Browsing by Author "Dobbels, Els"
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- ItemEarly antiretroviral therapy improves neurodevelopmental outcomes in infants(LIPPINCOTT WILLIAMS & WILKINS, 530 WALNUT ST, PHILADELPHIA, USA, PA,19106-3621, 2012) Laughton B; Cornell M; Grove D; Kidd M; Springer P; Dobbels, Els; Van Rensburg AJ; Violari A; Babiker AG; Madhi SA; Jean-Philippe P; Gibb DM; Cotton MF
- ItemEarly antiretroviral therapy reduces the incidence of otorrhea in a randomized study of early and deferred antiretroviral therapy : evidence from the Children with HIV Early antiretroviral therapy (CHER) Study.(2011-10) Hainline, Clotilde; Taliep, Reghana; Sorour, Gill; Nachman, Sharon; Rabie, Helena; Dobbels, Els; Janse van Rensburg, Anita; Cornell, Morna; Violari, Avy; Madhi, Shabir A.; Cotton, Mark F.Abstract Background Although otorrhea occurs commonly in HIV-infected infants, there are few data. We compared the incidence of otorrhea in infants receiving early vs deferred ART in the Children with HIV Early Antiretroviral (CHER) trial. Infants aged 6 to 12 weeks of age with confirmed HIV infection and a CD4 percentage greater than or equal to 25% were randomized to early or deferred ART at two sites in South Africa. Medical records from one study site were reviewed for otorrhea. Findings Data were reviewed from the start of the trial in July 2005 until 20 June 2007, when the Data Safety Monitoring Board recommended that randomization to the deferred arm should stop and that all infants in this arm be reviewed for commencing antiretroviral therapy. Infants entered the study at a median of 7.4 weeks of age. Eleven of 38 (29%) on deferred therapy and 7 of 75 (9%) in the early-therapy group developed otorrhea (risk ratio 3.1, 95% confidence interval (CI) 1.31-7.36; p = 0.01). Conclusions Early initiation of antiretroviral therapy is associated with significantly less otorrhea than when a deferred strategy is followed. Trial registration NCT00102960. ClinicalTrials.Gov
- ItemEarly antiretroviral treatment reduces risk of bacille Calmette- Guérin immune reconstitution adenitis(2011) Rabie H.; Violari A.; Duong T.; Madhi S.A.; Josipovic D.; Innes S.; Dobbels, Els; Lazarus E.; Panchia R.; Babiker A.G.; Gibb D.M.; Cotton M.F.SETTING: Two centres in Soweto and Cape Town, South Africa. OBJECTIVE: To assess the effects of timing of initiation of antiretroviral treatment (ART) and other factors on the risk of bacille Calmette-Guérin (BCG) related regional adenitis due to immune reconstitution infl ammatory syndrome (BCG-IRIS) in human immunodefi ciency virus (HIV) infected infants. DESIGN: HIV-infected infants aged 6-12 weeks with CD4 count ≥25% enrolled in the Children with HIV Early Antiretroviral Therapy (CHER) Trial received early (before 12 weeks) or deferred (after immunological or clinical progression) ART; infants with CD4 count <25% all received early ART. All received BCG vaccination after birth. Reactogenicity to BCG was assessed prospectively during routine study follow-up. RESULTS: Of 369 infants, 32 (8.7%) developed BCGIRIS within 6 months of starting ART, 28 (88%) within 2 months after ART initiation. Of the 32 cases, 30 (93.8%) had HIV-1 RNA > 750 000 copies/ml at initiation. Incidence of BCG-IRIS was 10.9 and 54.3 per 100 personyears (py) among infants with CD4 count ≥25% at enrolment receiving early (at median age 7.4 weeks) vs. deferred (23.2 weeks) ART, respectively (HR 0.24, 95%CI 0.11-0.53, P < 0.001). Infants with CD4 count <25% receiving early ART had intermediate incidence (41.7/ 100 py). Low CD4 counts and high HIV-1 RNA at initiation were the strongest independent risk factors for BCG-IRIS. CONCLUSIONS: Early ART initiation before immunological and/or clinical progression substantially reduces the risk of BCG-IRIS regional adenitis. © 2011 The Union.
