Journal Article > ResearchFull Text
S Afr Med J. 2009 September 1
Cornell M, Technau KG, Fairall L, Wood R, Moultrie H, et al.
S Afr Med J. 2009 September 1
OBJECTIVES: To introduce the combined South African cohorts of the International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration as reflecting the South African national antiretroviral treatment (ART) programme; to characterise patients accessing these services; and to describe changes in services and patients from 2003 to 2007. DESIGN AND SETTING: Multi-cohort study of 11 ART programmes in Gauteng, Western Cape, Free State and KwaZulu-Natal. SUBJECTS: Adults and children (<16 years old) who initiated ART with > or =3 antiretroviral drugs before 2008. RESULTS: Most sites were offering free treatment to adults and children in the public sector, ranging from 264 to 17,835 patients per site. Among 45,383 adults and 6,198 children combined, median age (interquartile range) was 35.0 years (29.8-41.4) and 42.5 months (14.7-82.5), respectively. Of adults, 68% were female. The median CD4 cell count was 102 cells/microl (44-164) and was lower among males than females (86, 34-150 v. 110, 50-169, p<0.001). Median CD4% among children was 12% (7-17.7). Between 2003 and 2007, enrolment increased 11-fold in adults and 3-fold in children. Median CD4 count at enrolment increased for all adults (67-111 cells/microl, p<0.001) and for those in stage IV (39-89 cells/microl, p<0.001). Among children <5 years, baseline CD4% increased over time (11.5-16.0%, p<0.001). CONCLUSIONS: IeDEA-SA provides a unique opportunity to report on the national ART programme. The study describes dramatically increased enrolment over time. Late diagnosis and ART initiation, especially of men and children, need attention. Investment in sentinel sites will ensure good individual-level data while freeing most sites to continue with simplified reporting.
Journal Article > ResearchFull Text
Southern African Journal of HIV medicine. 2019 November 8; Volume 20 (Issue 1); 1030.; DOI:10.4102/sajhivmed.v20i1.1030
Govender NP, Meintjes GA, Mangena PM, Nel J, Potgieter S, et al.
Southern African Journal of HIV medicine. 2019 November 8; Volume 20 (Issue 1); 1030.; DOI:10.4102/sajhivmed.v20i1.1030
Journal Article > ResearchFull Text
J Int AIDS Soc. 2017 March 16; Volume 20; DOI:10.7448/IAS.20.4.21668
Davies MA, Tsondai PR, Tiffin N, Eley B, Rabie H, et al.
J Int AIDS Soc. 2017 March 16; Volume 20; DOI:10.7448/IAS.20.4.21668
To evaluate long-term outcomes in HIV-infected adolescents, it is important to identify ways of tracking outcomes after transfer to a different health facility. The Department of Health (DoH) in the Western Cape Province (WCP) of South Africa uses a single unique identifier for all patients across the health service platform. We examined adolescent outcomes after transfer by linking data from four International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) cohorts in the WCP with DoH data.
Journal Article > ResearchFull Text
Pediatrics. 2012 September 17; Volume 130 (Issue 4); e966-e977.; DOI:10.1542/peds.2011-3020
Gsponer T, Weigel R, Davies MA, Bolton C, Moultrie H, et al.
Pediatrics. 2012 September 17; Volume 130 (Issue 4); e966-e977.; DOI:10.1542/peds.2011-3020
BACKGROUND
Poor growth is an indication for antiretroviral therapy (ART) and a criterion for treatment failure. We examined variability in growth response to ART in 12 programs in Malawi, Zambia, Zimbabwe, Mozambique, and South Africa.
METHODS
Treatment naïve children aged <10 years were included. We calculated weight for age z scores (WAZs), height for age z scores (HAZs), and weight for height z scores (WHZs) up to 3 years after starting ART, by using the World Health Organization standards. Multilevel regression models were used.
RESULTS
A total of 17 990 children (range, 238–8975) were followed for 36 181 person-years. At ART initiation, most children were underweight (50%) and stunted (66%). Lower baseline WAZ, HAZ, and WHZ were the most important determinants of faster catch-up growth on ART. WAZ and WHZ increased rapidly in the first year and stagnated or reversed thereafter, whereas HAZ increased continuously over time. Three years after starting ART, WAZ ranged from −2.80 (95% confidence interval [CI]: −3.66 to −2.02) to −1.98 (95% CI: −2.41 to −1.48) in children with a baseline z score < −3 and from −0.79 (95% CI: −1.62 to 0.02) to 0.05 (95% CI: −0.42 to 0.51) in children with a baseline WAZ ≥ −1. For HAZ, the corresponding range was −2.33 (95% CI: −2.62 to −2.02) to −1.27 (95% CI: −1.58 to −1.00) for baseline HAZ < −3 and −0.24 (95% CI: −0.56 to 0.15) to 0.84 (95% CI: 0.53 to 1.16) for HAZ ≥ −1.
CONCLUSIONS
Despite a sustained growth response and catch-up growth in children with advanced HIV disease treated with ART, normal weights and heights are not achieved over 3 years of ART.
