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Published in: BMC Public Health 1/2019

Open Access 01-12-2019 | Human Immunodeficiency Virus | Research article

Long-term survival outcomes of HIV infected children receiving antiretroviral therapy: an observational study from Zambia (2003–2015)

Authors: Jane N. Mutanga, Simon Mutembo, Amara E. Ezeamama, Xiao Song, Robert C. Fubisha, Kunda Mutesu-Kapembwa, Derrick Sialondwe, Brenda Simuchembu, Jelita Chinyonga, Philip E. Thuma, Christopher C. Whalen

Published in: BMC Public Health | Issue 1/2019

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Abstract

Background

In 2017, 64% of children living with HIV in Zambia accessed Antiretroviral Therapy (ART). Despite expanded ART coverage, there is paucity of information on effectiveness of pediatric ART in reducing mortality. The aim of this research is to describe treatment outcomes, measure mortality rates and assess predictors of mortality among children receiving ART.

Methods

Using a retrospective cohort study design, we abstracted routinely collected clinical data from medical records of children from birth to 15 years old, who had received ART for at least 6 months at Livingstone Central Hospital in Southern Province Zambia, between January 2003 and June 2015. The primary outcome was death. Cause of death was ascertained from medical records and death certificates. Distribution of survival times according to baseline covariates were estimated using Kaplan Meier and Cox Proportional Hazards methods.

Results

Overall, 1039 children were commenced on ART during the study period. The median age at treatment initiation was 3.6 years (IQR: 1.3–8.6) and 520 (50%) children were female. Of these, 71 (7%) died, 164 (16%) were lost to follow-up, 210 (20%) transferred and 594 (56%) were actively on treatment. After 4450 person years, mortality rate was 1.6/100 (95% CI: 1.4–1.8). Mortality was highest during the first 3 months of treatment (11.7/100 (95% CI: 7.6–16.3). In multivariable proportional hazards regression, the adjusted hazards of death were highest among children aged < 1 year (aHR = 3.1 (95% CI: 1.3–6.4), compared to those aged 6–15 years, WHO stage 4 (aHR =4.8 (95% CI: 2.3–10), compared to WHO stage 1 and 2. In the sensitivity analysis to address bias due to loss to follow-up, mortality increased 5 times when we assumed that all the children who were lost to follow up died within 90 days of their last visit.