- ItemEarly time-limited antiretroviral therapy versus deferred therapy in South African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial(LANCET LTD, 84 THEOBALDS RD, LONDON, ENGLAND, WC1X 8RR, 2013) Cotton MF; Violari A; Otwombe K; Panchia R; Dobbels, Els; Rabie H; Josipovic D; Liberty A; Lazarus E; Innes S; Janse Van Rensburg A; Pelser W; Truter H; Madhi S; Handelsman E; Jean-Philippe P; McIntyre JA; Gibb DM; Babiker AG
- ItemFive year neurodevelopment outcomes of perinatally HIV-infected children on early limited or deferred continuous antiretroviral therapy(Wiley Open Access, 2018) Laughton, Barbara; Cornell, Morna; Kidd, Martin; Springer, Priscilla Estelle; Dobbels, Els; Van Rensburg, Anita Janse; Otwombe, Kennedy; Babiker, Abdel; Gibb, Diana M.; Violari, Avy; Kruger, Mariana; Cotton, Mark F.Introduction: Early antiretroviral therapy (ART) has improved neurodevelopmental outcomes of HIV-infected (HIV-positive) children; however, little is known about the longer term outcomes in infants commencing early ART or whether temporary ART interruption might have long-term consequences. In the children with HIV early antiretroviral treatment (CHER) trial, HIVinfected infants ≤12 weeks of age with CD4 ≥25% were randomized to deferred ART (ART-Def); immediate time-limited ART for 40 weeks (ART-40W) or 96 weeks (ART-96W). ART was restarted in the time-limited arms for immunologic/clinical progression. Our objective was to compare the neurodevelopmental profiles in all three arms of Cape Town CHER participants. Methods: A prospective, longitudinal observational study was used. The Griffiths mental development scales (GMDS), which includes six subscales and a global score, were performed at 11, 20, 30, 42 and 60 months, and the Beery-Buktenica developmental tests for visual motor integration at 60 months. HIV-exposed uninfected (HEU) and HIV-unexposed (HU) children were enrolled for comparison. Mixed model repeated measures were used to compare groups over time, using quotients derived from standardized British norms. Results: In this study, 28 ART-Def, 35 ART-40W, 33 ART-96W CHER children, and 34 HEU and 39 HU controls were enrolled. GMDS scores over five years were similar between the five groups in all subscales except locomotor and general Griffiths (interaction p < 0.001 and p = 0.02 respectively), driven by early lower scores in the ART-Def arm. At 60 months, scores for all groups were similar in each GMDS scale. However, Beery visual perception scores were significantly lower in HIV-infected children (mean standard scores: 75.8 ART-Def, 79.8 ART-40W, 75.9 ART-96W) versus 84.4 in HEU and 90.5 in HU (p < 0.01)). Conclusions: Early locomotor delay in the ART-Def arm resolved by five years. Neurodevelopmental outcomes at five years in HIV-infected children on early time-limited ART were similar to uninfected controls, apart from visual perception where HIVinfected children scored lower. Poorer visual perception performance warrants further investigation.
