Outcomes after viral load rebound on first-line antiretroviral treatment in children with HIV in the UK and Ireland: an observational cohort study

Childs, Tristan; Shingadia, Delane; Goodall, Ruth; Doerholt, Katja; Lyall, Hermione; Duong, Trinh; Judd, Ali; Gibb, Diana M; Collins, Intira Jeannie

doi:10.1016/s2352-3018(15)00021-1

Cited by 14 publications

(17 citation statements)

References 29 publications

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“…Another South African study showed a higher VR rate at a plasma VL threshold >400 copies/ml among younger adolescents (aged 10-14 years; 6.3 per 100 PYFU) compared with older adolescents (aged 15-19 years; 3.8 per 100 PYFU) on first-line cART [24]. Additionally, we found that our cumulative incidence of post-suppression VR was lower than a 19% incidence demonstrated in the Collaborative HIV Paediatric Study (CHIPS; using the definition of VR as a plasma VL >400 copies/ml), which was conducted in antiretroviral-naïve children and adolescents receiving first-line regimens, over a median duration of 1.8 years after treatment initiation in the UK and Ireland [12]. These results emphasize that although adolescents may have a childhood history of viral suppression, they remain at risk of developing VR later in life.…”

Section: Discussionmentioning

confidence: 99%

“…Virologic rebound (VR) after suppression on cART has been reported in perinatally HIV-infected youth (cumulative incidence: 19%) and adults (cumulative incidence: 6-42%), using the definition of plasma viral load (VL) >400 copies/ml [12-15]. A study comparing the risk of VR between non-perinatally HIV-infected adolescents and adults found that adolescents had a significantly greater incidence than adults (6 months after initial suppression: cumulative incidence 31% vs. 17%; P = 0.02; and 12 months after initial suppression: cumulative incidence 42% vs. 20%; P = 0.004) [16].…”

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confidence: 99%

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Incidence of Postsuppression Virologic Rebound in Perinatally HIV-Infected Asian Adolescents on Stable Combination Antiretroviral Therapy

Sudjaritruk

Aurpibul

et al. 2017

Journal of Adolescent Health

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Purpose To assess the incidence and predictors of post-suppression virologic rebound (VR) among adolescents on stable combination antiretroviral therapy (cART) in Asia. Methods Perinatally HIV-infected Asian adolescents (10-19 years) with documented virologic suppression [two consecutive viral loads (VL) <400 copies/ml >6 months apart] were included. Baseline was the date of the first VL <400 copies/ml at age >10 years, or the 10th birthday for those with prior suppression. Cox proportional hazards models were used to identify predictors of post-suppression VR (VL >1000 copies/ml). Results Of 1379 eligible adolescents, 47% were males. At baseline, 22% were receiving protease inhibitor (PI)-containing regimens; median CD4 cell count (IQR) was 685 (448-937) cells/mm3; 2% had pre-adolescent virologic failure (VF) before subsequent suppression. During adolescence, 180 individuals (13%) experienced post-suppression VR at a rate of 3.4 (95%CI: 2.9-3.9) per 100 person-years, which was consistent over time. Median time to VR during adolescence (IQR) was 3.3 (2.1-4.8) years. Wasting (weight-for-age z-score <-2.5), being raised by grandparents, receiving second-line PI-based regimens, starting cART after 2005, and having pre-adolescent VF were independent predictors of adolescent VR. At VR, median age, CD4 cell count, and VL (IQR) were 14.8 (13.2-16.4) years, 507 (325-723) cells/mm3, and 4.1 (3.5-4.7) log10 copies/ml, respectively. Conclusions A modest and consistent incidence of post-suppression VR was documented during adolescence in our cohort. Having poor weight, receiving second-line regimens, and prior VF were associated with an increased VR rate. Adolescents at higher risk of VR may benefit from more intensive VL monitoring to enhance adherence management.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Incidence of Postsuppression Virologic Rebound in Perinatally HIV-Infected Asian Adolescents on Stable Combination Antiretroviral Therapy

