Exploring the Shift From HIV Pre-exposure Prophylaxis Awareness to Uptake Among Young Gay and Bisexual Men.

Introduction: HIV pre-exposure prophylaxis (PrEP) in the form of a daily oral medication is highly effective at preventing HIV. In the United States, awareness about PrEP has steadily increased over time among individuals vulnerable to HIV, however awareness has not translated into widescale uptake. Estimates are that fewer than 20% of 1.2 million Americans for whom PrEP is indicated are utilizing it. We sought to understand how individuals moved from PrEP awareness to PrEP utilization. Methods: We conducted a series (n = 31) of in-depth interviews with young people, predominantly gay and bisexual men, ages 18-29 years old between February 2015 and January 2016, as part of the evaluation of a multi-year demonstration project funded to test innovative approaches to improve sexual health outcomes and curb the HIV epidemic in California. Interviews were audio-recorded and transcribed verbatim. We conducted a thematic analysis. Results: We present a continuum of PrEP awareness that spans three phases-basic, moderate and advanced. Participants rarely reported becoming well-informed about PrEP over the course of an initial exposure to PrEP information. Learning occurred after multiple exposures to PrEP information through numerous intersecting forms, messengers and formal and informal communication channels. Positively framed messages delivered by formal messengers emphasizing PrEP as a sensible HIV prevention strategy and explicitly communicating a regard for sexual wellness were overwhelmingly persuasive and facilitated movement to the advanced awareness phase. Once participants reached the advanced phase of PrEP awareness, uptake was possible. Conclusions: Our analysis provides insights into how PrEP awareness led to PrEP uptake among young gay and bi-sexual men. Building demand among those in the basic awareness phase took longer than those in the moderate phase. Individuals involved in formal and informal PrEP education can set reasonable expectations about whether, when and how eventual uptake may occur when keeping the continuum of PrEP awareness framework in mind. Many young, gay and bi-sexual male prospective PrEP users will benefit from positively framed messages that emphasize personal well-being, including social, sexual and emotional benefits of PrEP use.

Adherence to PrEP Among Young Men Who Have Sex With Men Participating in a Sexual Health Services Demonstration Project in Alameda County, California.

BACKGROUND: Young men of color who have sex with men face a continual increase in rates of HIV infection. Pre-exposure prophylaxis (PrEP) is an important prevention method for these young men. SETTING: The Connecting Resources for Urban Sexual Health (CRUSH) demonstration project provided sexual health services, including PrEP, to young men who have sex with men aged 18-29 years. We report on adherence and factors influencing it. METHODS: Participants were offered HIV and sexually transmitted infection testing, prevention counseling, PrEP, and when appropriate, sexually transmitted infection treatment and postexposure prophylaxis. Participants taking PrEP had erythrocyte tenofovir diphosphate and emtricitabine levels measured through dried blood spot testing at 4, 12, and 24 weeks to estimate medication adherence. Participants also completed surveys to assess demographic and psychosocial measures. RESULTS: From February 2014 to November 2015, CRUSH enrolled 257 participants. Ninety-three percent started PrEP, 81% of whom initiated it at their first visit. Twelve percent required postexposure prophylaxis before starting PrEP. Adherence at protective levels was initially high with 87% demonstrating levels consistent with at least 4 doses per week at week 4, compared with 77% at the 48-week follow-up. African American race, exposure to violence, and having survival needs were associated with significantly lower levels of adherence [odds ratio (OR): 0.33; confidence interval (CI): 0.11 to 0.97, P < 0.04; OR: 0.79; CI: 0.59 to 1.04, P < 0.10; OR: 0.51; CI: 0.24 to 1.05, P < 0.07]. CONCLUSIONS: Most young men who initiate PrEP adhere at levels that confer protection against HIV infection. Interventions should account for differences in life experiences, particularly addressing the structural challenges facing young African American men.

"Losing the Phobia:" Understanding How HIV Pre-exposure Prophylaxis Facilitates Bridging the Serodivide Among Men Who Have Sex With Men.

