Assessing the individual benefits of reducing HIV diagnosis delay and increasing adherence to HIV care and treatment.

We used an agent-based simulation model (Progression and Transmission of HIV) to follow for 20 years a cohort of persons in the United States infected with HIV in 2015. We assessed the benefits of reducing the delay between HIV infection and diagnosis and increasing adherence to HIV care and treatment on the percent of persons surviving 20 years after infection, average annual HIV transmission rates, and time spent virally suppressed. We examined average diagnosis delays of 1.0-7.0 years, monthly care drop-out rates of 5% to 0.1%, and combinations of these strategies. The percent of the cohort surviving the first 20 years of infection varied from 70.8% to 77.5%, and the annual transmission risk, from 1.5 to 5.2 HIV transmissions per 100 person-years. Thus, individuals can enhance their survival and reduce their risk of transmission to partners by frequent testing for HIV and adhering to care and treatment.

The Estimated Number and Lifetime Medical Cost of HIV Infections Attributable to Sexually Transmitted Infections Acquired in the United States in 2018: A Compilation of Published Modeling Results.

BACKGROUND: The purpose of this study was to estimate the number and lifetime medical cost of HIV infections attributable to incident sexually transmitted infections (STIs) in the United States in 2018. METHODS: We combined data from published models regarding the number or percentage of HIV infections attributable to STIs with updated estimates of the lifetime medical cost per HIV infection. We used 2 distinct calculation methods. Our first calculation used recent estimates of the percentage of HIV infections in men who have sex with men (MSM) attributable to gonorrhea and chlamydia. Our second calculation, based on older studies, used estimates of the expected number of STI-attributable HIV infections per new STI infection, for gonorrhea, chlamydia, syphilis, and trichomoniasis. RESULTS: Our first calculation method suggested that 2489 (25th-75th percentiles, 1895-3000) HIV infections in 2018 among MSM could be attributed to gonorrhea and chlamydia, at an estimated lifetime medical cost of $1.05 billion (25th-75th percentiles, $0.79-$1.26 billion). Our second calculation method suggested that 2349 (25th-75th percentiles, 1948-2744) HIV infections in the general population (including MSM) could be attributed to chlamydia, gonorrhea, syphilis, and trichomoniasis acquired in 2018, at an estimated lifetime medical cost of $0.99 billion (25th-75th percentiles, $0.80-$1.16 billion). CONCLUSIONS: Despite ambiguity regarding the degree to which STIs affect HIV transmission, our combination of data from published STI/HIV transmission models and an HIV lifetime medical cost model can help to quantify the estimated burden of STI-attributable HIV infections in the United States.

Estimated Lifetime HIV-Related Medical Costs in the United States.

BACKGROUND: Lifetime cost estimates are a useful tool in measuring the economic burden of HIV in the United States. Previous estimation methods need to be updated, given improving antiretroviral therapy regimens and updated costs. METHODS: We used an updated version of the agent-based model progression and transmission of HIV (PATH) 3.0 to reflect current regimens and costs. We simulated a cohort of those infected in 2015 until the last person had died to track the lifetime costs for treatment of HIV, including HIV health care utilization costs (inpatient, outpatient, opportunistic infection prophylaxis, non-HIV medication, and emergency department), opportunistic infection treatment costs, and testing costs. We assumed a median per-person diagnosis delay of 3 years and a 3% base monthly probability of dropout from care for a base-case scenario. Additionally, we modeled a most favorable scenario (median diagnosis delay of 1 year and 1% base dropout rate) and a least favorable scenario (median diagnosis delay of 5 years and 5% base dropout rate). RESULTS: We estimated an average lifetime HIV-related medical cost for a person with HIV of $420,285 (2019 US$) discounted (3%) and $1,079,999 undiscounted for a median 3-year diagnosis delay and 3% base dropout rate. Our discounted cost estimate was $490,045 in our most favorable scenario and $326,411 in our least favorable scenario. CONCLUSIONS: Lifetime per-person HIV-related medical costs depend on the time from infection to diagnosis and the likelihood of dropping out of care. Our results, which are similar to previous studies, reflect updated antiretroviral therapy regimens and costs for HIV treatment.

The Estimated Direct Lifetime Medical Costs of Sexually Transmitted Infections Acquired in the United States in 2018.

