Total Lymphocyte Count: Not a Surrogate Marker for Risk of Death in HIV-Infected Ugandan Children

Musoke, Philippa; Young, Alicia; Owor, Maxensia; Lubega, Irene; Brown, Elizabeth R.; Mmiro, Francis; Mofenson, Lynne; Jackson, J. Brooks; Fowler, Mary Glenn; Guay, Laura

doi:10.1097/qai.0b013e318183a92a

Cited by 3 publications

(2 citation statements)

References 31 publications

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“…We found the WHO 2006 TLC thresholds defining immuno-suppression to have low sensitivity but high specificity for detecting severely depressed CD4 count in these Kenyan children, and sensitivity was lowest among young children under 5 years (<34%). In contrast to the CD4 count, there was very poor correlation between TLC and CD4% (r = 0.06) similar to weak correlation (r = 0.01) reported by Musoke in Ugandan children [ 24 ].…”

Section: Discussionsupporting

confidence: 52%

Utility of total lymphocyte count as a surrogate marker for CD4 counts in HIV-1 infected children in Kenya

et al. 2011

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BackgroundIn resource-limited settings, such as Kenya, access to CD4 testing is limited. Therefore, evaluation of less expensive laboratory diagnostics is urgently needed to diagnose immuno-suppression in children.ObjectivesTo evaluate utility of total lymphocyte count (TLC) as surrogate marker for CD4 count in HIV-infected children.MethodsThis was a hospital based retrospective study conducted in three HIV clinics in Kisumu and Nairobi in Kenya. TLC, CD4 count and CD4 percent data were abstracted from hospital records of 487 antiretroviral-naïve HIV-infected children aged 1 month - 12 years.ResultsTLC and CD4 count were positively correlated (r = 0.66, p < 0.001) with highest correlation seen in children with severe immuno-suppression (r = 0.72, p < 0.001) and children >59 months of age (r = 0.68, p < 0.001). Children were considered to have severe immuno-suppression if they met the following WHO set CD4 count thresholds: age below 12 months (CD4 counts < 1500 cells/mm3), age 12-35 months (CD4 count < 750 cells/mm3), age 36-59 months (CD4 count < 350 cells/mm3, and age above 59 months (CD4 count < 200 cells/mm3). WHO recommended TLC threshold values for severe immuno-suppression of 4000, 3000, 2500 and 2000 cells/mm3 for age categories <12, 12-35, 36-59 and >59 months had low sensitivity of 25%, 23%, 33% and 62% respectively in predicting severe immuno-suppression using CD4 count as gold standard. Raising TLC thresholds to 7000, 6000, 4500 and 3000 cells/mm3 for each of the stated age categories increased sensitivity to 71%, 64%, 56% and 86%, with positive predictive values of 85%, 61%, 37%, 68% respectively but reduced specificity to 73%, 62%, 54% and 68% with negative predictive values of 54%, 65%, 71% and 87% respectively.ConclusionTLC is positively correlated with absolute CD4 count in children but current WHO age-specific thresholds had low sensitivity to identify severely immunosuppressed Kenyan children. Sensitivity and therefore utility of TLC to identify immuno-suppressed children may be improved by raising the TLC cut off levels across the various age categories.

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Section: Discussionsupporting

confidence: 52%

Utility of total lymphocyte count as a surrogate marker for CD4 counts in HIV-1 infected children in Kenya

et al. 2011

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“…13,15,21 However, in low income settings, measurement of many of these prognostic factors, including CD4, is often unavailable. 22 The International epidemiologic Databases to Evaluate AIDS Southern Africa (IeDEA-SA) Collaboration includes data from children starting ART at 11 treatment programs in a range of settings in four countries. 3,20 We aimed to use these data to develop a prognostic model that estimates the cumulative probability of death at 3, 6 and 12 months after starting ART according to age, and prognostic factors commonly measured in resource-limited settings.…”

mentioning

confidence: 99%

Prognosis of Children With HIV-1 Infection Starting Antiretroviral Therapy in Southern Africa

Davies

May

Bolton‐Moore³

et al. 2014

Pediatric Infectious Disease Journal

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Background 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. Methods 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. Results 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). Conclusion 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.

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Monitoring HIV Treatment in Resource‐Limited Settings: Reassuring News on the Usefulness of CD4⁺Cell Counts

Fowler

Owor

2009

J INFECT DIS

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Total Lymphocyte Count: Not a Surrogate Marker for Risk of Death in HIV-Infected Ugandan Children

Cited by 3 publications

References 31 publications

Utility of total lymphocyte count as a surrogate marker for CD4 counts in HIV-1 infected children in Kenya

Utility of total lymphocyte count as a surrogate marker for CD4 counts in HIV-1 infected children in Kenya

Prognosis of Children With HIV-1 Infection Starting Antiretroviral Therapy in Southern Africa

Monitoring HIV Treatment in Resource‐Limited Settings: Reassuring News on the Usefulness of CD4⁺Cell Counts

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Total Lymphocyte Count: Not a Surrogate Marker for Risk of Death in HIV-Infected Ugandan Children

Cited by 3 publications

References 31 publications

Utility of total lymphocyte count as a surrogate marker for CD4 counts in HIV-1 infected children in Kenya

Utility of total lymphocyte count as a surrogate marker for CD4 counts in HIV-1 infected children in Kenya

Prognosis of Children With HIV-1 Infection Starting Antiretroviral Therapy in Southern Africa

Monitoring HIV Treatment in Resource‐Limited Settings: Reassuring News on the Usefulness of CD4+Cell Counts

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Monitoring HIV Treatment in Resource‐Limited Settings: Reassuring News on the Usefulness of CD4⁺Cell Counts