Helena Rabie

Stellenbosch University, Johannesburg, Gauteng, South Africa

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Publications (83)278.79 Total impact

  • Mark F Cotton, Helena Rabie
    The Lancet HIV 03/2015; DOI:10.1016/S2352-3018(15)00040-5
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    ABSTRACT: The risk of Kaposi sarcoma (KS) among HIV-infected persons on antiretroviral therapy (ART) is not well defined in resource-limited settings. We studied KS incidence rates and associated risk factors in children and adults on ART in Southern Africa.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 12/2014; 67(5):547-54. DOI:10.1097/QAI.0000000000000360 · 4.39 Impact Factor
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    Mark F Cotton, Helena Rabie
    Journal of the International AIDS Society 11/2014; 17(1):19875. DOI:10.7448/IAS.17.1.19875 · 4.21 Impact Factor
  • Mark F Cotton, Helena Rabie
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    ABSTRACT: Early initiation of combination antiretroviral therapy (ART) in infants below 12 weeks of age reduces morbidity and mortality. A recent report of transient HIV remission in a child beginning ART from the second day of life has focused attention on very early therapy in the first days of life.
    Current Opinion in HIV and AIDS 11/2014; DOI:10.1097/COH.0000000000000117 · 4.39 Impact Factor
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    ABSTRACT: Objectives: Many paediatric antiretroviral therapy (ART) programmes in Southern Africa rely on CD4(+) to monitor ART. We assessed the benefit of replacing CD4(+) by viral load monitoring. Design: A mathematical modelling study. Methods: A simulation model of HIV progression over 5 years in children on ART, parameterized by data from seven South African cohorts. We simulated treatment programmes with 6-monthly CD4(+) or 6- or 12-monthly viral load monitoring. We compared mortality, second-line ART use, immunological failure and time spent on failing ART. In further analyses, we varied the rate of virological failure, and assumed that the rate is higher with CD4(+) than with viral load monitoring. Results: About 7% of children were predicted to die within 5 years, independent of the monitoring strategy. Compared with CD4(+) monitoring, 12-monthly viral load monitoring reduced the 5-year risk of immunological failure from 1.6 to 1.0% and the mean time spent on failing ART from 6.6 to 3.6 months; 1% of children with CD4(+) compared with 12% with viral load monitoring switched to second-line ART. Differences became larger when assuming higher rates of virological failure. When assuming higher virological failure rates with CD4(+) than with viral load monitoring, up to 4.2% of children with CD4(+) compared with 1.5% with viral load monitoring experienced immunological failure; the mean time spent on failing ART was 27.3 months with CD4(+) monitoring and 6.0 months with viral load monitoring. Conclusion: Viral load monitoring did not affect 5-year mortality, but reduced time on failing ART, improved immunological response and increased switching to second-line ART. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
    AIDS (London, England) 10/2014; 28(16):2451-60. DOI:10.1097/QAD.0000000000000446 · 6.56 Impact Factor
  • Official journal of the South African Academy of Family Practice/Primary Care 08/2014; 49(2):40-45. DOI:10.1080/20786204.2007.10873517
  • Official journal of the South African Academy of Family Practice/Primary Care 08/2014; 48(6):34-41. DOI:10.1080/20786204.2006.10873407
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    Official journal of the South African Academy of Family Practice/Primary Care 08/2014; 48(7):54-59. DOI:10.1080/20786204.2006.10873429
  • Mark F Cotton, Amy Slogrove, Helena Rabie
    The Pediatric Infectious Disease Journal 08/2014; 33(10). DOI:10.1097/INF.0000000000000489 · 3.14 Impact Factor
  • Haseena Hassan, Mark F Cotton, Helena Rabie
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    ABSTRACT: We report 7 HIV-infected children with cryptococcosis. Median age and CD4-counts were 9.3 years and 12 cells/mm, respectively. Two children died early. Of 4 children requiring prolonged amphotericin B and fluconazole at a dosage above 12mg/kg/day, 3 presented with meningitis and one with fever. Immune reconstitution inflammatory syndrome contributed to morbidity through exacerbations at the primary site and elsewhere.
    The Pediatric Infectious Disease Journal 07/2014; DOI:10.1097/INF.0000000000000480 · 3.14 Impact Factor
