Long-term virological outcome in children receiving first-line antiretroviral therapy

Padmapriyadarsini Chandrasekaran, Anita Shet, Ramalingam Srinivasan, G. N. Sanjeeva, Sudha Subramanyan, Suba Sunderesan, Karunaianantham Ramesh, Bindu Gopalan, Elumalai Suresh, Navaneethan Poornagangadevi, Luke E. Hanna, Chockalingam Chandrasekar, Christine Wanke, Soumya Swaminathan

Research output: Contribution to journalArticle

Abstract

Background: Studies relating to long-term virological outcomes among children on first-line antiretroviral therapy (ART) from low and middle-income countries are limited. Methods: Perinatally HIV infected, ART-naive children, between 2 and 12years of age, initiating NNRTI-based ART during 2010-2015, with at least 12months of follow-up, were included in the analysis. CD4 cell counts and plasma HIV-1 RNA were measured every 24weeks post-ART initiation. Immunologic failure was defined as a decrease in the CD4 count to pre-therapy levels or below and virologic failure as HIV-RNA of >1000copies/ml at 48weeks after ART initiation. Genotypic resistance testing was performed for children with virologic failure. Logistic regression analysis was done to identify predictors of virologic failure. Results: Three hundred and ninety-three ART-naïve children living with HIV [mean (SD) age: 7.6 (3) years; mean (SD) CD4%: 16% (8); median (IQR) HIV-RNA: 5.1 (3.5-5.7) log10copies/ml] were enrolled into the study. At 48weeks, significant improvement occurred in weight-for-age and height-for-age z-scores from baseline (all p<0.001). The immunologic response was good; almost 90% of children showing an increase in their absolute CD4+ T cell count to more than 350 cells/mm3. Immunological failure was noted among 11% (28/261) and virologic failure in 29% (94/328) of children. Of the 94 children with virologic failure at 12months, 36 children showed immunologic failure while the rest had good immunologic improvement. There was no demonstrable correlation between virologic and immunologic failure. 62% had reported >90% adherence to ART. At the time of virologic failure, multiple NNRTI-associated mutations were observed: 80%-K103N and Y181C being the major NNRTI mutations-observed. Sensitivity (95% CI) of immunologic failure to detect virologic failure was 7% (2-12), specificity 97% (92.4-98.9), PPV 44% (13.7-78.8) and NPV was 72% (65-77.9). There were no statistically significant predictors to detect children who will develop virologic failure on treatment. Conclusions: Considerable immunological improvement is seen in children with ART initiation, but may not be an effective tool to monitor treatment response in the long-term. There is a lack of correlation between immunologic and virologic response while on ART, which may lead to a delay in identifying treatment failures. Periodic viral load monitoring is, therefore, a priority.

Original languageEnglish (US)
Article number23
JournalAIDS Research and Therapy
Volume15
Issue number1
DOIs
StatePublished - Nov 26 2018

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Therapeutics
HIV
RNA
CD4 Lymphocyte Count
Treatment Failure
Mutation
Viral Load
HIV-1
Logistic Models
Regression Analysis
Weights and Measures

Keywords

  • Antiretroviral therapy
  • First-line
  • Pediatrics
  • Treatment outcome
  • Viral load

ASJC Scopus subject areas

  • Molecular Medicine
  • Virology
  • Pharmacology (medical)

Cite this

Chandrasekaran, P., Shet, A., Srinivasan, R., Sanjeeva, G. N., Subramanyan, S., Sunderesan, S., ... Swaminathan, S. (2018). Long-term virological outcome in children receiving first-line antiretroviral therapy. AIDS Research and Therapy, 15(1), [23]. https://doi.org/10.1186/s12981-018-0208-9

Long-term virological outcome in children receiving first-line antiretroviral therapy. / Chandrasekaran, Padmapriyadarsini; Shet, Anita; Srinivasan, Ramalingam; Sanjeeva, G. N.; Subramanyan, Sudha; Sunderesan, Suba; Ramesh, Karunaianantham; Gopalan, Bindu; Suresh, Elumalai; Poornagangadevi, Navaneethan; Hanna, Luke E.; Chandrasekar, Chockalingam; Wanke, Christine; Swaminathan, Soumya.

In: AIDS Research and Therapy, Vol. 15, No. 1, 23, 26.11.2018.

Research output: Contribution to journalArticle

Chandrasekaran, P, Shet, A, Srinivasan, R, Sanjeeva, GN, Subramanyan, S, Sunderesan, S, Ramesh, K, Gopalan, B, Suresh, E, Poornagangadevi, N, Hanna, LE, Chandrasekar, C, Wanke, C & Swaminathan, S 2018, 'Long-term virological outcome in children receiving first-line antiretroviral therapy', AIDS Research and Therapy, vol. 15, no. 1, 23. https://doi.org/10.1186/s12981-018-0208-9
Chandrasekaran P, Shet A, Srinivasan R, Sanjeeva GN, Subramanyan S, Sunderesan S et al. Long-term virological outcome in children receiving first-line antiretroviral therapy. AIDS Research and Therapy. 2018 Nov 26;15(1). 23. https://doi.org/10.1186/s12981-018-0208-9
Chandrasekaran, Padmapriyadarsini ; Shet, Anita ; Srinivasan, Ramalingam ; Sanjeeva, G. N. ; Subramanyan, Sudha ; Sunderesan, Suba ; Ramesh, Karunaianantham ; Gopalan, Bindu ; Suresh, Elumalai ; Poornagangadevi, Navaneethan ; Hanna, Luke E. ; Chandrasekar, Chockalingam ; Wanke, Christine ; Swaminathan, Soumya. / Long-term virological outcome in children receiving first-line antiretroviral therapy. In: AIDS Research and Therapy. 2018 ; Vol. 15, No. 1.
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abstract = "Background: Studies relating to long-term virological outcomes among children on first-line antiretroviral therapy (ART) from low and middle-income countries are limited. Methods: Perinatally HIV infected, ART-naive children, between 2 and 12years of age, initiating NNRTI-based ART during 2010-2015, with at least 12months of follow-up, were included in the analysis. CD4 cell counts and plasma HIV-1 RNA were measured every 24weeks post-ART initiation. Immunologic failure was defined as a decrease in the CD4 count to pre-therapy levels or below and virologic failure as HIV-RNA of >1000copies/ml at 48weeks after ART initiation. Genotypic resistance testing was performed for children with virologic failure. Logistic regression analysis was done to identify predictors of virologic failure. Results: Three hundred and ninety-three ART-na{\"i}ve children living with HIV [mean (SD) age: 7.6 (3) years; mean (SD) CD4{\%}: 16{\%} (8); median (IQR) HIV-RNA: 5.1 (3.5-5.7) log10copies/ml] were enrolled into the study. At 48weeks, significant improvement occurred in weight-for-age and height-for-age z-scores from baseline (all p<0.001). The immunologic response was good; almost 90{\%} of children showing an increase in their absolute CD4+ T cell count to more than 350 cells/mm3. Immunological failure was noted among 11{\%} (28/261) and virologic failure in 29{\%} (94/328) of children. Of the 94 children with virologic failure at 12months, 36 children showed immunologic failure while the rest had good immunologic improvement. There was no demonstrable correlation between virologic and immunologic failure. 62{\%} had reported >90{\%} adherence to ART. At the time of virologic failure, multiple NNRTI-associated mutations were observed: 80{\%}-K103N and Y181C being the major NNRTI mutations-observed. Sensitivity (95{\%} CI) of immunologic failure to detect virologic failure was 7{\%} (2-12), specificity 97{\%} (92.4-98.9), PPV 44{\%} (13.7-78.8) and NPV was 72{\%} (65-77.9). There were no statistically significant predictors to detect children who will develop virologic failure on treatment. Conclusions: Considerable immunological improvement is seen in children with ART initiation, but may not be an effective tool to monitor treatment response in the long-term. There is a lack of correlation between immunologic and virologic response while on ART, which may lead to a delay in identifying treatment failures. Periodic viral load monitoring is, therefore, a priority.",
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author = "Padmapriyadarsini Chandrasekaran and Anita Shet and Ramalingam Srinivasan and Sanjeeva, {G. N.} and Sudha Subramanyan and Suba Sunderesan and Karunaianantham Ramesh and Bindu Gopalan and Elumalai Suresh and Navaneethan Poornagangadevi and Hanna, {Luke E.} and Chockalingam Chandrasekar and Christine Wanke and Soumya Swaminathan",
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TY - JOUR

T1 - Long-term virological outcome in children receiving first-line antiretroviral therapy

AU - Chandrasekaran, Padmapriyadarsini

AU - Shet, Anita

AU - Srinivasan, Ramalingam

AU - Sanjeeva, G. N.

AU - Subramanyan, Sudha

AU - Sunderesan, Suba

AU - Ramesh, Karunaianantham

AU - Gopalan, Bindu

AU - Suresh, Elumalai

AU - Poornagangadevi, Navaneethan

AU - Hanna, Luke E.

