Modelling CD4 T Cell Recovery in Hepatitis C and HIV Co-infected Children Receiving Antiretroviral Therapy

Majekodunmi, Adedeji O.; Thorne, Claire; Malyuta, Ruslan; Volokha, Alla; Callard, Robin E.; Klein, Nigel; Lewis, Joanna

doi:10.1097/inf.0000000000001478

Cited by 8 publications

(3 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…CD4% response following restart of ART up to 24 months after the first TI was modelled using nonlinear asymptotic mixed effects models, with all CD4% measurements in this period included with the exception of those occurring after the start of a subsequent TI. Such models have previously been shown to describe CD4 response after ART initiation well .…”

Section: Methodsmentioning

confidence: 99%

CD4 recovery following antiretroviral treatment interruptions in children and adolescents with HIV infection in Europe and Thailand

Galli¹,

Crichton²,

Buzzoni³

et al. 2019

HIV Medicine

View full text Add to dashboard Cite

The aim of the study was to explore factors associated with CD4 percentage (CD4%) reconstitution following treatment interruptions (TIs) of antiretroviral therapy (ART). MethodsData from paediatric HIV-infected cohorts across 17 countries in Europe and Thailand were pooled. Children on combination ART (cART; at least three drugs from at least two classes) for > 6 months before TI of ≥ 30 days while aged < 18 years were included. CD4% at restart of ART (r-ART) and in the long term (up to 24 months after r-ART) following the first TI was modelled using asymptotic regression. ResultsIn 779 children with at least one TI, the median age at first TI was 10.1 [interquartile range (IQR) 6.4, 13.6] years and the mean CD4% was 27.3% [standard deviation (SD) 11.0%]; the median TI duration was 9.0 (IQR 3.5, 22.5) months. In regression analysis, the mean CD4% was 19.2% [95% confidence interval (CI) 18.3, 20.1%] at r-ART, and 27.1% (26.2, 27.9%) in the long term, with half this increase in the first 6 months. r-ART and long-term CD4% values were highest in female patients and in children aged < 3 years at the start of TI. Long-term CD4% was highest in those with a TI lasting 1 to <3 months, those with r-ART after year 2000 and those with a CD4% nadir ≥ 25% (all P < 0.001). The effect of CD4% nadir during the TI differed significantly (P = 0.038) by viral suppression at the start of the TI; in children with CD4% nadir < 15% during TI, recovery was better in those virally suppressed prior to the TI; viral suppression was not associated with recovery in children with CD4% nadir ≥ 25%. ConclusionsAfter restart of ART following TI, most children reconstituted well immunologically. Nevertheless, several factors predicted better immunological reconstitution, including younger age and higher nadir CD4% during TI.Parameters were estimated using multilevel asymptotic regression models. The intercept represents the CD4% at restart of ART, with b representing the difference in mean CD4% in patients with specific characteristics and the reference group. Similarly, the asymptote represents the longer term CD4% (up to 24 months after restart) and b represents longer term differences in mean CD4%. C is a rate parameter; negative values indicate a slower increase in CD4% and positive values indicate a faster increase. The intercept, asymptote and C constants represent the mean CD4% at restart and in the long term and the rate parameter for patients in the reference groups. Time to half the total CD4% recovery can be estimated as In(2)/c. CI, confidence interval; VL, viral load.

show abstract

Section: Methodsmentioning

confidence: 99%

CD4 recovery following antiretroviral treatment interruptions in children and adolescents with HIV infection in Europe and Thailand

Galli¹,

Crichton²,

Buzzoni³

et al. 2019

HIV Medicine

View full text Add to dashboard Cite

show abstract

“…Viral hepatitis is also associated with extrahepatic complications in PLHIV such as increased risk of non-Hodgkin lymphoma [ 19 ▪ ], kidney disease [ 20 , 21 ▪ ], osteoporosis and fractures [ 21 ▪ ], and more severe cognitive impairment [ 22 ]. Hepatitis virus co-infection also slows immunological recovery in pregnant women [ 23 ▪ ] and children [ 24 ▪ ] with HIV, and HCV contributes to an ongoing immune activation and immune dysfunction even in controlled HIV infection [ 25 ▪ , 26 , 27 ].…”

Section: Co-infections In Hivmentioning

confidence: 99%

When do co-infections matter?

McArdle¹,

Turkova

Cunnington

2018

Current Opinion in Infectious Diseases

View full text Add to dashboard Cite

Purpose of reviewAdvances in diagnostic methods mean that co-infections are increasingly being detected in clinical practice, yet their significance is not always obvious. In parallel, basic science studies are increasingly investigating interactions between pathogens to try to explain real-life observations and elucidate biological mechanisms.Recent findingsCo-infections may be insignificant, detrimental, or even beneficial, and these outcomes can occur through multiple levels of interactions which include modulation of the host response, altering the performance of diagnostic tests, and drug–drug interactions during treatment. The harmful effects of chronic co-infections such as tuberculosis or Hepatitis B and C in association with HIV are well established, and recent studies have focussed on strategies to mitigate these effects. However, consequences of many acute co-infections are much less certain, and recent conflicting findings simply highlight many of the challenges of studying naturally acquired infections in humans.SummaryTackling these challenges, using animal models, or careful prospective studies in humans may prove to be worthwhile. There are already tantalizing examples where identification and treatment of relevant co-infections seems to hold promise for improved health outcomes.

show abstract

“…We appreciate the interest shown by McPhee et al [1] in our recent article on modelling CD4 T cell recovery in HIV/HCV co-infected and HIV-mono-infected children on antiretroviral therapy [2], and the additional evidence from the Spanish Cohort of HIV Infected Children which they report. The higher CD4 counts in HIV/HCV co-infected children on antiretroviral therapy than in similar, HIV-mono-infected children is interesting, and perhaps not surprising given their superior HIV suppression.…”

mentioning

confidence: 99%