CD4 Cell Response Before and After HAART Initiation According to Viral Load and Growth Indicators in HIV-1-Infected Children in Abidjan, Côte d'Ivoire

Beaudrap, Pierre De; Raffi, François; Franco, Patricia; Kouakoussui, A.; Mercier, Sabine; Écochard, René; Msellati, Philippe

doi:10.1097/qai.0b013e3181831847

Cited by 21 publications

(23 citation statements)

References 39 publications

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“…[17][18][19][20]24,27,28 Some longitudinal studies have quantified long-term CD4 trajectories on HAART based on pretreatment CD4 and age, allowing predictions that are child-specific. 24,29 However, projected immunologic impacts at population levels have not been established.…”

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confidence: 99%

Using CD4 Percentage and Age to Optimize Pediatric Antiretroviral Therapy Initiation

Yin

Warshaw

Miller³

et al. 2014

Pediatrics

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WHAT'S KNOWN ON THIS SUBJECT:In HIV-infected children, decisions to start antiretroviral therapy must weigh immunologic benefits against potential risks. Current guidelines recommend using CD4 percentage and age when deciding to start treatment. Population-level effects of these factors on immunologic recovery are unknown. WHAT THIS STUDY ADDS:Starting antiretroviral therapy at higher CD4 percentages and younger ages maximizes potential for immunologic recovery. However, not all benefits are sustained, and viral failure may occur. Our results help clinicians better weigh immunologic benefits against viral failure risks. abstract BACKGROUND: Quantifying pediatric immunologic recovery by highly active antiretroviral therapy (HAART) initiation at different CD4 percentage (CD4%) and age thresholds may inform decisions about timing of treatment initiation.METHODS: HIV-1-infected, HAART-naive children in Europe and the Americas were followed from 2002 through 2009 in PENPACT-1. Data from 162 vertically infected children, with at least World Health Organization "mild" immunosuppression and CD4% ,10th percentile, were analyzed for improvement to a normal CD4% ($10th percentile) within 4 years after HAART initiation. Data from 209 vertically infected children, regardless of immune status, were analyzed for CD4% outcomes at 4 years and viral failure within 4 years.RESULTS: Seventy-two percent of baseline immunosuppressed children recovered to normal within 4 years. Compared with "severe" immunosuppression, more children with "mild" immunosuppression (difference 36%, 95% confidence interval [CI]: 22% to 49%) or "advanced" immunosuppression (difference 20.8%, 95% CI: 5.8% to 35.9%) recovered a normal CD4%. For each 5-year increase in baseline age, the proportion of children achieving a normal CD4% declined by 19% (95% CI: 11% to 27%). Combining baseline CD4% and age effects resulted in .90% recovery when initiating HAART with "mild" immunosuppression at any age or "advanced" immunosuppression at age ,3 years. Baseline CD4% effects became greater with increasing age (P = .02). At 4 years, most immunologic benefits were still significant but diminished. Viral failure was highest in infancy (56%) and adolescence (63%).CONCLUSIONS: Initiating HAART at higher CD4% and younger ages maximizes potential for immunologic recovery. Guidelines should weigh immunologic benefits against long-term risks.

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confidence: 99%

Using CD4 Percentage and Age to Optimize Pediatric Antiretroviral Therapy Initiation

Yin

Warshaw

Miller³

et al. 2014

Pediatrics

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“…Surprisingly, patients included in the present study had comparable mean CD4 + % independently of age at HAART initiation. It was not the case in European and West African studies [14,23] who showed more severe immunosuppression when treatment was started later in life (-0.82% of mean CD4 + % per year of HAART initiation delay) [14]. This difference could be explained in our study by the exclusion of rapid progressors [24] who possibly died before 2 years (before HAART initiation) in the LSC.…”

Section: Discussionmentioning

confidence: 42%

“…Results were unconclusive. Four studies [25][26][27][28] concluded the absence of influence of age at baseline and five studies [14,23,[29][30][31] [16]. In our study, mean CD4 + % was normal in both cohorts.…”

Section: Discussionmentioning

confidence: 50%

“…Influence of age at baseline, independently of immunological status, was studied in European [23,[25][26][27][28][29] and a few African cohorts (1-8.7 years follow-up) [14,30]. Results were unconclusive.…”

Section: Discussionmentioning

confidence: 99%

“…Between 2005 and 2014, children treated with HAART increased from 71.500 to 824.000 [11] but long-term (>3 years) virological and immunological data collected in Sub-Saharan Africa are scarce [12][13][14][15][16]. Children are at risk to develop treatment failure due to inappropriate antiretroviral formulations, adherence difficulties, drug toxicity or development of resistance [17].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Virological and Immunological Long-Term Outcome of Human Immunodeficiency Virus-1 Infected Children Treated before One Year and after Two Years of Age in a Resource-Limited Setting of South Africa

J¹,

Ruelle²,

Goubau³

et al. 2017

J AIDS Clin Res

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Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology

Barker

Germovsek²,

Hoare³

et al. 2014

Advanced Drug Delivery Reviews

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Pharmacokinetic/pharmacodynamic (PKPD) modelling is used to describe and quantify dose–concentration–effect relationships. Within paediatric studies in infectious diseases and immunology these methods are often applied to developing guidance on appropriate dosing. In this paper, an introduction to the field of PKPD modelling is given, followed by a review of the PKPD studies that have been undertaken in paediatric infectious diseases and immunology. The main focus is on identifying the methodological approaches used to define the PKPD relationship in these studies. The major findings were that most studies of infectious diseases have developed a PK model and then used simulations to define a dose recommendation based on a pre-defined PD target, which may have been defined in adults or in vitro. For immunological studies much of the modelling has focused on either PK or PD, and since multiple drugs are usually used, delineating the relative contributions of each is challenging. The use of dynamical modelling of in vitro antibacterial studies, and paediatric HIV mechanistic PD models linked with the PK of all drugs, are emerging methods that should enhance PKPD-based recommendations in the future.

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CD4 Cell Response Before and After HAART Initiation According to Viral Load and Growth Indicators in HIV-1-Infected Children in Abidjan, Côte d'Ivoire

Abstract: Before HAART initiation, the CD4 cell percentage was associated with growth indicators whereas, after HAART, an early increase and a long-term plateau were negatively associated with the viral load and age at HAART initiation.

Cited by 21 publications

References 39 publications

Using CD4 Percentage and Age to Optimize Pediatric Antiretroviral Therapy Initiation

Using CD4 Percentage and Age to Optimize Pediatric Antiretroviral Therapy Initiation

Virological and Immunological Long-Term Outcome of Human Immunodeficiency Virus-1 Infected Children Treated before One Year and after Two Years of Age in a Resource-Limited Setting of South Africa

Pharmacokinetic/pharmacodynamic modelling approaches in paediatric infectious diseases and immunology

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