Human Immunodeficiency Virus (HIV) Drug Resistance in African Infants and Young Children Newly Diagnosed With HIV: A Multicountry Analysis

Jordan, Michael R.; Penazzato, Martina; Cournil, Amandine; Vubil, Adolfo; Jani, Ilesh; Hunt, Gillian; Carmona, Sergio; Maphalala, Gugu; Mthethwa, Nobuhle; Watera, Christine; Kaleebu, Pontiano; Musanhu, Christine Chakanyuka; Mtapuri-Zinyowera, Sekesai; Dzangare, Janet; Peeters, Martine; Yang, Chunfu; Parkin, Neil; Bertagnolio, Silvia

doi:10.1093/cid/cix698

Cited by 42 publications

(26 citation statements)

References 15 publications

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“…While the incidence of VS <1000 copies/mL was similar for children one to five years and six to twelve years (85% and 84% at 12 months), for VS <50 copies/mL there were more pronounced differences with only 68% of one to five year olds achieving this outcome compared to 77% of older children. High rates of pretreatment HIV drug resistance, particularly nucleoside reverse transcriptase inhibitors and non‐nucleoside reverse transcriptase inhibitors mutations, have been found in HIV‐infected infants and children and can impact ART efficacy; however, it is unlikely to explain the differences observed by age in our study, as the youngest children, who had the lowest rates of suppression, received PI‐based regimens .…”

Section: Discussionmentioning

confidence: 72%

HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape, South Africa

et al. 2018

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IntroductionThere are limited data on viral suppression (VS) in children with HIV receiving antiretroviral therapy (ART) in routine care in low‐resource settings. We examined VS in a cohort of children initiating ART in routine HIV care in Eastern Cape Province, South Africa.MethodsThe Pediatric Enhanced Surveillance Study enrolled HIV‐infected ART eligibility children zero to twelve years at five health facilities from 2012 to 2014. All children received routine HIV care and treatment services and attended quarterly study visits for up to 24 months. Time to VS among those starting treatment was measured from ART start date to first viral load (VL) result <1000 and VL <50 copies/mL using competing risk estimators (death as competing risk). Multivariable sub‐distributional hazards models examined characteristics associated with VS and VL rebound following suppression among those with a VL >30 days after the VS date.ResultsOf 397 children enrolled, 349 (87.9%) started ART: 118 (33.8%) children age <12 months, 122 (35.0%) one to five years and 109 (31.2%) six to twelve years. At study enrolment, median weight‐for‐age z‐score (WAZ) was −1.7 (interquartile range (IQR):−3.1 to −0.4) and median log VL was 5.6 (IQR: 5.0 to 6.2). Cumulative incidence of VS <1000 copies/mL at six, twelve and twenty‐four months was 57.6% (95% CI 52.1 to 62.7), 78.7% (95% CI 73.7 to 82.9) and 84.0% (95% CI 78.9 to 87.9); for VS <50 copies/mL: 40.3% (95% CI 35.0 to 45.5), 63.9% (95% CI 58.2 to 69.0) and 72.9% (95% CI 66.9 to 78.0). At 12 months only 46.6% (95% CI 36.6 to 56.0) of children <12 months had achieved VS <50 copies/mL compared to 76.9% (95% CI 67.9 to 83.7) of children six to twelve years (p < 0.001). In multivariable models, children with VL >1 million copies/mL at ART initiation were half as likely to achieve VS <50 copies/mL (adjusted sub‐distributional hazards 0.50; 95% CI 0.36 to 0.71). Among children achieving VS <50 copies/mL, 37 (19.7%) had VL 50 to 1000 copies/mL and 31 (16.5%) had a VL >1000 copies/mL. Children <12 months had twofold increased risk of VL rebound to VL >1000 copies/mL (adjusted relative risk 2.03, 95% CI: 1.10 to 3.74) compared with six to twelve year olds.ConclusionsWe found suboptimal VS among South African children initiating treatment and high proportions experiencing VL rebound, particularly among younger children. Greater efforts are needed to ensure that all children achieve optimal outcomes.

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Section: Discussionmentioning

confidence: 72%

HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape, South Africa

et al. 2018

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“…They are superior and more effective than the non-nucleoside reverse transcriptase inhibitors (NNRTIs) such as nevirapine (NVP) and efavirenz (EFV) [11]. There is also comparatively high resistance to NNRTIs, particularly in children whose mothers received NNRTIs to prevent mother to child transmission, which further limits the use of this drug class as first line [22]. Table 2 illustrates the WHO recommended first line paediatric ART regimens for neonates and children.…”

Section: Antiretroviral Therapy Challenges In Children and Adolescentsmentioning

confidence: 99%

Immune Dysfunction and Antiretroviral Therapy Challenges in Children and Adolescents Living with Human Immunodeficiency Virus

Said¹,

Bartlett²

2021

Innate Immunity in Health and Disease

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Human immunodeficiency virus (HIV) infection results in progressive decline in immune function ultimately leading to acquired immunodeficiency syndrome (AIDS) characterised by increased susceptibility to opportunistic infections and malignancies. In addition, it causes immune dysfunction, which manifests as a persistent inflammatory state due to dysregulation of cytokine production. Antiretroviral therapy (ART) not only improves immune function but also mitigates systemic immune activation associated with disease progression. Early initiation of ART in children living with HIV has led to a growing cohort surviving into adolescence and beyond. As such, they will experience lifelong exposure to an array of physiologic processes associated with systemic infection, immune dysfunction and antiretroviral medications. This leaves them not only susceptible to a range of morbidities associated with chronic inflammation, immune dysregulation, and drug toxicity but also vulnerable to treatment fatigue leading to issues with treatment adherence and engagement in care. Children experience additional barriers to maintaining suppressive ART due to limited paediatric-friendly formulations that are palatable and contribute to regimen complexity. Tolerability and durability of long-term ART are integral in optimising outcomes for children and adolescents living with HIV and maximising viability of future ART regimens throughout adulthood.

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“…Protease inhibitor (PI) ART should ideally be initiated if there is a history of non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure, but this can be challenging to access. This study2 in Africa aimed to assess the prevalence of drug resistance in children <18 months in five countries (Mozambique, Swaziland, Zimbabwe, Uganda and South Africa). A random sample or remnant dried blood spot collected as part of routine early infant diagnosis (EID) testing was used; number of specimens contributed per laboratory was proportional to the number of EID specimens tested or percentage of HIV-positive infants diagnosed per laboratory in the previous year.…”

Section: Hiv and Drug Resistance In African Children Newly Diagnosedmentioning

confidence: 99%

Clinical round-up

Chung¹,

Herbert²

2019

Sex Transm Infect

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Human Immunodeficiency Virus (HIV) Drug Resistance in African Infants and Young Children Newly Diagnosed With HIV: A Multicountry Analysis

Cited by 42 publications

References 15 publications

HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape, South Africa

HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape, South Africa

Immune Dysfunction and Antiretroviral Therapy Challenges in Children and Adolescents Living with Human Immunodeficiency Virus

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