HIV-Infected Children in Rural Zambia Achieve Good Immunologic and Virologic Outcomes Two Years after Initiating Antiretroviral Therapy

Dijk, Janneke H. van; Sutcliffe, Catherine G.; Munsanje, Bornface; Sinywimaanzi, Pamela; Hamangaba, Francis; Thuma, Philip E.; Moss, William J.

doi:10.1371/journal.pone.0019006

Cited by 64 publications

(70 citation statements)

References 32 publications

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“…Median CD4 + T cell percentage increased from 3.16 (IQR 1-18) % to 11.0 (IQR 2-32) %, whereas median CD4 + absolute cell count increased from 9.5 (IQR 3-176) cell/mm 3 to 419.5 (IQR 202-1428) cell/mm 3 . Baseline level of CD4 + cell count in our study was very low compared with other studies [15,[19][20][21][22], but this result was not much different from baseline levels from 8 sites in Asia [14]. After ART initiation, CD4…”

Section: Discussioncontrasting

confidence: 71%

Immunological outcomes after six months with first line antiretroviral therapy: a lesson from Yogyakarta, Indonesia

Pangarungan¹,

Arguni²

2018

J Infect Dev Ctries

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Introduction: More than 1,300 children aged 0-14 years were infected with HIV in Indonesia by 2016. Adequate antiretroviral therapy (ART) can increase nutritional and immunological status, reduce incidence of opportunistic infection and mortality caused by HIV infection. After ART initiation, the children's treatment response needs to be monitored with CD4 + cell count and Viral Load (VL) evaluation. In resourcelimited setting, clinical and immunological parameters can be used to evaluate ART outcomes. The aimed of this study to know immunological status of the patient after 6 months ART in Dr. Sardjito Hospital in Yogyakarta, Indonesia. Methodology: A retrospective study was conducted from January 2010 to May 2016. HIV-infected children aged 0-18 years who were given first-line ART at least 6 months were included in this study. Age when ART initiation, gender, residence, nutritional status, clinical staging based on WHO criteria, incidence of hospitalization, baseline CD4 + cell count and CD4 + cell count after 6 months of therapy, tuberculosis treatment, and ART regimens were collected from medical records. Data were entered and analyzed using SPSS version 20.0 Results: Thirty-five subjects were included in this study. Median CD4 + T cell percentage increased from 3.16 (IQR 1-18) % to 11.0 (IQR 2-32) %, whereas median CD4 + absolute cell count increased from 9.5 (IQR 3-176) cell/mm 3 to 419.5 (IQR 202-1428) cell/mm 3 . Conclusion: Immunologic conditions could improve even with very low levels of CD4 + T cell percentage and CD4 + absolute cell count. Monitoring immunologic conditions and adherence of children with ART are essential to improve treatment outcomes.

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Section: Discussioncontrasting

confidence: 71%

Immunological outcomes after six months with first line antiretroviral therapy: a lesson from Yogyakarta, Indonesia

Pangarungan¹,

Arguni²

2018

J Infect Dev Ctries

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“…6,8 The overall and early mortality rates of 4.17 and 7.95 deaths per 100 py observed in this cohort were lower than rates observed in other studies of children receiving HAART in sub-Saharan Africa. [3][4][5][6]8,28 A mortality rate of 17.4 deaths per 100 py was observed within the first 90 days of HAART in a large study of Zambian children in urban Lusaka. 5 Within 4 months of beginning HAART, Kenyan children died at the strikingly high rate of 46 deaths per 100 py.…”

Section: Discussionmentioning

confidence: 99%

“…1 However, mortality rates of children during the first few months of HAART remain comparable to rates prior to HAART eligibility and approximately 10-20% of children die within the first few months of starting HAART. [2][3][4][5][6][7] In Kenyan children, 90% of deaths occurred within 90 days of starting HAART, and 77% of deaths in children in the Democratic Republic of the Congo were within 60 days of starting HAART. 6,8 Similarly, a recent metaanalysis estimated that 17% of HIV-infected adults initiating HAART in sub-Saharan Africa died within 12 months.…”

Section: Introductionmentioning

confidence: 99%

“…9 Several studies assessed clinical and demographic risk factors for mortality in HIV-infected children beginning HAART and consistently identified low CD4 + T cell percentage or count, low weight-for-age z-score, young age, and increased severity of coinfections to be associated with mortality after treatment initiation. 2,4,5,8,10 Only one assessed the relationship with plasma HIV viral load and found higher HIV viral load was associated with an increased risk of mortality. 4 T cell activation markers, particularly HLA-DR and CD38, have been associated with HIV disease progression, [11][12][13] but beyond CD4 + T cell levels, few reports link specific T cell subsets with the risk of mortality.…”

Section: Introductionmentioning

confidence: 99%

“…2,4,5,8,10 Only one assessed the relationship with plasma HIV viral load and found higher HIV viral load was associated with an increased risk of mortality. 4 T cell activation markers, particularly HLA-DR and CD38, have been associated with HIV disease progression, [11][12][13] but beyond CD4 + T cell levels, few reports link specific T cell subsets with the risk of mortality. 14 In addition to depleting CD4 + T cells, HIV infection induces a chronic state of immune activation that impairs emigration of naive T cells from the thymus, 15 increases T cell activation and turnover, 16,17 and results in increased levels of effector cells as well as decreased proliferative and functional capacity.…”

