Evaluating the impact of antiretroviral therapy on HIV transmission

Department of Population and International Health, Harvard School of Public Health, Boston, Massachusetts, USA.
AIDS (London, England) (Impact Factor: 5.55). 08/2008; 22 Suppl 1(Suppl 1):S149-59. DOI: 10.1097/01.aids.0000327636.82542.87
Source: PubMed


As global efforts proceed to scale up the delivery of antiretroviral therapy (ART) to HIV-infected persons in most urgent need, it is essential to understand the potential impact of treatment expansion on the transmission of new HIV infections. In this study, we use a series of simple mathematical models to explore the direction and magnitude of treatment effects on the sexual transmission of HIV. By defining the circumstances under which ART can reduce the number of new infections transmitted by treated patients, we provide critical benchmarks to aid in prioritizing efforts to maximize the population health impact of treatment and in evaluating the performance of different treatment programmes. We find that, based on the best currently available evidence of possible treatment effects on patient infectiousness, survival and behavior, the potential remains for either positive or negative changes in overall transmission. In relation to the total number of expected secondary infections caused by each infected person, however, these net treatment effects are relatively modest, particularly if treatment is initiated at advanced stages of the disease. This finding implies that treatment alone should not be expected to alter the population-level incidence of new infections dramatically, in the absence of changes in other factors including possible behavioral responses among uninfected persons and among infected persons who are not yet treatment candidates.