The use of HIV serostatus information has played a pivotal role in partner selection norms. A phenomenon known as serosorting is the practice of selecting a partner based on a perception that they are of the same HIV status in order to avoid transmission from one partner to the other. An understudied aspect of serosorting is that it has a divisive effect-one accepts or rejects a potential partner based on a singular characteristic, the partner's HIV status, and thus excludes all others. This division has been formally referred to as the HIV serodivide. In this study, we explored partner selection strategies among a group of HIV-negative, young men who have sex with men (n = 29) enrolled in a PrEP demonstration project in Northern California. We found that trends in serosorting were in fact shifting, and that a new and opposite phenomenon was emerging, something we labeled "seromixing" and that PrEP use played a part in why norms were changing. We present three orientations in this regard: (1) maintaining the phobia: in which men justified the continued vigilance and exclusion of people living with HIV as viable sex or romantic partners, (2) loosening/relaxation of phobia: among men who were reflecting on their stance on serosorting and its implications for future sexual and/or romantic partnerships, and (3) losing the phobia: among men letting go of serosorting practices and reducing sentiments of HIV-related stigma. The majority of participants spoke of changing or changed attitudes about intentionally accepting rather than rejecting a person living with HIV as a sex partner. For those who maintained strict serosorting practices, their understandings of HIV risk were not erased as a result of PrEP use. These overarching themes help explain how PrEP use is contributing to a closing of the HIV serodivide.

Non-nucleoside reverse transcriptase inhibitor (NNRTI) cross-resistance: implications for preclinical evaluation of novel NNRTIs and clinical genotypic resistance testing.

OBJECTIVES: The introduction of two new non-nucleoside reverse transcriptase inhibitors (NNRTIs) in the past 5 years and the identification of novel NNRTI-associated mutations have made it necessary to reassess the extent of phenotypic NNRTI cross-resistance. METHODS: We analysed a dataset containing 1975, 1967, 519 and 187 genotype-phenotype correlations for nevirapine, efavirenz, etravirine and rilpivirine, respectively. We used linear regression to estimate the effects of RT mutations on susceptibility to each of these NNRTIs. RESULTS: Sixteen mutations at 10 positions were significantly associated with the greatest contribution to reduced phenotypic susceptibility (≥10-fold) to one or more NNRTIs, including: 14 mutations at six positions for nevirapine (K101P, K103N/S, V106A/M, Y181C/I/V, Y188C/L and G190A/E/Q/S); 10 mutations at six positions for efavirenz (L100I, K101P, K103N, V106M, Y188C/L and G190A/E/Q/S); 5 mutations at four positions for etravirine (K101P, Y181I/V, G190E and F227C); and 6 mutations at five positions for rilpivirine (L100I, K101P, Y181I/V, G190E and F227C). G190E, a mutation that causes high-level nevirapine and efavirenz resistance, also markedly reduced susceptibility to etravirine and rilpivirine. K101H, E138G, V179F and M230L mutations, associated with reduced susceptibility to etravirine and rilpivirine, were also associated with reduced susceptibility to nevirapine and/or efavirenz. CONCLUSIONS: The identification of novel cross-resistance patterns among approved NNRTIs illustrates the need for a systematic approach for testing novel NNRTIs against clinical virus isolates with major NNRTI-resistance mutations and for testing older NNRTIs against virus isolates with mutations identified during the evaluation of a novel NNRTI.

Surrogate decision makers' responses to physicians' predictions of medical futility.

BACKGROUND: Although physicians sometimes use the futility rationale to limit the use of life-sustaining treatments, little is known about how surrogate decision makers view this rationale. We sought to determine the attitudes of surrogates of patients who are critically ill toward whether physicians can predict futility and whether these attitudes predict surrogates' willingness to discontinue life support when faced with predictions of futility. METHODS: This multicenter, mixed qualitative and quantitative study took place at three hospitals in California from 2006 to 2007. We conducted semistructured interviews with surrogate decision makers for 50 patients who were critically ill and incapacitated that addressed their beliefs about medical futility and inductively developed an organizing framework to describe these beliefs. We used a hypothetical scenario with a modified time-trade-off design to examine the relationship between a patient's prognosis and a surrogate's willingness to withdraw life support. We used a mixed-effects regression model to examine the association between surrogates' attitudes about futility and their willingness to limit life support in the face of a very poor prognosis. Validation methods included the use and integration of multiple data sources, multidisciplinary analysis, and member checking. RESULTS: Sixty-four percent of surrogates (n = 32; 95% confidence interval [CI], 49 to 77%) expressed doubt about the accuracy of physicians' futility predictions, 32% of surrogates (n = 16; 95% CI, 20 to 47%) elected to continue life support with a < 1% survival estimate, and 18% of surrogates (n = 9; 95% CI, 9 to 31%) elected to continue treatment when the physician believed that the patient had no chance of survival. Surrogates with religious objections to the futility rationale (n = 18) were more likely to request continued life support (odds ratio, 4; 95% CI, 1.2 to 14.0; p = 0.03) than those with secular or experiential objections (n = 15; odds ratio, 0.95; 95% CI, 0.3 to 3.4; p = 0.90). CONCLUSIONS: Doubt about physicians' ability to predict medical futility is common among surrogate decision makers. The nature of the doubt may have implications for responding to conflicts about futility in clinical practice.

