Abstract

Many models of infectious disease ignore the underlying contact structure through which the disease spreads. However, in order to evaluate the efficacy of certain disease control interventions, it may be important to include this network structure. We present a network modeling framework of the spread of disease and a methodology for inferring important model parameters, such as those governing network structure and network dynamics, from readily available data sources. This is a general and flexible framework with wide applicability to modeling the spread of disease through sexual or close contact networks. To illustrate, we apply this modeling framework to evaluate HIV control programs in sub-Saharan Africa, including programs aimed at concurrent partnership reduction, reductions in risky sexual behavior, and scale up of HIV treatment.

Abstract

We estimated the effectiveness and cost-effectiveness of changes in concurrent sexual partnerships in reducing the spread of HIV in sub-Saharan Africa. Using data from Swaziland, Tanzania, Uganda and Zambia, we estimated country-specific concurrency behaviour from sexual behaviour survey data on the number of partners in the past 12 months, and we developed a network model to compare the impact of three behaviour changes on the HIV epidemic: (1) changes in concurrent partnership patterns to strict monogamy; (2) partnership reduction among those with the greatest number of partners; and (3) partnership reduction among all individuals. We estimated the number of new HIV infections over 10 years and the cost per infection averted. Given our assumptions and model structure, we find that reducing concurrency among high-risk individuals averts the most infections and increasing monogamy the least (11.7% versus 8.7% reduction in new infections, on average, for a 10% reduction in concurrent partnerships). A campaign that costs US$1 per person annually is likely cost-saving if it reduces concurrency by 9% on average, given our baseline estimates of concurrency. In sensitivity analysis, the rank ordering of behaviour change scenarios was unaffected by potential over-estimation of concurrency, though the number of infections averted decreased and the cost per HIV infection averted increased. Concurrency reduction programmes may be effective and cost-effective in reducing HIV incidence in sub-Saharan Africa if they can achieve even modest impacts at similar costs to past mass media campaigns in the region. Reduced concurrency among high-risk individuals appears to be most effective in reducing HIV incidence, but concurrency reduction in other risk groups may yield nearly as much benefit.

Venture capital investment has become globalized in the business landscape. Scholars
have reported an increasing globalization trend in the VC industry, as measured by VC
investment across national borders (Wright et al., 2005). Aylward (1998) found that Asian
countries/economies (e.g., Singapore, Hong Kong, and India) largely sourced their venture funds internationally. Baygan (2000) demonstrated that European countries experienced increases of cross-border VC flow. Aizenman & Kendall (2008) found that the number/volume of VC deals with international participation has increased in recent years. Finally, according to the Deloitte Touche Tohmatsu 2009 Global Venture Capital Survey, 52% of VCs already invest outside their home countries (Deloitte, 2009). Researchers also examine mechanisms behind this globalization trend: Guler & Guillen (2010) analyze the influence of recipient countries’ institutions on U.S. VC firms’ international investment decision. Aizenman & Kendall analyze the determinants of global VC flow using the gravity model framework. My two studies, both of which examine determinants and patterns of VC investment globalization, are positioned in this stream of research.

BACKGROUND:

The effect of adherence, treatment failure, and comorbidities on the cost of HIV care is not well understood.

OBJECTIVE:

To characterize the cost of HIV care including combination antiretroviral treatment (ART).

RESEARCH DESIGN:

Observational study of administrative data.

SUBJECTS:

Total 1896 randomly selected HIV-infected patients and 288 trial participants with multidrug-resistant HIV seen at the US Veterans Health Administration (VHA).

MEASURES:

Comorbidities, cost, pharmacy, and laboratory data.

RESULTS:

Many HIV-infected patients (24.5%) of the random sample did not receive ART. Outpatient pharmacy accounted for 62.8% of the costs of patients highly adherent with ART, 32.2% of the cost of those with lower adherence, and 6.2% of the cost of those not receiving ART. Compared with patients not receiving ART, high adherence was associated with lower hospital cost, but no greater total cost. Individuals with a low CD4 count (500. Most patients had medical, psychiatric, or substance abuse comorbidities. These conditions were associated with greater cost. Trial participants were less likely to have psychiatric and substance abuse comorbidities than the random sample of VHA patients with HIV.

CONCLUSIONS:

Patients receiving combination ART had higher medication costs but lower acute hospital cost. Poor control of HIV was associated with higher cost. The cost of psychiatric, substance abuse, rehabilitation, and long-term care and medications other than ART, often overlooked in HIV studies, was substantial.

OBJECTIVE:

Acute HIV infection often causes influenza-like illness (ILI) and is associated with high infectivity. We estimated the effectiveness and cost-effectiveness of strategies to identify and treat acute HIV infection in men who have sex with men (MSM) in the USA.

DESIGN:

Dynamic model of HIV transmission and progression.

INTERVENTIONS:

We evaluated three testing approaches: viral load testing for individuals with ILI, expanded screening with antibody testing, and expanded screening with antibody and viral load testing. We included treatment with antiretroviral therapy for individuals identified as acutely infected.

MAIN OUTCOME MEASURES:

New HIV infections, discounted quality-adjusted life years (QALYs) and costs, and incremental cost-effectiveness ratios.

RESULTS:

At the present rate of HIV-antibody testing, we estimated that 538,000 new infections will occur among MSM over the next 20 years. Expanding antibody screening coverage to 90% of MSM annually reduces new infections by 2.8% and costs US$ 12,582 per QALY gained. Symptom-based viral load testing with ILI is more expensive than expanded antibody screening, but is more effective and costs US$ 22,786 per QALY gained. Combining expanded antibody screening with symptom-based viral load testing prevents twice as many infections compared to expanded antibody screening alone, and costs US$ 29,923 per QALY gained. Adding viral load testing to all annual HIV tests costs more than US$ 100,000 per QALY gained.

CONCLUSION:

Use of HIV viral load testing in MSM with ILI prevents more infections than does expanded annual antibody screening alone and is inexpensive relative to other screening interventions. Clinicians should consider symptom-based viral load testing in MSM, in addition to encouraging annual antibody screening.

BACKGROUND:

The prime-boost HIV vaccine regimen used in the recent RV144 trial resulted in modest efficacy of 31% over 3.5 years, but was substantially higher in the first year post-vaccination. We sought to explore the potential impact of a vaccine with rapidly waning efficacy in a South African population.

METHODS:

We explored two strategies using a dynamic compartmental epidemic model for heterosexual transmission of HIV: [1] vaccination of a single cohort (30%, 60% or 90% of the initial population), with exponentially waning efficacy, but booster vaccinations at 5- or 2-year intervals, and [2] continuous vaccination of the unvaccinated population at the same coverage levels (30%, 60% or 90%) but with a constant efficacy vaccine of short duration. We also examined potential changes in post-vaccination condom use.

RESULTS:

The single cohort vaccination strategies did not have a substantial impact on HIV prevalence, although without boosters they still prevented 2-6% of the expected infections at 20 years, depending on the population coverage. The 5-year and 2-year booster strategies prevented 8-24% and 17-45% of the expected infections, respectively. Continuous vaccination to maintain population coverage levels resulted in more substantial reductions in population HIV prevalence and greater numbers of infections prevented: HIV prevalence at 20 years was reduced from 23% to 8-14% and the number of expected infections was decreased by 34-59%, depending on the population coverage level. Moderate changes in post-vaccination condom use did not substantially affect these outcomes.

CONCLUSIONS:

An HIV vaccine with partial efficacy and declining protection similar to the RV144 vaccine could prevent a substantial proportion of HIV infections if booster vaccinations were effective and available. Our estimates of the population impact of vaccination would be improved by further understanding of the duration of protection, the effectiveness of booster vaccination, and whether the vaccine efficacy varies between subpopulations at higher and lower risk of exposure.