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    ABSTRACT: Background Early initiation of antiretroviral therapy (ART) in HIV-infected infants reduces mortality and opportunistic infections including tuberculosis (TB). However, young HIV-infected children remain at high risk of TB disease following mycobacterial infection. We document the spectrum of TB disease in HIV-infected children <2 years of age on ART. Methods Retrospective cohort study; records of children <2 years of age initiating routine ART at Tygerberg Children's Hospital, Cape Town, January 2003-December 2010 were reviewed. Clinical data at ART initiation (baseline) and TB episodes after ART initiation, to June 2012, were recorded. TB immune reconstitution syndrome (TB-IRIS) and incident TB were defined as TB diagnosed within 3 months, and >3 months after, ART initiation respectively. Baseline characteristics were compared in children with TB-IRIS and those with incident TB. Results In 494 children, median follow-up time on ART was 10.7 months. Fifty-five TB treatment episodes occurred after ART initiation: 23 (42%) TB-IRIS (incidence 21.9/100 person years (py)) and 32 (58%) incident TB (incidence 3.9/100 py). Children with TB-IRIS and those with incident TB had similar baseline characteristics. Eight of 10 cases of extrapulmonary TB were severe: 4 IRIS (2 meningitis, 1 disseminated, 1 pericarditis) and 4 incident cases (1 each miliary, meningitis, pericarditis and spinal). Fifty-one children (10%) died (mortality rate 5.96/100 py). Starting ART at <1 year of age approached significance as a risk factor for TB-IRIS (adjusted OR (AOR) 8.64, p=0.06); weight-for-age Z score <-2 predicted death (AOR 6.37, p<0.001). Conclusions Severe TB manifestations were observed among young HIV-infected children on ART.
    Archives of Disease in Childhood 06/2014; 99(11). DOI:10.1136/archdischild-2013-305509 · 2.91 Impact Factor
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    ABSTRACT: Prognostic models for children starting antiretroviral therapy (ART) in Africa are lacking. We developed models to estimate the probability of death during the first year receiving ART in Southern Africa. We analyzed data from children ≤10 years old who started ART in Malawi, South Africa, Zambia or Zimbabwe from 2004-2010. Children lost to follow-up or transferred were excluded. The primary outcome was all-cause mortality in the first year of ART. We used Weibull survival models to construct two prognostic models: one with CD4%, age, WHO clinical stage, weight-for-age z-score (WAZ) and anemia and one without CD4%, because it is not routinely measured in many programs. We used multiple imputation to account for missing data. Among 12655 children, 877 (6.9%) died in the first year of ART. 1780 children were lost to follow-up/transferred and excluded from main analyses; 10875 children were included. With the CD4% model probability of death at 1 year ranged from 1.8% (95% CI: 1.5-2.3) in children 5-10 years with CD4% ≥10%, WHO stage I/II, WAZ ≥-2 and without severe anemia to 46.3% (95% CI: 38.2-55.2) in children <1 year with CD4% <5%, stage III/IV, WAZ< -3 and severe anemia. The corresponding range for the model without CD4% was 2.2% (95% CI: 1.8-2.7) to 33.4% (95% CI: 28.2-39.3). Agreement between predicted and observed mortality was good (C-statistics=0.753 and 0.745 for models with and without CD4% respectively). These models may be useful to counsel children/caregivers, for program planning and to assess program outcomes after allowing for differences in patient disease severity characteristics.
    The Pediatric Infectious Disease Journal 12/2013; 33(6). DOI:10.1097/INF.0000000000000214 · 3.14 Impact Factor
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    ABSTRACT: Since 2005, increasing numbers of children have started antiretroviral therapy (ART) in sub-Saharan Africa and, in recent years, WHO and country treatment guidelines have recommended ART initiation for all infants and very young children, and at higher CD4 thresholds for older children. We examined temporal changes in patient and regimen characteristics at ART start using data from 12 cohorts in 4 countries participating in the IeDEA-SA collaboration. Data from 30,300 ART-naïve children aged <16 years at ART initiation who started therapy between 2005 and 2010 were analysed. We examined changes in median values for continuous variables using the Cuzick's test for trend over time. We also examined changes in the proportions of patients with particular disease severity characteristics (expressed as a binary variable e.g. WHO Stage III/IV vs I/II) using logistic regression. Between 2005 and 2010 the number of children starting ART each year increased and median age declined from 63 months (2006) to 56 months (2010). Both the proportion of children <1 year and ≥10 years of age increased from 12 to 19% and 18 to 22% respectively. Children had less severe disease at ART initiation in later years with significant declines in the percentage with severe immunosuppression (81 to 63%), WHO Stage III/IV disease (75 to 62%), severe anemia (12 to 7%) and weight-for-age z-score<-3 (31 to 28%). Similar results were seen when restricting to infants with significant declines in the proportion with severe immunodeficiency (98 to 82%) and Stage III/IV disease (81 to 63%). First-line regimen use followed country guidelines. Between 2005 and 2010 increasing numbers of children have initiated ART with a decline in disease severity at start of therapy. However, even in 2010, a substantial number of infants and children started ART with advanced disease. These results highlight the importance of efforts to improve access to HIV diagnostic testing and ART in children.
