Potential risks and benefits of HIV treatment simplification: a simulation model of a proposed clinical trial.

TitlePotential risks and benefits of HIV treatment simplification: a simulation model of a proposed clinical trial.
Publication TypeJournal Article
Year of Publication2007
AuthorsSchackman BR, Scott CA, Sax PE, Losina E, Wilkin TJ, McKinnon JE, Swindells S, Weinstein MC, Freedberg KA
JournalClin Infect Dis
Volume45
Issue8
Pagination1062-70
Date Published2007 Oct 15
ISSN1537-6591
KeywordsAdult, Anti-HIV Agents, Computer Simulation, Drug Costs, Drug Therapy, Combination, Female, HIV Infections, HIV Protease Inhibitors, Humans, Life Expectancy, Male, Middle Aged, Models, Biological, Quality-Adjusted Life Years, Risk Assessment, Treatment Outcome
Abstract

BACKGROUND: In recent studies, subjects who had achieved suppression of the human immunodeficiency virus (HIV) RNA level while receiving an initial 3-drug antiretroviral regimen successfully maintained suppression while receiving treatment with a "boosted" protease inhibitor (PI) alone. We projected the long-term outcomes of this treatment simplification strategy to inform the design of a proposed multicenter, randomized clinical trial.

METHODS: We used published studies to estimate the efficacy, adverse effects, and cost of a sequence of HIV drug regimens for the simplification strategy, compared with those outcomes for the current standard-of-care (SOC) strategy. Using a published simulation model of HIV disease, we projected life expectancy, discounted quality-adjusted life expectancy (QALE), and discounted lifetime medical costs for each strategy.

RESULTS: Subjects who have not developed PI-resistant HIV infection at the time of failure of the simplification regimen have a greater life expectancy (27.9 vs. 27.1 years) and QALE (14.9 vs. 14.7 years), compared with SOC subjects, because they receive an additional line of therapy without negative consequences for future treatment options. The QALE for the simplification strategy remains higher than that for the SOC, unless a large proportion of patients experiencing virologic failure while receiving the simplification regimen develop PI resistance. Depending on the probability of simplification regimen failure, the advantage is maintained even if HIV develops PI resistance in 42%-70% of subjects. Projected lifetime costs are $26,500-$72,400 per person lower for the simplification strategy than for the SOC strategy.

CONCLUSIONS: An HIV treatment simplification strategy involving use of a boosted PI alone may lead to longer survival overall at lower cost, compared with the SOC combination therapy, because the simplification strategy potentially adds an additional line of therapy. The risk of emergence of PI resistance during treatment with a simplified regimen is a critical determinant of the viability of this strategy.

DOI10.1086/521933
Alternate JournalClin. Infect. Dis.
PubMed ID17879926
PubMed Central IDPMC2365723
Grant ListK01 DA017179 / DA / NIDA NIH HHS / United States
K01 DA017179 / DA / NIDA NIH HHS / United States
K01 DA017179-05 / DA / NIDA NIH HHS / United States
K23 AI055038 / AI / NIAID NIH HHS / United States
K23 AI055038 / AI / NIAID NIH HHS / United States
K23 AI055038-05 / AI / NIAID NIH HHS / United States
K23 AI55038 / AI / NIAID NIH HHS / United States
K24 AI062476 / AI / NIAID NIH HHS / United States
K24 AI062476 / AI / NIAID NIH HHS / United States
K24 AI062476-01 / AI / NIAID NIH HHS / United States
K25 AI050436 / AI / NIAID NIH HHS / United States
K25 AI050436-05 / AI / NIAID NIH HHS / United States
K25 AI50436 / AI / NIAID NIH HHS / United States
KL2 RR024154 / RR / NCRR NIH HHS / United States
KL2 RR024154 / RR / NCRR NIH HHS / United States
KL2 RR024154-02 / RR / NCRR NIH HHS / United States
KL2 TR000146 / TR / NCATS NIH HHS / United States
M01-RR00047 / RR / NCRR NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
P30 AI060354-03 / AI / NIAID NIH HHS / United States
R37 AI042006 / AI / NIAID NIH HHS / United States
R37 AI042006 / AI / NIAID NIH HHS / United States
R37 AI042006-10A1 / AI / NIAID NIH HHS / United States
U01 AI027661 / AI / NIAID NIH HHS / United States
U01 AI046383 / AI / NIAID NIH HHS / United States
U01 AI046383-05 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI068636-01 / AI / NIAID NIH HHS / United States
U01 AI069419 / AI / NIAID NIH HHS / United States
U01 AI069419-01 / AI / NIAID NIH HHS / United States
U01 AI069472 / AI / NIAID NIH HHS / United States
U01 AI069472-02 / AI / NIAID NIH HHS / United States
U01 AI27661 / AI / NIAID NIH HHS / United States
U01 AI46383 / AI / NIAID NIH HHS / United States
U01 AI68636 / AI / NIAID NIH HHS / United States
U01 AI69419 / AI / NIAID NIH HHS / United States
U01 AO069472 / AO / NIAID NIH HHS / United States