Adherence to antiretroviral HIV drugs: how many doses can you miss before resistance emerges?

Proceedings. Biological Sciences
R J Smith

Abstract

The question of determining how many doses may be skipped before HIV treatment response is adversely affected by the emergence of drug-resistance is addressed. Impulsive differential equations are used to develop a prescription to minimize the emergence of drug-resistance for protease-sparing regimens. A threshold for the maximal number of missable doses is determined. If the number of missed doses is below this threshold, then resistance levels are negligible and dissipate quickly, assuming perfect adherence subsequently. If the number of missed doses exceeds this threshold, even for 24h, resistance levels are extremely high and will not dissipate for weeks, even assuming perfect adherence subsequently. After this interruption, the minimum number of successive doses that should be taken is determined. Estimates are provided for all protease-sparing drugs approved by the US Food and Drug Administration. Estimates for the basic reproductive ratios for the wild-type and mutant strains of the virus are also calculated, for a long-term average fractional degree of adherence. There are regions within this fraction of adherence where the outcome is not predictable and may depend on a patient's entire history of drug-taking.

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Citations

Apr 24, 2007·Bulletin of Mathematical Biology·Libin RongAlan S Perelson
Sep 4, 2012·Nature Medicine·Daniel I S RosenbloomMartin A Nowak
Jan 13, 2010·BMC Infectious Diseases·Rachelle E Miron, Robert J Smith
Dec 30, 2015·Journal of Microbiology, Immunology, and Infection = Wei Mian Yu Gan Ran Za Zhi·Rodgers LupiaFeng-Jen Tsai
Oct 5, 2010·Journal of Theoretical Biology·Jie Lou, Robert J Smith
Jun 23, 2009·Journal of Theoretical Biology·Libin Rong, Alan S Perelson
Feb 27, 2007·Journal of Theoretical Biology·O Krakovska, L M Wahl
Nov 7, 2013·Bulletin of Mathematical Biology·Rachelle E Miron, Robert J Smith
Dec 23, 2014·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Haftamu EbuyMussie Alemayehu
Jan 20, 2017·Theoretical Biology & Medical Modelling·Yanni XiaoNing Wang
Jul 16, 2008·Journal of the International Association of Physicians in AIDS Care : JIAPAC·John ChalkerDennis Ross-Degnan
Mar 2, 2019·BMC Pregnancy and Childbirth·Dawit Jember TesfayeFanuel Belayneh Bekele
Sep 6, 2012·Journal of Theoretical Biology·Xiunan Wang, Wendi Wang
Jun 29, 2018·Journal of Chemical Information and Modeling·Thomas M KaiserDennis C Liotta

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