Sudjaritruk

Aurpibul

et al. 2017

Journal of Adolescent Health

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“…This observation of constant one-off rate of VF emphasizes the need of strengthening education and adherence counseling in HIV infected children at each contact, as almost 1 child in 5 was exposed to permanent VF in our centre. We are tempted to attribute our results to the routine practice of therapeutic education, anticipating that it may have helped achieving such low rate of VF in routine care settings [13] [17] [18]. Unfortunately in this report, we were limited to analyze the impact of therapeutic education on viral suppression, due to poor data collection of our process of adherence counseling, which was done at many points of care.…”

Section: Discussionmentioning

confidence: 99%

Viral Monitoring and Prevalence of Viral Failure in HIV-1 Infected Children under First Line Antiretroviral Therapy during the First 60 Months of Treatment in Yaoundé, Cameroon: A Serial Cross Sectional Analysis

Nlend¹,

Lyeb²,

Moyo³

et al. 2016

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Objective: The objective was to measure the prevalence of viral failure (VF) in HIV-1-infected children on first-line antiretroviral therapy (ART) in routine practice. Methods: Serial cross sectional analysis of viral load (VL) in HIV-1 infected children on first-line ART for ≥24 weeks was done. VL was measured by Real-Time-Polymerase chain reaction (biocentrics). Samples were collected at 6, 12, 24, 36, 48, 60 months of treatment. Main measurement: Virological failure (VF) defined by a one-off VL > 1000 copies/ml. Results: 375 children aged ≤16 years on first-line-ART were included. Median age at ART start was 4.2 years and ≥50% have started ART ≤3 rd birthday. A total of 717 measurements of VL were collected. VF was rated between 18% and 26% from 6-60 months (mean 20.2%), 95% IC [13.1-27.3] at the threshold of 1000 copies/ml, not too different at the threshold of 400 copies/ml, 21%-30% (mean 23.9%), 95% IC [16.3-31.5], p = 0.9. Conclusion: In Yaounde, almost 20% of children on first-line of adherent-ART can experiment VF while improving immune status urging improvement of adherence.

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“…Responses to first‐line ART among children have been evaluated in large randomized trials and observational studies [4‐12]. Studies evaluating outcomes on second‐line ART in children; however, have been limited by small sample sizes in both resource‐rich and resource‐limited settings [6,13‐21]. Of the four published studies on second‐line ART with larger sample sizes, ranging from 111 to 277 children, three were conducted in Thailand or the Asia‐Pacific region [18‐20], and one followed Ugandan children who were switched to a lopinavir/ritonavir (LPV/r)‐based second‐line regimen [21].…”

Section: Introductionmentioning

confidence: 99%

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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Outcomes after viral load rebound on first-line antiretroviral treatment in children with HIV in the UK and Ireland: an observational cohort study

Cited by 14 publications

References 29 publications

Incidence of Postsuppression Virologic Rebound in Perinatally HIV-Infected Asian Adolescents on Stable Combination Antiretroviral Therapy

Incidence of Postsuppression Virologic Rebound in Perinatally HIV-Infected Asian Adolescents on Stable Combination Antiretroviral Therapy

Viral Monitoring and Prevalence of Viral Failure in HIV-1 Infected Children under First Line Antiretroviral Therapy during the First 60 Months of Treatment in Yaoundé, Cameroon: A Serial Cross Sectional Analysis

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

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Outcomes after viral load rebound on first-line antiretroviral treatment in children with HIV in the UK and Ireland: an observational cohort study

Cited by 14 publications

References 29 publications

Incidence of Postsuppression Virologic Rebound in Perinatally HIV-Infected Asian Adolescents on Stable Combination Antiretroviral Therapy

Incidence of Postsuppression Virologic Rebound in Perinatally HIV-Infected Asian Adolescents on Stable Combination Antiretroviral Therapy

Viral Monitoring and Prevalence of Viral Failure in HIV-1 Infected Children under First Line Antiretroviral Therapy during the First 60 Months of Treatment in Yaound&#233;, Cameroon: A Serial Cross Sectional Analysis

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

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Viral Monitoring and Prevalence of Viral Failure in HIV-1 Infected Children under First Line Antiretroviral Therapy during the First 60 Months of Treatment in Yaoundé, Cameroon: A Serial Cross Sectional Analysis