Engagement in HIV care and viral suppression following changes in long-term opioid therapy for treatment for chronic pain.

Chronic pain is common among persons living with HIV and changes in opioid prescribing practices may complicate HIV care management. Using medical record data from a retrospective cohort study conducted January 1, 2012 to June 30, 2019 for 300 publicly insured HIV-positive primary care patients prescribed opioids for chronic non-cancer pain in San Francisco, we examined associations between opioid dose changes and both time to disengagement from HIV care and experiencing virologic failure using logistic regression. Discontinuation of prescribed opioids was associated with increased odds of disengagement in care at 3, 6, and 9 months after discontinuation. There were no associations with virologic failure. Providers and policy makers must weigh impacts on HIV care when implementing necessary changes in opioid prescribing.

Evidence of Pre-mortem Opioid Use among Fentanyl Overdose Decedents in a Safety Net Healthcare System.

The rapid increase in fentanyl overdose deaths, particularly those also attributed to stimulants, has led to concerns about unintentional fentanyl exposure. Utilizing vital and medical record data, we identified overdose decedents from 2018 to 2021 in San Francisco who received care in the safety net system in the 3 years preceding death. Among 506 decedents, medical record evidence of pre-mortem opioid use was present for 48% of stimulant-only, 56% of stimulant-fentanyl, 65% of fentanyl-only, and 82% of non-fentanyl opioid decedents (p<0.001). Among stimulant-fentanyl decedents, an increase in 10 years of age (adjusted odds ratio (aOR) 0.74 [95% CI:0.59-0.94]) and race other than White or Black (aOR 0.36 [95% CI:0.15-0.87]) had lower odds of evidence of pre-mortem opioid use. While not conclusive, these findings raise the possibility that a significant proportion of fentanyl overdose decedents in San Francisco may have not intended to consume an opioid on the occasion of their death.

Heroin pipe distribution to reduce high-risk drug consumption behaviors among people who use heroin: a pilot quasi-experimental study.

BACKGROUND: Heroin pipe distribution may encourage people who use heroin (PWUH) to transition from injecting to smoking heroin, reducing harms associated with injection drug use. A syringe services program (SSP) in Seattle, Washington, led by people who use drugs developed a heroin pipe distribution program. METHODS: We conducted a pretest-posttest quasi-experimental study to evaluate the impact of heroin pipe distribution on drug consumption behaviors among PWUH between March and December 2019. SSP clients were surveyed during three weeklong timepoints before and four weeklong timepoints after heroin pipe distribution. Primary outcomes were change in proportion of SSP clients who exclusively injected heroin, exclusively smoked heroin, and both injected and smoked heroin in the past seven days comparing the pre- and post-intervention periods. RESULTS: Across the seven observation timepoints, 694 unique respondents completed 957 surveys. Multiple responses from a single respondent in a given period were collapsed, resulting in 360 pre-intervention and 430 post-intervention records. Heroin use was reported in over half of pre-intervention (56%, 201/360) and post-intervention records (58%, 251/430). Compared to pre-intervention behaviors, the proportion of respondents who exclusively injected heroin was lower after the start of heroin pipe distribution (32%, 80/251 vs 43%, 86/201, p = 0.02), while the proportion of respondents who both injected and smoked heroin was higher (45%, 113/251 vs 36%, 72/201, p = 0.048). Just under half (44%, 110/251) of respondents who used heroin during the post-intervention period used a heroin pipe obtained from the SSP, of which 34% (37/110) reported heroin pipe distribution had reduced their heroin injection frequency. Self-reported hospitalization for a pulmonary cause was not associated with using a heroin pipe. CONCLUSIONS: The proportion of SSP clients who exclusively injected heroin was lower after implementation of heroin pipe distribution. Randomized studies with longer follow-up are needed to investigate whether heroin pipe distribution reduces heroin injection and improves health outcomes associated with drug use. Limited intervention exposure, loss to follow-up, and pipe availability from other sources pose methodological challenges to evaluations of route transition interventions in community settings. This pilot highlights the potential for organizations led by people who use drugs to develop, implement, and evaluate novel public health programming.

