Simplified Clinical Prediction Scores to Target Viral Load Testing in Adults with Suspected First Line Treatment Failure in Phnom Penh, Cambodia

Abstract

BackgroundFor settings with limited laboratory capacity, 2013 World Health Organization (WHO) guidelines recommend targeted HIV-1 viral load (VL) testing to identify virological failure. We previously developed and validated a clinical prediction score (CPS) for targeted VL testing, relying on clinical, adherence and laboratory data. While outperforming the WHO failure criteria, it required substantial calculation and review of all previous laboratory tests. In response, we developed four simplified, less error-prone and broadly applicable CPS versions that can be done ‘on the spot’.Methodology/PrincipalFindings From May 2010 to June 2011, we validated the original CPS in a non-governmental hospital in Phnom Penh, Cambodia applying the CPS to adults on first-line treatment >1 year. Virological failure was defined as a single VL >1000 copies/ml. The four CPSs included CPS1 with ‘current CD4 count’ instead of %-decline-from-peak CD4; CPS2 with hemoglobin measurements removed; CPS3 having ‘decrease in CD4 count below baseline value’ removed; CPS4 was purely clinical. Score development relied on the Spiegelhalter/Knill-Jones method. Variables independently associated with virological failure with a likelihood ratio ≥1.5 or ≤0.67 were retained. CPS performance was evaluated based on the area-under-the-ROC-curve (AUROC) and 95% confidence intervals (CI). The CPSs were validated in an independent dataset. A total of 1490 individuals (56.6% female, median age: 38 years (interquartile range (IQR 33–44)); median baseline CD4 count: 94 cells/µL (IQR 28–205), median time on antiretroviral therapy 3.6 years (IQR 2.1–5.1)), were included. Forty-five 45 (3.0%) individuals had virological failure. CPS1 yielded an AUROC of 0.69 (95% CI: 0.62–0.75) in validation, CPS2 an AUROC of 0.68 (95% CI: 0.62–0.74), and CPS3, an AUROC of 0.67 (95% CI: 0.61–0.73). The purely clinical CPS4 performed poorly (AUROC-0.59; 95% CI: 0.53–0.65).ConclusionsSimplified CPSs retained acceptable accuracy as long as current CD4 count testing was included. Ease of field application and field accuracy remains to be defined.

Development of an algorithm for determination of the likelihood of virological failure in HIV-positive adults receiving antiretroviral therapy in decentralized care

“…We decided to use only robust parameters that have low inter- and intra-observer variability. Furthermore, we did not consider data on trends in laboratory results since such information could be lacking at peripheral clinics and criteria requiring calculations can be error-prone [29]. …”

Predictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy

“…In clinical practice, such a subgroup might be identified for more frequent virologic monitoring or adherence-based intervention. A key finding, also apparent in other studies, 5–8 is that to achieve high sensitivity, that is to identify a subgroup which included the large majority of participants who experienced late virologic failure, the subgroup also included a large majority of participants. For example, the subgroup of participants who reported missed doses or who had a pre-ART hemoglobin <12.4 mg/dL included 82% of participants who experienced late virologic failure (sensitivity of 82%) but also included 78% of participants.…”

“…4 Other studies have evaluated scoring systems based on more extensive immunologic, clinical, laboratory and adherence evaluations with modest improvements. 5–8 …”

Electrolyte and Metabolic Disturbances in Ebola Patients during a Clinical Trial, Guinea, 2015

“…Absolute risks for death could easily be calculated via a spreadsheet or smartphone application. Alternatively, scoring systems could be developed for bedside use ( 29 , 30 ). …”