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Published on: October 31, 2010
Optimizing frequency of CD4 assays in the era of highly active antiretroviral therapy
Aditya H Gaur1, Patricia M Flynn, Wally Bitar
1Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. aditya.gaur@stjude.org
Insights
This study suggests CD4 counts for children with HIV can be monitored less frequently than current guidelines recommend. Predictive modeling accurately identifies CD4 levels, potentially reducing testing frequency and costs.
Area of Science:
- Pediatric Infectious Diseases
- Clinical Immunology
- HIV Medicine
Background:
- Current HIV guidelines advocate for CD4 monitoring every 3-4 months.
- The advent of highly active antiretroviral therapy (HAART) and HIV PCR necessitates reevaluation of CD4 assay frequency.
- CD4 counts are crucial for assessing immune status and guiding prophylaxis in HIV-infected children.
Purpose of the Study:
- To reexamine the required frequency of CD4 assays in HIV-infected children and adolescents.
- To determine if CD4 count monitoring can be reduced in the era of HAART and HIV PCR.
- To assess the predictive accuracy of modeling for CD4 count thresholds relevant to Pneumocystis jiroveci pneumonia (PCP) prophylaxis.
Main Methods:
- Retrospective analysis of CD4 counts and HIV viral loads (VL) in children and adolescents.
- Utilized recursive partitioning-based regression tree analysis to predict CD4 count outcomes.
- Model validation performed using learning and training datasets, with 1,000 random repeats for robust assessment.
Main Results:
- Predictive models demonstrated high accuracy: 93% (Group I) and 97% (Group II) on initial testing, and 89.6% (SE 2.3%) (Group I) and 95.6% (SE 1%) (Group II) after 1,000 repeats.
- Key predictors for CD4 count included age, prior CD4 count, HIV VL, time interval since last VL/CD4, and antiretroviral history.
- The classification tree effectively predicted CD4 counts relative to the PCP prophylaxis cutoff.
Conclusions:
- CD4 assay frequency can likely be reduced in HIV-infected children and adolescents, challenging current 3-4 month monitoring guidelines.
- Modeling-based approaches offer a reliable method to determine appropriate CD4 monitoring intervals.
- This strategy holds potential for significant cost savings and broader applicability in HIV management.
Abstract:
Current HIV guidelines recommend monitoring CD4 counts every 3-4 months. In the era of highly active antiretroviral therapy (HAART) and HIV PCR, this retrospective study reexamines the required frequency of the CD4 assay. Predictor variables, including age, previous CD4 count, HIV viral load (VL), time interval since last VL and CD4 count (TINT), and antiretroviral history, were abstracted. A recursive partitioning-based regression tree analysis was used to determine if the absolute current CD4 count was above or below the age appropriate Pneumocystis jiroveci pneumonia (PCP) prophylaxis cutoff. We analyzed concurrently obtained VLs and CD4 count including 601 results from 43 HIV-infected children aged 1-<6 years (Group I) and 1,364 results from 93 children/adolescents 6-<23 years (Group II). Using 75% of observations to build a predictive model (learning dataset), the ability to correctly predict the range of the outcome variable in the remaining 25% of observations (training dataset) was 93% in Group I and 97% in Group II. Predictor variables included age, recent VL and CD4 count, and TINT. A total of 1,000 repeats of this model building using randomly selected observations showed a correct predictive ability of 89.6% [standard error (SE) 2.3%] in Group I and 95.6% (SE 1%) in Group II. The ability of a classification tree to determine if the current CD4 count is above or below the age-specific cutoff for PCP prophylaxis is very good and allows less frequent CD4 assays. The principles underlying this modeling-based approach have broad applicability and cost saving implications.
