Conservation of first-line antiretroviral treatment regimen where therapeutic options are limited

The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, South Africa.
Antiviral therapy (Impact Factor: 3.02). 01/2007; 12(1):83-8.
Source: PubMed


To determine rates and causes of switching from first- to second-line antiretroviral treatment (ART) regimens in a large treatment-naive cohort (a South African community-based ART service) where a targeted adherence intervention was used to manage initial virological breakthrough.
ART-naive adults (n=929) commencing first-line non-nucleoside-based ART [according to WHO (2002) guidelines] between September 2002 and August 2005 were studied prospectively. Viral load (VL) and CD4+ T-cell counts were monitored every 4 months. All drug switches were recorded. Counsellor-driven adherence interventions were targeted to patients with a VL > 1000 copies/ml at any visit (virological breakthrough) and the VL measurement was repeated within 8 weeks. Two consecutive VL measurements > 1000 copies/ml was considered virological failure, triggering change to a second-line regimen.
During 760 person-years of observation [median (IQR) 189 (85-441) days], 823 (89%) patients were retained on ART, 2% transferred elsewhere, 7% died and 3% were lost to follow-up. A total of 893 (96%) patients remained on first-line therapy and 16 (1.7%) switched to second-line due to hypersensitivity reactions (n=9) or lactic acidosis (n=7). A Kaplan-Meier estimate for switching to second-line due to toxicity was 3.0% at 32 months. Virological breakthrough occurred in 67 (7.2%) patients, but, following use of a targeted adherence intervention, virological failure was confirmed in just 20 (2.2%). Kaplan-Meier estimates at 32 months were 20% for virological breakthrough but only 5.6% for confirmed virological failure.
Regimen switches were due to virological failure or toxicity. Although follow-up time was limited, over 95% of individuals remained on first-line ART using a combination of viral monitoring and a targeted adherence intervention.

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Available from: Linda-Gail Bekker, Oct 03, 2015
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    • "We assumed a 2% annual rate of loss-to-follow-up throughout the time horizon. Although studies report a higher rate of loss-to-follow-up in the short term, our estimate is consistent with long-term experience, and the higher efforts to retain patients in care [34,35]. Individuals who discontinue ART do not re-start treatment. "
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    • "Alternatively, the regimen switch rates reported in this study were an underestimation of the true virological failure rates as they excluded patients who failed to switch to second-line therapy due to programme losses. Nevertheless, our findings are similar to other studies from resource limited settings [11], [24], [25]. Kaplan-Meier plots showed that losses to the programme (death/loss to follow-up) were comparable across groups, a finding that has been reported in other cohorts [10], [26]. "
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    • "Unsuccessful treatment, leading to virological failure, may be due to a number of reasons, including drug interactions, malabsorption and poor adherence [19–21]. While viral load has been seen as a tool to diagnose failure, the main benefit is the prevention of treatment failure by identifying patients in need of intensive adherence counselling. "
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