Conclusion

We observed low attrition due to mortality among children on ART. Loss to follow-up was high (16%). Mortality was highest during the first 3 months of treatment. Children aged less than one year and those with advanced WHO disease stage had higher mortality. We recommend effective interventions to improve retention in care and early diagnosis of HIV in children.
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Literature
1.
go back to reference Joint United Nations Programme on HIV/AIDS U. On the fast track to an AIDS free generation; the incredible journey of the global plan towards the elimination of new HIV infections by 2015 among children and keeping their mothers alive. Geneva Switzerland: UNAIDS; 2016. Joint United Nations Programme on HIV/AIDS U. On the fast track to an AIDS free generation; the incredible journey of the global plan towards the elimination of new HIV infections by 2015 among children and keeping their mothers alive. Geneva Switzerland: UNAIDS; 2016.
4.
go back to reference Joint United Nations Programme on HIV/AIDS U. 90–90-90 an ambitious target to help end the AIDS epidemic. Geneva Switzerland: UNAIDS; 2014. Joint United Nations Programme on HIV/AIDS U. 90–90-90 an ambitious target to help end the AIDS epidemic. Geneva Switzerland: UNAIDS; 2014.
5.
go back to reference Violari A, Cotton M, Gibb D, Babiker A, Steyn J, Madhi S, et al. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med. 2008;359(21):2233–44.CrossRef Violari A, Cotton M, Gibb D, Babiker A, Steyn J, Madhi S, et al. Early antiretroviral therapy and mortality among HIV-infected infants. N Engl J Med. 2008;359(21):2233–44.CrossRef
6.
go back to reference MOH/CSO/PEPFAR/ICAP/CDC/TDRC/UTH/UNZA. Zambia Population-Based HIV Impact Assessment ZAMPHIA 2015-2016. 2016. MOH/CSO/PEPFAR/ICAP/CDC/TDRC/UTH/UNZA. Zambia Population-Based HIV Impact Assessment ZAMPHIA 2015-2016. 2016.
8.
go back to reference Bolton-Moore C, Mubiana-Mbewe M, Cantrell RA, et al. Clinical outcomes and cd4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia. JAMA. 2007;298(16):1888–99.CrossRef Bolton-Moore C, Mubiana-Mbewe M, Cantrell RA, et al. Clinical outcomes and cd4 cell response in children receiving antiretroviral therapy at primary health care facilities in Zambia. JAMA. 2007;298(16):1888–99.CrossRef
9.
go back to reference Dijk JH, Sutcliffe CG, Munsanje B, Sinywimaanzi P, Hamangaba F, Thuma PE, et al. HIV-infected children in rural Zambia achieve good immunologic and virologic outcomes two years after initiating antiretroviral therapy. PLoS One. 2011;6. Dijk JH, Sutcliffe CG, Munsanje B, Sinywimaanzi P, Hamangaba F, Thuma PE, et al. HIV-infected children in rural Zambia achieve good immunologic and virologic outcomes two years after initiating antiretroviral therapy. PLoS One. 2011;6.
10.
go back to reference Davies M-A, May M, Bolton-Moore C, Chimbetete C, Eley B, Garone D, et al. Prognosis of children with HIV-1 infection starting antiretroviral therapy in southern Africa: a collaborative analysis of treatment programs. Pediatr Infect Dis J. 2014;33(6):608–16.CrossRef Davies M-A, May M, Bolton-Moore C, Chimbetete C, Eley B, Garone D, et al. Prognosis of children with HIV-1 infection starting antiretroviral therapy in southern Africa: a collaborative analysis of treatment programs. Pediatr Infect Dis J. 2014;33(6):608–16.CrossRef
11.
go back to reference Davies M-A, Gibb D, Turkova A. Survival of HIV-1 vertically infected children. Curr Opin HIV AIDS. 2016;11(5):455–64 Web.CrossRef Davies M-A, Gibb D, Turkova A. Survival of HIV-1 vertically infected children. Curr Opin HIV AIDS. 2016;11(5):455–64 Web.CrossRef
12.