Doubt and belief in physicians' ability to prognosticate during critical illness: the perspective of surrogate decision makers.

OBJECTIVES: Although discussing a prognosis is a duty of physicians caring for critically ill patients, little is known about surrogate decision-makers' beliefs about physicians' ability to prognosticate. We sought to determine: 1) surrogates' beliefs about whether physicians can accurately prognosticate for critically ill patients; and 2) how individuals use prognostic information in their role as surrogate decision-makers. DESIGN, SETTING, AND PATIENTS: Multicenter study in intensive care units of a public hospital, a tertiary care hospital, and a veterans' hospital. We conducted semistructured interviews with 50 surrogate decision-makers of critically ill patients. We analyzed the interview transcripts using grounded theory methods to inductively develop a framework to describe surrogates' beliefs about physicians' ability to prognosticate. Validation methods included triangulation by multidisciplinary analysis and member checking. MEASUREMENTS AND MAIN RESULTS: Overall, 88% (44 of 50) of surrogates expressed doubt about physicians' ability to prognosticate for critically ill patients. Four distinct themes emerged that explained surrogates' doubts about prognostic accuracy: a belief that God could alter the course of the illness, a belief that predicting the future is inherently uncertain, prior experiences where physicians' prognostications were inaccurate, and experiences with prognostication during the patient's intensive care unit stay. Participants also identified several factors that led to belief in physicians' prognostications, such as receiving similar prognostic estimates from multiple physicians and prior experiences with accurate prognostication. Surrogates' doubts about prognostic accuracy did not prevent them from wanting prognostic information. Instead, most surrogate decision-makers view physicians' prognostications as rough estimates that are valuable in informing decisions, but are not determinative. Surrogates identified the act of prognostic disclosure as a key step in preparing emotionally and practically for the possibility that a patient may not survive. CONCLUSIONS: Although many surrogate decision-makers harbor some doubt about the accuracy of physicians' prognostications, they highly value discussions about prognosis and use the information for multiple purposes.

Genetic susceptibility testing for Alzheimer disease: motivation to obtain information and control as precursors to coping with increased risk.

OBJECTIVE: This study investigated appraisals, including motivation, and coping preferences for undergoing Apolipoprotein E (APOE) susceptibility testing for Alzheimer disease (AD). METHODS: Participants were 60 adult children of individuals affected with AD enrolled in a trial investigating use and impact of APOE susceptibility testing. An exploratory qualitative study was undertaken in which participants were interviewed about their testing experience. RESULTS: Most participants viewed genetic testing as providing valuable information that could help direct future health care decisions and meet their emotional concerns about living at increased risk. Participants related their motivation for genetic testing to their worries about developing AD, preference to seek information about health threats, and need to feel in control of their health. CONCLUSION: Even without prevention or treatment options, genetic testing may be a useful coping strategy for some at-risk individuals. PRACTICE IMPLICATIONS: Once testing becomes clinically available, practitioners need to address the value and limitations of testing as well as appraisals and efforts to cope.

Genetic susceptibility testing from a stress and coping perspective.

Four theories of health behavior and of stress and coping are reviewed for their ability to illuminate interest in uptake and outcomes of genetic testing for adult-onset diseases. These theories are the Health Belief Model, the Theory of Planned Behavior (TPB), the Common Sense Model of Self-regulation (CSM), and the Transactional Model of Stress and Coping (TMSC). Basic concepts of each theory are discussed, followed by evidence from the literature supporting the relevance of these concepts to the understanding of genetic testing for four adult-onset diseases: Huntington's disease, Alzheimer's disease, hereditary breast/ovarian cancer, and hereditary colorectal cancer. Emphasis is placed on the finding that a decision to undergo genetic testing may be considered as a way to cope with both the cognitive and affective concerns that arise from living at increased risk of developing a disease in the future. The potential value of genetic testing for reducing uncertainty about and gaining a sense of control over one's risk of developing a chronic disease is highlighted. We argue that theories which focus on stress and coping provide a useful framework for future studies of genetic testing decisions for adult-onset disease risk.