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Background Results of international clinical trials assessing when to initiate antiretroviral therapy (ART) will not be available for several years. Objective To inform HIV treatment decisions over the short- and long-term regarding the optimal CD4 threshold at which to initiate ART in South Africa, while awaiting “when to start” trial results. Design Cost-effectiveness analysis using a computer simulation model of HIV disease. Data Sources Published data from randomized trials and observational cohorts in South Africa. Target Population HIV-infected patients in South Africa. Time Horizon Five-year and lifetime. Perspective Modified societal. Interventions No treatment, initiate ART at CD4<250/μl, and initiate ART at CD4<350/μl. Outcome Measures Morbidity, mortality, life expectancy, medical costs, and cost-effectiveness. Results of Base-Case Analysis If 10-100% of HIV-infected patients are diagnosed and linked to care, initiating ART at CD4<350/μl would reduce severe opportunistic diseases by 22,000-221,000 and deaths by 25,000-253,000 during the next 5 years, compared to initiating ART at CD4<250/μl; cost increases would range from $142 million (10%) to $1.4 billion (100%). Either ART strategy increased long-term survival by at least 7.9 years, with a mean per person life expectancy of 3.8 years for no ART and 12.5 years for ART at <350/μl. Compared to initiating ART at <250/μl, initiating ART at <350/μl had an incremental cost-effectiveness ratio of $1,200/year of life saved. Results of Sensitivity Analysis Initiating ART at CD4<350/μl remained cost-effective over the next 5 years even if the probability that the trial would demonstrate superiority to earlier therapy is as low as 17%. Limitations This model does not consider the possible benefits of ART initiation at CD4>350/μl nor reduced HIV transmission. Conclusions Earlier ART initiation in South Africa will likely reduce morbidity and mortality, improve long-term survival, and be very cost-effective. While awaiting trial results, treatment guidelines should be liberalized to allow for earlier ART initiation (CD4<350/μl) than is currently recommended.

Esophageal squamous cell carcinoma (ESCC) is endemic in regions of sub-Saharan Africa (SSA), where it is the third most common cancer. Here, we describe whole-exome tumor/normal sequencing and RNA transcriptomic analysis of 59 patients with ESCC in Malawi. We observed similar genetic aberrations as reported in Asian and North American cohorts, including mutations of ,, ,, ,, and . Analyses for nonhuman sequences did not reveal evidence for infection with HPV or other occult pathogens. Mutational signature analysis revealed common signatures associated with aging, cytidine deaminase activity (APOBEC), and a third signature of unknown origin, but signatures of inhaled tobacco use, aflatoxin and mismatch repair were notably absent. Based on RNA expression analysis, ESCC could be divided into 3 distinct subtypes, which were distinguished by their expression of cell cycle and neural transcripts. This study demonstrates discrete subtypes of ESCC in SSA, and suggests that the endemic nature of this disease reflects exposure to a carcinogen other than tobacco and oncogenic viruses.

Adherence to antiretroviral medications has been shown to be an important factor in predicting viral suppression and clinical outcomes. The objective of this analysis was to assess the cost-effectiveness of a nursing intervention on antiretroviral adherence using data from a randomized controlled clinical trial as input to a computer-based simulation model of HIV disease. For a cohort of HIV-infected patients similar to those in the clinical trial (mean initial CD4 count of 319 cells/mm), implementing the nursing intervention in addition to standard care yielded a 63% increase in virologic suppression at 48 weeks. This produced increases in expected survival (from 94.5 to 100.9 quality-adjusted life months) and estimated discounted direct lifetime medical costs ($253,800 to $261,300). The incremental cost-effectiveness ratio for the intervention was $14,100 per quality-adjusted life year gained compared with standard care. Adherence interventions with modest effectiveness are likely to provide long-term survival benefit to patients and to be cost-effective compared with other uses of HIV care funds.

IMPORTANCE Trauma is the leading cause of death and disability among young adults, who are also among the most likely to be uninsured. Efforts to increase insurance coverage, including passage of the Patient Protection and Affordable Care Act (ACA), were intended to improve access to care and promote improvements in outcomes. However, despite reported gains in coverage, the ACA's success in promoting use of high-quality care and enacting changes in clinical end points remains unclear. OBJECTIVES To assess for observed changes in insurance coverage and rehabilitation use among young adult trauma patients associated with the ACA, including the Dependent Coverage Provision (DCP) and Medicaid expansion/open enrollment, and to consider possible insurance and rehabilitation differences between DCP-eligible vs-ineligible patients and among stratified demographic and community subgroups. DESIGN, SETTING, AND PARTICIPANTS A longitudinal assessment of DCP implementation and Medicaid expansion/open enrollment using risk-adjusted before-and-after, difference-indifference, and interrupted time-series analyses was conducted. Eleven years (January 1, 2005, to September 31, 2015) of Maryland Health Services Cost Review Commission data, representing complete patient records from all payers within the state, were used to identify all hospitalized young adult (aged 18-34 years) trauma patients in Maryland during the study period. RESULTS Of the 69 507 hospitalized patients included, 50 548 (72.7%) were male, and the mean (SD) age was 25 (5) years. Before implementation of the DCP, 1 of 4 patients was uninsured. After ACA implementation, the number fell to less than 1 of 10, with similar patterns emerging in emergency department and outpatient settings. The change was primarily driven by Medicaid expansion/open enrollment, which corresponded to a 20.1 percentage-point increase in Medicaid (95% CI, 18.9-21.3) and an 18.2 percentage-point decrease in uninsured (95% CI, −19.3 to −17.2). No changes were detected among privately insured patients. Rehabilitation use increased by 5.4 percentage points (95% CI, 4.5-6.2)-a 60% relative increase from a baseline of 9%. Mortality (−0.5; 95% CI, −0.9 to −0.1) and failure-to-rescue rates (−4.5; 95% CI, −7.4 to −1.6) also significantly declined. Stratified changes point to significant differences in the percentage of uninsured patients and rehabilitation access across the board, mitigating or even eradicating disparities in certain cases. CONCLUSIONS AND RELEVANCE For patients who are injured, young, and uninsured, Medicaid expansion/open enrollment in Maryland changed insurance coverage and altered patient outcomes in ways that the DCP alone was never intended to do. Implementation of Medicaid expansion/open enrollment transformed the landscape of trauma coverage, directly affecting the health of one of the country's most vulnerable at-risk groups.