go back to reference Koller M, Patel K, Chi BH, Wools-Kaloustian K, Dicko F, Chokephaibulkit K, et al. Immunodeficiency in Children Starting Antiretroviral Therapy in Low-, Middle-, and High-income countries. J Acquir Immune Defic Syndr (1999). 2015;68(1):62–72. Koller M, Patel K, Chi BH, Wools-Kaloustian K, Dicko F, Chokephaibulkit K, et al. Immunodeficiency in Children Starting Antiretroviral Therapy in Low-, Middle-, and High-income countries. J Acquir Immune Defic Syndr (1999). 2015;68(1):62–72.
13.
go back to reference Ardura-Garcia C, Feldacker C, Tweya H, Chaweza T, Kalulu M, Phiri S, et al. Implementation and Operational Research: Early Tracing of Children Lost to Follow-Up From Antiretroviral Treatment: True Outcomes and Future Risks. J Acquir Immune Defic Syndr (1999). 2015;70(5):e160-e1e7. Ardura-Garcia C, Feldacker C, Tweya H, Chaweza T, Kalulu M, Phiri S, et al. Implementation and Operational Research: Early Tracing of Children Lost to Follow-Up From Antiretroviral Treatment: True Outcomes and Future Risks. J Acquir Immune Defic Syndr (1999). 2015;70(5):e160-e1e7.
14.
go back to reference Mutanga J, Raymond J, Towle M, Mutembo S, Fubisha R, Lule F, et al. Institutionalizing provider-initiated HIV testing and counselling for children: an observational case study from Zambia. PLoS One. 2012;7(4):e29656.CrossRef Mutanga J, Raymond J, Towle M, Mutembo S, Fubisha R, Lule F, et al. Institutionalizing provider-initiated HIV testing and counselling for children: an observational case study from Zambia. PLoS One. 2012;7(4):e29656.CrossRef
15.
go back to reference Kankasa C, Carter RJ, Briggs N, Bulterys M, Chama E, Cooper ER, et al. Routine Offering of HIV Testing to Hospitalized Pediatric Patients at University Teaching Hospital, Lusaka, Zambia: Acceptability and Feasibility. J Acquir Immune Defic Syndr (1999). 2009;51(2):202–208. Kankasa C, Carter RJ, Briggs N, Bulterys M, Chama E, Cooper ER, et al. Routine Offering of HIV Testing to Hospitalized Pediatric Patients at University Teaching Hospital, Lusaka, Zambia: Acceptability and Feasibility. J Acquir Immune Defic Syndr (1999). 2009;51(2):202–208.
16.
go back to reference Stringer JA, Zulu I, Levy J, et al. Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA. 2006;296(7):782–93.CrossRef Stringer JA, Zulu I, Levy J, et al. Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes. JAMA. 2006;296(7):782–93.CrossRef
17.
go back to reference Ministry of Health Z. Zambia Consolidated Guidelines for Prevention and Treatment of HIV Infection. 2018. Ministry of Health Z. Zambia Consolidated Guidelines for Prevention and Treatment of HIV Infection. 2018.
18.
go back to reference Newell M-L, Coovadia H, Cortina Borja M, Rollins N, Gaillard P, Dabis F. Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet. 2004;364(9441):1236–43.CrossRef Newell M-L, Coovadia H, Cortina Borja M, Rollins N, Gaillard P, Dabis F. Mortality of infected and uninfected infants born to HIV-infected mothers in Africa: a pooled analysis. Lancet. 2004;364(9441):1236–43.CrossRef
19.
go back to reference Chammartin F, Zürcher K, Keiser O, Weigel R, Chu K, Kiragga AN, et al. Outcomes of patients lost to follow-up in African antiretroviral therapy programs: individual patient data meta-analysis. Clin Infect Dis. 2018;67(11):1643–52.CrossRef Chammartin F, Zürcher K, Keiser O, Weigel R, Chu K, Kiragga AN, et al. Outcomes of patients lost to follow-up in African antiretroviral therapy programs: individual patient data meta-analysis. Clin Infect Dis. 2018;67(11):1643–52.CrossRef
20.
go back to reference Team RC. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2017. Team RC. R: a language and environment for statistical computing. Vienna, Austria: R Foundation for Statistical Computing; 2017.
23.
go back to reference van Dijk JH, Sutcliffe CG, Munsanje B, Sinywimaanzi P, Hamangaba F, Thuma PE, et al. HIV-infected children in rural Zambia achieve good immunologic and Virologic outcomes two years after initiating antiretroviral therapy. PLoS One. 2011;6(4):e19006.CrossRef van Dijk JH, Sutcliffe CG, Munsanje B, Sinywimaanzi P, Hamangaba F, Thuma PE, et al. HIV-infected children in rural Zambia achieve good immunologic and Virologic outcomes two years after initiating antiretroviral therapy. PLoS One. 2011;6(4):e19006.CrossRef
