What can modeling tell us about the threat of antiviral drug resistance?

Purpose of review Currently, antiviral resistance is a major public health concern. Here, we review how mathematical models have been used to provide insights into the emerging threat of antiviral resistance. We focus mainly on the problem of drug resistance to HIV. Recent findings We review how antiviral models of HIV have been used: (1) to understand the evolution of an epidemic of drug-resistant HIV, (2) to predict the incidence and prevalence of drug-resistant HIV, (3) to conduct biological ‘cost-benefit’ analyses, and(4) to make public health policy recommendations. We also briefly discuss antiviral resistance for HSV-2 and influenza. Recent studies indicate that for HSV-2 and influenza drug resistance is not likely to become a major public health problem. However, for HIV the situation is very different. Results from several studies predict that a high prevalence of drug-resistant HIV will be an inevitable consequence of more widespread usage of antiretroviral therapies (ART). However more widespread usage of ART will save a substantial number of lives, and could even result in epidemic eradication. Summary Models have been used in many ways to provide insight into the emerging threat of antiviral resistance, particularly for HIV. At this stage in the HIV epidemic the most important future use of models may be that they will force the goals of public health policies to be clearly defined. Once goals have been defined it can then be decided whether a high prevalence of drug-resistant HIV is a threat or simply a justified means to an end.

[1]  Jon C. Helton,et al.  An Approach to Sensitivity Analysis of Computer Models: Part II - Ranking of Input Variables, Response Surface Validation, Distribution Effect and Technique Synopsis , 1981 .

[2]  H. Gershengorn,et al.  A tale of two futures: HIV and antiretroviral therapy in San Francisco. , 2000, Science.

[3]  H. Gershengorn,et al.  Predicting the unpredictable: Transmission of drug-resistant HIV , 2001, Nature Medicine.

[4]  A S Perelson,et al.  Emergence of drug resistance during an influenza epidemic: insights from a mathematical model. , 1998, The Journal of infectious diseases.

[5]  J. Kahn,et al.  Time trends in primary HIV-1 drug resistance among recently infected persons. , 2002, JAMA.

[6]  S. Blower,et al.  Predicting and preventing the emergence of antiviral drug resistance in HSV-2 , 1998, Nature Medicine.

[7]  S. Blower,et al.  Prophylactic vaccines, risk behavior change, and the probability of eradicating HIV in San Francisco. , 1994, Science.

[8]  S. Blower,et al.  The intrinsic transmission dynamics of tuberculosis epidemics , 1995, Nature Medicine.

[9]  James E. Campbell,et al.  An Approach to Sensitivity Analysis of Computer Models: Part I—Introduction, Input Variable Selection and Preliminary Variable Assessment , 1981 .

[10]  To treat or not to treat? , 1998, Nature Medicine.

[11]  S. Kippax,et al.  Modelling the effect of combination antiretroviral treatments on HIV incidence , 2001, AIDS.

[12]  S. Blower,et al.  Uncertainty and sensitivity analysis of the basic reproductive rate. Tuberculosis as an example. , 1997, American journal of epidemiology.

[13]  E. H. Kaplan,et al.  Public Health Consequences of Screening Patients for Adherence to Highly Active Antiretroviral Therapy , 2001, Journal of acquired immune deficiency syndromes.

[14]  Roy M. Anderson,et al.  Mathematical Models and the Design of Public Health Policy: Hiv and Antiviral Therapy , 1993, SIAM Rev..

[15]  Katia Koelle,et al.  Antibiotic resistance—to treat... , 1999, Nature Medicine.

[16]  S. Blower,et al.  Live attenuated HIV vaccines: Predicting the tradeoff between efficacy and safety , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[17]  S. Blower,et al.  Control Strategies for Tuberculosis Epidemics: New Models for Old Problems , 1996, Science.

[18]  M. Boerlijst,et al.  Carrier rate of zidovudine-resistant HIV-1: the impact of failing therapy on transmission of resistant strains , 2001, AIDS.

[19]  H. Gershengorn,et al.  Could widespread use of combination antiretroviral therapy eradicate HIV epidemics? , 2002, The Lancet. Infectious diseases.

[20]  H. Gershengorn,et al.  Impact of antivirals and emergence of drug resistance: HSV-2 epidemic control. , 2000, AIDS patient care and STDs.

[21]  Katia Koelle,et al.  Health Policy Modeling: Epidemic Control, HIV Vaccines, and Risky Behavior , 2001 .

[22]  Ying-Hen Hsieh,et al.  Modelling the effect of treatment and behavioral change in HIV transmission dynamics , 1994, Journal of mathematical biology.

[23]  B. Gazzard,et al.  1998 revision to the British HIV Association guidelines for antiretroviral treatment of HIV seropositive individuals , 1998, The Lancet.

[24]  A D Paltiel,et al.  Modeling zidovudine therapy: a cost-effectiveness analysis. , 1991, Journal of acquired immune deficiency syndromes.

[25]  J. Gerberding,et al.  Understanding, predicting and controlling the emergence of drug-resistant tuberculosis: a theoretical framework , 1998, Journal of Molecular Medicine.

[26]  R M May,et al.  Drugs, sex and HIV: a mathematical model for New York City. , 1991, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[27]  Hadi Dowlatabadi,et al.  Sensitivity and Uncertainty Analysis of Complex Models of Disease Transmission: an HIV Model, as an Example , 1994 .

[28]  Elizabeth Connick,et al.  Antiretroviral-drug resistance among patients recently infected with HIV. , 2002, The New England journal of medicine.

[29]  R. Brookmeyer,et al.  Quantitative evaluation of HIV prevention programs , 2001 .

[30]  F. Brauer,et al.  Effects of treatment and prevalence-dependent recruitment on the dynamics of a fatal disease. , 1996, IMA journal of mathematics applied in medicine and biology.

[31]  J. Velasco-Hernández,et al.  Community treatment of HIV-1: initial stage and asymptotic dynamics. , 1995, Bio Systems.

[32]  R. M. May,et al.  Potential of community-wide chemotherapy or immunotherapy to control the spread of HIV-1 , 1991, Nature.