Poor growth is an indication for antiretroviral therapy (ART) and a criterion for treatment failure. We examined variability in growth response to ART in 12 programs in Malawi, Zambia, Zimbabwe, Mozambique, and South Africa.
METHODS
Treatment naïve children aged <10 years were included. We calculated weight for age z scores (WAZs), height for age z scores (HAZs), and weight for height z scores (WHZs) up to 3 years after starting ART, by using the World Health Organization standards. Multilevel regression models were used.
RESULTS
A total of 17 990 children (range, 238–8975) were followed for 36 181 person-years. At ART initiation, most children were underweight (50%) and stunted (66%). Lower baseline WAZ, HAZ, and WHZ were the most important determinants of faster catch-up growth on ART. WAZ and WHZ increased rapidly in the first year and stagnated or reversed thereafter, whereas HAZ increased continuously over time. Three years after starting ART, WAZ ranged from −2.80 (95% confidence interval [CI]: −3.66 to −2.02) to −1.98 (95% CI: −2.41 to −1.48) in children with a baseline z score < −3 and from −0.79 (95% CI: −1.62 to 0.02) to 0.05 (95% CI: −0.42 to 0.51) in children with a baseline WAZ ≥ −1. For HAZ, the corresponding range was −2.33 (95% CI: −2.62 to −2.02) to −1.27 (95% CI: −1.58 to −1.00) for baseline HAZ < −3 and −0.24 (95% CI: −0.56 to 0.15) to 0.84 (95% CI: 0.53 to 1.16) for HAZ ≥ −1.
CONCLUSIONS
Despite a sustained growth response and catch-up growth in children with advanced HIV disease treated with ART, normal weights and heights are not achieved over 3 years of ART.
Journal Article > Short ReportFull Text
Southern African Journal of HIV medicine. 2015 April 28; DOI:10.4102/hivmed.v16i1.376
Nelson AM, Maritz J, Giddy J, Frigati L, Rabie H, et al.
Southern African Journal of HIV medicine. 2015 April 28; DOI:10.4102/hivmed.v16i1.376
Journal Article > ResearchFull Text
PLOS One. 2018 October 11; Volume 13 (Issue 10); DOI:10.1371/journal.pone.0205455
Patten GE, Bernheimer J, Fairlie L, Rabie H, Sawry S, et al.
PLOS One. 2018 October 11; Volume 13 (Issue 10); DOI:10.1371/journal.pone.0205455
BACKGROUND:
In resource-limited settings holding regimens, such as lamivudine monotherapy (LM), are used to manage HIV-positive children failing combination antiretroviral therapy (cART) to mitigate the risk of drug resistance developing, whilst adherence barriers are addressed or when access to second- or third-line regimens is restricted. We aimed to investigate characteristics of children placed on LM and their outcomes.
METHODS:
We describe the characteristics of children (age <16 years at cART start) from 5 IeDEA-SA cohorts with a record of LM during their treatment history. Among those on LM for >90 days we describe their immunologic outcomes on LM and their immunologic and virologic outcomes after resuming cART.
FINDINGS:
We included 228 children in our study. At LM start their median age was 12.0 years (IQR 7.3-14.6), duration on cART was 3.6 years (IQR 2.0-5.9) and median CD4 count was 605.5 cells/μL (IQR 427-901). Whilst 110 (48%) had no prior protease inhibitor (PI)-exposure, of the 69 with recorded PI-exposure, 9 (13%) patients had documented resistance to all PIs. After 6 months on LM, 70% (94/135) experienced a drop in CD4, with a predicted average CD4 decline of 46.5 cells/μL (95% CI 37.7-55.4). Whilst on LM, 46% experienced a drop in CD4 to <500 cells/μL, 18 (8%) experienced WHO stage 3 or 4 events, and 3 children died. On resumption of cART the average gain in CD4 was 15.65 cells/uL per month and 66.6% (95% CI 59.3-73.7) achieved viral suppression (viral load <1000) at 6 months after resuming cART.
INTERPRETATION:
Most patients experienced immune decline on LM. Its use should be avoided in those with low CD4 counts, but restricted use may be necessary when treatment options are limited. Managing children with virologic failure will continue to be challenging until more treatment options and better adherence strategies are available.
In resource-limited settings holding regimens, such as lamivudine monotherapy (LM), are used to manage HIV-positive children failing combination antiretroviral therapy (cART) to mitigate the risk of drug resistance developing, whilst adherence barriers are addressed or when access to second- or third-line regimens is restricted. We aimed to investigate characteristics of children placed on LM and their outcomes.
METHODS:
We describe the characteristics of children (age <16 years at cART start) from 5 IeDEA-SA cohorts with a record of LM during their treatment history. Among those on LM for >90 days we describe their immunologic outcomes on LM and their immunologic and virologic outcomes after resuming cART.