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    • "While it is unlikely that mathematical model-based analyses of the type used here can validate this assumption, alternative scenarios which consider the effects of relaxing this assumption in data-driven analyses should be explored in detail in future work (Anderson et al., 1991; Bogaards et al., 2005; Salomon and Hogan 2008; Wilson et al., 2008). Previous modelling studies focussing on hypothetical scenarios have emphasised the potential that ongoing transmission during incompletely suppressive antiretroviral therapy could have in driving epidemics (Anderson et al., 1991; Baggaley et al., 2005; Blower et al., 2000; Clements et al., 2004; Goudsmit et al., 2001; Law et al., 2002; Nagelkerke et al., 2002; Salomon and Hogan 2008; Velasco-Hernandez et al., 2002; Wilson et al., 2008; Xiridou et al., 2003). We cannot rule out such a contribution to the Dutch HIV epidemic, an issue that could be best addressed by empirical discordant pair studies. "
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    ABSTRACT: There has been increasing concern about a resurgent epidemic of HIV-1 amongst men having sex with men in the Netherlands, which has parallels with similar epidemics now occurring in many other countries. A transmission model applicable to HIV-1 epidemics, including the use of antiretroviral therapy, is presented in a set of ordinary differential equations. The model is fitted by maximum likelihood to national HIV-1 and AIDS diagnosis data from 1980 to 2006, estimating parameters on average changes in unsafe sex and time to diagnosis. Robustness is studied with a detailed univariate sensitivity analysis, and a range of hypothetical scenarios are explored for the past and next decade. With a reproduction number around the epidemic threshold one, the HIV-1 epidemic amongst men having sex with men in the Netherlands is still not under control. Scenario analysis showed that in the absence of antiretroviral therapy limiting infectiousness in treated patients, the epidemic could have been more than double its current size. Ninety percent of new HIV transmissions are estimated to take place before diagnosis of the index case. Decreasing time from infection to diagnosis, which was 2.5 years on average in 2006, can prevent many future infections. Sexual risk behaviour amongst men having sex with men who are not aware of their infection is the most likely factor driving this epidemic.
    06/2010; 2(2):66-79. DOI:10.1016/j.epidem.2010.04.001
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    • "Mathematical models are useful tools for examining the potential effects of the proximate biological and behavioral determinants of human immunodeficiency virus (HIV) transmission dynamics, such as condom use, circumcision, and antiretroviral treatment (Baggaley, Ferguson, & Garnett, 2005; Cassels, Clark, & Morris, 2008; Law, Prestage, Grulich, Van de Ven, & Kippax, 2001; Salomon & Hogan, 2008; Tuckwell, Shipmana, & Perelson, 2008). However, mathematical models vary considerably, defined by the way the model elements (e.g., people) are organized into states (e.g., susceptible, infected, or recovered) and how the model characterizes the movement of those elements between states. "
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    ABSTRACT: Mathematical models are increasingly used in social and behavioral studies of HIV transmission; however, model structures must be chosen carefully to best answer the question at hand and conclusions must be interpreted cautiously. In Pearson et al. (2007), we presented a simple analytically tractable deterministic model to estimate the number of secondary HIV infections stemming from a population of HIV-positive Mozambicans and to evaluate how the estimate would change under different treatment and behavioral scenarios. In a subsequent application of the model with a different data set, we observed that the model produced an unduly conservative estimate of the number of new HIV-1 infections. In this brief report, our first aim is to describe a revision of the model to correct for this underestimation. Specifically, we recommend adjusting the population-level sexually transmitted infection (STI) parameters to be applicable to the individual-level model specification by accounting for the proportion of individuals uninfected with an STI. In applying the revised model to the original data, we noted an estimated 40 infections/1000 HIV-positive persons per year (versus the original 23 infections/1000 HIV-positive persons per year). In addition, the revised model estimated that highly active antiretroviral therapy (HAART) along with syphilis and herpes simplex virus type 2 (HSV-2) treatments combined could reduce HIV-1 transmission by 72% (versus 86% according to the original model). The second aim of this report is to discuss the advantages and disadvantages of mathematical models in the field and the implications of model interpretation. We caution that simple models should be used for heuristic purposes only. Since these models do not account for heterogeneity in the population and significantly simplify HIV transmission dynamics, they should be used to describe general characteristics of the epidemic and demonstrate the importance or sensitivity of parameters in the model.
    AIDS Care 07/2009; 21(7):858-62. DOI:10.1080/09540120802626204 · 1.60 Impact Factor
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    ABSTRACT: ENGLISH ABSTRACT: This thesis takes into account the different levels of infectiousness of the human immunodeficiency virus (HIV) infected individuals throughout their period of infection. Infectiousness depends on the time since infection. It is high shortly after the infection occurs and then much lower for several years, and thereafter a higher plateau is reached before the acquired immunodeficiency syndrome (AIDS) phase sets in. In line with this, we formulated a mathematical model which is structured according to the age of infection. To understand the dynamics of the disease, we first discuss and analyse a simple model in which the age of infection is not considered, but progression of the HIV-AIDS transmission is taken into consideration by introducing three stages of infection. Analysis of these models tells us that the disease can be eradicated from the population only if on average one infected individual infects less than one person in his or her infectious period, otherwise the disease persists. To investigate the reduction of the number of infections caused by a single infectious individual to less than one, we introduce different treatment strategies for a model which depends on the age of infection, and we analyse it numerically. Current strategies amount to introducing treatment only at a late stage of infection when the infected individual has already lived through most of the infectious period. From our numerical results, this strategy does not result in eradication of the disease, even though it does reduce the burden for the individual. To eradicate the disease from the population, everyone would need to be HIV tested regularly and undergo immediate treatment if found positive. AFRIKAANSE OPSOMMING: Hierdie tesis hou rekening met die verskillende aansteeklikheidsvlakke van die menslike immuniteitsgebreksvirus (MIV) deur besmette individue gedurende hulle aansteeklikheidstydperk. Die graad van aansteeklikheid hang af van die tydperk sedert infeksie. Dit is hoog kort nadat die infeksie plaasvind en daarna heelwat laer vir etlike jare, en dan volg n hoer plato voordat uiteindelik die Verworwe-Immuniteitsgebreksindroom (VIGS) fase intree. In ooreenstemming hiermee, formuleer ons n wiskundige model van MIV-VIGSoordrag met n struktureer waarin die tydperk sedert infeksie bevat is. Om die dinamika van die siekte te verstaan, bespreek en analiseer ons eers n eenvoudige model sonder inagneming van die tydperk sedert infeksie, terwyl die progressie van MIV-VIGS-oordrag egter wel in ag geneem word deur die beskouing van drie stadiums van infeksie. Analise van die modelle wys dat die siekte in die bevolking slegs uitgeroei kan word as elke besmette mens gemiddeld minder as een ander individu aansteek gedurende die tydperk waarin hy of sy self besmet is, anders sal die siekte voortduur. Vir die ondersoek oor hoe om die aantal infeksies per besmette individu tot onder die waarde van een te verlaag, beskou ons verskeie behandelingsstrategiee binne die model, wat afhang van die tydperk sedert infeksie, en ondersoek hulle numeries. Die huidige behandelingstrategiee kom neer op behandeling slegs gedurende die laat sta- dium van infeksie, wanneer die besmette individu reeds die grootste deel van die aansteeklikheidsperiode deurleef het. Ons numeriese resultate toon dat hierdie strategie nie lei tot uitroeiing van die siekte nie, alhoewel dit wel die las van die siekte vir die individu verminder. Om die siekte binne die bevolking uit te roei, sou elkeen gereeld vir MIV getoets moes word en indien positief gevind, dadelik met behandeling moes begin. Thesis (MSc (Mathematical Sciences))--University of Stellenbosch, 2011. Includes bibliography.
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