by Jeffrey T. Kirchner, DO, AAHIVS, AAHIVM Chief Medical Officer

May 30, 2019

Featured Literature:
Hyle, EP et a. Clinical impact and cost-effectiveness of genotype testing at HIV diagnosis in the United States. Clinical Infectious Diseases, published May 4, 2019. ciz372,

Current DHHS and IAS guidelines recommended baseline genotype testing for all persons newly diagnosed with HIV infection. This has been standard of care since 2006 and can determine if the patient has acquired drug resistance and thus guide selection of the initial ART regimen. When these recommendations were published, the majority of patients were being treated with a protease inhibitor or Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI) as first line therapy. Current treatment guidelines now recommend an integrase strand inhibitor (INSTI) with an NRTI as first-line therapy, thus genotype testing, which routinely does not test for INSTI resistance – only provides information regarding the NRTI. Moreover, even in the face of NRTI resistance, the new INSTIs (bictegravir and dolutegravir) appear to remain very effective in attaining viral suppression. This paper re-evaluated the clinical and economic impact of baseline resistance testing in the US. The authors used the Cost-effectiveness of Preventing AIDS Complications (CEPAC) model which is a validated microsimulation model of HIV disease, clinical care, and costs. They compared two strategies: no baseline genotype versus baseline genotype and applied this to four subgroups: no transmitted drug resistance (84%), transmitted NRTI-R (6%), transmitted NNRTI-R (7%), and transmitted PI-R (3%). The authors assumed NO transmitted INSTI resistance which is known to be very rare. This study found that compared to no baseline resistance testing, performing an HIV genotype would result in < 1 additional undiscounted quality-adjusted life day and cost about $420,000 per quality-adjusted life year. The authors state that for patients starting bictegravir or dolutegravir-based regimens baseline genotype testing offers minimal clinical benefit for persons newly diagnosed with HIV, provides only a very small survival benefit, and even with a cost of $320 offers poor value relative to other HIV interventions.

This is a very significant paper and I believe once these data have been fully reviewed and the DHHS guidelines are updated, baseline genotype testing will no longer be recommended. In a 2017 analysis this group determined that baseline INSTI resistance testing was not helpful. In addition, with the growing emphasis on testing and same-day initiation of treatment, the results of genotype testing for newly diagnosed patients offers no practical benefit to most patients or providers.

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