FINDINGS:
We included 228 children in our study. At LM start their median age was 12.0 years (IQR 7.3-14.6), duration on cART was 3.6 years (IQR 2.0-5.9) and median CD4 count was 605.5 cells/μL (IQR 427-901). Whilst 110 (48%) had no prior protease inhibitor (PI)-exposure, of the 69 with recorded PI-exposure, 9 (13%) patients had documented resistance to all PIs. After 6 months on LM, 70% (94/135) experienced a drop in CD4, with a predicted average CD4 decline of 46.5 cells/μL (95% CI 37.7-55.4). Whilst on LM, 46% experienced a drop in CD4 to <500 cells/μL, 18 (8%) experienced WHO stage 3 or 4 events, and 3 children died. On resumption of cART the average gain in CD4 was 15.65 cells/uL per month and 66.6% (95% CI 59.3-73.7) achieved viral suppression (viral load <1000) at 6 months after resuming cART.
INTERPRETATION:
Most patients experienced immune decline on LM. Its use should be avoided in those with low CD4 counts, but restricted use may be necessary when treatment options are limited. Managing children with virologic failure will continue to be challenging until more treatment options and better adherence strategies are available.
Journal Article > ResearchFull Text
Int J Tuberc Lung Dis. 2023 August 1; Volume 27 (Issue 8); 584-598.; DOI:10.5588/ijtld.23.0085
Chiang SS, Graham SM, Schaaf HS, Marais BJ, Sant’Anna CC, et al.
Int J Tuberc Lung Dis. 2023 August 1; Volume 27 (Issue 8); 584-598.; DOI:10.5588/ijtld.23.0085
BACKGROUND
These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.
METHODS
Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.
RESULTS
Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.
CONCLUSION
These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.
These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.
METHODS
Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.
RESULTS
Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.
CONCLUSION
These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.
Journal Article > ResearchFull Text
AIDS. 2014 October 23; Volume 28 (Issue 16); 2451-60.; DOI:10.1097/qad.0000000000000446
Salazar-Vizcaya L, Keiser O, Technau KG, Davies MA, Haas AD, et al.
AIDS. 2014 October 23; Volume 28 (Issue 16); 2451-60.; DOI:10.1097/qad.0000000000000446
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.
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.
Journal Article > ResearchFull Text
Trop Med Int Health. 2012 September 1; Volume 7 (Issue 11); 1386-1390.; DOI:10.1111/j.1365-3156.2012.03073.x
Davies MA, Boulle AM, Technau KG, Eley B, Moultrie H, et al.
Trop Med Int Health. 2012 September 1; Volume 7 (Issue 11); 1386-1390.; DOI:10.1111/j.1365-3156.2012.03073.x
OBJECTIVES
To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV-infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure.
METHODS
Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Immunological failure was defined according to both WHO 2010 and United States Department of Health and Human Services (DHHS) 2008 criteria. Confirmed virological failure was defined as HIV-RNA >5000 copies/ml on two consecutive occasions <365 days apart in a child on ART for ≥18 months.
RESULTS
Among 2798 children on ART for ≥18 months [median (IQR) age 50 (21-84) months at ART initiation], the cumulative probability of confirmed virological failure by 42 months on ART was 6.3%. Using targeted viral load after meeting DHHS immunological failure criteria rather than DHHS immunological failure criteria alone increased positive predictive value from 28% to 82%. Targeted viral load improved the positive predictive value of WHO 2010 criteria for identifying confirmed virological failure from 49% to 82%.
CONCLUSION
The addition of a single viral load measurement in children identified as failing immunologically will prevent most switches to second-line treatment in virologically suppressed children.
To determine the improvement in positive predictive value of immunological failure criteria for identifying virological failure in HIV-infected children on antiretroviral therapy (ART) when a single targeted viral load measurement is performed in children identified as having immunological failure.
METHODS
Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Immunological failure was defined according to both WHO 2010 and United States Department of Health and Human Services (DHHS) 2008 criteria. Confirmed virological failure was defined as HIV-RNA >5000 copies/ml on two consecutive occasions <365 days apart in a child on ART for ≥18 months.
RESULTS
Among 2798 children on ART for ≥18 months [median (IQR) age 50 (21-84) months at ART initiation], the cumulative probability of confirmed virological failure by 42 months on ART was 6.3%. Using targeted viral load after meeting DHHS immunological failure criteria rather than DHHS immunological failure criteria alone increased positive predictive value from 28% to 82%. Targeted viral load improved the positive predictive value of WHO 2010 criteria for identifying confirmed virological failure from 49% to 82%.
CONCLUSION
The addition of a single viral load measurement in children identified as failing immunologically will prevent most switches to second-line treatment in virologically suppressed children.
Journal Article > ResearchFull Text
J Acquir Immune Defic Syndr. 2011 March 1; Volume 56 (Issue 3); DOI:10.1097/QAI.0b013e3182060610
Davies MA, Moultrie H, Eley B, Rabie H, van Cutsem G, et al.
J Acquir Immune Defic Syndr. 2011 March 1; Volume 56 (Issue 3); DOI:10.1097/QAI.0b013e3182060610
With expanding pediatric antiretroviral therapy (ART) access, children will begin to experience treatment failure and require second-line therapy. We evaluated the probability and determinants of virologic failure and switching in children in South Africa.