Resistance testing: not cost-effective in determining switches to second-line therapy

Cost-effectiveness of HIV drug resistance testing to inform switching to second line antiretroviral therapy in low income settings.

Phillips A, Cambiano V, Nakagawa F, Magubu T, Miners A, Ford D, Pillay D, De Luca A, Lundgren J, Revill P. PLoS One. 2014 Oct 7;9(10):e109148. doi: 10.1371/journal.pone.0109148. eCollection 2014.

Background: To guide future need for cheap resistance tests for use in low income settings, we assessed cost-effectiveness of drug resistance testing as part of monitoring of people on first line ART - with switching from first to second line ART being conditional on NNRTI drug resistance mutations being identified.

Methods: An individual level simulation model of HIV transmission, progression and the effect of ART which accounts for adherence and resistance development was used to compare outcomes of various potential monitoring strategies in a typical low income setting in sub-Saharan Africa. Underlying monitoring strategies considered were based on clinical disease, CD4 count or viral load. Within each we considered a strategy in which no further measures are performed, one with a viral load measure to confirm failure, and one with both a viral load measure and a resistance test. Predicted outcomes were assessed over 2015-2025 in terms of viral suppression, first line failure, switching to second line regimen, death, HIV incidence, disability-adjusted-life-years averted and costs. Potential future low costs of resistance tests ($30) were used.

Results: The most effective strategy, in terms of DALYs averted, was one using viral load monitoring without confirmation. The incremental cost-effectiveness ratio for this strategy was $2113 (the same as that for viral load monitoring with confirmation). ART monitoring strategies which involved resistance testing did not emerge as being more effective or cost effective than strategies not using it. The slightly reduced ART costs resulting from use of resistance testing, due to less use of second line regimens, was of similar magnitude to the costs of resistance tests.

Conclusion: Use of resistance testing at the time of first line failure as part of the decision whether to switch to second line therapy was not cost-effective, even though the test was assumed to be very inexpensive.

Abstract  Full-text [free] access

Editor’s notes: The landscape around first-line treatment modification is changing. The price of second-line treatment has dropped substantially in recent years and several new point-of-care monitoring technologies (CD4 count tests and viral load tests) are (or will soon be) on the market. It is within this context that this article looks at whether drug resistance testing could play a key role in antiretroviral therapy (ART) monitoring in low- and middle-income settings. Simulating the progression of the HIV epidemic in adults in Zimbabwe, Phillips et al. examined different combinations of monitoring strategies. These included CD4 count monitoring, viral load monitoring and confirmation, and resistance testing. They found that the most cost effective option involved using viral load monitoring without confirmation. The reduced costs of ART due to a decrease in use of second-line regimes as a result of the implementation of resistance tests were offset by the costs of the resistance tests themselves. However, the authors do not rule out potential cost-effectiveness for resistance testing under certain circumstances. This could be in ART initiation clinics where large numbers of people have resistance to first-line treatment, or in selecting drug regimens for ART-naïve pregnant women (as it is important to maximise the chance of viral suppression at the time of birth). Future modelling exercises on this issue may benefit from including real-life implementation issues such as health worker deviation from guidelines and system delays in returning of results.

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