Stimulant use for self-management of pain among safety-net patients with chronic non-cancer pain.

BACKGROUND: Chronic pain affects one-fifth of US adults. Reductions in opioid prescribing have been associated with increased non-prescription opioid use and, chronologically, increased stimulant (methamphetamine and cocaine) use. While non-prescription opioid use is commonly attributed to pain self-management, the role of stimulants in managing pain is unclear. METHODS: We analyzed baseline data from a longitudinal study of patients with chronic non-cancer pain in an urban safety-net healthcare system who had been prescribed an opioid for ≥3 of the last 12 months, and had a history of non-prescription opioid, cocaine, or amphetamine use (N = 300). We estimated the prevalence and identified correlates of stimulant use to treat pain among a subgroup of patients who reported past-year stimulant use (N = 105). Data sources included computer-assisted questionnaire (demographics, substance use, pain), clinical exam and procedures (pain, pain tolerance), and chart abstraction (opioid prescriptions). We conducted bivariate analyses to assess associations between demographics, pain characteristics, non-opioid therapies, substance use, opioid prescriptions, and self-reported symptoms, with reporting using stimulants to treat pain. Demographic variables and those with significant bivariate associations were included in a multivariable logistic regression model. RESULTS: Fifty-two percent of participants with past-year stimulant use reported using stimulants in the past year to treat pain. Participants who used stimulants for pain reported slightly higher average pain in the past 3 months (median of 8 (IQR: 6-8) vs 7 (7-9) out of 10, p = 0.049). In the multivariable analysis, female gender (AOR= 3.20, 95% CI: 1.06-9.63, p = 0.039) and higher score on the Douleur Neuropathique 4 neuropathic pain questionnaire (AOR = 1.34, 95% CI: 1.05-1.70, p = 0.017) were associated with past-year stimulant use to treat pain. CONCLUSION: Stimulants may be used for pain self-management, particularly for neuropathic pain and among women. Our findings suggest an underexplored motivation for stimulant use in an era of reduced access to prescribed opioids.

Administrative and Related Barriers to Covering the Costs of Preexposure Prophylaxis at a Safety-net Clinic in Seattle, Washington.

One barrier to human immunodeficiency virus preexposure prophylaxis (PrEP) is lack or perceived lack of health insurance or financial assistance. We performed a medical records review at a safety-net PrEP clinic in Seattle, Washington, and found that barriers to obtaining financial assistance were commonly recorded in association with initiation and persistence on PrEP.

Pre-exposure Prophylaxis Awareness and Use Among Cisgender Men Who Have Sex With Men and Use Methamphetamine in 3 Western US Cities.

BACKGROUND: In the United States, cisgender men who have sex with men (MSM) who use methamphetamine are at substantial risk for HIV and can benefit from pre-exposure prophylaxis (PrEP). METHODS: We used data from the National HIV Behavioral Surveillance 2017 survey from Seattle, WA; Portland, OR; and Denver, CO, to estimate PrEP awareness and use in the past 12 months among MSM who use methamphetamine. We then compared these estimates with participants who do not use methamphetamine but meet other criteria for PrEP use (i.e., condomless anal sex or a bacterial sexually transmitted infection). We explored reasons for not using PrEP and challenges using PrEP. RESULTS: Of the 1602 MSM who participated in the 2017 National HIV Behavioral Surveillance survey in Seattle, WA; Portland, OR; and Denver, CO, 881 met the inclusion criteria for this study, of whom 88 (10%) reported methamphetamine use in the past 12 months. Most (95%) participants had heard of PrEP, and 35% had used it in the past 12 months. Pre-exposure prophylaxis awareness was lower among MSM who used methamphetamine (P = 0.01), but use was not different (P = 0.26). Among those who had not used PrEP, the most common reason for not using it was not thinking one's HIV risk was high enough (51%). Men who have sex with men who used methamphetamine were more likely to report that they were not sure PrEP would prevent them from getting HIV (38% vs. 19%, P = 0.002). CONCLUSIONS: These results highlight the need for continued efforts to educate and promote PrEP uptake among MSM, particularly those who use methamphetamine.

