Remdesivir for Severe Coronavirus Disease 2019 (COVID-19) Versus a Cohort Receiving Standard of Care.

BACKGROUND: We compared the efficacy of the antiviral agent, remdesivir, versus standard-of-care treatment in adults with severe coronavirus disease 2019 (COVID-19) using data from a phase 3 remdesivir trial and a retrospective cohort of patients with severe COVID-19 treated with standard of care. METHODS: GS-US-540-5773 is an ongoing phase 3, randomized, open-label trial comparing two courses of remdesivir (remdesivir-cohort). GS-US-540-5807 is an ongoing real-world, retrospective cohort study of clinical outcomes in patients receiving standard-of-care treatment (non-remdesivir-cohort). Inclusion criteria were similar between studies: patients had confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, were hospitalized, had oxygen saturation ≤94% on room air or required supplemental oxygen, and had pulmonary infiltrates. Stabilized inverse probability of treatment weighted multivariable logistic regression was used to estimate the treatment effect of remdesivir versus standard of care. The primary endpoint was the proportion of patients with recovery on day 14, dichotomized from a 7-point clinical status ordinal scale. A key secondary endpoint was mortality. RESULTS: After the inverse probability of treatment weighting procedure, 312 and 818 patients were counted in the remdesivir- and non-remdesivir-cohorts, respectively. At day 14, 74.4% of patients in the remdesivir-cohort had recovered versus 59.0% in the non-remdesivir-cohort (adjusted odds ratio [aOR] 2.03: 95% confidence interval [CI]: 1.34-3.08, P < .001). At day 14, 7.6% of patients in the remdesivir-cohort had died versus 12.5% in the non-remdesivir-cohort (aOR 0.38, 95% CI: .22-.68, P = .001). CONCLUSIONS: In this comparative analysis, by day 14, remdesivir was associated with significantly greater recovery and 62% reduced odds of death versus standard-of-care treatment in patients with severe COVID-19. CLINICAL TRIALS REGISTRATION: NCT04292899 and EUPAS34303.

Evidence of an Association of Increases in Pre-exposure Prophylaxis Coverage With Decreases in Human Immunodeficiency Virus Diagnosis Rates in the United States, 2012-2016.

BACKGROUND: Annual human immunodeficiency virus (HIV) diagnoses in the United States (US) have plateaued since 2013. We assessed whether there is an association between uptake of pre-exposure prophylaxis (PrEP) and decreases in HIV diagnoses. METHODS: We used 2012-2016 data from the US National HIV Surveillance System to estimate viral suppression (VS) and annual percentage change in diagnosis rate (EAPC) in 33 jurisdictions, and data from a national pharmacy database to estimate PrEP uptake. We used Poisson regression with random effects for state and year to estimate the association between PrEP coverage and EAPC: within jurisdictional quintiles grouped by changes in PrEP coverage, regressing EAPC on time; and among all jurisdictions, regressing EAPC on both time and jurisdictional changes in PrEP coverage with and without accounting for changes in VS. RESULTS: From 2012 to 2016, across the 10 states with the greatest increases in PrEP coverage, the EAPC decreased 4.0% (95% confidence interval [CI], -5.2% to -2.9%). On average, across the states and District of Columbia, EAPC for a given year decreased by 1.1% (95% CI, -1.77% to -.49%) for an increase in PrEP coverage of 1 per 100 persons with indications. When controlling for VS, the state-specific EAPC for a given year decreased by 1.3% (95% CI, -2.12% to -.57%) for an increase in PrEP coverage of 1 per 100 persons with indications. CONCLUSIONS: We found statistically significant associations between jurisdictional increases in PrEP coverage and decreases in EAPC independent of changes in VS, which supports bringing PrEP use to scale in the US to accelerate reductions in HIV infections.

Contrasting serum biomarker profiles in two Colombian populations with different risks for progression of premalignant gastric lesions during chronic Helicobacter pylori infection.

BACKGROUND: Colombians in coastal Tumaco have a lower incidence of Helicobacter pylori-associated gastric cancer compared to individuals from Tuquerres in the high Andes. This is despite nearly universal prevalence of H. pylori infection and chronic gastritis. METHODS: H. pylori infection was confirmed by Steiner stain and serology using African and European-origin strains. Gastric histology and serum inflammatory biomarkers in dyspeptic Tumaco or Tuquerres patients were evaluated to predict progression of gastric lesions. RESULTS: H. pylori infection was nearly universal by Steiner stain and serology. IgG response to European-origin H. pylori strains were greater than African-origin. High gastric cancer-risk Tuquerres patients, compared to low-risk Tumaco, had significant odds ratios for lesion progression associated with serum IL-5, trefoil factor 3 (TFF3), and low pepsinogen I/II ratio. Sensitivity and specificity for these parameters was 63.8% and 67.9%, respectively, with correctly classifying patients at 66.7%. Most odds ratios for 26 other biomarkers were significant for the town of residency, indicating an environmental impact on Tumaco patients associated with decreased lesion progression. CONCLUSION: An IL-5 association with progression of gastric lesions is novel and could be evaluated in addition to TFF3 and pepsinogen I/II ratio as a non-invasive prognostic screen. Results suggest Tumaco patients were exposed to infectious diseases beyond H. pylori such as the documented high incidence of helminthiasis and toxoplasmosis. IMPACT: Results support a prior recommendation to evaluate TFF3 and pepsinogen I/II together to predict aggressive gastric histology. Our data indicate IL-5 should be further evaluated as prognostic parameter.

Small-area spatial-temporal changes in pre-exposure prophylaxis (PrEP) use in the general population and among men who have sex with men in the United States between 2012 and 2018.

PURPOSE: Oral emtricitabine/tenofovir disoproxil fumarate was approved for use as pre-exposure prophylaxis (PrEP) by the U.S. Food and Drug Administration in 2012. We used national pharmacy data to examine trends of PrEP use in U.S. counties from 2012 to 2018. METHODS: Using multi-level small-area spatio-temporal modeling, we calculated the estimated annual percentage change (EAPC) in prevalence of PrEP use in the general population from 2012 to 2018. We also used a proxy measure for prevalence of PrEP use among men who have sex with men (MSM) to evaluate trends of use among MSM, the PrEP use-to-MSM ratio (PmR) or number of male PrEP users per 1000 MSM population. RESULTS: The prevalence of PrEP use and PmR increased (EAPC range: (+26.9%, +71.0%) and (+28.4%, +158.7%), respectively) in all counties with varying magnitude of increase. Counties of the Midwest and the upper South and upper West had the slowest increase in prevalence of PrEP use (EAPC range: (+26.9%; +52.9%)). Counties of the northern part of the South had the lowest PmR (EAPC range: (+28.4%; +76.0%)). Counties of the most populous core-based statistical areas had a relatively faster increase in population prevalence of PrEP use but slower increase in PmR. CONCLUSIONS: All counties in the U.S. have witnessed an increase in PrEP use with important geographic variabilities. Identifying areas with slow improvement in PrEP use, as well as "model counties" with the fastest pace of progress in PrEP coverage, is critical to inform local and state-level policies and program evaluation for PrEP scale up, particularly among MSM at higher risk for HIV.