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In an analysis of randomized trials, use of efavirenz for treatment of human immunodeficiency virus (HIV) infection was associated with increased suicidal thoughts/behaviors. However, analyses of observational data have found no evidence of increased risk. To assess whether population differences might explain this divergence, we transported the effect of efavirenz use from these trials to a specific target population. Using inverse odds weights and multiple imputation, we transported the effect of efavirenz on suicidal thoughts/behaviors in these randomized trials (participants were enrolled in 2001–2007) to a trials-eligible cohort of US adults initiating antiretroviral therapy while receiving HIV clinical care at medical centers between 1999 and 2015. Overall, 8,291 cohort participants and 3,949 trial participants were eligible. Prescription of antidepressants (19% vs. 13%) and injection drug history (16% vs. 10%) were more frequent in the cohort than in the trial participants. Compared with the effect in trials, the estimated hazard ratio for efavirenz on suicidal thoughts/behaviors was attenuated in our target population (trials: hazard ratio (HR) = 2.3 (95% confidence interval (CI): 1.2, 4.4); transported: HR = 1.8 (95% CI: 0.9, 4.4)), whereas the incidence rate difference was similar (trials: HR = 5.1 (95% CI: 1.6, 8.7); transported: HR = 5.4 (95% CI: −0.4, 11.4)). In our target population, there was greater than 20% attenuation of the hazard ratio estimate as compared with the trials-only estimate. Transporting results from trials to a target population is informative for addressing external validity. [ABSTRACT FROM AUTHOR]

Summary: Results obtained in randomized trials may not easily generalize to target populations. Whereas in randomized trials the treatment assignment mechanism is known, the sampling mechanism by which individuals are selected to participate in the trial is typically not known and assuming random sampling from the target population is often dubious. We consider an inverse probability of sampling weighted (IPSW) estimator for generalizing trial results to a target population. The IPSW estimator is shown to be consistent and asymptotically normal. A consistent sandwich‐type variance estimator is derived and simulation results are presented comparing the IPSW estimator with a previously proposed stratified estimator. The methods are then utilized to generalize results from two randomized trials of human immunodeficiency virus treatment to all people living with the disease in the USA. [ABSTRACT FROM AUTHOR]

The article explores prospective study of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) household transmission in the United States (US) by Lewis and colleagues. Household transmission of SARS-CoV-2 is an important contributor to R0 and cannot be realistically addressed by continuous masking and social distancing. Use of data from contact tracing likely leads to an underestimate of household transmission.

Antiretroviral therapy (ART) requires lifelong daily oral therapy. While patient characteristics associated with suboptimal ART adherence and persistence have been described in cohorts of HIV-infected persons, these factors are poor predictors of individual medication taking behaviors. We aimed to create and test instruments for the estimation of future ART adherence and persistence for clinical and research applications. Following formative work, a battery of 148 items broadly related to HIV infection and treatment was developed and administered to 181 HIV-infected patients. ART adherence and persistence were assessed using electronic monitoring for 3 months. Perceived confidence in medication taking and self-reported barriers to adherence were strongest in predicting non-adherence over time. Barriers to adherence (e.g., affordability, scheduling) were the strongest predictors of non-adherence, as well as 3- and 7-day non-persistence. A ten-item battery for prediction of these outcomes ( www.med.unc.edu/ncaidstraining/adherence/for-providers ) and a 30-item battery reflective of underlying psychological constructs can help identify and study individuals at risk for suboptimal ART adherence and persistence.