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

Department of Infectious Disease Epidemiology, Imperial College London, Norfolk Place, London W2 1PG, UK.
Emerging Themes in Epidemiology (Impact Factor: 2.59). 10/2005; 2(1):9. DOI: 10.1186/1742-7622-2-9
Source: PubMed


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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Available from: Rebecca F Baggaley, Sep 18, 2014
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    • "However, many of the most affected countries lack the complete vital registration-type data needed to generate direct population-level impact data such as national AIDS-related mortality estimates (7–9). Consequently, statistical modelling and estimation account for much of what is known about the reduction in population-level impact of HIV, particularly with regard to mortality (10–12). "
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    ABSTRACT: Background: The Spectrum computer package is used to generate national AIDS mortality estimates in settings where vital registration systems are lacking. Similarly, InterVA-4 (the latest version of the InterVA programme) is used to estimate cause-of-mortality data in countries where cause-specific mortality data are not available. Objective: This study aims to compare trends in adult AIDS-related mortality estimated by Spectrum with trends from the InterVA-4 programme applied to data from a Health and Demographic Surveillance System (HDSS) in Nairobi, Kenya. Design: A Spectrum model was generated for the city of Nairobi based on HIV prevalence data for Nairobi and national antiretroviral therapy coverage, underlying mortality, and migration assumptions. We then used data, generated through verbal autopsies, on 1,799 deaths that occurred in the HDSS area from 2003 to 2010 among adults aged 15-59. These data were then entered into InterVA-4 to estimate causes of death using probabilistic modelling. Estimates of AIDS-related mortality rates and all-cause mortality rates from Spectrum and InterVA-4 were compared and presented as annualised trends. Results: Spectrum estimated that HIV prevalence in Nairobi was 7%, while the HDSS site measured 12% in 2010. Despite this difference, Spectrum estimated higher levels of AIDS-related mortality. Between 2003 and 2010, the proportion of AIDS-related mortality in Nairobi decreased from 63 to 40% according to Spectrum and from 25 to 16% according to InterVA. The net AIDS-related mortality in Spectrum was closer to the combined mortality rates when AIDS and tuberculosis (TB) deaths were included for InterVA-4. Conclusion: Overall trends in AIDS-related deaths from both methods were similar, although the values were closer when TB deaths were included in InterVA. InterVA-4 might not accurately differentiate between TB and AIDS deaths.
    Full-text · Article · Oct 2013 · Global Health Action
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    • "Unfortunately, most resource-poor countries that bear the highest burden of HIV also lack complete vital registration-type data needed to generate actual population-level figures such as national HIV mortality estimates [21-23]. As a result, much of what is known about population-level mortality in such settings, are based on statistical modelling and estimation [24-26]. In the absence of vital registration systems and data on causes of death, Health and Demographic Surveillance Systems (HDSS) provide a useful platform for contributing to the understanding of the population-level mortality. "
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    ABSTRACT: Background It has been almost a decade since HIV was declared a national disaster in Kenya. Antiretroviral therapy (ART) provision has been a mainstay of HIV treatment efforts globally. In Kenya, the government started ART provision in 2003 with significantly scale-up after 2006. This study aims to demonstrate changes in population-level HIV mortality in two high HIV prevalence slums in Nairobi with respect to the initiation and subsequent scale-up of the national ART program. Methods We used data from 2070 deaths of people aged 15–54 years that occurred between 2003 and 2010 in a population of about 72,000 individuals living in two slums covered by the Nairobi Urban Health and Demographic Surveillance System. Only deaths for which verbal autopsy was conducted were included in the study. We divided the analysis into two time periods: the “early” period (2003–2006) which coincides with the initiation of ART program in Kenya, and the “late” period (2007–2010) which coincides with the scale up of the program nationally. We calculated the mortality rate per 1000 person years by gender and age for both periods. Poisson regression was used to predict the risk of HIV mortality in the two periods while controlling for age and gender. Results Overall, HIV mortality declined significantly from 2.5 per 1,000 person years in the early period to 1.7 per 1,000 person years in the late period. The risk of dying from HIV was 53 percent less in the late period compared to the period before, controlling for age and gender. Women experienced a decline in HIV mortality between the two periods that was more than double that of men. At the same time, the risk of non-HIV mortality did not change significantly between the two time periods. Conclusions Population-level HIV mortality in Nairobi’s slums was significantly lower in the approximate period coinciding with the scale-up of ART provision in Kenya. However, further studies that incorporate ART coverage data in mortality estimates are needed. Such information will enhance our understanding of the full impact of ART scale-up in reducing adult mortality among marginalized slum populations in Kenya.
    Full-text · Article · Jun 2013 · BMC Public Health
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    • "Based on the paradigm of treatment as prevention, one would expect that widespread use of ART will reduce the incidence of HIV transmission by reducing the community viral load [8]. However, mathematical models show effectiveness of combination prevention efforts will be dampened if large-scale treatment is accompanied with sexual behavioral disinhibition [9-11]. Population-based studies in Uganda show that there has been an increase in the number of casual partners accompanied by a decline in condom use among those in the middle age groups [12]. "
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    ABSTRACT: Background Antiretroviral treatment restores the physical and immunological function for patients with HIV/AIDS and the return of sexual desire. The frequency and correlates of sexual activity among patients receiving ART have not been widely studied. There is concern that widespread availability of ART may result in sexual disinhibition including practice of high-risk sexual behavior. We determined the correlates of sexual activity and high-risk sexual behavior in an ART-treated population in rural and urban Uganda. Methods We conducted a cross-sectional study among 329 ART-treated adult patients at two hospitals, one located in rural and another in urban western Uganda. We collected data on sexual activity, frequency of condom use, pregnancy, viral load (VL) and CD4. Patients were considered sexually active if they had had sexual intercourse in the last 6 months. Any unprotected sex was considered high-risk sex. A two-stage logistic regression was performed to determine factors associated with sexual activity and high-risk sex among those sexually active. Results Overall, 222 (67%) patients were women, 138 (41.2%) had been on ART for at least one year, and 168 (51.4%) were sexually active of whom 127 (75.6%) used condoms at the last intercourse. Younger age (<=30 years) (Odds ratio; OR=2.3, 95% CI 1.2, 4.2), higher monthly income (OR=4.1, 95% CI 2.4, 7.4), and being married (OR=22.7, 95% CI 8.2, 62.9) were associated with being sexually active. Undetectable VL, CD4 count and treatment duration were not significantly associated with sexual activity. Among the sexually active, alcohol consumption (OR=3.3, 95% CI 1.2, 9.1) and unknown serostatus of partner (OR=5.8, 95% CI 1.5, 21.4) were significant predictors of high-risk sexual behavior. The frequency of unprotected sex at the last intercourse was 25.9% and 22.1% among the men and women respectively and was not significantly different (p value for chi square test =0.59). Conclusion Younger persons receiving ART are more likely to be sexually active. ART clients are more likely to engage in unprotected sex when sero-status of partner is unknown or report use of alcohol. Counseling on alcohol use and disclosure of sero-status may be useful in reducing high risk sexual behavior.
    Full-text · Article · May 2013 · BMC Public Health
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