- ItemFunctional connectivity alterations between networks and associations with infant immune health within networks in HIV infected children on early treatment : a study at 7 years(Frontiers Media, 2018) Toich, Jadrana T. F.; Taylor, Paul A.; Holmes, Martha J.; Gohel, Suril; Cotton, Mark F.; Dobbels, Els; Laughton, Barbara; Little, Francesca; Van Der Kouwe, Andre J. W.; Biswal, Bharat; Meintjes, Ernesta M.ENGLISH ABSTRACT: Although HIV has been shown to impact brain connectivity in adults and youth, it is not yet known to what extent long-term early antiretroviral therapy (ART) may alter these effects, especially during rapid brain development in early childhood. Using both independent component analysis (ICA) and seed-based correlation analysis (SCA), we examine the effects of HIV infection in conjunction with early ART on resting state functional connectivity (FC) in 7 year old children. HIV infected (HIV+) children were from the Children with HIV Early Antiretroviral Therapy (CHER) trial and all initiated ART before 18 months; uninfected children were recruited from an interlinking vaccine trial. To better understand the effects of current and early immune health on the developing brain, we also investigated among HIV+ children the association of FC at 7 years with CD4 count and CD4%, both in infancy (6–8 weeks) and at scan. Although we found no differences within any ICA-generated resting state networks (RSNs) between HIV+ and uninfected children (27 HIV+, 18 uninfected), whole brain connectivity to seeds located at RSN connectivity peaks revealed several loci of FC differences, predominantly from seeds in midline regions (posterior cingulate cortex, paracentral lobule, cuneus, and anterior cingulate). Reduced long-range connectivity and increased short-range connectivity suggest developmental delay. Within the HIV+ children, clinical measures at age 7 years were not associated with FC values in any of the RSNs; however, poor immune health during infancy was associated with localized FC increases in the somatosensory, salience and basal ganglia networks. Together these findings suggest that HIV may affect brain development from its earliest stages and persist into childhood, despite early ART.
- ItemImmunogenicity following the first and second doses of 7-valent pneumococcal conjugate vaccine in HIV-infected and -uninfected infants.(ELSEVIER SCI LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND,OXON, OX5 1GB, 2013) Madhi SA; Izu A; Violari A; Cotton MF; Panchia R; Dobbels, Els; Sewraj P; Van Niekerk N; Jean-Philippe P; Adrian P
- ItemNeurodevelopment at 11 months after starting antiretroviral therapy within 3 weeks of life(AOSIS, 2019-10-03) Laughton, Barbara; Naidoo, Shalena; Dobbels, Els; Boivin, Michael J.; Janse van Rensburg, Anita; Glashoff, Richard H.; Van Zyl, Gert U.; Kruger, Mariana; Cotton, Mark F.Background: Antiretroviral therapy (ART) started between 7 and 12 weeks of age improves neurodevelopmental outcomes in HIV-infected (HIV+) infants, but the impact of even earlier initiation is not yet described. Objectives: We assessed the early neurodevelopment of HIV+ infants who started ART within 21 days of life. Method: Participants were enrolled from the public sector birth HIV-diagnosis programme. Inclusion criteria included the following: birth weight > 2000 g, infant commencing ART < 6 weeks and no infant cytomegalovirus disease. Antiretroviral therapy included Zidovudine/Lamivudine/Nevirapine for the first 2 weeks, the latter then replaced by Lopinavir/Ritonavir. Once body weight > 3 kg and gestational age > 44 weeks, Abacavir replaced Zidovudine. The Griffiths mental development scales (GMDS) were administered at 10–12 months. Results: Of 29 infants assessed, 23 (79%) were girls. Mean birth weight was 3002 ± 501 g. Twenty-four mothers (83%) received ART during pregnancy. Seven (24%) infants were diagnosed HIV+ within 48 h of birth. Median [interquartile range] viral load (VL) at diagnosis was 3904 [259–16 922] copies/mL, age starting ART was 6.0 [3–10] days and age at VL suppression was 19.1 [15–36] weeks. At the GMDS assessment, nine (31%) participants had detectable VL and 26 (90%) had World Health Organization (WHO) clinical stage I disease. The GMDS was performed at a mean age of 11.5 ± 0.8 months. Mean quotients were within the average range: Global Griffiths score was 103.6 ± 10.9 and mean quotients on the subscales ranged from lowest 95.9 ± 13.4 for locomotor to highest 112.8 ± 11.3 for hearing-and-language. Conclusion: Preliminary findings in this small group suggest that early neurodevelopmental scores are within the normal range in infants with perinatal HIV infection who started ART at a median of 6 days.
