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
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 > 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 > Meta-AnalysisFull Text
J Acquir Immune Defic Syndr. 2010 August 1; Volume 54 (Issue 5); DOI:10.1097/QAI.0b013e3181e0c4cf
Fenner L, Brinkhof MW, Keiser O, Weigel R, Cornell M, et al.
J Acquir Immune Defic Syndr. 2010 August 1; Volume 54 (Issue 5); DOI:10.1097/QAI.0b013e3181e0c4cf
BACKGROUND: Many HIV-infected children in Southern Africa have been started on antiretroviral therapy (ART), but loss to follow up (LTFU) can be substantial. We analyzed mortality in children retained in care and in all children starting ART, taking LTFU into account. PATIENTS AND METHODS: Children who started ART before the age of 16 years in 10 ART programs in South Africa, Malawi, Mozambique, and Zimbabwe were included. Risk factors for death in the first year of ART were identified in Weibull models. A meta-analytic approach was used to estimate cumulative mortality at 1 year. RESULTS: Eight thousand two hundred twenty-five children (median age 49 months, median CD4 cell percent 11.6%) were included; 391 (4.8%) died and 523 (7.0%) were LTFU in the first year. Mortality at 1 year was 4.5% [95% confidence interval (CI): 2.8% to 7.4%] in children remaining in care, but 8.7% (5.4% to 12.1%) at the program level, after taking mortality in children and LTFU into account. Factors associated with mortality in children remaining in care included age [adjusted hazard ratio (HR) 0.37; 95% CI: 0.25 to 0.54 comparing > or =120 months with <18 months], CD4 cell percent (HR: 0.56; 95% CI: 0.39 to 0.78 comparing > or =20% with <10%), and clinical stage (HR: 0.12; 95% CI: 0.03 to 0.45 comparing World Health Organization stage I with III/IV). CONCLUSIONS: In children starting ART and remaining in care in Southern Africa mortality at 1 year is <5% but almost twice as high at the program level, when taking LTFU into account. Age, CD4 percentage, and clinical stage are important predictors of mortality at the individual level.
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
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.
Journal Article > ResearchFull Text
AIDS. 2021 January 21; Volume 35 (Issue 6); DOI:10.1097/QAD.0000000000002818
Nyakato P, Schomaker M, Sipambo N, Technau KG, Fatti G, et al.
AIDS. 2021 January 21; Volume 35 (Issue 6); DOI:10.1097/QAD.0000000000002818
Background and objectives:
Adolescents living with perinatally acquired HIV (ALPHIV) on antiretroviral therapy (ART) have been noted to have poorer adherence, retention and virologic control compared to adolescents with nonperinatally acquired HIV, children or adults. We aimed to describe and examine factors associated with longitudinal virologic response during early adolescence.
Design:
A retrospective cohort study
Methods:
We included ALPHIV who initiated ART before age 9.5 years in South African cohorts of the International epidemiology Database to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration (2004–2016); with viral load (VL) values <400 copies/ml at age 10 years and at least one VL measurement after age 10 years. We used a log-linear quantile mixed model to assess factors associated with elevated (75th quantile) VLs.
Results:
We included 4396 ALPHIV, 50.7% were male, with median (interquartile range) age at ART start of 6.5 (4.5, 8.1) years. Of these, 74.9% were on a nonnucleoside reverse transcriptase inhibitor (NNRTI) at age 10 years. After adjusting for other patient characteristics, the 75th quantile VLs increased with increasing age being 3.13-fold (95% CI 2.66, 3.68) higher at age 14 versus age 10, were 3.25-fold (95% CI 2.81, 3.75) higher for patients on second-line protease-inhibitor and 1.81-fold for second-line NNRTI-based regimens (versus first-line NNRTI-based regimens). There was no difference by sex.
Conclusions:
As adolescents age between 10 and 14 years, they are increasingly likely to experience higher VL values, particularly if receiving second-line protease inhibitor or NNRTI-based regimens, which warrant adherence support interventions.
Adolescents living with perinatally acquired HIV (ALPHIV) on antiretroviral therapy (ART) have been noted to have poorer adherence, retention and virologic control compared to adolescents with nonperinatally acquired HIV, children or adults. We aimed to describe and examine factors associated with longitudinal virologic response during early adolescence.
Design:
A retrospective cohort study
Methods:
We included ALPHIV who initiated ART before age 9.5 years in South African cohorts of the International epidemiology Database to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration (2004–2016); with viral load (VL) values <400 copies/ml at age 10 years and at least one VL measurement after age 10 years. We used a log-linear quantile mixed model to assess factors associated with elevated (75th quantile) VLs.
Results:
We included 4396 ALPHIV, 50.7% were male, with median (interquartile range) age at ART start of 6.5 (4.5, 8.1) years. Of these, 74.9% were on a nonnucleoside reverse transcriptase inhibitor (NNRTI) at age 10 years. After adjusting for other patient characteristics, the 75th quantile VLs increased with increasing age being 3.13-fold (95% CI 2.66, 3.68) higher at age 14 versus age 10, were 3.25-fold (95% CI 2.81, 3.75) higher for patients on second-line protease-inhibitor and 1.81-fold for second-line NNRTI-based regimens (versus first-line NNRTI-based regimens). There was no difference by sex.
Conclusions:
As adolescents age between 10 and 14 years, they are increasingly likely to experience higher VL values, particularly if receiving second-line protease inhibitor or NNRTI-based regimens, which warrant adherence support interventions.
Journal Article > ResearchFull Text
Trop Med Int Health. 2011 August 11; Volume 16 (Issue 11); DOI:10.1111/j.1365-3156.2011.02854.x
Davies MA, Boulle AM, Eley B, Moultrie H, Technau KG, et al.
Trop Med Int Health. 2011 August 11; Volume 16 (Issue 11); DOI:10.1111/j.1365-3156.2011.02854.x
Objectives To determine the diagnostic accuracy of World Health Organization (WHO) 2010 and 2006 as well as United States Department of Health and Human Services (DHHS) 2008 definitions of immunological failure for identifying virological failure (VF) in children on antiretroviral therapy (ART). 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. Incomplete virological suppression (IVS) was defined as failure to achieve ≥1 HIV-RNA ≤400 copies/ml between 6 and 15 months on ART and viral rebound (VR) as confirmed HIV-RNA ≥5000 copies/ml in a child on ART for ≥18 months who had achieved suppression during the first year on treatment. Results Among 3115 children [median (interquartile range) age 48 (20-84) months at ART initiation] on treatment for ≥1 year, sensitivity of immunological criteria for IVS was 10%, 6% and 26% for WHO 2006, WHO 2010 and DHHS 2008 criteria, respectively. The corresponding positive predictive values (PPV) were 31%, 20% and 20%. Diagnostic accuracy for VR was determined in 2513 children with ≥18 months of follow-up and virological suppression during the first year on ART with sensitivity of 5% (WHO 2006/2010) and 27% (DHHS 2008). PPV results were 42% (WHO 2010), 43% (WHO 2006) and 20% (DHHS 2008). Conclusion Current immunological criteria are unable to correctly identify children failing ART virologically. Improved access to viral load testing is needed to reliably identify VF in children.