Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second-Line Antiretroviral Therapy in Asia

Prasitsuebsai, Wasana; Teeraananchai, Sirinya; Singtoroj, Thida; Truong, Khanh Huu; Ananworanich, Jintanat; Chau, Viet; Nguyen, Lam Van; Kosalaraksa, Pope; Kurniati, Nia; Sudjaritruk, Tavitiya; Chokephaibulkit, Kulkanya; Kerr, Stephen J.; Sohn, Annette H.

doi:10.1097/qai.0000000000000971

Cited by 17 publications

(31 citation statements)

References 30 publications

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“…This finding was robust across several sensitivity analyses. This result is in line with previous paediatric studies which also identified adolescents to be at increased risk of treatment failure on first-and second-line ART [17,18,31,32]. Studies on treatment outcomes of adolescents living with HIV in LMIC are scarce, but the available data are worrisome.…”

Section: Discussionsupporting

confidence: 89%

Multicentre analysis of second‐line antiretroviral treatment in HIV‐infected children: adolescents at high risk of failure

Boerma

Bunupuradah

Dow

et al. 2017

Journal of the International AIDS Society

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Introduction: The number of HIV-infected children and adolescents requiring second-line antiretroviral treatment (ART) is increasing in low- and middle-income countries (LMIC). However, the effectiveness of paediatric second-line ART and potential risk factors for virologic failure are poorly characterized. We performed an aggregate analysis of second-line ART outcomes for children and assessed the need for paediatric third-line ART. Methods: We performed a multicentre analysis by systematically reviewing the literature to identify cohorts of children and adolescents receiving second-line ART in LMIC, contacting the corresponding study groups and including patient-level data on virologic and clinical outcomes. Kaplan–Meier survival estimates and Cox proportional hazard models were used to describe cumulative rates and predictors of virologic failure. Virologic failure was defined as two consecutive viral load measurements >1000 copies/ml after at least six months of second-line treatment. Results: We included 12 cohorts representing 928 children on second-line protease inhibitor (PI)-based ART in 14 countries in Asia and sub-Saharan Africa. After 24 months, 16.4% (95% confidence interval (CI): 13.9–19.4) of children experienced virologic failure. Adolescents (10–18 years) had failure rates of 14.5 (95% CI 11.9–17.6) per 100 person-years compared to 4.5 (95% CI 3.4–5.8) for younger children (3–9 years). Risk factors for virologic failure were adolescence (adjusted hazard ratio [aHR] 3.93, p < 0.001) and short duration of first-line ART before treatment switch (aHR 0.64 and 0.53, p = 0.008, for 24–48 months and >48 months, respectively, compared to <24 months). Conclusions: In LMIC, paediatric PI-based second-line ART was associated with relatively low virologic failure rates. However, adolescents showed exceptionally poor virologic outcomes in LMIC, and optimizing their HIV care requires urgent attention. In addition, 16% of children and adolescents failed PI-based treatment and will require integrase inhibitors to construct salvage regimens. These drugs are currently not available in LMIC.

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Section: Discussionsupporting

confidence: 89%

Multicentre analysis of second‐line antiretroviral treatment in HIV‐infected children: adolescents at high risk of failure

Boerma

Bunupuradah

Dow

et al. 2017

Journal of the International AIDS Society

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“…Overall, 277 children were enrolled in the TASER-P study between February 2011 and December 2012 [9] of whom 244 met inclusion criteria for the present analysis. At enrolment, 55% of participants were Vietnamese, 34% were Thai and 11% were Indonesian (Table 1).…”

Section: Resultsmentioning

confidence: 99%

“…Eligibility and recruitment at the 8 sites of TASER-P have been previously described [9] . Briefly, children were enrolled if they were HIV-infected, <18 years old, experienced first-line treatment failure and had already switched or were currently switching to second-line ART (defined as an ARV class switch from a non-nucleoside reverse transcriptase inhibitor [NNRTI] to a protease inhibitor [PI]).…”

Section: Methodsmentioning

confidence: 99%

“…Participants were included in the present analysis if they had one or more hair specimens collected at least 3 months after switching to second-line therapy and were on a LPV-based regimen (91% of participants were on LPV/r-based regimens in the TASER-P cohort) [9] . At any visit where the HIV RNA level was >1000 copies/ml, standard genotyping of the viral reverse transcriptase and protease gene was performed.…”

Section: Methodsmentioning

confidence: 99%

“…We used separate time-to-first-event discrete-time Cox regression models to identify predictors of experiencing viremia defined as either an HIV-1 RNA level >400 copies/ml or an HIV-1 RNA level >1000 copies/ml. Characteristics assessed as potential predictors of viremia were those evaluated in the parent study [9] and included age ≤11 years, sex, country, self-reported adherence over the last 30 days, LPV hair concentrations, CD4 percentage and HIV-1 RNA level upon switching to second-line ART; hair levels and self-reported adherence were included in models as time-varying covariates. Statistical significance was based on a 2-sided p-value of <0.05.…”

