Helena Rabie

Stellenbosch University, Stellenbosch, Western Cape, South Africa

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Publications (79)275.66 Total impact

  • [Show abstract] [Hide abstract]
    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. · 4.39 Impact Factor
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    Mark F Cotton, Helena Rabie
    Journal of the International AIDS Society 11/2014; 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; · 4.39 Impact Factor
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    ABSTRACT: 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.
    AIDS (London, England) 10/2014; 28(16):2451-60. · 6.56 Impact Factor
  • Official journal of the South African Academy of Family Practice/Primary Care 08/2014; 48(7):54-59.
  • Mark F Cotton, Amy Slogrove, Helena Rabie
    The Pediatric Infectious Disease Journal 08/2014; · 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; · 3.14 Impact Factor
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    ABSTRACT: 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.
    Archives of Disease in Childhood 06/2014; · 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; · 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. · 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.
    Infectious disorders drug targets. 11/2013;
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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. · 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. · 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.
    Paediatrics and international child health. 09/2013;
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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).
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    ABSTRACT: BACKGROUND:: Initiation criteria and pediatric antiretroviral treatment (ART) regimens have changed over the past few years in South Africa. We reported worse early virological outcomes associated with the use abacavir (ABC)-based regimens at one large site: here we expand this analysis to multiple sites in the IeDEA-Southern Africa collaboration. METHODS:: Data for 9543 ART-naive children <16 years at treatment initiation started on either stavudine/lamivudine (d4T/3TC) or ABC/3TC with efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r) treated at six clinics in Johannesburg and Cape Town, South Africa, were analysed with Chi-square tests and logistic regression to evaluate viral suppression at six and twelve months. RESULTS:: Prevalence of viral suppression at six months in 2174 children started on a d4T-based LPV/r regimen was greater (70%) than among 438 children started on an ABC-based LPV/r regimen (54%, p<0.0001). Among 3189 children started on a d4T-based EFV regimen a higher proportion (86%) achieved suppression at six months compared to 391 children started on ABC-containing EFV regimens (78%, p<0.0001). Relative benefit of d4T vs. ABC on six month suppression remained in multivariate analysis after adjustment for pre-treatment characteristics, cohort and year of program (LPV/r - OR 0.57 [CI: 0.46-0.72]; EFV - OR 0.46 [CI: 0.32-0.65]). CONCLUSION:: This expanded analysis is consistent with our previous report of worse virological outcomes after ABC was introduced as part of first-line ART in South Africa. Whether due to the drug itself or coincident with other changes over time, continued monitoring and analyses must clarify causes and prevent suboptimal long term outcomes.
    The Pediatric Infectious Disease Journal 01/2013; · 3.14 Impact Factor
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    ABSTRACT: BACKGROUND:: The prevalence of potentially stigmatizing lipoatrophy in children receiving antiretroviral therapy in Southern Africa is high, affecting around a third of children. Early diagnosis of lipoatrophy is essential for effective intervention to arrest progression. METHODS:: Pre-pubertal children receiving antiretroviral therapy were recruited from a hospital-based family HIV clinic in Cape Town and followed up prospectively. Lipoatrophy was identified and graded by consensus between two HIV pediatricians. A dietician performed anthropometric measurements of trunk and limb fat. Anthropometric measurements in children with and without lipoatrophy were compared using multivariable linear regression adjusting for age and gender. The most discerning anthropometric indicators of lipoatrophy underwent Receiver Operating Characteristic curve analysis. The precision of anthropometric measurements performed by an inexperienced healthcare worker was compared with that of a research dietician. RESULTS:: Of 100 recruits, 36 had lipoatrophy at baseline and a further 9 developed lipoatrophy by 15 month follow-up. Annual incidence of lipoatrophy was 12% (confidence interval [CI]: 5-20%) per person-year of follow-up. A biceps skin-fold thickness <5mm at baseline had a sensitivity of 89% (CI: 67-100%) and a specificity of 60% (CI: 46-75%) for predicting development of lipoatrophy by 15 month follow-up. Negative and positive predictive values were 97% (CI: 91-100%) and 32% (CI: 14-50%). CONCLUSION:: Biceps skin-fold thickness <5mm in pre-pubertal children exposed to thymidine analogue-based antiretroviral therapy may be a useful screening tool to identify children who are likely to develop lipoatrophy. The variation in precision of measurements performed by an inexperienced healthcare worker only marginally impacted performance.