'I make sure my doctor doesn't know that I use meth': perceived barriers to pre-exposure prophylaxis (PrEP) uptake among community peer educators in Seattle (WA, USA).

Background HIV disproportionately affects cisgender men and transgender people who have sex with men (MSM/TG) and use methamphetamine. Pre-exposure prophylaxis (PrEP) uptake has been slow in this group. It is important to understand perceptions about PrEP and barriers to its use among MSM/TG who use methamphetamine to reduce new HIV infections. METHODS: We conducted four focus groups with peer educators of a harm reduction program. We assessed their perspectives of PrEP and barriers across the PrEP continuum among MSM/TG who use methamphetamine. RESULTS: Notably, stigma related to the multiple marginalised identities of MSM/TG who use methamphetamine (e.g. MSM/TG-related stigma, methamphetamine-related stigma) was a barrier at each step. We developed a framework that combined the PrEP continuum and a stigma-based treatment cascade to explore these themes and describe the effects of stigma on PrEP engagement. Methamphetamine-related barriers were also identified. CONCLUSIONS: The findings of this study emphasise the importance of incorporating stigma reduction into PrEP delivery for MSM/TG who use methamphetamine.

Development of a targeted educational intervention to increase pre-exposure prophylaxis uptake among cisgender men and transgender individuals who have sex with men and use methamphetamine in Seattle (WA, USA).

Background Cisgender men and transgender individuals who have sex with men (MSM/TG) and use methamphetamine are at elevated risk for HIV and have had limited pre-exposure prophylaxis (PrEP) uptake. The aim of this study was to quantify the knowledge and use of PrEP, identify barriers to PrEP use, and develop a targeted educational campaign to promote PrEP among MSM/TG who use methamphetamine. METHODS: We conducted three consultations with peer educators of Project Needle and Sex Education Outreach Network (NEON) to develop and disseminate educational materials. We surveyed the peers' HIV-negative contacts before and after this work to explore knowledge and opinions about PrEP and to assess the effect of our materials. RESULTS: There were 221 respondents at baseline (August 2016) and 100 at follow-up (April-May 2017). At baseline, nearly all participants had 'heard of PrEP' (96%) and were insured (97%). However, only 3% had ever used PrEP. Peers suggested educational cards that included a definition of PrEP, adherence tips and that PrEP does not prevent other sexually transmissible infections. Peers distributed approximately 2560 educational cards. At follow-up, approximately half the respondents (53%) had seen the cards, and those who did reported significantly more agreement with the majority of the card messages about PrEP. Significantly more participants reported ever receiving PrEP at follow-up (21%; P<0.001). There was a trend between seeing the cards and PrEP use (P=0.053). CONCLUSIONS: Although we cannot be certain that the effect was due to our intervention, a greater number of the peers' contacts reported receiving PrEP at follow-up, and those who saw our materials were more likely to agree with factual statements about PrEP. There is continued need for PrEP education for MSM/TG who use methamphetamine.

Metabolic Effects of Preexposure Prophylaxis With Coformulated Tenofovir Disoproxil Fumarate and Emtricitabine.

Background: Antiretroviral drugs have been associated with changes in lipids, fat mass and dat distribution. Tenofovir disoproxil fumarate (TDF) has been shown to have a more favorable metabolic profile than other drugs in its class. However, the metabolic effects of TDF in preexposure prophylaxis (PrEP) are unknown. Methods: We evaluated the effects of TDF/emtricitabine (FTC) on lipids and body composition in a blinded, placebo-controlled PrEP trial. Participants enrolled in a metabolic subcohort (N = 251, TDF/FTC; N = 247, placebo) consented to fasting lipid panels, dual-energy X-ray absorptiometry scans for body composition, and pharmacologic testing of drug metabolites at baseline and every 24 weeks thereafter. Results: Lean body mass was stable and unaffected by TDF/FTC. Body weight increased in both groups but was lower on TDF/FTC through week 72. This difference was explained by lower fat accumulation on TDF/FTC. The net median percent difference (standard error, P value) for TDF/FTC vs placebo at week 24 was -0.8% (0.4%, P = .02), +0.3% (0.4%, P = .46), and -3.8% (1.4%, P = .009) for total, lean, and fat mass, respectively. There was no apparent differential regional fat accumulation on TDF/FTC. Decreases in cholesterol, but not triglycerides, were seen in TDF/FTC participants, with detectable drug levels compared to placebo. Conclusions: TDF/FTC for PrEP showed cholesterol reductions and appeared to transiently suppress the accumulation of weight and body fat compared to placebo. There was no evidence of altered fat distribution or lipodystrophy during daily oral TDF/FTC PrEP. Clinical Trials Registration: NCT00458393.