- ItemPerinatal HIV infection or exposure is associated with low N-acetylaspartate and glutamate in basal ganglia at age 9 but not 7 years(Frontiers Media, 2018) Robertson, Frances C.; Holmes, Martha J.; Cotton, Mark F.; Dobbels, Els; Little, Francesca; Laughton, Barbara; Van Der Kouwe, Andre J. W.; Meintjes, Ernesta M.ENGLISH ABSTRACT: Abnormalities of the basal ganglia are frequently seen in HIV-infected (HIV+) children despite antiretroviral treatment (ART) initiation during childhood. Assessment of metabolites associated with neuronal integrity or with glial proliferation can present a sensitive description of metabolic events underlying basal ganglia structural changes. We used magnetic resonance spectroscopy to examine differences in creatine, choline, N-acetylaspartate (NAA), glutamate, and myo-inositol between HIV+ children and HIV-unexposed controls, as well as between HIV-exposed uninfected (HEU) children and HIV-unexposed controls at age 7 and at age 9. No differences in metabolites relative to the HIV-unexposed control group were found at age 7. However, at 9 years, both HIV+ and HEU had lower NAA and glutamate than unexposed control children. HEU children also had lower creatine and choline than control children. At age 7, lower CD4/CD8 ratio at enrollment was associated with lower choline levels. At age 9 lower CD4/CD8 at enrollment was associated with lower myo-inositol. Low NAA and glutamate at age 9, but not 7, suggest that basal ganglia neurons may be particularly affected by perinatal HIV/ART and that neuronal damage may be ongoing despite early ART and viral suppression. Reduced basal ganglia metabolite levels in HEU children suggest an effect of HIV exposure on childhood brain development that merits further investigation using neuroimaging and neurocognitive testing.
- ItemUtility of clinical parameters to identify HIV infection in infants below ten weeks of age in South Africa : a prospective cohort study(BioMed Central, 2011-11) Jaspan, Heather B.; Myer, Landon; Madhi, Shabir A.; Violari, Avy; Gibb, Diana M.; Stevens, Wendy S.; Dobbels, Els; Cotton, Mark F.ABSTRACT: Background: As HIV-infected infants have high mortality, the World Health Organization now recommends initiating antiretroviral therapy as early as possible in the first year of life. However, in many settings, laboratory diagnosis of HIV in infants is not readily available. We aimed to develop a clinical algorithm for HIV presumptive diagnosis in infants < 10 weeks old using screening data from the Children with HIV Early Antiretroviral therapy (CHER) study in South Africa. HIV-infected and HIV-uninfected exposed infants < 10 weeks of age were identified through Vertical Transmission Prevention programs. Clinical and laboratory data were systematically recorded, groups were compared using Kruskal-Wallis, analysis of variance (ANOVA), and Fisher's exact tests. Receiver Operating Characteristic (ROC) curves were compiled using combinations of clinical findings. Results 417 HIV-infected and 125 HIV-exposed, uninfected infants, median age 46 days (IQR 38-55), were included. The median CD4 percentage in HIV-infected infants was 34 (IQR 28-41)%. HIV-infected infants had lower weight-for-age, more lymphadenopathy, oral thrush, and hepatomegaly than exposed uninfected infants (Adjusted Odds Ratio 0.51, 8.8, 5.6 and 23.5 respectively; p < 0.001 for all). Sensitivity of individual signs was low (< 20%) but specificity high (98-100%). If any one of oral thrush, hepatomegaly, splenomegaly, lymphadenopathy, diaper dermatitis, weight < 50th centile are present, sensitivity for HIV infection amongst HIV-exposed infants was 86%. These algorithms performed similarly when used to predict severe immune suppression. Conclusions A combination of physical findings is helpful in identifying infants most likely to be HIV-infected. This may inform management algorithms and provide guidance for focused laboratory testing in some settings, and should be further validated in these settings and elsewhere.
- ItemWhite matter lesions in children with HIV encephalopathy: correlating with Griffiths mental scale(2010) Ackermann, C.; Andronikou, S.; Laughton, Barbara; Dobbels, Els; Innes, S.; Taliep, R.; Cotton, M.; Van Toorn, R.
- ItemWhite matter signal abnormalities on MRI in children with HIV encephalopathy(2010) Ackermann, C.; Andronikou, S.; Laughton, Barbara; Van Toorn, R.; Dobbels, Els; Innes, S.; Taliep, R.