    The Pediatric Infectious Disease Journal 12/2012; · 3.14 Impact Factor
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    ABSTRACT: BACKGROUND:: Accurate identification of Mycobacterium tuberculosis (M.tb) infection in young and HIV-infected children could guide delivery of preventive therapy, improve resource utilization, and help prevent tuberculosis. METHODS:: We assessed the performance of the tuberculin skin test (TST) and interferon-gamma release assays (IGRAs) for identifying M.tb infection in South African children presenting for out-patient care. Tuberculosis contact was quantified using a standardized measure of M.tb exposure. Logistic regression assessed the association between test positivity, age, nutritional and HIV status, while controlling for M.tb exposure, BCG vaccination and prior tuberculosis treatment. RESULTS:: Among 250 (130 HIV-infected) children (age 0.25-14.6 years, median 39 months), the proportion positive for each test varied: 34% (TST), 21% (T-SPOT.TB), 25% (QuantiFERON-TB Gold In-Tube, QFT-IT). IGRAs were more likely to be positive in HIV-uninfected compared with HIV-infected children; TST positivity did not differ between these groups. Agreement between tests was good-to-excellent in HIV-uninfected children and poor- to-good in HIV-infected children. In adjusted models, TST and T-Spot.TB were positively associated with age; this effect varied by HIV-status. The QFT-IT was negatively associated with chronic malnutrition; this effect varied by HIV-status. Since 93% of children had received BCG, we could not assess the contribution of BCG to false-positive TST results. CONCLUSIONS:: Our findings indicate that the TST and IGRAs perform similarly for the detection of M.tb infection in well-nourished HIV-uninfected children, but test performance is differentially affected by chronic malnutrition, HIV infection, and age. Similar to TST interpretation, clinicians and researchers should interpret IGRAs in children with caution taking age, nutritional, and HIV-status into consideration.
    The Pediatric Infectious Disease Journal 11/2012; · 3.14 Impact Factor
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    ABSTRACT: BACKGROUND:: We investigated 18-month incidence and determinants of death and loss-to-follow-up of children after antiretroviral therapy (ART) initiation in a multiregional collaboration in lower-income countries. METHODS:: HIV-infected children (positive PCR <18 months or positive serology ≥18 months) from IeDEA cohorts, <16 years, initiating ART were eligible. A competing risk regression model was used to analyze the independent risk of two failure types: death and loss-to-follow-up (>6 months). FINDINGS:: Data on 13611 children, from Asia (N=1454), East-Africa (N=3114), Southern-Africa (N=6212) and West-Africa (N=2881) contributed 20,417 person-years of follow-up. At 18 months, the adjusted risk of death was 4.3% in East-Africa, 5.4% in Asia, 5.7% in Southern-Africa and 7.4% in West-Africa (P=0.01). Age<24 months, WHO stage 4, CD4<10%, attending a private sector clinic, larger cohort size and living in West-Africa were independently associated with poorer survival. The adjusted risk of loss-to-follow-up was 4.1% in Asia, 9.0% in Southern-Africa, 14.0% in East-Africa, and 21.8% in West-Africa (P <0.01). Age<12 months, non NNRTI-based ART regimen, WHO stage 4 at ART start, ART initiation after 2005, attending a public sector or a non-urban clinic, having to pay for laboratory tests or antiretroviral drugs, larger cohort size, and living in East or West-Africa were significantly associated with higher loss-to-follow-up. CONCLUSION:: Findings differed substantially across regions but raise overall concerns about delayed ART start, low access to free HIV-services for children, and increased workload on program retention in lower-income countries. Universal free access to ART services and innovative approaches are urgently needed to improve pediatric outcomes at program level.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 11/2012; · 4.39 Impact Factor

Publication Stats

663 Citations
275.66 Total Impact Points


  • 2004–2014
    • Stellenbosch University
      • Department of Paediatrics and Child Health
      Stellenbosch, Western Cape, South Africa
  • 2012
    • Universität Bern
      • Institute of Social and Preventive Medicine
      Bern, BE, Switzerland
  • 2011
    • University of the Western Cape
      • School of Pharmacy
      Cape Town, Province of the Western Cape, South Africa
  • 2009
    • University of Cape Town
      • Institute of Infectious Disease & Molecular Medicine (IIDMM)
      Cape Town, Province of the Western Cape, South Africa
  • 2008
    • Royal College Of Paediatrics and Child Health
      Londinium, England, United Kingdom
  • 2006
    • University of Amsterdam
      Amsterdamo, North Holland, Netherlands
  • 2001–2006
    • Tygerberg Hospital
      Kaapstad, Western Cape, South Africa