Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand

Collins, Intira Jeannie; Ene, Luminiţa; Foster, Caroline; Kahlert, Christian R.; Smit, Colette; Goodall, Ruth; Marquès, Laura; Judd, Ali; Gibb, Diana; Noguera-Julián, Antoni; Guillén, Sara; Conejo, Pablo Rojo; Warszawski, Josiane; Koenigs, Chris; Spoulou, Vana; Prata, Filipa; Goetghebuer, Tessa; Martino, Maurizio de; Gabiano, Clara; Navér, Lars; Giaquinto, Carlo; Thorne, Claire; Marczyńska, Magdalena; Okhonskaia, Liubov; Jourdain, Gonzague; Lertpienthum, Narong; Puangsombat, Achara; Bailey, Heather; Malyuta, Ruslan; Volokha, Alla; Rădoi, Roxana

doi:10.1093/cid/cix854

Cited by 13 publications

(12 citation statements)

References 33 publications

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“…Data from the EPPICC Paediatric merger 2014 ( n = 3953) were used, as described previously [23,24]. In brief, the EPPICC merged individual patient data on routine demographic, clinical, laboratory and treatment-related variables from 19 observational cohorts across 17 countries prepared according to a standardised data specification.…”

Section: Methodsmentioning

confidence: 99%

“…We evaluated the following factors: age at cART initiation, baseline viral load, CD4 + % and cell count, sex, ethnicity, initial cART regimen (bPI or NNRTI and two or more NRTI), infant antiretroviral prevention of mother-to-child transmission (PMTCT) prophylaxis regimen given within 4 weeks of birth, maternal antiretroviral PMTCT regimen used in the prenatal and delivery period, birth abroad (whether infants were born in the same country in which they were enrolled for HIV care), year of birth, year of cART initiation, Centers for Disease Control and Prevention (CDC) C event by cART initiation and geographical region. Geographical region of cohort was categorised a priori , as described previously [24]: Eastern Europe (Russia and Ukraine), Central and Western Europe (Belgium, Germany, Italy, Netherlands, Poland, Portugal, Romania, Spain, Sweden, Switzerland, France and Greece), United Kingdom/Ireland and Thailand. Missing values for baseline viral load (18%) and CD4 + % (22%) were multiply imputed by chained equations (20 cycles), on the complete EPPICC dataset to avoid imputation bias.…”

Section: Methodsmentioning

confidence: 99%

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Predictors of faster virological suppression in early treated infants with perinatal HIV from Europe and Thailand

2019

Aids

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Predictors of faster virological suppression in early treated infants with perinatal HIV from Europe and Thailand

2019

Aids

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“…Ninety percent of switches to second‐line ART in our study had confirmed VF, with a median time to switch of 1.5 years. Our finding indicates a lower cumulative incidence of switching to second‐line ART after 3 years of rapid ART initiation (5.3%) compared to an individual patient data meta‐analysis study from Thailand (8%) and Europe (14–16%) before the era of treating at any CD4 levels [ 39 ]. Moreover, the proportion with confirmed VF with switching to second‐line ART in our study was also higher than adults living with HIV where rates ranged from 43% to 66% in studies from Eswatini, Uganda and Lesotho [ 40 , 41 , 42 ].…”

Section: Discussionmentioning

confidence: 86%

Long‐term outcomes of rapid antiretroviral NNRTI‐based initiation among Thai youth living with HIV: a national registry database study