    PLoS ONE 12/2013; 8(12):e81037. DOI:10.1371/journal.pone.0081037 · 3.53 Impact Factor
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    ABSTRACT: Malaria causes a quarter of all childhood deaths in SubSaharan Africa. Considerable gains in global malaria control have been achieved in the last decade but coverage of effective interventions remains low in areas of greatest malaria burden. Some countries have achieved reduced malaria related mortality through application of recent advances in malaria prevention and treatment of children. Artemisinin combination therapies (particularly artesunate) are highly efficacious and welltolerated in children, although several alternative treatments are available. However, the evolution of drug resistance (including emerging resistance to artemisinin derivatives) threatens the success of malaria treatment programmes. This special issue review is aimed at paediatric clinicians in resourcepoor settings and provides a summary of recent data from paediatric trials of malaria treatment and prevention interventions.
    11/2013; DOI:10.2174/1871526513666131129154446
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    ABSTRACT: Interim results from the children with HIV early antiretroviral (CHER) trial showed that early antiretroviral therapy (ART) was life-saving for infants infected with HIV. In view of the few treatment options and the potential toxicity associated with lifelong ART, in the CHER trial we compared early time-limited ART with deferred ART. CHER was an open-label randomised controlled trial of HIV-infected asymptomatic infants younger than 12 weeks in two South African trial sites with a percentage of CD4-positive T lymphocytes (CD4%) of 25% or higher. 377 infants were randomly allocated to one of three groups: deferred ART (ART-Def), immediate ART for 40 weeks (ART-40W), or immediate ART for 96 weeks (ART-96W), with subsequent treatment interruption. The randomisation schedule was stratified by clinical site with permuted blocks of random sizes to balance the numbers of infants allocated to each group. Criteria for ART initiation in the ART-Def group and re-initiation after interruption in the other groups were CD4% less than 25% in infancy; otherwise, the criteria were CD4% less than 20% or Centers for Disease Control and Prevention severe stage B or stage C disease. Combination therapy of lopinavir-ritonavir, zidovudine, and lamivudine was the first-line treatment regimen at ART initiation and re-initiation. The primary endpoint was time to failure of first-line ART (immunological, clinical, or virological) or death. Comparisons were done by intention-to-treat analysis, with use of time-to-event methods. This trial is registered with ClinicalTrials.gov, number NCT00102960. 377 infants were enrolled, with a median age of 7·4 weeks, CD4% of 35%, and HIV RNA log 5·7 copies per mL. Median follow-up was 4·8 years; 34 infants (9%) were lost to follow-up. Median time to ART initiation in the ART-Def group was 20 weeks (IQR 16-25). Time to restarting of ART after interruption was 33 weeks (26-45) in ART-40W and 70 weeks (35-109) in ART-96W; at the end of the trial, 19% of patients in ART-40W and 32% of patients in ART-96W remained off ART. Proportions of follow-up time spent on ART were 81% in the ART-Def group, 70% in the ART-40W group, and 69% in the ART-96W group. 48 (38%) of 125 children in the ART-Def group, 32 (25%) of 126 in the ART-40W group, and 26 (21%) of 126 in the ART-96W group reached the primary endpoint. The hazard ratio, relative to ART-Def, was 0·59 (95% CI 0·38-0·93, p=0·02) for ART-40W and 0·47 (0·27-0·76, p=0·002) for ART-96W. Three children in ART-Def, three in ART-40W, and one in ART-96W switched to second-line ART. Early time-limited ART had better clinical and immunological outcomes than deferred ART, with no evidence of excess disease progression during subsequent treatment interruption and less overall ART exposure than deferred ART. Longer time on primary ART permits longer subsequent interruption, with marginally better outcomes. US National Institutes of Health.
    The Lancet 11/2013; 382(9904):1555-63. DOI:10.1016/S0140-6736(13)61409-9 · 39.21 Impact Factor
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    ABSTRACT: There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2-5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2-5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4 percentage (CD4%) <25%. ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm(3) (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1-6.5) (no ART) to 2.1% (95% CI: 1.3%-3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%-3.5%) and 2.2% (95% CI: 1.4%-3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data. The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm(3) or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors' Summary.