Section: Methodsmentioning

confidence: 99%

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Brief Report: Lopinavir Hair Concentrations Are the Strongest Predictor of Viremia in HIV-Infected Asian Children and Adolescents on Second-Line Antiretroviral Therapy

Pintye

Bacchetti

Teeraananchai

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Children/adolescents display suboptimal antiretroviral therapy (ART) adherence and outcomes versus adults. Hair ART concentrations are objective adherence measures that predict viremia in adults but longitudinal data on hair levels in pediatric populations is limited. We assessed the predictive utility of hair lopinavir levels on viremia among youth on second-line ART. Methods We examined predictors of viremia (HIV-1 RNA >400 and >1000 copies/ml) at least 24 weeks after switch to lopinavir-based second-line ART in a cohort of HIV-infected Asian children followed between 2011 and 2014. Small hair samples, HIV-1 RNA, and self-reported adherence were collected biannually. Hair concentrations of lopinavir were measured via liquid-chromatography/tandem-mass-spectrometry using validated methods. Time-to-first viremia was examined using discrete-time Cox models. Results Overall, 244 children met inclusion criteria for the present analysis. Approximately half (55%) were males and the median age 10 years (interquartile range [IQR] 7–13); 40% were >11 years. At switch to second-line ART, median CD4 count was 300 (IQR 146–547) cells/mm3 and median HIV-RNA level was 5.0 (IQR 4.3–5.6) log10/mL. Median time of study follow-up was 48 weeks and a median of 3 (range 1–5) hair samples collected from each participant. Adjusting for age, sex, country, self-reported adherence, CD4, and HIV-RNA, higher lopinavir hair concentrations were the strongest predictor of lower odds of viremia (HIV-RNA >400 copies/ml adjusted odds ratio [aOR]=0.41 per doubling in hair concentration, 95% 0.29–0.58, p<0.001; HIV-RNA >1000 copies/ml aOR=0.54, 95% CI 0.45–0.65, p<0.001). Conclusions Hair concentrations predict viremia among children with HIV on 2nd-line ART and could guide clinical decisions for this population.

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Outcomes of second‐line antiretroviral therapy among children living with HIV: a global cohort analysis

Patel¹,

Smith²,

Collins³

et al. 2020

J Intern AIDS Soc

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Introduction Limited data describe outcomes on second‐line antiretroviral therapy (ART) among children globally. Our objective was to contribute data on outcomes among children living with HIV after initiation of second‐line ART in the context of routine care within a large global cohort collaboration. Methods Patient‐level data from 1993 through 2015 from 11 paediatric HIV cohorts were pooled. Characteristics at switch and through two years of follow‐up were summarized for children who switched to second‐line ART after starting a standard first‐line regimen in North America, Latin America, Europe, Asia, Southern Africa (South Africa & Botswana) and the rest of sub‐Saharan Africa (SSA). Cumulative incidences of mortality and loss to follow‐up (LTFU) were estimated using a competing risks framework. Results Of the 85,389 children on first‐line ART, 3,555 (4%) switched to second‐line after a median of 2.8 years on ART (IQR: 1.6, 4.7); 69% were from Southern Africa or SSA and 86% of second‐line regimens were protease inhibitor‐based. At switch, median age was 8.4 years and 50% had a prior AIDS diagnosis. Median follow‐up after switch to second‐line ranged from 1.8 years in SSA to 5.3 years in North America. Median CD4 counts at switch to second‐line ranged from 235 cells/mm3 in SSA to 828 cells/mm3 in North America. Improvements in CD4 counts were observed over two years of follow‐up, particularly in regions with lower CD4 counts at second‐line switch. Improvements in weight‐for‐age z‐scores were not observed during follow‐up. Cumulative incidence of LTFU at two years was <5% in all regions except SSA (7.1%) and Southern Africa (7.4%). Risk of mortality was <3% at two years of follow‐up in all regions, except Latin America (4.9%) and SSA (5.5%). Conclusions Children switched to second‐line ART experience CD4 count increases as well as low to moderate rates of LTFU and mortality within two years after switch. Severe immune deficiency at time of switch in some settings suggests need for improved recognition and management of treatment failure in children.

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Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second-Line Antiretroviral Therapy in Asia

Cited by 17 publications

References 30 publications

Multicentre analysis of second‐line antiretroviral treatment in HIV‐infected children: adolescents at high risk of failure

Multicentre analysis of second‐line antiretroviral treatment in HIV‐infected children: adolescents at high risk of failure

Brief Report: Lopinavir Hair Concentrations Are the Strongest Predictor of Viremia in HIV-Infected Asian Children and Adolescents on Second-Line Antiretroviral Therapy

Outcomes of second‐line antiretroviral therapy among children living with HIV: a global cohort analysis

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