Knowledge, Practices, and Barriers to HIV Preexposure Prophylaxis Prescribing Among Washington State Medical Providers.

BACKGROUND: We aimed to assess HIV preexposure prophylaxis (PrEP) awareness and prescribing practices among Washington State medical providers from diverse professional disciplines and practice types. METHODS: In May 2016, we administered an anonymous online survey to licensed medical practitioners who provide primary, longitudinal, walk-in, emergency, obstetric, gynecologic, sexually transmitted infection, or family planning care. RESULTS: Of 735 eligible providers, 64.8% had heard of PrEP. Younger providers and providers with a doctor of medicine degree were more likely to be aware of PrEP compared with older providers (P = 0.0001) and providers of other training backgrounds (advanced registered nurse practitioner, doctor of osteopathic medicine, or physician assistant; P = 0.04). Among providers aware of PrEP, most frequent reported concerns about prescribing were adherence (46.0%) and costs (42.9%). Providers felt very (20.1%) or somewhat (33.8%) comfortable discussing PrEP overall, but very (26.8%) or somewhat (44.7%) uncomfortable discussing cost and insurance issues. The 124 PrEP prescribers reported a median of 2 (range, 1-175; total, 1142) patients prescribed PrEP. Prior authorizations and insurance denials had prevented prescriptions for 28.7% and 12.1% of prescribers, respectively. CONCLUSIONS: Interventions to improve PrEP access should include education to inform medical providers about PrEP, with particular attention to provider types less likely to be aware. Continued efforts to eliminate cost and insurance barriers and educate providers regarding financial resources would help improve PrEP access.

The Role of Social Relationships in PrEP Uptake and Use Among Transgender Women and Men Who Have Sex with Men.

Qualitative studies suggest that social relationships play an important role in HIV pre-exposure prophylaxis (PrEP) use, but there have been few quantitative assessments of the role of social relationships in PrEP uptake or adherence. We examined the association between disclosure of study participation or LGBT identity and PrEP use in the 1603 HIV-negative participants enrolled in the iPrEx OLE study. We also evaluated the association between LGBT social group involvement and PrEP use. Study participation disclosure to parents and LGBT identity disclosure to anyone in a participant's social network were associated with greater PrEP uptake. Study participation disclosure to partners was associated with higher probability of having protective PrEP drug concentrations compared [risk difference 0.15 95% CI (0.01, 0.30)]. For each additional type of LGBT organization a participant was involved in, the probability of PrEP uptake and having protective drug concentrations increased by 0.04 [95% CI (0.03, 0.06)] and 0.04 (95% CI (0.02, 0.07)] respectively. Overall, social context was associated with PrEP use in iPrEx OLE, and should be taken into consideration when designing future PrEP implementation programs.

HIV sero disclosure among men who have sex with men and transgender women on HIV pre-exposure prophylaxis.

