Jane Carter
    Abstract:

    BACKGROUND: The Monitoring of patients with human immunodeficiency virus (HIV) infection who are treated with antiretroviral medications in resource-limited settings is typically performed by use of clinical and Immunological criteria. The early identification of first-line antiretroviral treatment failure is critical to prevent morbidity mortality and drug resistance. Misclassification of failure may result in premature switching to second-line therapy. METHODS: Adult patients in western Kenya had their viral loads (VLs) determined if they had adhered to first-line therapy for >6 months and were suspected of experiencing Immunological failure (ie their CD4 cell count decreased by 25% in 6 months). Misclassification of treatment failure was defined as a 25% decrease in CD4 cell count with a VL of

Smita Kulkarni - One of the best experts on this subject based on the ideXlab platform.

  • antiretroviral resistance following Immunological Monitoring in a resource limited setting of western india a cross sectional study
    PLOS ONE, 2017
    Co-Authors: Santosh Karade, Smita Kulkarni, Manisha Ghate, Ajit Patil, Rajkumar Londhe, Sonali Salvi, Dileep Kadam, Rajneesh K Joshi
    Abstract:

    Background The free antiretroviral therapy (ART) program in India still relies on the clinico-Immunological Monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following Immunological Monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART. Methods and findings This cross-sectional study was performed at a state-sponsored ART clinic of Pune city in western India between January and June 2016. Consecutive adults receiving first-line ART with Immunological failure (IF) were recruited for plasma viral load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL underwent HIV drug resistance genotyping. Of these, 75 plasma sample were successfully genotyped. The median CD4 count and duration of ART at the time of failure were 98 (IQR: 61.60–153.50) cells/μL and 4.62 (IQR: 3.17–6.15) years, respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first-line failure, sequences from 56.67% of individuals indicated low- to high-level resistance to all available NRTI. The proportion of sequences with ≥2 thymidine analogue mutations (TAMs) and ≥3 TAMs were 62.12% and 39.39%, respectively. An average of 1.98 TAMs per sequence were observed following IF as compared to 0.37 TAMs per sequence following targeted PVL Monitoring at 12 months of ART from a prior study; this difference was significant (p<0.001). Conclusion The option of cycling of NRTI analogues between first- and second-line regimens would no longer be effective if individuals are followed-up by Immunological Monitoring due to accumulation of mutations. Introduction of routine PVL Monitoring is a priority for the long-term sustainability of free ART program in India.

  • Antiretroviral resistance following Immunological Monitoring in a resource-limited setting of western India: A cross-sectional study.
    PLOS ONE, 2017
    Co-Authors: Santosh Karade, Smita Kulkarni, Manisha Ghate, Rajkumar Londhe, Sonali Salvi, Dileep Kadam, Rajneesh K Joshi, Ajit A. Patil, Bharat B. Rewari, Raman R. Gangakhedkar
    Abstract:

    Background The free antiretroviral therapy (ART) program in India still relies on the clinico-Immunological Monitoring for diagnosis of treatment failure. As the nucleoside reverse transcriptase inhibitor (NRTI) backbone is shared in first- and second-line regimens, accumulation of drug resistant mutations (DRMs) can compromise the efficacy of NRTI. This study was undertaken to describe the pattern of HIV DRMs following Immunological Monitoring and investigate its impact on the cycling of NRTI between first- and second-line ART. Methods and findings This cross-sectional study was performed at a state-sponsored ART clinic of Pune city in western India between January and June 2016. Consecutive adults receiving first-line ART with Immunological failure (IF) were recruited for plasma viral load (PVL) estimation. Randomly selected 80 participants with PVL >1000 copies/mL underwent HIV drug resistance genotyping. Of these, 75 plasma sample were successfully genotyped. The median CD4 count and duration of ART at the time of failure were 98 (IQR: 61.60–153.50) cells/μL and 4.62 (IQR: 3.17–6.15) years, respectively. The prevalence of NRTI, non-NRTI, and major protease inhibitor resistance mutations were 89.30%, 96%, and 1.33%, respectively. Following first-line failure, sequences from 56.67% of individuals indicated low- to high-level resistance to all available NRTI. The proportion of sequences with ≥2 thymidine analogue mutations (TAMs) and ≥3 TAMs were 62.12% and 39.39%, respectively. An average of 1.98 TAMs per sequence were observed following IF as compared to 0.37 TAMs per sequence following targeted PVL Monitoring at 12 months of ART from a prior study; this difference was significant (p