BACKGROUND: We estimated the lifetime medical costs attributable to sexually transmitted infections (STIs) acquired in 2018, including sexually acquired human immunodeficiency virus (HIV). METHODS: We estimated the lifetime medical costs of infections acquired in 2018 in the United States for 8 STIs: chlamydia, gonorrhea, trichomoniasis, syphilis, genital herpes, human papillomavirus (HPV), hepatitis B, and HIV. We limited our analysis to lifetime medical costs incurred for treatment of STIs and for treatment of related sequelae; we did not include other costs, such as STI prevention. For each STI, except HPV, we calculated the lifetime medical cost by multiplying the estimated number of incident infections in 2018 by the estimated lifetime cost per infection. For HPV, we calculated the lifetime cost based on the projected lifetime incidence of health outcomes attributed to HPV infections acquired in 2018. Future costs were discounted at 3% annually. RESULTS: Incident STIs in 2018 imposed an estimated $15.9 billion (25th-75th percentile: $14.9-16.9 billion) in discounted, lifetime direct medical costs (2019 US dollars). Most of this cost was due to sexually acquired HIV ($13.7 billion) and HPV ($0.8 billion). STIs in women accounted for about one fourth of the cost of incident STIs when including HIV, but about three fourths when excluding HIV. STIs among 15- to 24-year-olds accounted for $4.2 billion (26%) of the cost of incident STIs. CONCLUSIONS: Incident STIs continue to impose a considerable lifetime medical cost burden in the United States. These results can inform health economic analyses to promote the use of cost-effective STI prevention interventions to reduce this burden.

Putative biomarkers for predicting tumor sample purity based on gene expression data.

BACKGROUND: Tumor purity is the percent of cancer cells present in a sample of tumor tissue. The non-cancerous cells (immune cells, fibroblasts, etc.) have an important role in tumor biology. The ability to determine tumor purity is important to understand the roles of cancerous and non-cancerous cells in a tumor. METHODS: We applied a supervised machine learning method, XGBoost, to data from 33 TCGA tumor types to predict tumor purity using RNA-seq gene expression data. RESULTS: Across the 33 tumor types, the median correlation between observed and predicted tumor-purity ranged from 0.75 to 0.87 with small root mean square errors, suggesting that tumor purity can be accurately predicted υσινγ expression data. We further confirmed that expression levels of a ten-gene set (CSF2RB, RHOH, C1S, CCDC69, CCL22, CYTIP, POU2AF1, FGR, CCL21, and IL7R) were predictive of tumor purity regardless of tumor type. We tested whether our set of ten genes could accurately predict tumor purity of a TCGA-independent data set. We showed that expression levels from our set of ten genes were highly correlated (ρ = 0.88) with the actual observed tumor purity. CONCLUSIONS: Our analyses suggested that the ten-gene set may serve as a biomarker for tumor purity prediction using gene expression data.

Is more better? Higher sterilization of infected hosts need not result in reduced pest population size.

We analyze the effect of sterilization in the infected hosts in several epidemiological models involving infectious diseases that can be transmitted both vertically and horizontally. Sterilizing pathogens can be used as pest control agents by intentionally inoculating the target population, with the goal of reducing or eliminating it completely. Contrary to previous models that did not include vertical transmission we found that the population size at the endemic equilibrium may actually increase with higher levels of sterility. This effect is proved to exist for low to high efficiencies of vertical transmission. On the other hand, if the disease is sexually transmitted and the host reproduction and disease transmission are both consistently mediated by mating, we do not observe such a counter-intuitive effect and the population size in the stable endemic equilibrium is decreasing with higher levels of sterility. We suggest that models of the pest control techniques involving the release of sterilizing pathogens have to carefully consider the routes such pathogens use for transmission.

The effect of cooperator recognition on competition among clones in spatially structured microbial communities.

In spatially structured microbial communities, clonal growth of stationary cells passively generates clusters of related individuals. This can lead to stable cooperation without the need for recognition mechanisms. However, recent research suggests that some biofilm-forming microbes may have mechanisms of kin recognition. To explore this unexpected observation, we studied the effects of different types of cooperation in a microbial colony using spatially explicit, agent-based simulations of two interacting strains. We found scenarios that favor a form of kin recognition in spatially structured microbial communities. In the presence of a "cheater" strain, a strain with greenbeard cooperation was able to increase in frequency more than a strain with obligate cooperation. This effect was most noticeable in high density colonies and when the cooperators were not as abundant as the cheaters. We also studied whether a polychromatic greenbeard, in which cells only cooperate with their own type, could provide a numerical benefit beyond a simple, binary greenbeard. We found the greatest benefit to a polychromatic greenbeard when cooperation is highly effective. These results suggest that in some ecological scenarios, recognition mechanisms may be beneficial even in spatially structured communities.