et al. 2023

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Introduction The Thai National AIDS programme (NAP) treatment guidelines have recommended rapid antiretroviral therapy (ART) initiation, regardless of CD4 count since 2014. We assessed treatment outcomes among youth living with HIV (YLHIV), initiating first‐line ART and assessed the association between virological failure (VF) and timing of ART initiation. Methods We retrospectively reviewed data for YLHIV aged 15–24 years, initiating non‐nucleoside reverse transcriptase inhibitor‐based ART from 2014 to 2019, through the NAP database. We classified the timing of ART into three groups based on duration from HIV‐positive diagnosis or system registration to ART initiation: (1) <1 month (rapid ART); (2) 1–3 months (intermediate ART); and (3) >3 months (delayed ART). VF was defined as viral load (VL) ≥ 1000 copies/ml after at least 6 months of first‐line ART. Factors associated with VF were analysed using generalized estimating equations. Results Of 19,825 YLHIV who started ART, 78% were male. Median (interquartile range, IQR) age was 21 (20–23) years and CD4 count was 338 (187–498) cells/mm3. After registration, 12,216 (62%) started rapid ART, 4272 (22%) intermediate ART and 3337 (17%) delayed ART. The proportion of YLHIV starting ART <30 days significantly increased from 43% to 57% from 2014–2016 to 2017–2019 (p < 0.001). The median duration of first‐line therapy was 2 (IQR 1–3) years and 89% started with efavirenz‐based regimens. Attrition outcomes showed that 325 (2%) died (0.73 [95% CI 0.65–0.81] per 100 person‐years [PY]) and 1762 (9%) were loss to follow‐up (3.96 [95% CI 3.78–4.15] per 100 PY). Of 17,512 (88%) who had VL checked from 6 to 12 months after starting treatment, 80% achieved VL <200 copies/ml. Overall, 2512 experienced VF 5.87 (95% CI 5.65–6.11) per 100 PY). In a multivariate model, the adjusted incidence rate ratio for VF was 1.47 (95% CI 1.33–1.63, p < 0.001) in the delayed ART group and 1.14 (95% CI 1.03–1.25, p< 0.001) in the intermediate ART group, compared to YLHIV in the rapid ART group. Conclusions Rapid ART initiation after diagnosis was associated with significantly reduced risks of VF and death in YLHIV, supporting the implementation of rapid ART for optimizing health outcomes.

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“…Second-and third-line antiretroviral treatments (ART) are needed for children and adolescents living with HIV who experience treatment failure and have limited ART options, due to multidrug resistance or drug intolerance [1][2][3]. Etravirine is a second-generation non-nucleoside reversetranscriptase inhibitor (NNRTI) approved for use as part of second or third-line ART in children and adolescents aged ≥6 years [4].…”

Section: Introductionmentioning

confidence: 99%

Outcomes of etravirine-based antiretroviral treatment in treatment-experienced children and adolescents living with HIV in Europe and Thailand

Collabor¹,

Lyons

Thompson

et al. 2022

Antiviral Therapy

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Background Etravirine (ETR) is approved as a component of second or third-line antiretroviral treatment (ART) for children living with HIV. We assessed the outcomes of ETR-based ART in children in routine care in Europe and Thailand. Methods Data on children aged <18 years at ETR start were pooled from 17 observational cohorts. Characteristics at ETR start, immunological and virological outcomes at 12 months, discontinuations, adverse events (AEs) and serious adverse events (SAEs) were described. Follow-up was censored at ETR discontinuation, death or last visit. Results 177 children ever received ETR. At ETR start, median [IQR] age was 15 [12,16] years, CD4 count 480 [287, 713] cells/mm3, 70% had exposure to ≥3 ART classes and 20% had viral load (VL) <50 copies/mL. 95% received ETR in combination with ≥1 potent drug class, mostly protease inhibitor-based regimens. Median time on ETR was 24 [7, 48] months. Amongst those on ETR at 12 months ( n=141), 69% had VL<50 copies/mL. Median CD4 increase since ETR start ( n=83) was 147 [16, 267] cells/mm3. Overall, 81 (46%) discontinued ETR by last follow-up. Median time to discontinuation was 23 [8, 47] months. Common reasons for discontinuation were treatment simplification (19%), treatment failure (16%) and toxicity (12%). Eight children (5%) had AEs causally associated with ETR, all dermatological/hypersensitivity reactions. Two were SAEs, both Stevens–Johnson Syndrome in children on regimens containing ETR and darunavir and were causally related to either drugs; both resolved following ART discontinuation. Conclusion Children receiving ETR were predominantly highly treatment-experienced, over two-thirds were virally suppressed at 12 months.

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Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand

Abstract: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch.

Cited by 13 publications

References 33 publications

Predictors of faster virological suppression in early treated infants with perinatal HIV from Europe and Thailand

Predictors of faster virological suppression in early treated infants with perinatal HIV from Europe and Thailand

Long‐term outcomes of rapid antiretroviral NNRTI‐based initiation among Thai youth living with HIV: a national registry database study

Outcomes of etravirine-based antiretroviral treatment in treatment-experienced children and adolescents living with HIV in Europe and Thailand

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