Development and Validation of Decision Rules to Guide Frequency of Monitoring CD4 Cell Count in HIV-1 Infection before Starting Antiretroviral Therapy

Abstract

BackgroundAlthough CD4 cell count monitoring is used to decide when to start antiretroviral therapy in patients with HIV-1 infection, there are no evidence-based recommendations regarding its optimal frequency. It is common practice to monitor every 3 to 6 months, often coupled with viral load monitoring. We developed rules to guide frequency of CD4 cell count monitoring in HIV infection before starting antiretroviral therapy, which we validated retrospectively in patients from the Swiss HIV Cohort Study.Methodology/Principal FindingsWe built up two prediction rules (“Snap-shot rule” for a single sample and “Track-shot rule” for multiple determinations) based on a systematic review of published longitudinal analyses of CD4 cell count trajectories. We applied the rules in 2608 untreated patients to classify their 18 061 CD4 counts as either justifiable or superfluous, according to their prior ≥5% or <5% chance of meeting predetermined thresholds for starting treatment. The percentage of measurements that both rules falsely deemed superfluous never exceeded 5%. Superfluous CD4 determinations represented 4%, 11%, and 39% of all actual determinations for treatment thresholds of 500, 350, and 200×106/L, respectively. The Track-shot rule was only marginally superior to the Snap-shot rule. Both rules lose usefulness for CD4 counts coming near to treatment threshold.Conclusions/SignificanceFrequent CD4 count monitoring of patients with CD4 counts well above the threshold for initiating therapy is unlikely to identify patients who require therapy. It appears sufficient to measure CD4 cell count 1 year after a count >650 for a threshold of 200, >900 for 350, or >1150 for 500×106/L, respectively. When CD4 counts fall below these limits, increased monitoring frequency becomes advisable. These rules offer guidance for efficient CD4 monitoring, particularly in resource-limited settings.

Factors Affecting Timing of Antiretroviral Treatment Initiation Based on Monitoring CD4 Counts

“…For all three thresholds considered, decreasing the frequency to 12-monthly led to a potentially unacceptable increase in the proportion starting ART very late (e.g., 11.5% for the 350 threshold), consistent with a study which suggested 12-monthly monitoring only at very high counts (e.g. > 900 cells/ μ l when using the 350 threshold) [16]. For the 200 and 350 thresholds, if the proportion starting very late with 6-monthly monitoring is considered too high, our results for adaptive algorithms involving 6-monthly and then 3- or 4-monthly monitoring after an initial count below 500 cells/ μ l appears to perform about as well as 4- or 3-monthly monitoring throughout with similar or lower monitoring and treatment costs.…”

Surveillance for ocular hypertension: an evidence synthesis and economic evaluation

“…[230][231][232] This research suggests that, in most cases, measurements are carried out too frequently and that most of the change identified is owing to biological (day-to-day) variability and inherent measurement error and therefore not a real change in the health status of the individual. Clinical decisions such as changes to medication titration based on such measurements are potentially detrimental to a patient's health.…”

The basis for monitoring strategies in clinical guidelines: a case study of prostate-specific antigen for monitoring in prostate cancer

“…More pertinently, statistical models using estimates of mean change and variability in a measurement over time to suggest optimal intervals for monitoring are being developed. A review of four case studies 35 found that for each topic (assessing chol esterol levels for secondary prevention of coronary artery disease, 36 long-term monitoring of blood pressure, 37 measurement of glycated hemoglobin in type 2 diabetes 38 and monitoring of CD4 cell counts in HIV-1 infection 39 ) the results suggested frequent monitoring. There is clear potential for the extension of this work to monitoring in other settings.…”

“…Our use of the original Appraisal of Guidelines for Research and Evaluation instrument 39 may be criticized given that it has been 10 years since its publication; however, at the time the framework was chosen, the update to the original instrument 41 and other potentially useful frameworks 42,43 were not yet available. Nevertheless, our approach to assessing the development and content of the guidelines was systematic and provides a reasonable means of comparing guidelines.…”