The epidemiological impact of antiretroviral use predicted by mathematical models: a review - PubMed (original) (raw)

The epidemiological impact of antiretroviral use predicted by mathematical models: a review

Rebecca F Baggaley et al. Emerg Themes Epidemiol. 2005.

Abstract

This review summarises theoretical studies attempting to assess the population impact of antiretroviral therapy (ART) use on mortality and HIV incidence. We describe the key parameters that determine the impact of therapy, and argue that mathematical models of disease transmission are the natural framework within which to explore the interaction between antiviral use and the dynamics of an HIV epidemic. Our review focuses on the potential effects of ART in resource-poor settings. We discuss choice of model type and structure, the potential for risk behaviour change following widespread introduction of ART, the importance of the stage of HIV infection at which treatment is initiated, and the potential for spread of drug resistance. These issues are illustrated with results from models of HIV transmission. We demonstrate that HIV transmission models predicting the impact of ART use should incorporate a realistic progression through stages of HIV infection in order to capture the effect of the timing of treatment initiation on disease spread. The realism of existing models falls short of properly reproducing patterns of diagnosis timing, incorporating heterogeneity in sexual behaviour, and describing the evolution and transmission of drug resistance. The uncertainty surrounding certain effects of ART, such as changes in sexual behaviour and transmission of ART-resistant HIV strains, demands exploration of best and worst case scenarios in modelling, but this must be complemented by surveillance and behavioural surveys to quantify such effects in settings where ART is implemented.

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Figures

Figure 1

Figure 1

Model predictions of the effect of ART on a mature epidemic, under various assumptions. Model simulations of the potential impact of ART on a mature epidemic, varied by treatment uptake rate, reduction in infectivity due to treatment and impact on risk behaviour at the population level (see Endnote for model description). The model used only incorporates one stage of HIV infection and so individuals initiate treatment at an earlier stage of infection than is realistic, and there is homogeneous sexual mixing. Scenario A – ART uptake = 50% per year, sexual activity post ART = unchanged (2.5 partners per year), reduction in infectivity due to ART = 50-fold. Scenario B – ART uptake = 50% per year, sexual activity post ART halves (1.25 partners per year), reduction in infectivity due to ART = 50-fold. Scenario C – ART uptake = 50% per year, sexual activity post ART = unchanged (2.5 partners per year), reduction in infectivity due to ART = 1000-fold. Scenario D – ART uptake = 90% per year, sexual activity post ART = unchanged (2.5 partners per year), reduction in infectivity due to ART = 1000-fold. Scenario E – ART uptake = 90% per year, sexual activity post ART = reduced by 20% (2 partners per year), reduction in infectivity due to ART = 1000-fold.

Figure 2

Figure 2

Predictions of the impact of ART by stage of infection at which treatment is initiated. Predictions of the impact of the introduction of ART in terms of HIV incidence, by stage of infection at which treatment is initiated (for a brief description of the four stage infection model used, see Endnote). Scenario A – No treatment. Scenario B – ART uptake: AIDS patients only (after a mean of 1 month). Scenario C – ART uptake: AIDS patients (after mean 1 month) and pre-AIDS (after mean 6 months). Scenario D – ART uptake: AIDS patients (after mean 1 month) and pre-AIDS (after mean 6 months) and incubation stage (after mean 4 years). Scenario E – ART uptake: all four stages, after mean 1 month.

Figure 3

Figure 3

Model predictions of transmission of ART drug resistance by relative fitness of strains. Predictions of the spread of transmitted (primary) ART resistance under various scenarios, using a simplified ART model (see Endnote). Model output is 10 years after ART introduction. ART is introduced once the epidemic has reached equilibrium. Superinfection refers to the infection with ART-resistant HIV of individuals previously infected with ART-sensitive HIV and successfully undergoing treatment. These are the only individuals without viral outgrowth, and thus will have a pool of target cells rendering them susceptible to infection. Evolution of drug resistance within an individual is at a rate of 10% per year.

Figure 4

Figure 4

Model of HIV transmission and treatment, with one stage of infection only. Schematic illustration of the structure of the one stage HIV transmission model. 1° Res designates those with primary (transmitted) resistance, while 2° Res designates those with secondary (acquired) resistance. ART-Sens denotes people infected with ART-sensitive virus. For clarity, death rates are not shown.

Figure 5

Figure 5

Model of HIV transmission and treatment, with four stages of infection. Schematic illustration of the structure of the stages of HIV infection for the four stage model. Individuals progress from one stage to the next exponentially, with an average duration in each stage as shown in the figure. Individuals have no HIV-related mortality during primary infection or incubation, a very slightly elevated baseline death rate during pre-AIDS and an average one year life expectancy once AIDS has developed.

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