HIV pre-exposure prophyalxis (PrEP) might lead individuals to view serodisclosure as unnecessary. We examined the prevalence of non-disclosure and lack of knowledge of partner status in a global cohort of men who have sex with men (MSM) and transgender women (TW) enrolled in the iPrEx Open Label Extension (OLE). We calculated prevalence ratios by fitting a logistic model and estimating predicted probabilities using marginal standardization. Prevalence of non-disclosure and lack of knowledge of partner status were highest in Thailand (73% and 74%, respectively) and lowest in the USA (23% and 37%, respectively). In adjusted analyses, PrEP use was not significantly associated with non-disclosure or lack of knowledge of partner status (p-values>0.05). We found that relationship characteristics were significantly associated with both outcomes. Non-disclosure was higher among casual (adjusted prevalence ratio [aPR] 1.54, [95% confidence interval 1.24-1.84]) and transactional sex partners (aPR 2.03, [1.44-2.62]), and among partners whom participants have known only minutes or hours before their first sexual encounter (aPR 1.62, [1.33-1.92]). Similarly, participants were less likely to know the HIV status of casual partners (aPR 1.50, [1.30-1.71]), transactional sex partners (aPR 1.62, [1.30-1.95]), and those they have known for only days or weeks (aPR 1.13, [0.99-1.27]) or minutes or hours (aPR 1.27, [1.11-1.42]). Our findings underscore the role of dyadic factors in influencing serodisclosure. Comprehensive risk reduction counseling provided in conjunction with PrEP that address relationship characteristics are needed to help patients navigate discussions around HIV status.

Cellular immune correlates analysis of an HIV-1 preexposure prophylaxis trial.

HIV-1-specific T-cell responses in exposed seronegative subjects suggest that a viral breach of the exposure site is more common than current transmission rates would suggest and that host immunity can extinguish subsequent infection foci. The Preexposure Prophylaxis Initiative (iPrEx) chemoprophylaxis trial provided an opportunity to rigorously investigate these responses in a case-control immunology study; 84 preinfection peripheral blood mononuclear cell samples from individuals enrolled in the iPrEx trial who later seroconverted were matched with 480 samples from enrolled subjects who remained seronegative from both the placebo and active treatment arms. T-cell responses to HIV-1 Gag, Protease, Integrase, Reverse Transcriptase, Vif, and Nef antigens were quantified for all subjects in an IFN-γ enzyme-linked immunospot (ELISpot) assay. IFN-γ responses varied in magnitude and frequency across subjects. A positive response was more prevalent in those who remained persistently HIV-1-negative for Gag (P = 0.007), Integrase (P < 0.001), Vif (P < 0.001), and Nef (P < 0.001). When correlated with outcomes in the iPrEx trial, Vif- and Integrase-specific T-cell responses were associated with reduced HIV-1 infection risk [hazard ratio (HR) = 0.36, 95% confidence interval (95% CI) = 0.19-0.66 and HR = 0.52, 95% CI = 0.28-0.96, respectively]. Antigen-specific responses were independent of emtricitabine/tenofovir disoproxil fumarate use. IFN-γ secretion in the ELISpot was confirmed using multiparametric flow cytometry and largely attributed to effector memory CD4+ or CD8+ T cells. Our results show that HIV-1-specific T-cell immunity can be detected in exposed but uninfected individuals and that these T-cell responses can differentiate individuals according to infection outcomes.

Risk, safety and sex among male PrEP users: time for a new understanding.

Recent advances in biomedical HIV prevention have led to optimistic projections of a dramatic worldwide reduction of new infections by 2030. This optimism is counterbalanced by concerns that the protective benefits of one such technology, HIV pre-exposure prophylaxis (PrEP), may be negated by increases in other behaviours that offset these benefits (risk compensation). To contribute to a deeper understanding of concepts of safety and risk in the context of HIV PrEP, we draw on the narrative accounts of 61 male PrEP users who participated in the inaugural PrEP demonstration project: the iPrEx open-label extension study. We conducted in-depth interviews with a purposeful sample of iPrEx participants. Overall, participants did not report significant changes to their sexual practices once they had begun taking PrEP. Rather, participants reported experiencing a sense of relief or reprieve from HIV-related stress. This unburdening of fear did not necessarily lead to condomless sex. Instead, men expressed feeling a sense of security and less free-floating fear of HIV. We contend that no longer living under the threat of HIV is a significant benefit that has not been adequately explored in HIV prevention research.

Symptoms, Side Effects and Adherence in the iPrEx Open-Label Extension.

