Optimizing Viral Load Testing in Suspected First-Line ART Failure
Optimizing Viral Load Testing in Suspected First-Line ART Failure
Objective: To develop an algorithm for optimal use of viral load testing in patients with suspected first-line antiretroviral treatment (ART) failure.
Methods: Data from a cohort of patients on first-line ART in Cambodia were analyzed in a cross-sectional way to detect markers for treatment failure. Markers with an adjusted likelihood ratio < 0.67 or > 1.5 were retained to calculate a predictor score. The accuracy of a 2-step algorithm based on this score followed by targeted viral load testing was compared with World Health Organization criteria for suspected treatment failure.
Results: One thousand eight hundred three viral load measurements of 764 patients were available for analysis. Prior ART exposure, CD4 count below baseline, 25% and 50% drop from peak CD4 count, hemoglobin drop of ≥1 g/dL, CD4 count < 100 cells per microliter after 12 months of treatment, new onset of papular pruritic eruption, and visual analog scale < 95% were included in the predictor score. A score ≥2 had the best combination of sensitivity and specificity and required confirmatory viral load testing for only 9% of patients. World Health Organization criteria had a similar sensitivity but a lower specificity and required viral load testing for 24.9% of patients.
Conclusion: An algorithm combining a predictor score with targeted viral load testing in patients with an intermediate probability of failure optimizes the use of scarce resources.
Since 2003, access to antiretroviral therapy (ART) for persons living with HIV in low- and middle-income countries (LMICs) has improved dramatically. In some countries, the coverage of ART for adults and children with advanced HIV is as high as 80%. In Cambodia, a country with one of the highest HIV prevalence in Southeast Asia, 26,664 (67% of estimated need) persons living with HIV were on ART by the end of 2007.
In high-income countries, treatment failure is detected mainly by monitoring viral load. In resource-limited settings, many obstacles make this kind of monitoring difficult. Indeed, viral load testing is costly and technologically complex. Therefore, the World Health Organization (WHO) has proposed guidelines for switching to second-line ART based on clinical and immunological criteria and assessment of adherence. Preliminary studies have shown that immunological and clinical criteria alone are not sensitive enough and have a low positive predictive value (PPV). We and others have tried to develop an alternative set of criteria with higher diagnostic accuracy. We proposed an algorithm based on early clinical indicators, CD4 count, drug history, and adherence data, but this empirical algorithm did not perform well in South Africa.
We did further work on data obtained from an ART cohort study in Cambodia and developed a scoring system that identifies patients with a low, intermediate, and high probability of treatment failure and, as such, allows restricting viral load testing to those patients with an intermediate risk of failure. The goal of this scoring system is to minimize the number of inappropriate switches to second-line treatment while limiting monitoring costs. In this article, we present the development of the scoring system, as well as an evaluation of its accuracy.
Abstract and Introduction
Abstract
Objective: To develop an algorithm for optimal use of viral load testing in patients with suspected first-line antiretroviral treatment (ART) failure.
Methods: Data from a cohort of patients on first-line ART in Cambodia were analyzed in a cross-sectional way to detect markers for treatment failure. Markers with an adjusted likelihood ratio < 0.67 or > 1.5 were retained to calculate a predictor score. The accuracy of a 2-step algorithm based on this score followed by targeted viral load testing was compared with World Health Organization criteria for suspected treatment failure.
Results: One thousand eight hundred three viral load measurements of 764 patients were available for analysis. Prior ART exposure, CD4 count below baseline, 25% and 50% drop from peak CD4 count, hemoglobin drop of ≥1 g/dL, CD4 count < 100 cells per microliter after 12 months of treatment, new onset of papular pruritic eruption, and visual analog scale < 95% were included in the predictor score. A score ≥2 had the best combination of sensitivity and specificity and required confirmatory viral load testing for only 9% of patients. World Health Organization criteria had a similar sensitivity but a lower specificity and required viral load testing for 24.9% of patients.
Conclusion: An algorithm combining a predictor score with targeted viral load testing in patients with an intermediate probability of failure optimizes the use of scarce resources.
Introduction
Since 2003, access to antiretroviral therapy (ART) for persons living with HIV in low- and middle-income countries (LMICs) has improved dramatically. In some countries, the coverage of ART for adults and children with advanced HIV is as high as 80%. In Cambodia, a country with one of the highest HIV prevalence in Southeast Asia, 26,664 (67% of estimated need) persons living with HIV were on ART by the end of 2007.
In high-income countries, treatment failure is detected mainly by monitoring viral load. In resource-limited settings, many obstacles make this kind of monitoring difficult. Indeed, viral load testing is costly and technologically complex. Therefore, the World Health Organization (WHO) has proposed guidelines for switching to second-line ART based on clinical and immunological criteria and assessment of adherence. Preliminary studies have shown that immunological and clinical criteria alone are not sensitive enough and have a low positive predictive value (PPV). We and others have tried to develop an alternative set of criteria with higher diagnostic accuracy. We proposed an algorithm based on early clinical indicators, CD4 count, drug history, and adherence data, but this empirical algorithm did not perform well in South Africa.
We did further work on data obtained from an ART cohort study in Cambodia and developed a scoring system that identifies patients with a low, intermediate, and high probability of treatment failure and, as such, allows restricting viral load testing to those patients with an intermediate risk of failure. The goal of this scoring system is to minimize the number of inappropriate switches to second-line treatment while limiting monitoring costs. In this article, we present the development of the scoring system, as well as an evaluation of its accuracy.
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