A new model to monitor the virological efficacy of antiretroviral treatment in resource-poor countries

Infectious Disease Institute, Faculty of Medicine, Makerere University, Kampala, Uganda.
The Lancet Infectious Diseases (Impact Factor: 22.43). 02/2006; 6(1):53-9. DOI: 10.1016/S1473-3099(05)70327-3
Source: PubMed


Monitoring the efficacy of antiretroviral treatment in developing countries is difficult because these countries have few laboratory facilities to test viral load and drug resistance. Those that exist are faced with a shortage of trained staff, unreliable electricity supply, and costly reagents. Not only that, but most HIV patients in resource-poor countries do not have access to such testing. We propose a new model for monitoring antiretroviral treatment in resource-limited settings that uses patients' clinical and treatment history, adherence to treatment, and laboratory indices such as haemoglobin level and total lymphocyte count to identify virological treatment failure, and offers patients future treatment options. We believe that this model can make an accurate diagnosis of treatment failure in most patients. However, operational research is needed to assess whether this strategy works in practice.

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Available from: Robert Colebunders,
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    • "A different approach to the diagnosis of ART failure in settings where viral load testing is not available is therefore urgently required. Diagnosis of ART failure based on a combination of treatment and adherence history details, clinical events, haemoglobin concentration and total lymphocyte or CD4 count (Colebunders et al. 2006) holds promise but was based on expert opinion and needs validation. "
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    ABSTRACT: In antiretroviral therapy (ART) scale-up programmes in sub-Saharan Africa viral load monitoring is not recommended. We wanted to study the impact of only using clinical and immunological monitoring on the diagnosis of virological ART failure under routine circumstances. Clinicians in two urban ART clinics in Malawi used clinical and immunological monitoring to identify adult patients for switching to second-line ART. If patients met clinical and/or immunological failure criteria of WHO guidelines and had a viral load <400 copies/ml there was misclassification of virological ART failure. Between January 2006 and July 2007, we identified 155 patients with WHO criteria for immunological and/or clinical failure. Virological ART failure had been misclassified in 66 (43%) patients. Misclassification was significantly higher in patients meeting clinical failure criteria (57%) than in those with immunological criteria (30%). On multivariate analysis, misclassification was associated with being on ART <2 years [OR = 7.42 (2.63, 20.95)] and CD4 > 200 cells/microl [OR = 5.03 (2.05, 12.34)]. Active tuberculosis and Kaposi's sarcoma were the most common conditions causing misclassification of virological ART failure. Misclassification of virological ART failure occurs frequently using WHO clinical and immunological criteria of ART failure for poor settings. A viral load test confirming virological ART failure is therefore advised to avoid unnecessary switching to second-line regimens.
    Tropical Medicine & International Health 06/2009; 14(8):856-61. DOI:10.1111/j.1365-3156.2009.02309.x · 2.33 Impact Factor
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    • "In this study, we investigated the utility of a combination of adherence patterns, clinical events and CD4 cell count criteria to determine the viral status of Ugandans on ART. The goal was to determine if the criteria listed above could be used to minimize viral load testing and detect viral failure among patients on ART [16]. A clinical monitoring algorithm was designed to classify patients into groups of viral status, including "failure likely", "failure possible", and "failure unlikely". "
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    ABSTRACT: Routine viral load monitoring of patients on antiretroviral therapy (ART) is not affordable in most resource-limited settings. A cross-sectional study of 496 Ugandans established on ART was performed at the Infectious Diseases Institute, Kampala, Uganda. Adherence, clinical and laboratory parameters were assessed for their relationship with viral failure by multivariate logistic regression. A clinical algorithm using targeted viral load testing was constructed to identify patients for second-line ART. This algorithm was compared with the World Health Organization (WHO) guidelines, which use clinical and immunological criteria to identify failure in the absence of viral load testing. Forty-nine (10%) had a viral load of >400 copies/mL and 39 (8%) had a viral load of >1000 copies/mL. An algorithm combining adherence failure (interruption >2 days) and CD4 failure (30% fall from peak) had a sensitivity of 67% for a viral load of >1000 copies/mL, a specificity of 82%, and identified 22% of patients for viral load testing. Sensitivity of the WHO-based algorithm was 31%, specificity was 87%, and would result in 14% of those with viral suppression (<400 copies/mL) being switched inappropriately to second-line ART. Algorithms using adherence, clinical and CD4 criteria may better allocate viral load testing, reduce the number of patients continued on failing ART, and limit the development of resistance.
    Journal of the International AIDS Society 03/2009; 12:3. DOI:10.1186/1758-2652-12-3 · 5.09 Impact Factor
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    • "Other low-cost means of detecting virological failure must therefore be considered. Colebunders and colleagues, for example, proposed an algorithm based on clinical and treatment history and inexpensive laboratory indices such as haemoglobin level and total lymphocyte count [6]. However, when evaluated in a South African cohort, the sensitivity and specificity of the algorithm were unacceptably low [7]. "
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    ABSTRACT: Background Viral load monitoring is not available for the vast majority of patients receiving antiretroviral therapy in resource-limited settings. However, the practical utility of CD4 cell count measurements as an alternative monitoring strategy has not been rigorously assessed. Methods In this study, we used a novel modelling approach that accounted for all CD4 cell count and VL values measured during follow-up from the first date that VL suppression was achieved. We determined the associations between CD4 counts (absolute values and changes during ART), VL measurements and risk of virological failure (VL > 1,000 copies/ml) following initial VL suppression in 330 patients in South Africa. CD4 count changes were modelled both as the difference from baseline (ΔCD4 count) and the difference between consecutive values (CD4 count slope) using all 3-monthly CD4 count measurements during follow-up. Results During 7093.2 patient-months of observation 3756 paired CD4 count and VL measurements were made. In patients who developed virological failure (n = 179), VL correlated significantly with absolute CD4 counts (r = - 0.08, P = 0.003), ΔCD4 counts (r = - 0.11, P < 0.01), and most strongly with CD4 count slopes (r = - 0.30, P < 0.001). However, the distributions of the absolute CD4 counts, ΔCD4 counts and CD4 count slopes at the time of virological failure did not differ significantly from the corresponding distributions in those without virological failure (P = 0.99, P = 0.92 and P = 0.75, respectively). Moreover, in a receiver operating characteristic (ROC) curve, the association between a negative CD4 count slope and virological failure was poor (area under the curve = 0.59; sensitivity = 53.0%; specificity = 63.6%; positive predictive value = 10.9%). Conclusion CD4 count changes correlated significantly with VL at group level but had very limited utility in identifying virological failure in individual patients. CD4 count is an inadequate alternative to VL measurement for early detection of virological failure.
    BMC Infectious Diseases 07/2008; 8(1). DOI:10.1186/1471-2334-8-89 · 2.61 Impact Factor
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