BACKGROUND: Blinded clinical trials have reported a modest and transient "start-up syndrome" with initiation of tenofovir-based pre-exposure prophylaxis (PrEP). We evaluate this phenomenon and its effect on adherence in an open-label PrEP study. METHODS: In the iPrEx open-label extension (OLE) study, an 18-month open-label, multi-site PrEP cohort taking daily oral co-formulated tenofovir/emtricitabine, we examined the prevalence and duration of PrEP-associated symptoms and their effect on adherence, assessed by drug levels in dried blood spots tested monthly for the first 3 months. RESULTS: Symptom reports peaked within the first month, with 39% reporting potentially PrEP-related symptoms compared to 22% at baseline. Symptoms largely resolved to pre-PrEP levels by 3 months.Symptoms varied substantially in frequency by study site (range in 1-month symptoms: 11% to 70%). Nongastrointestinal (GI) symptoms were not associated with adherence (odds ratio [OR] = 1.2, 95% confidence interval [CI], .4-3.7); however, GI-associated symptoms in the first 4 weeks were inversely associated with adherence at 4 weeks (OR = 0.47, 95% CI, .23-.96). Reports of GI symptoms were associated with 7% (95% CI, 4%-11%) of suboptimal adherence in this cohort. CONCLUSIONS: PrEP-associated symptoms in the open-label setting occur in a minority of users and largely resolve within 3 months. GI symptoms are associated with a modest reduction in PrEP adherence, but good adherence is possible even in the presence of frequent symptom reports. CLINICAL TRIALS REGISTRATION: Clinicaltrials.govNCT00458393.

Self-reported Recent PrEP Dosing and Drug Detection in an Open Label PrEP Study.

Monitoring adherence to pre-exposure prophylaxis (PrEP) is part of the recommended package for PrEP prescribing, yet ongoing concerns about how to do so confidently are exacerbated by gross discrepancies in reported and actual use in clinical trials. We evaluated concordance between reports of recent PrEP dosing collected via neutral interviewing and drug quantitation in the iPrEx open-label extension, where participants (n = 1172) had the choice to receive or not receive PrEP. Self-report of recent dosing (at least one PrEP dose in the past 3-day) was the most common report (84 % of participants), and among these 83 % did have quantifiable levels of drug. The vast majority of those reporting no doses in the past 3-day (16 % of the sample) did not have quantifiable levels of drug (82 %). Predictors of over-report of dosing included younger age and lower educational attainment. Monitoring recent PrEP use through neutral interviewing may be a productive approach for clinicians to consider in implementation of real-world PrEP. Strategies to capture longer term or prevention-effective PrEP use, particularly for younger cohorts, are needed.

Depression and Oral FTC/TDF Pre-exposure Prophylaxis (PrEP) Among Men and Transgender Women Who Have Sex With Men (MSM/TGW).

We conducted a longitudinal and cross-sectional analysis of depressive symptomology in iPrEx, a randomized, placebo-controlled trial of daily, oral FTC/TDF HIV pre-exposure prophylaxis (PrEP) in men and transgender women who have sex with men. Depression-related adverse events (AEs) were the most frequently reported severe or life-threatening AEs and were not associated with being randomized to the FTC/TDF arm (152 vs. 144 respectively OR 0.66 95 % CI 0.35-1.25). Center for Epidemiologic Studies Depression scale (CES-D) and a four questions suicidal ideation scale scores did not differ by arm. Participants reporting forced sex at anal sexual debut had higher CES-D scores (coeff: 3.23; 95 % CI 1.24-5.23) and were more likely to have suicidal ideation (OR 2.2; 95 % CI 1.09-4.26). CES-D scores were higher among people reporting non-condom receptive anal intercourse (ncRAI) (OR 1.46; 95 % CI 1.09-1.94). We recommend continuing PrEP during periods of depression in conjunction with provision of mental health services.

The Effect of Depressive Symptoms on Adherence to Daily Oral PrEP in Men who have Sex with Men and Transgender Women: A Marginal Structural Model Analysis of The iPrEx OLE Study.

