Publications

BACKGROUND

Integrating home-based HIV counseling and testing (HCT) with tuberculosis (TB) evaluation could improve the uptake of HIV testing among household contacts of patients with active TB. We sought to identify the facilitators of and barriers to HCT during household contact investigation for TB in Kampala, Uganda.

METHODS

We nested semi-structured interviews with 28 household contacts who were offered home-based HCT in a household-randomized trial of home-based strategies for TB contact investigation. Respondents reflected on their experiences of the home visit, the social context of the household, and their decision to accept or decline HIV testing. We used content analysis to identify and evaluate facilitators of and barriers to testing, then categorized the emergent themes using the Capability, Opportunity, Motivation, and Behavior (COM-B) model.

RESULTS

Facilitators included a preexisting desire to confirm HIV status or to show support for the index TB patient; a perception that home-based services are convenient; and positive perceptions of lay health workers. Key barriers included fear of results and feeling psychologically unprepared to receive results. The social influence of other household members operated as both a facilitator and a barrier.

CONCLUSIONS

Preexisting motivation, psychological readiness to test, and the social context of the household are major contributors to the decision to test for HIV at home. Uptake might be improved by providing normalizing information about HCT before the visit, by offering a second HCT opportunity, by offering self-tests with follow-up counseling, or by introducing HCT using "opt-out" language.

Inhibition of the bile salt export pump (BSEP) by a drug has been implicated as a risk factor for a drug's potential to cause drug-induced liver injury (DILI) and is thought to be an important mechanism leading to DILI. For a wide variety of drugs a correlation has been observed between the potency of in vitro BSEP inhibition and its propensity to cause DILI in humans. These findings were interpreted to suggest that BSEP inhibition could be an important mechanism to help explain how some drugs initiate DILI. Because the Biopharmaceutics Drug Disposition Classification System (BDDCS) can be useful in characterizing and predicting some important transporter effects in terms of drug-drug interactions, we evaluated the information provided by BDDCS in order to understand the inhibition propensity of BSEP. Here we analyze the relationship between a compound's ability to inhibit BSEP function and cause liver injury in humans using a compilation of published DILI datasets that have screened for BSEP inhibitors, other hepatic transporters and other mechanism-based toxicity key events. Our results demonstrate that there is little support for in vitro BSEP inhibition being universally DILI predictive. Rather we show that most potent BSEP inhibitors are BDDCS class 2 drugs, which we have demonstrated previously is the BDDCS class most likely to be DILI related. Since BDDCS class is not related to any proposed DILI mechanistic hypotheses, we maintain that if measures of BSEP inhibition alone or together with inhibition of other transporters cannot be differentiated from class 2 assignment, there is no support for in vitro BSEP inhibition being DILI predictive.