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.

Abstract

OBJECTIVES:

To estimate the potentially inappropriate use of implantable cardioverter-defibrillator ICDs in older U.S. adults.

DESIGN:

Retrospective study.

SETTING:

The National Cardiovascular Data ICD Registry.

PARTICIPANTS:

Forty-four thousand eight hundred five individuals in the National Cardiovascular Data's ICD Registry(™) who had received ICDs for primary prevention from January 2006 to December 2008. Individuals with a prior myocardial infarction and ejection fraction less than 30% were included.

MEASUREMENTS:

Mortality risk was categorized using the Multicenter Automatic Defibrillator Implantation (MADIT) II risk-stratification system. Low-risk and very-high-risk individuals were considered potentially inappropriate recipients.

RESULTS:

Of 44,805 individuals, 67% (n=29,893) were aged 65 and older, of whom 51% were aged 75 and older. A significant proportion of ICD recipients had a low risk of death (16%, n=6,969) or very high risk of nonarrhythmic death (8%, n=3,693). Potentially inappropriate ICD use was 10% in those aged 75 and older, much less than in younger groups (40%,

CONCLUSION:

Potentially inappropriate ICD use appears significantly less-and at modest rates-in older Americans than in younger age groups. Overall, almost one-quarter of individuals may have received ICDs inappropriately based on their risk of death. Physicians appear to be conservatively referring older adults and wisely deferring those with high comorbid burden.

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.

Background

Cardiovascular diseases represent an increasing share of the global disease burden. There is concern that increased consumption of palm oil could exacerbate mortality from ischemic heart disease (IHD) and stroke, particularly in developing countries where it represents a major nutritional source of saturated fat.

Methods

The study analyzed country-level data from 1980-1997 derived from the World Health Organization's Mortality Database, U.S. Department of Agriculture international estimates, and the World Bank (234 annual observations; 23 countries). Outcomes included mortality from IHD and stroke for adults aged 50 and older. Predictors included per-capita consumption of palm oil and cigarettes and per-capita Gross Domestic Product as well as time trends and an interaction between palm oil consumption and country economic development level. Analyses examined changes in country-level outcomes over time employing linear panel regressions with country-level fixed effects, population weighting, and robust standard errors clustered by country. Sensitivity analyses included further adjustment for other major dietary sources of saturated fat.

Results

In developing countries, for every additional kilogram of palm oil consumed per-capita annually, IHD mortality rates increased by 68 deaths per 100,000 (95% CI [21-115]), whereas, in similar settings, stroke mortality rates increased by 19 deaths per 100,000 (95% CI [-12-49]) but were not significant. For historically high-income countries, changes in IHD and stroke mortality rates from palm oil consumption were smaller (IHD: 17 deaths per 100,000 (95% CI [5.3-29]); stroke: 5.1 deaths per 100,000 (95% CI [-1.2-11.0])). Inclusion of other major saturated fat sources including beef, pork, chicken, coconut oil, milk cheese, and butter did not substantially change the differentially higher relationship between palm oil and IHD mortality in developing countries.

Conclusions

Increased palm oil consumption is related to higher IHD mortality rates in developing countries. Palm oil consumption represents a saturated fat source relevant for policies aimed at reducing cardiovascular disease burdens.