    PLoS Medicine 11/2013; 10(11):e1001555. DOI:10.1371/journal.pmed.1001555 · 14.00 Impact Factor
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    ABSTRACT: In antiretroviral treatment the role of therapeutic drug monitoring via measurement of serum levels remains unclear, especially in children. To quantify exposure to LPV and EFV in children receiving therapy in a routine clinical setting in order to identify risk factors associated with inadequate drug exposure. A prospective study was conducted in a routine clinical setting in Tygerberg Children?s Hospital, South Africa. A total of 53 random serum levels were analyzed. Serum concentrations were determined by an established high-performance liquid chromatography method. Of 53 HIV-infected children treated with lopinavir (n=29, median age 1.83 y) or efavirenz (n=24, median age 9.3 years), 12 showed serum levels outside the therapeutic range (efavirenz) or below Cmin (lopinavir). Low bodyweight, rifampicin co-treatment, and significant comorbidity were potential risk factors for inadequate drug exposure. These findings, together with previous studies, indicate that therapeutic drug monitoring can improve the management of antiretroviral therapy in children at risk.
    09/2013; 34(2). DOI:10.1179/2046905513Y.0000000090
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    The Southern African journal of epidemiology & infection: official journal of the Sexually Transmitted Diseases, Infectious Diseases and Epidemiological Societies of Southern Africa 08/2013; 29(1):33-36.
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    ABSTRACT: We describe an expansile necrotising pneumonia caused by Norcardia in a HIV-infected 3-week-old baby. The radiological images and treatment of Norcardia in immune deficient children are discussed.
    Case Reports 07/2013; 2013(jul31 1). DOI:10.1136/bcr-2013-010479
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    ABSTRACT: The neonatal and pediatric antimicrobial point prevalence survey (PPS) of the Antibiotic Resistance and Prescribing in European Children project (http://www.arpecproject.eu/) aims to standardize a method for surveillance of antimicrobial use in children and neonates admitted to the hospital within Europe. This article describes the audit criteria used and reports overall country-specific proportions of antimicrobial use. An analytical review presents methodologies on antimicrobial use. A 1-day PPS on antimicrobial use in hospitalized children was organized in September 2011, using a previously validated and standardized method. The survey included all inpatient pediatric and neonatal beds and identified all children receiving an antimicrobial treatment on the day of survey. Mandatory data were age, gender, (birth) weight, underlying diagnosis, antimicrobial agent, dose and indication for treatment. Data were entered through a web-based system for data-entry and reporting, based on the WebPPS program developed for the European Surveillance of Antimicrobial Consumption project. There were 2760 and 1565 pediatric versus 1154 and 589 neonatal inpatients reported among 50 European (n = 14 countries) and 23 non-European hospitals (n = 9 countries), respectively. Overall, antibiotic pediatric and neonatal use was significantly higher in non-European (43.8%; 95% confidence interval [CI]: 41.3-46.3% and 39.4%; 95% CI: 35.5-43.4%) compared with that in European hospitals (35.4; 95% CI: 33.6-37.2% and 21.8%; 95% CI: 19.4-24.2%). Proportions of antibiotic use were highest in hematology/oncology wards (61.3%; 95% CI: 56.2-66.4%) and pediatric intensive care units (55.8%; 95% CI: 50.3-61.3%). An Antibiotic Resistance and Prescribing in European Children standardized web-based method for a 1-day PPS was successfully developed and conducted in 73 hospitals worldwide. It offers a simple, feasible and sustainable way of data collection that can be used globally.
    The Pediatric Infectious Disease Journal 06/2013; 32(6):e242-53. DOI:10.1097/INF.0b013e318286c612 · 3.14 Impact Factor

Publication Stats

758 Citations
278.79 Total Impact Points

Institutions

  • 2004–2015
    • Stellenbosch University
      • Department of Paediatrics and Child Health
      Johannesburg, Gauteng, South Africa
  • 2011
    • University of the Western Cape
      • School of Pharmacy
      Cape Town, Province of the Western Cape, South Africa
  • 2001–2009
    • Tygerberg Hospital
      Kaapstad, Western Cape, South Africa
  • 2008
    • Royal College Of Paediatrics and Child Health
      Londinium, England, United Kingdom
  • 2006
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands