Story Summary: Low CD4 counts at the start of antiretroviral therapy were predictive of switching in programmes with or without viral load monitoring. This finding lends support to arguments for earlier initiation of antiretroviral therapy to help reduce high mortality during the first few months on ART as well as help preserve first-line regimens. While viral load monitoring is common practice in the diagnosis of treatment failure and a guide in switching to alternative regimens in industrialised countries, its use in resource-limited settings is restricted due to cost and availability. Second-line regimens are the final option for many in resource-limited settings. Conversely, some studies have found that unnecessary treatment switches are occurring in large numbers of patients who experience Cd4 cell declines without ciological failure. In these cases the lack of viral load testing is leading to switches to more expensive second-line treatment, wasting scarce and diminishing future treatment options. Data from these programmes are collected on patient characteristics and treatment outcomes. All sites monitored CD4 cell counts and provided access to second-line antiretroviral regimens. Rates of switching, time to switching and determinants of switching were compared between sites that offered viral load monitoring and those that did not. Out of a database of close to 35,000 patients, data from 20,113 patients were analysed. The rate of switching was higher in programmes with viral load monitoring than those without: 3. Median time to switching in programmes with viral-load monitoring was 16. Switching was more likely in programmes with access to viral load monitoring during months 7-18 following the start of antiretroviral therapy (adjusted HR 1. 9% (316 patients) who switched changed both nucleoside reverse transcriptase inhibitors (NRTIs). Median CD4 cell count at the time of switching in programmes with viral load monitoring was 161 cells/mm3 (IQR: 77-265) compared to 102 cells/mm3 IQR: 44-181) in those without. Low CD4 cell count at the start of antiretroviral therapy, but not clinical stage, was a predictor for switching in all sites. Of these patients, 66% or 263 patients had immunological failure, virological failure or both. The authors point out that the sites in their study represent those with medical record systems, access to CD4 cell counts and second-line regimens and as such are not necessarily representative of all sites in these countries providing antiretroviral therapy. In addition they note that they did not examine for clinical failure, no information on adherence or drug resistance was available and information about reasons for switching was only available for some patients. The authors cite a recent multi-country survey by the WHO that revealed considerable variability in rates of switching to second-line regimens. The authors do not believe that significant differences in primary resistance to NRTIs or non-nucleoside reverse transcriptase inhibitors (NNRTIs) is the cause but rather the availability or not of viral load monitoring and differences in clinical practice within and between countries. They cite the example within South Africa in two township programmes in Cape Town, where therapy is switched after two consecutive viral loads above 5000 copies/ml in Khayelitsha, whereas in Gugulethu the threshold is 1000 copies/ml. As a result of their finding that in programmes with access to viral load monitoring, patients are switched earlier and with higher CD4 cell counts, the authors suggest that future studies examine what the consequences of earlier or later switching are for clinical outcomes. Also, further research is required to determine the optimal frequency of determining CD4 cell counts and of measuring viral load to maximize cost-effectiveness and optimize patient outcomes in different settings in lower income countries, they conclude….Read the Full Story

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