Section: Introductionmentioning

confidence: 99%

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Immunologic Risk Factors for Early Mortality After Starting Antiretroviral Therapy in HIV-Infected Zambian Children

Rainwater-Lovett

Nkamba

Mubiana‐Mbewe

et al. 2013

AIDS Research and Human Retroviruses

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To explore immunologic risk factors for death within 90 days of highly active antiretroviral therapy (HAART) initiation, CD4(+) and CD8(+) T cell subsets were measured by flow cytometry and characterized by logistic regression in 149 Zambian children between 9 months and 10 years of age enrolled in a prospective, observational study of the impact of HAART on measles immunity. Of 21 children who died during follow-up, 17 (81%) had known dates of death and 16 (76%) died within 90 days of initiating HAART. Young age and low weight-for-age z-scores were associated with increased risks of mortality within 90 days of starting HAART, whereas CD4(+) T cell percentage was not associated with mortality. After adjusting for these factors, each 10% increase in CD8(+) effector T cells increased the odds of overall mortality [OR=1.43 (95% CI: 1.08, 1.90)] and was marginally associated with early mortality [OR=1.29 (95% CI: 0.97, 1.72)]. Conversely, each 10% increase in CD4(+) central memory T cells decreased the odds of overall [OR=0.06 (95% CI: 0.01, 0.59)] and early mortality [OR=0.09 (95% CI: 0.01, 0.97)]. Logistic regression prediction models demonstrated areas under the receiver-operator characteristic curves of ≥85% for early and overall mortality, with bootstrapped sensitivities of 82-85% upon validation, supporting the predictive accuracy of the models. CD4(+) and CD8(+) T cell subsets may be more accurate predictors of early mortality than CD4(+) T cell percentages and could be used to identify children who would benefit from more frequent clinical monitoring after initiating HAART.

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HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape, South Africa

et al. 2018

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IntroductionThere are limited data on viral suppression (VS) in children with HIV receiving antiretroviral therapy (ART) in routine care in low‐resource settings. We examined VS in a cohort of children initiating ART in routine HIV care in Eastern Cape Province, South Africa.MethodsThe Pediatric Enhanced Surveillance Study enrolled HIV‐infected ART eligibility children zero to twelve years at five health facilities from 2012 to 2014. All children received routine HIV care and treatment services and attended quarterly study visits for up to 24 months. Time to VS among those starting treatment was measured from ART start date to first viral load (VL) result <1000 and VL <50 copies/mL using competing risk estimators (death as competing risk). Multivariable sub‐distributional hazards models examined characteristics associated with VS and VL rebound following suppression among those with a VL >30 days after the VS date.ResultsOf 397 children enrolled, 349 (87.9%) started ART: 118 (33.8%) children age <12 months, 122 (35.0%) one to five years and 109 (31.2%) six to twelve years. At study enrolment, median weight‐for‐age z‐score (WAZ) was −1.7 (interquartile range (IQR):−3.1 to −0.4) and median log VL was 5.6 (IQR: 5.0 to 6.2). Cumulative incidence of VS <1000 copies/mL at six, twelve and twenty‐four months was 57.6% (95% CI 52.1 to 62.7), 78.7% (95% CI 73.7 to 82.9) and 84.0% (95% CI 78.9 to 87.9); for VS <50 copies/mL: 40.3% (95% CI 35.0 to 45.5), 63.9% (95% CI 58.2 to 69.0) and 72.9% (95% CI 66.9 to 78.0). At 12 months only 46.6% (95% CI 36.6 to 56.0) of children <12 months had achieved VS <50 copies/mL compared to 76.9% (95% CI 67.9 to 83.7) of children six to twelve years (p < 0.001). In multivariable models, children with VL >1 million copies/mL at ART initiation were half as likely to achieve VS <50 copies/mL (adjusted sub‐distributional hazards 0.50; 95% CI 0.36 to 0.71). Among children achieving VS <50 copies/mL, 37 (19.7%) had VL 50 to 1000 copies/mL and 31 (16.5%) had a VL >1000 copies/mL. Children <12 months had twofold increased risk of VL rebound to VL >1000 copies/mL (adjusted relative risk 2.03, 95% CI: 1.10 to 3.74) compared with six to twelve year olds.ConclusionsWe found suboptimal VS among South African children initiating treatment and high proportions experiencing VL rebound, particularly among younger children. Greater efforts are needed to ensure that all children achieve optimal outcomes.

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HIV-Infected Children in Rural Zambia Achieve Good Immunologic and Virologic Outcomes Two Years after Initiating Antiretroviral Therapy

Cited by 64 publications

References 32 publications

Immunological outcomes after six months with first line antiretroviral therapy: a lesson from Yogyakarta, Indonesia

Immunological outcomes after six months with first line antiretroviral therapy: a lesson from Yogyakarta, Indonesia

Immunologic Risk Factors for Early Mortality After Starting Antiretroviral Therapy in HIV-Infected Zambian Children

HIV viral suppression and longevity among a cohort of children initiating antiretroviral therapy in Eastern Cape, South Africa

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