AU - Chandrasekar, Chockalingam

AU - Wanke, Christine

AU - Swaminathan, Soumya

PY - 2018/11/26

Y1 - 2018/11/26

N2 - Background: Studies relating to long-term virological outcomes among children on first-line antiretroviral therapy (ART) from low and middle-income countries are limited. Methods: Perinatally HIV infected, ART-naive children, between 2 and 12years of age, initiating NNRTI-based ART during 2010-2015, with at least 12months of follow-up, were included in the analysis. CD4 cell counts and plasma HIV-1 RNA were measured every 24weeks post-ART initiation. Immunologic failure was defined as a decrease in the CD4 count to pre-therapy levels or below and virologic failure as HIV-RNA of >1000copies/ml at 48weeks after ART initiation. Genotypic resistance testing was performed for children with virologic failure. Logistic regression analysis was done to identify predictors of virologic failure. Results: Three hundred and ninety-three ART-naïve children living with HIV [mean (SD) age: 7.6 (3) years; mean (SD) CD4%: 16% (8); median (IQR) HIV-RNA: 5.1 (3.5-5.7) log10copies/ml] were enrolled into the study. At 48weeks, significant improvement occurred in weight-for-age and height-for-age z-scores from baseline (all p<0.001). The immunologic response was good; almost 90% of children showing an increase in their absolute CD4+ T cell count to more than 350 cells/mm3. Immunological failure was noted among 11% (28/261) and virologic failure in 29% (94/328) of children. Of the 94 children with virologic failure at 12months, 36 children showed immunologic failure while the rest had good immunologic improvement. There was no demonstrable correlation between virologic and immunologic failure. 62% had reported >90% adherence to ART. At the time of virologic failure, multiple NNRTI-associated mutations were observed: 80%-K103N and Y181C being the major NNRTI mutations-observed. Sensitivity (95% CI) of immunologic failure to detect virologic failure was 7% (2-12), specificity 97% (92.4-98.9), PPV 44% (13.7-78.8) and NPV was 72% (65-77.9). There were no statistically significant predictors to detect children who will develop virologic failure on treatment. Conclusions: Considerable immunological improvement is seen in children with ART initiation, but may not be an effective tool to monitor treatment response in the long-term. There is a lack of correlation between immunologic and virologic response while on ART, which may lead to a delay in identifying treatment failures. Periodic viral load monitoring is, therefore, a priority.

AB - Background: Studies relating to long-term virological outcomes among children on first-line antiretroviral therapy (ART) from low and middle-income countries are limited. Methods: Perinatally HIV infected, ART-naive children, between 2 and 12years of age, initiating NNRTI-based ART during 2010-2015, with at least 12months of follow-up, were included in the analysis. CD4 cell counts and plasma HIV-1 RNA were measured every 24weeks post-ART initiation. Immunologic failure was defined as a decrease in the CD4 count to pre-therapy levels or below and virologic failure as HIV-RNA of >1000copies/ml at 48weeks after ART initiation. Genotypic resistance testing was performed for children with virologic failure. Logistic regression analysis was done to identify predictors of virologic failure. Results: Three hundred and ninety-three ART-naïve children living with HIV [mean (SD) age: 7.6 (3) years; mean (SD) CD4%: 16% (8); median (IQR) HIV-RNA: 5.1 (3.5-5.7) log10copies/ml] were enrolled into the study. At 48weeks, significant improvement occurred in weight-for-age and height-for-age z-scores from baseline (all p<0.001). The immunologic response was good; almost 90% of children showing an increase in their absolute CD4+ T cell count to more than 350 cells/mm3. Immunological failure was noted among 11% (28/261) and virologic failure in 29% (94/328) of children. Of the 94 children with virologic failure at 12months, 36 children showed immunologic failure while the rest had good immunologic improvement. There was no demonstrable correlation between virologic and immunologic failure. 62% had reported >90% adherence to ART. At the time of virologic failure, multiple NNRTI-associated mutations were observed: 80%-K103N and Y181C being the major NNRTI mutations-observed. Sensitivity (95% CI) of immunologic failure to detect virologic failure was 7% (2-12), specificity 97% (92.4-98.9), PPV 44% (13.7-78.8) and NPV was 72% (65-77.9). There were no statistically significant predictors to detect children who will develop virologic failure on treatment. Conclusions: Considerable immunological improvement is seen in children with ART initiation, but may not be an effective tool to monitor treatment response in the long-term. There is a lack of correlation between immunologic and virologic response while on ART, which may lead to a delay in identifying treatment failures. Periodic viral load monitoring is, therefore, a priority.

KW - Antiretroviral therapy

KW - First-line

KW - Pediatrics

KW - Treatment outcome

KW - Viral load

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