We assessed the role of depressive symptoms on adherence to daily oral FTC/TDF for HIV PrEP in cisgender men who have sex with men (MSM) and transgender women who have sex with men (TGW) using data from the iPrEx OLE study. A marginal structural logistic regression model was used to estimate the effect of time-varying CES-D scores on having protective levels of drug concentration, adjusting for confounding by sexual practices over time, prior adherence, and baseline demographic characteristics. We found a non-monotonic relationship between CES-D score and odds of protective FTC/TDF levels in MSM. We found evidence that the effect of depression on adherence varied between MSM and TGW, and that depressive symptoms did not contribute greatly to decreased adherence on a population scale. We recommend that depressive symptoms not preclude the prescription of PrEP, and that MSM and TGW be studied separately.

SEXUAL PRACTICES AMONG MEN WHO HAVE SEX WITH MEN IN CHIANG MAI, THAILAND: PART OF THE ANTIRETROVIRAL PRE-EXPOSURE PROPHYLAXIS TRIAL.

This study aimed to gain a better understanding of the association between participation in a blinded antiretroviral pre-exposure prophylaxis (PrEP) clinical trial and sexual practices among men who have sex with men and transgender women. This study utilized both quantitative and qualitative methodologies. Data included reported PrEP medication adherence and sexual behavior among 114 study participants. Forty-six participants took part in qualitative data collection, 32 were interviewed and 14 participated in one of three focus group discussions. The average percentage of study medication adherence, number of sex partners and rates of sex without a condom were calculated. For qualitative data, content analysis was used to identify repeated normative themes, some of which arose spontaneously from interview interactions. Participants at the Chiang Mai site reported good adherence to the study medication. The sexual risk behavior of these participants had decreased by their final study visit; this was unrelated to level of adherence. Qualitative findings describe sexual practices that were highly contextual; participants used risk assessments to determine sex practices. Condoms were used with casual partners but not necessarily with primary partners. Our findings suggest that while PrEP is an exciting new development for HIV prevention, it must be paired with behavioral interventions to fully address sexual risk among this population. Interventions should provide this population with skills to negotiate condom use with their primary partners as well as in situations in which their sexual partners do not support condom use.

Effects of Emtricitabine/Tenofovir on Bone Mineral Density in HIV-Negative Persons in a Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Daily preexposure prophylaxis (PrEP) with oral emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) decreases the risk of human immunodeficiency virus (HIV) acquisition. Initiation of TDF decreases bone mineral density (BMD) in HIV-infected people. We report the effect of FTC/TDF on BMD in HIV-seronegative men who have sex with men and in transgender women. METHODS: Dual-energy X-ray absorptiometry was performed at baseline and 24-week intervals in a substudy of iPrEx, a randomized, double-blind, placebo-controlled trial of FTC/TDF PrEP. Plasma and intracellular tenofovir concentrations were measured in participants randomized to FTC/TDF. RESULTS: In 498 participants (247 FTC/TDF, 251 placebo), BMD in those randomized to FTC/TDF decreased modestly but statistically significantly by 24 weeks in the spine (net difference, -0.91% [95% confidence interval {CI}, -1.44% to -.38%]; P = .001) and hip (-0.61% [95% CI, -.96% to -.27%], P = .001). Changes within each subsequent 24-week interval were not statistically significant. Changes in BMD by week 24 correlated inversely with intracellular tenofovir diphosphate (TFV-DP), which was detected in 53% of those randomized to FTC/TDF. Net BMD loss by week 24 in participants with TFV-DP levels indicative of consistent dosing averaged -1.42% ± 29% and -0.85% ± 19% in the spine and hip, respectively (P < .001 vs placebo). Spine BMD tended to rebound following discontinuation of FTC/TDF. There were no differences in fractures (P = .62) or incidence of low BMD. CONCLUSIONS: In HIV-uninfected persons, FTC/TDF PrEP was associated with small but statistically significant decreases in BMD by week 24 that inversely correlated with TFV-DP, with more stable BMD thereafter. CLINICAL TRIALS REGISTRATION: NCT00458393.