24.
go back to reference Brophy JC, Hawkes MT, Mwinjiwa E, Mateyu G, Sodhi SK, Chan AK. Survival outcomes in a pediatric antiretroviral treatment cohort in southern Malawi. PLoS One. 2016;11(11):e0165772.CrossRef Brophy JC, Hawkes MT, Mwinjiwa E, Mateyu G, Sodhi SK, Chan AK. Survival outcomes in a pediatric antiretroviral treatment cohort in southern Malawi. PLoS One. 2016;11(11):e0165772.CrossRef
25.
go back to reference Cohen S, Smit C, van Rossum AMC, Fraaij PLA, Wolfs TFW, Geelen SPM, et al. Long-term response to combination antiretroviral therapy in HIV-infected children in the Netherlands registered from 1996 to 2012. AIDS. 2013;27(16):2567–75.CrossRef Cohen S, Smit C, van Rossum AMC, Fraaij PLA, Wolfs TFW, Geelen SPM, et al. Long-term response to combination antiretroviral therapy in HIV-infected children in the Netherlands registered from 1996 to 2012. AIDS. 2013;27(16):2567–75.CrossRef
26.
go back to reference Wamalwa DC, Obimbo EM, Farquhar C, Richardson BA, Mbori-Ngacha DA, Inwani I, et al. Predictors of mortality in HIV-1 infected children on antiretroviral therapy in Kenya: a prospective cohort. BMC Pediatr. 2010;10:33.CrossRef Wamalwa DC, Obimbo EM, Farquhar C, Richardson BA, Mbori-Ngacha DA, Inwani I, et al. Predictors of mortality in HIV-1 infected children on antiretroviral therapy in Kenya: a prospective cohort. BMC Pediatr. 2010;10:33.CrossRef
27.
go back to reference Walker AS, Prendergast AJ, Mugyenyi P, Munderi P, Hakim J, Kekitiinwa A, et al. Mortality in the year following antiretroviral therapy initiation in HIV-infected adults and children in Uganda and Zimbabwe. Clin Infect Dis. 2012;55(12):1707–18.CrossRef Walker AS, Prendergast AJ, Mugyenyi P, Munderi P, Hakim J, Kekitiinwa A, et al. Mortality in the year following antiretroviral therapy initiation in HIV-infected adults and children in Uganda and Zimbabwe. Clin Infect Dis. 2012;55(12):1707–18.CrossRef
28.
go back to reference Njom Nlend AE, Loussikila AB. Predictors of mortality among HIV-infected children receiving highly active antiretroviral therapy. Med Mal Infect. 2017;47(1):32–7.CrossRef Njom Nlend AE, Loussikila AB. Predictors of mortality among HIV-infected children receiving highly active antiretroviral therapy. Med Mal Infect. 2017;47(1):32–7.CrossRef
29.
go back to reference Braitstein PBM, Dabis F. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet. 2006;367(9513):817–24.CrossRef Braitstein PBM, Dabis F. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet. 2006;367(9513):817–24.CrossRef
30.
go back to reference Cotton M, Violari A, Otwombe K, Panchia R, Dobbels E, Rabie H, et al. Early time-limited antiretroviral therapy versus deferred therapy in south African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial. Lancet. 2013;382(9904):1555–63.CrossRef Cotton M, Violari A, Otwombe K, Panchia R, Dobbels E, Rabie H, et al. Early time-limited antiretroviral therapy versus deferred therapy in south African infants infected with HIV: results from the children with HIV early antiretroviral (CHER) randomised trial. Lancet. 2013;382(9904):1555–63.CrossRef
31.
go back to reference Ministry of Health Z, National AIDS Council, Zambia. Zambia Country Report: Monitoring the declaration of commitment on HIV/AIDS and the Universal Access. Lusaka, Zambia; 2015 5/2/2017. Ministry of Health Z, National AIDS Council, Zambia. Zambia Country Report: Monitoring the declaration of commitment on HIV/AIDS and the Universal Access. Lusaka, Zambia; 2015 5/2/2017.
32.
