Diagnosis of antiretroviral therapy failure in Malawi: Poor performance of clinical and immunological WHO criteria

Department of Medicine, University of Malawi College of Medicine, Blantyre, Malawi.
Tropical Medicine & International Health (Impact Factor: 2.33). 06/2009; 14(8):856-61. DOI: 10.1111/j.1365-3156.2009.02309.x
Source: PubMed


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.

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Available from: Ralf Weigel, Nov 26, 2014
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    • "Most of these individuals live in settings where laboratory monitoring is limited and treatment failure is determined using either clinical or immunological criteria. Concern has been raised regarding the performance of clinical and immunologic treatment failure criteria to correctly identify individuals with virologic failure [2-7]. Prolonged virologic failure may result in accumulation of resistance mutations to commonly used first-line ART as observed in Malawi and elsewhere [8,9]. "
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    ABSTRACT: Background Viral load monitoring (VLM) to identify individuals failing antiretroviral therapy (ART) is not widely available in resource-limited settings. We compared the genotypic resistance patterns between clients with VLM versus immunological monitoring (IM). Methods Between 2004–2008, 559 ART naïve clients were enrolled in a prospective cohort, initiated on ART, and monitored with viral load (VL) and CD4+ cell counts every 6 months (VLM group). From February 2008 through June 2009, 998 clients on ART for 36–40 months (corresponding to the follow-up time of the VLM group) at the same clinic and monitored with CD4+ cell counts every 6 months were recruited into a cross sectional study (IM group). Samples from VLM clients at 12, 24 and 36 months and IM clients at 36–40 months with VL > 2000 copies/ml underwent genotypic drug resistance testing. Results Baseline characteristics were similar. Virologic failure (VL > 400 copies/ml) at 12, 24 and 36 months in the VLM group were 12%, 6% and 8% respectively, and in the IM group 10% at 36–40 months. Samples from 39 VLM and 70 IM clients were genotyped. 23/39 (59%) clients in the VLM group (at 12, 24 or 36 months) compared to 63/70 (90%) in the IM group, (P < 0.0001) had at least 1 non-nucleoside reverse transcriptase mutation. 19/39 (49%) of VLM clients had an M184V mutation compared to 61/70 (87%) in the IM group (P < 0.0001). Only 2/39 (5%) of VLM clients developed thymidine analogue mutations compared to 34/70 (49%) of IM clients (P < 0.0001). Conclusions Routine VL monitoring reduced the rate of accumulated genotypic resistance to commonly used ART in Uganda.
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    • "Relying solely on clinical presentation for ART initiation can result in poor patient care and can lead to AIDS progression or death. Clinical presentation had a low sensitivity of 15.2% in determining ART eligibility in South Africa [28] and resulted in 57% of patients being misclassified in Malawi [27]. It also has correlated with death within 30 months among 41.3% of patients followed in Uganda [29]. "
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    • "Viral load testing is the only definitive method for early detection of ART failure4950. Assessment of viral load is one of the best predictors of HIV disease progression, as well as the main parameter to assess ART response. "
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    ABSTRACT: Use of a combination of CD4 counts and HIV viral load testing in the management of antiretroviral therapy (ART) provides higher prognostic estimation of the risk of disease progression than does the use of either test alone. The standard methods to monitor HIV infection are flow cytometry based for CD4+ T cell count and molecular assays to quantify plasma viral load of HIV. Commercial assays have been routinely used in developed countries to monitor ART. However, these assays require expensive equipment and reagents, well trained operators, and established laboratory infrastructure. These requirements restrict their use in resource-limited settings where people are most afflicted with the HIV-1 epidemic. With the advent of low-cost and/or low-tech alternatives, the possibility of implementing CD4 count and viral load testing in the management of ART in resource-limited settings is increasing. However, an appropriate validation should have been done before putting them to use for patient testing.
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