Potential Impact of Antiretroviral Therapy on HIV-1 Transmission and AIDS Mortality in Resource-Limited Settings

Division of Infectious Diseases, School of Medicine, Falk Medical Building, University of Pittsburgh, 3601 Fifth Avenue, Pittsburgh, PA 15213, USA.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 05/2006; 41(5):632-41. DOI: 10.1097/
Source: PubMed


To estimate the potential impact of antiretroviral therapy on the heterosexual spread of HIV-1 infection and AIDS mortality in resource-limited settings.
A mathematic model of HIV-1 disease progression and transmission was used to assess epidemiologic outcomes under different scenarios of antiretroviral therapy, including implementation of World Health Organization guidelines.
Implementing antiretroviral therapy at 5% HIV-1 prevalence and administering it to 100% of AIDS cases are predicted to decrease new HIV-1 infections and cumulative deaths from AIDS after 10 years by 11.2% (inter-quartile range [IQR]: 1.8%-21.4%) and 33.4% (IQR: 26%-42.8%), respectively. Later implementation of therapy at endemic equilibrium (40% prevalence) is predicted to be less effective, decreasing new HIV-1 infections and cumulative deaths from AIDS by 10.5% (IQR: 2.6%-19.3%) and 27.6% (IQR: 20.8%-36.8%), respectively. Therapy is predicted to benefit the infected individual and the uninfected community by decreasing transmission and AIDS deaths. The community benefit is greater than the individual benefit after 25 years of treatment and increases with the proportion of AIDS cases treated.
Antiretroviral therapy is predicted to have individual and public health benefits that increase with time and the proportion of infected persons treated. The impact of therapy is greater when introduced earlier in an epidemic, but the benefit can be lost by residual infectivity or disease progression on treatment and by sexual disinhibition of the general population.

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    • "An important public health benefit of HIV screening is reduced transmission due to (1) effective counseling aimed at reducing risky behavior, and (2) earlier ART initiation, which suppresses viral load, reducing the chance of transmission.[29]–[35] The model was explicitly designed to capture the population-level benefits of reduced transmission, as well as the individual benefits of reduced disease progression, morbidity, and mortality. "
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    ABSTRACT: At least 10% of the 56,000 annual new HIV infections in the United States are caused by individuals with acute HIV infection (AHI). It unknown whether the health benefits and costs of routine nucleic acid amplification testing (NAAT) are justified, given the availability of newer fourth-generation immunoassay tests. Using a dynamic HIV transmission model instantiated with U.S. epidemiologic, demographic, and behavioral data, I estimated the number of acute infections identified, HIV infections prevented, quality-adjusted life years (QALYs) gained, and the cost-effectiveness of alternative screening strategies. I varied the target population (everyone aged 15-64, injection drug users [IDUs] and men who have sex with men [MSM], or MSM only), screening frequency (annually, or every six months), and test(s) utilized (fourth-generation immunoassay only, or immunoassay followed by pooled NAAT). Annual immunoassay testing of MSM reduces incidence by 9.5% and costs <$10,000 per QALY gained. Adding pooled NAAT identifies 410 AHI per year, prevents 9.6% of new cases, costs $92,000 per QALY gained, and remains <$100,000 per QALY gained in settings where undiagnosed HIV prevalence exceeds 4%. Screening IDUs and MSM annually with fourth-generation immunoassay reduces incidence by 13% with cost-effectiveness <$10,000 per QALY gained. Increasing the screening frequency to every six months reduces incidence by 11% (MSM only) or 16% (MSM and IDUs) and costs <$20,000 per QALY gained. Pooled NAAT testing every 12 months of MSM and IDUs in the United States prevents a modest number of infections, but may be cost-effective given sufficiently high HIV prevalence levels. However, testing via fourth-generation immunoassay every six months prevents a greater number of infections, is more economically efficient, and may obviate the benefits of acute HIV screening via NAAT.
    PLoS ONE 11/2011; 6(11):e27625. DOI:10.1371/journal.pone.0027625 · 3.23 Impact Factor
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    • "The reduction in viral load in individuals treated with ART has led to optimistic expectations about the ability of treatment to limit the HIV epidemic, and several studies support ART as a prevention strategy [3]. However, this is still an ongoing international debate: several epidemiological models do not support this assumption [4,5]. In addition, several studies have reported that although genital shedding of HIV does decrease after initiation of ART, there is often incomplete suppression with a low correlation between HIV-RNA levels in blood compared with semen and vaginal fluids [6-8]. "
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    ABSTRACT: Our intention was to analyze demographic and contextual factors associated with sexual risk taking among HIV-infected patients on antiretroviral treatment (ART) in Africa's largest informal urban settlement, Kibera in Nairobi, Kenya. We used a cross-sectional survey in a resource-poor, urban informal settlement in Nairobi; 515 consecutive adult patients on ART attending the African Medical and Research Foundation clinic in Kibera in Nairobi were included in the study. Interviewers used structured questionnaires covering socio-demographic characteristics, time on ART, number of sexual partners during the previous six months and consistency of condom use. Twenty-eight percent of patients reported inconsistent condom use. Female patients were significantly more likely than men to report inconsistent condom use (aOR 3.03; 95% CI 1.60-5.72). Shorter time on ART was significantly associated with inconsistent condom use. Multiple sexual partners were more common among married men than among married women (adjusted OR 4.38; 95% CI 1.82-10.51). Inconsistent condom use was especially common among women and patients who had recently started ART, i.e., when the risk of HIV transmission is higher. Having multiple partners was quite common, especially among married men, with the potential of creating sexual networks and an increased risk of HIV transmission. ART needs to be accompanied by other preventive interventions to reduce the risk of new HIV infections among sero-discordant couples and to increase overall community effectiveness.
    Journal of the International AIDS Society 04/2011; 14(1):20. DOI:10.1186/1758-2652-14-20 · 5.09 Impact Factor
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    • "With a recently developed mathematical model, which explicitly takes into account that the majority of people on cART are successfully treated and maintain very low HIV RNA levels, and are thus presumed largely uninfectious, we found evidence that increased risk behaviour amongst undiagnosed individuals may have counterbalanced the beneficial effect of cART amongst MSM in the Netherlands (Bezemer et al., 2008). Other models looking at the impact of cART treatment have found that treatment of the HIV infected population in an advanced stage of disease progression alone might not halt epidemic spread but that expanded and earlier access to cART can reduce the growth of the epidemic (Abbas et al., 2006; Lima et al., 2008; Salomon and Hogan, 2008). Besides pre-exposure prophylaxis of high risk HIV-negative MSM (Desai et al., 2008), and testing for acute primary infection, more routine health care interventions such as earlier treatment and more frequent testing Epidemics 2 (2010) 66–79 ⁎ Corresponding author. "
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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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