Treatment Failure in HIV-Infected Children on Second-line Protease Inhibitor–Based Antiretroviral Therapy

Suaysod, Rapeepan; Ngo‐Giang‐Huong, Nicole; Salvadori, Nicolas; Cressey, Tim R.; Kanjanavanit, Suparat; Techakunakorn, Pornchai; Krikajornkitti, Sawitree; Srirojana, Sakulrat; Laomanit, Laddawan; Chalermpantmetagul, Suwalai; Lallemant, Marc; Cœur, Sophie Le; McIntosh, Kenneth; Traisathit, Patrinee; Jourdain, Gonzague

doi:10.1093/cid/civ271

Cited by 24 publications

(31 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our results show a clear trend of increasing rates of detectable VL as the cohort ages. This is in keeping with findings from other studies that show older adolescents to be at higher risk of detectable VL . Detectable VL was not sustained throughout the follow‐up period in a majority of adolescents, and showed a dynamic pattern of adherence and virological outcomes.…”

Section: Resultssupporting

confidence: 90%

Patterns of detectable viral load in a cohort of HIV‐positive adolescents on antiretroviral therapy in South Africa

2020

View full text Add to dashboard Cite

Introduction Despite improved treatment and access to care, adolescent AIDS deaths are decreasing more slowly than in any other age group. There is lack of longitudinal data around adolescent adherence and the dynamics of viraemia over time. We aimed to describe patterns of detectable viral load (VL) in a cohort of adolescents attending an ARV clinic in Cape Town, South Africa. Methods We conducted a retrospective cohort study of all patients on antiretroviral therapy aged 10 to 19 years. Participants were included if they underwent at least two VL measurements and remained in care at the Groote Schuur Hospital HIV Clinic for at least 24 months between 2002 and 2016. The primary outcome was two consecutive HIV VL >100 copies/mL, in line with the lower limit of detection of assays in use over the follow‐up period. Results and discussion Of the 482 screened participants, 327 met inclusion criteria. Most participants had perinatally acquired HIV (n = 314; 96%), and 170 (52%) were males. Overall, there were 203 episodes of confirmed detectable VL involving 159 (49% (95% CI 43% to 54%)) participants during the follow‐up period. Six participants had genotyped resistance to protease inhibitors. Four of these never suppressed, while two suppressed on salvage regimens. Total follow‐up time was 1723 person years (PY), of which 880 (51%) were contributed by the 159 participants who experienced detectable VL. Overall time with detectable VL was 370 PY. This comprised 22% of total follow‐up time, and 42% of the follow‐up time contributed by those who experienced detectable VL. The rate of detectable VL was 11.8 (95% CI 10.3 to 13.5) episodes per 100 PY. The risk increased by 24% for each year of increasing age (Relative Risk 1.24 (95% CI 1.17 to 1.31); p < 0.0001). There was no sex difference with respect to duration (p = 0.4), prevalence (p = 0.46) and rate (p = 0.608) of detectable VL. Conclusions Clinicians need to be alert to the high prevalence of detectable VL during adolescence so as to pre‐empt it and act swiftly once it is diagnosed. This study helps to highlight the risk of detectable VL that is associated with increase in age as well the high proportion of time that poorly adherent adolescents spend in this state.

show abstract

Section: Resultssupporting

confidence: 90%

Patterns of detectable viral load in a cohort of HIV‐positive adolescents on antiretroviral therapy in South Africa

2020

View full text Add to dashboard Cite

show abstract

“…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%

“…To our knowledge, only two published cohort studies in Asia described HIVDR patterns in a cohort of children on second-line ART. These reported relatively low rates of PI resistance of 11.3% and 8.0% in children failing second line [18,32]. In a cohort of 64 children on second line in Uganda, no PI mutations were detected after failure [42].…”

Section: Discussionmentioning

confidence: 99%

“…In order to ensure adequate long-term treatment for children and adolescents, evaluation of current secondline treatment outcomes is essential. Data, however, are scarce [15], and the available studies have small sample sizes, use different definitions of virologic failure and have different follow-up periods [16][17][18][19]. Therefore, it is hard to compare results across different cohorts.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

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.

show abstract

“…The increasing failure rate of second-line boosted PI regimens over time raises questions about the need for more aggressive treatment monitoring. Known risk factors for ART failure include high baseline viral load, low baseline CD4 cell count, inadequate drug concentrations, and non-adherence [4,5]. There is no single standard method to measure treatment adherence.…”

Section: Introductionmentioning

confidence: 99%

Therapeutic Drug Monitoring of Lopinavir in HIV-Infected Children on Second-Line Antiretroviral Therapy in Asia

Aurpibul

Teerananchai

Prasitsuebsai

et al. 2016

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

Background Failure rates of second-line boosted protease inhibitor antiretroviral therapy regimens in children rise over time. Therapeutic drug monitoring (TDM) can contribute to assessments of adherence. The authors assessed the performance characteristics of the US DHHS-recommended lopinavir (LPV) concentration of 1.0 mg/L for predicting virologic failure (VF) and intermediate-to-high level LPV resistance in Asian children. Materials and Methods LPV concentration, HIV RNA level, and adherence data from study participants in Indonesia, Thailand, and Vietnam receiving second-line LPV-based ART and followed for ≥24 weeks were analyzed. Results A total of 223 children at a median age of 10.4 (interquartile range, IQR 7.9–13.4) years were enrolled, 61% were male. Their mean CD4 was 842±438 cells/mm3, and the median LPV duration was 2.5 (IQR 1.3–4.2) years. Five out of 84 (6%) and 18 out of 139 (13%) children had LPV trough and random concentrations <1.0 mg/L at study week 24. Using either of these trough or random LPV concentrations, a cutoff at 1.0 mg/L gave an area under the receiver operating characteristics (AROC) curve of 0.69 in predicting VF with sensitivity of 44% (95% CI 23–66) and specificity of 94% (95% CI 89–97). Seven of 21 with VF and resistance results available had ≥1 major protease inhibitor mutation. Multivariate logistic regression found LPV concentrations <1.0 mg/L (OR 6.47; 95% CI 2.15–19.50, P = 0.001) and CD4 ≤20% (OR 2.83; 95% CI 1.01–7.89, P = 0.05) were independently associated with HIV RNA >1000 copies/mL. No factors predicted major LPV resistance mutations. Conclusions The authors support that the DHHS target LPV concentration of <1.0 mg/L is predictive of virologic failure (VF), but not of the presence of major LPV mutations.

show abstract

Treatment Failure in HIV-Infected Children on Second-line Protease Inhibitor–Based Antiretroviral Therapy

Abstract: Children with longer exposure to first-line ART, entry to adolescence, underweight, and/or undetectable drug levels were at higher risk of failing second-line ART and thus should be closely monitored.

Cited by 24 publications

References 18 publications

Patterns of detectable viral load in a cohort of HIV‐positive adolescents on antiretroviral therapy in South Africa

Patterns of detectable viral load in a cohort of HIV‐positive adolescents on antiretroviral therapy in South Africa

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

Therapeutic Drug Monitoring of Lopinavir in HIV-Infected Children on Second-Line Antiretroviral Therapy in Asia

Contact Info

Product

Resources

About