The mechanism by which strictly CCR5 using HIV-1 clade C variants exacerbate disease progression in absence of coreceptor switch is not clearly known. We previously reported HIV-1 cladeC envelopes (Env) obtained from late stage Indian patients with expanded coreceptor tropism. Here we compared such Envs (having expanded coreceptor tropism) with strictly CCR5 using Envs also obtained from late stage in their capacity to utilize CD4 and CCR5 for productive entry. We found that while envelopes with low CD4 dependence tend to infect primary CD4(+) T cells better than those required optimum CD4 for entry, no significant association was found between low CD4 usage and infectivity of primary CD4(+) T cells by Env-pseudotyped viruses and theirsensitivity to CCR5 antagonist TAK-779. Interestingly, Envs that readily infected HeLa cells expressing low CD4 showed relative resistance to T20 indicating that conformational intermediates of these envelopes remained for a shorter period of time than is required for efficient inhibition by T20.

Identification of vulnerability in the HIV-1 envelope (Env) will aid in Env-based vaccine design. We recently found an HIV-1 clade C Env clone (4-2.J45) amplified from a recently infected Indian patient showing exceptional neutralization sensitivity to autologous plasma in contrast to other autologous Envs obtained at the same time point. By constructing chimeric Envs and fine mapping between sensitive and resistant Env clones, we found that substitution of highly conserved isoleucine (I) with methionine (M) (ATA to ATG) at position 424 in the C4 domain conferred enhanced neutralization sensitivity of Env-pseudotyped viruses to autologous and heterologous plasma antibodies. When tested against monoclonal antibodies targeting different sites in gp120 and gp41, Envs expressing M424 showed significant sensitivity to anti-V3 monoclonal antibodies and modestly to sCD4 and b12. Substitution of I424M in unrelated Envs also showed similar neutralization phenotype, indicating that M424 in C4 region induces exposure of neutralizing epitopes particularly in CD4 binding sites and V3 loop.

The four-volume Encyclopedia of Global Studies covers the field of global studies and subjects related to it, such as globalization, transnational activity and themes of global society. This encyclopedia is written for the educated general reader as well as students and professionals working in the field of global studies. It is the first encyclopedia of its kind, and aims to become the internationally-recognized reference work for academics, policymakers, and practitioners interested in the various dimensions of globalization. It provides succinct summaries of concepts and theories, definitions of terms, biographical entries, and organizational profiles; offers a guide to sources of information; and establishes an overview of Global Studies in different parts of the world and across cultures and historical periods.  The wide range of subjects covered include the following:
            - intellectual approaches, such as global sociology, political economy, world systems theory, peace and conflict studies, and communications;
            - global and transnational topics, such as cross-border conflicts and terrorism, worldwide health crises and climate disruption, the planetary immigration patterns and new cultural diasporas, and the seemingly boundless global market, rapid communications, and transnational cyberspaces devised by technology and new media.

The four-volume Encyclopedia of Global Studies covers the field of global studies and subjects related to it, such as globalization, transnational activity and themes of global society. This encyclopedia is written for the educated general reader as well as students and professionals working in the field of global studies. It is the first encyclopedia of its kind, and aims to become the internationally-recognized reference work for academics, policymakers, and practitioners interested in the various dimensions of globalization. It provides succinct summaries of concepts and theories, definitions of terms, biographical entries, and organizational profiles; offers a guide to sources of information; and establishes an overview of Global Studies in different parts of the world and across cultures and historical periods.  The wide range of subjects covered include the following:
            - intellectual approaches, such as global sociology, political economy, world systems theory, peace and conflict studies, and communications;
            - global and transnational topics, such as cross-border conflicts and terrorism, worldwide health crises and climate disruption, the planetary immigration patterns and new cultural diasporas, and the seemingly boundless global market, rapid communications, and transnational cyberspaces devised by technology and new media.