go back to reference Marston M, Becquet R, Zaba B, Moulton L, Gray G, Coovadia H, et al. Net survival of perinatally and postnatally HIV-infected children: a pooled analysis of individual data from sub-Saharan Africa. Int J Epidemiol. 2011;40(2):385–96.CrossRef Marston M, Becquet R, Zaba B, Moulton L, Gray G, Coovadia H, et al. Net survival of perinatally and postnatally HIV-infected children: a pooled analysis of individual data from sub-Saharan Africa. Int J Epidemiol. 2011;40(2):385–96.CrossRef
33.
go back to reference Luzuriaga K. Early combination antiretroviral therapy limits HIV-1 persistence in children. Annu Rev Med. 2016;67(1):201–13.CrossRef Luzuriaga K. Early combination antiretroviral therapy limits HIV-1 persistence in children. Annu Rev Med. 2016;67(1):201–13.CrossRef
34.
go back to reference Wagner A, Slyker J, Langat A, Inwani I, Adhiambo J, Benki-Nugent S, et al. High mortality in HIV-infected children diagnosed in hospital underscores need for faster diagnostic turnaround time in prevention of mother-to-child transmission of HIV (PMTCT) programs. BMC Pediatr. 2015;15:10.CrossRef Wagner A, Slyker J, Langat A, Inwani I, Adhiambo J, Benki-Nugent S, et al. High mortality in HIV-infected children diagnosed in hospital underscores need for faster diagnostic turnaround time in prevention of mother-to-child transmission of HIV (PMTCT) programs. BMC Pediatr. 2015;15:10.CrossRef
35.
go back to reference Central Statistics Office MoH, Tropical Disease Research Centre University of Zambia and Macro International Inc. Zambia Demographic and Health Survey Maryland, USA: ICF International Rockville; 2014. p. 13–4.; 2013-2014. Central Statistics Office MoH, Tropical Disease Research Centre University of Zambia and Macro International Inc. Zambia Demographic and Health Survey Maryland, USA: ICF International Rockville; 2014. p. 13–4.; 2013-2014.
37.
go back to reference Boulware DR, Callens S, Pahwa S. Pediatric HIV immune reconstitution inflammatory syndrome. Curr Opin HIV AIDS. 2008;3(4):461–7.CrossRef Boulware DR, Callens S, Pahwa S. Pediatric HIV immune reconstitution inflammatory syndrome. Curr Opin HIV AIDS. 2008;3(4):461–7.CrossRef
38.
go back to reference Escamilla V, Chibwesha CJ, Gartland M, Chintu N, Mubiana-Mbewe M, Musokotwane K, et al. Distance from household to clinic and its association with the uptake of prevention of mother-to-child HIV transmission regimens in rural Zambia. J Acquir Immune Defic Syndr (1999). 2015;70(3):e94-e101. Escamilla V, Chibwesha CJ, Gartland M, Chintu N, Mubiana-Mbewe M, Musokotwane K, et al. Distance from household to clinic and its association with the uptake of prevention of mother-to-child HIV transmission regimens in rural Zambia. J Acquir Immune Defic Syndr (1999). 2015;70(3):e94-e101.
39.
go back to reference Sam-Agudu NA, Ramadhani HO, Isah C, Erekaha S, Fan-Osuala C, Anaba U, et al. The Impact of Structured Mentor Mother Programs on Presentation for Early Infant Diagnosis Testing in Rural North-Central Nigeria: A Prospective Paired Cohort Study. J Acquir Immune Defic Syndr (1999). 2017;75:S182-S1S9. Sam-Agudu NA, Ramadhani HO, Isah C, Erekaha S, Fan-Osuala C, Anaba U, et al. The Impact of Structured Mentor Mother Programs on Presentation for Early Infant Diagnosis Testing in Rural North-Central Nigeria: A Prospective Paired Cohort Study. J Acquir Immune Defic Syndr (1999). 2017;75:S182-S1S9.
Metadata
Title
Long-term survival outcomes of HIV infected children receiving antiretroviral therapy: an observational study from Zambia (2003–2015)
Authors
Jane N. Mutanga
Simon Mutembo
Amara E. Ezeamama
Xiao Song
Robert C. Fubisha
Kunda Mutesu-Kapembwa
Derrick Sialondwe
Brenda Simuchembu
Jelita Chinyonga
Philip E. Thuma
Christopher C. Whalen
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Public Health / Issue 1/2019
Electronic ISSN: 1471-2458
DOI
https://doi.org/10.1186/s12889-019-6444-7

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