Second- and Third-line Antiretroviral Therapy for Children and Adolescents

Lazarus, Erica; Nicol, Simone; Frigati, Lisa; Penazzato, Martina; Cotton, Mark F.; Centeno‐Tablante, Elizabeth; Violari, Avy; Nicol, Liesl

doi:10.1097/inf.0000000000001481

Cited by 8 publications

(5 citation statements)

References 41 publications

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“…These results signify the amount of ART exposure across multiple drug classes, either due to treatment failure or ART intolerances, thereby narrowing future therapeutic options throughout adulthood, and highlights the need for better access to newer antiretroviral agents in resource limited settings. 28 Given the move towards commencing cART on all children with PHIV as early as possible and the complexities in choosing subsequent cART regimens, 29 these figures, in conjunction with the association of receiving ≥2 nd cART and PHIVA mortality, highlights the importance of continuing evaluations on the durability and tolerability of 1 st -line cART options.…”

Section: Discussionmentioning

confidence: 99%

Characteristics, mortality and outcomes at transition for adolescents with perinatal HIV infection in Asia

Bartlett¹,

Truong

Songtaweesin

et al. 2018

Aids

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Section: Discussionmentioning

confidence: 99%

Characteristics, mortality and outcomes at transition for adolescents with perinatal HIV infection in Asia

Bartlett¹,

Truong

Songtaweesin

et al. 2018

Aids

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“…Similarly, a recent systematic review showed that after undergoing enhanced adherence counselling upon detection of viremia, subsequent resuppression was achieved by a little over half (50.4%) of adults, but only 31.2 and 40.4% of children and adolescents, respectively [ 33 ]. Even among children whose ART regimen is switched to second-line, resuppression rates remain low [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Genotype-Informed Versus Empiric Management Of VirEmia (GIVE MOVE): study protocol of an open-label randomised clinical trial in children and adolescents living with HIV in Lesotho and Tanzania

Brown

Ringera²,

Luoga

et al. 2020

BMC Infect Dis

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Background Globally, the majority of people living with HIV have no or only limited access to HIV drug resistance testing to guide the selection of antiretroviral drugs. This is of particular concern for children and adolescents, who experience high rates of treatment failure. The GIVE MOVE trial assesses the clinical impact and cost-effectiveness of routinely providing genotypic resistance testing (GRT) to children and adolescents living with HIV who have an unsuppressed viral load (VL) while taking antiretroviral therapy (ART). Methods GIVE MOVE is an open-label randomised clinical trial enrolling children and adolescents (≥6 months to <19 years) living with HIV with a VL ≥400 copies/mL (c/mL) while taking first-line ART. Recruitment takes place at sites in Lesotho and Tanzania. Participants are randomised in a 1:1 allocation to a control arm receiving the standard of care (3 sessions of enhanced adherence counselling, a follow-up VL test, continuation of the same regimen upon viral resuppression or empiric selection of a new regimen upon sustained elevated viremia) and an intervention arm (GRT to inform onward treatment). The composite primary endpoint is the occurrence of any one or more of the following events during the 36 weeks of follow-up period: i) death due to any cause; ii) HIV- or ART-related hospital admission of ≥24 h duration; iii) new clinical World Health Organisation stage 4 event (excluding lymph node tuberculosis, stunting, oral or genital herpes simplex infection and oesophageal candidiasis); and iv) no documented VL <50 c/mL at 36 weeks follow-up. Secondary and exploratory endpoints assess additional health-related outcomes, and a nested study will assess the cost-effectiveness of the intervention. Enrolment of a total of 276 participants is planned, with an interim analysis scheduled after the first 138 participants have completed follow-up. Discussion This randomised clinical trial will assess if the availability of resistance testing improves clinical outcomes in children and adolescents with elevated viremia while taking ART. Trial registration This trial is registered with ClinicalTrials.gov (NCT04233242; registered 18.01.2020). More information: www.givemove.org.

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“…There is an urgent need for evidence to inform the optimal management of children with virological failure, as well as to inform second- and third-line options for children in resource-limited settings. [ 26 ] As new antiretrovirals such as the integrase inhibitors dolutegravir and raltegravir become more widely accessible, giving children more treatment options, the use if LM as an initial strategy to manage virologic failure in children should be reconsidered. Our findings that adolescents were less likely to achieve virologic suppression on resumption of cART, highlights the challenge of managing treatment failure and maintaining life-long adherence in this vulnerable population.…”

Section: Discussionmentioning

confidence: 99%

Lamivudine monotherapy as a holding regimen for HIV-positive children

et al. 2018

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BackgroundIn resource-limited settings holding regimens, such as lamivudine monotherapy (LM), are used to manage HIV-positive children failing combination antiretroviral therapy (cART) to mitigate the risk of drug resistance developing, whilst adherence barriers are addressed or when access to second- or third-line regimens is restricted. We aimed to investigate characteristics of children placed on LM and their outcomes.MethodsWe describe the characteristics of children (age <16 years at cART start) from 5 IeDEA-SA cohorts with a record of LM during their treatment history. Among those on LM for >90 days we describe their immunologic outcomes on LM and their immunologic and virologic outcomes after resuming cART.FindingsWe included 228 children in our study. At LM start their median age was 12.0 years (IQR 7.3–14.6), duration on cART was 3.6 years (IQR 2.0–5.9) and median CD4 count was 605.5 cells/μL (IQR 427–901). Whilst 110 (48%) had no prior protease inhibitor (PI)-exposure, of the 69 with recorded PI-exposure, 9 (13%) patients had documented resistance to all PIs. After 6 months on LM, 70% (94/135) experienced a drop in CD4, with a predicted average CD4 decline of 46.5 cells/μL (95% CI 37.7–55.4). Whilst on LM, 46% experienced a drop in CD4 to <500 cells/μL, 18 (8%) experienced WHO stage 3 or 4 events, and 3 children died. On resumption of cART the average gain in CD4 was 15.65 cells/uL per month and 66.6% (95% CI 59.3–73.7) achieved viral suppression (viral load <1000) at 6 months after resuming cART.InterpretationMost patients experienced immune decline on LM. Its use should be avoided in those with low CD4 counts, but restricted use may be necessary when treatment options are limited. Managing children with virologic failure will continue to be challenging until more treatment options and better adherence strategies are available.

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Second- and Third-line Antiretroviral Therapy for Children and Adolescents

Cited by 8 publications

References 41 publications

Characteristics, mortality and outcomes at transition for adolescents with perinatal HIV infection in Asia

Characteristics, mortality and outcomes at transition for adolescents with perinatal HIV infection in Asia

Genotype-Informed Versus Empiric Management Of VirEmia (GIVE MOVE): study protocol of an open-label randomised clinical trial in children and adolescents living with HIV in Lesotho and Tanzania

Lamivudine monotherapy as a holding regimen for HIV-positive children

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