To disclose or not to disclose: an ethnographic exploration of factors contributing to the (non) disclosure of Ghanaian women's breast cancer diagnosis to social networks.

BACKGROUND: Although there may be theoretical support linking positive health outcomes with cancer disclosure to social networks, women from contexts such as Ghana where cancer is not openly talked about may have concerns around breast cancer disclosure. Women may not be able to share their experiences about their diagnosis, which may prevent them from receiving support. This study aimed to obtain the views of Ghanaian women diagnosed with breast cancer about factors contributing to (non) disclosure. METHODS: This study is based on secondary findings from an ethnographic study that employed participant observation and semi-structured face to face interviews. The study was conducted at a breast clinic in a Teaching Hospital in southern Ghana. 16 women diagnosed with breast cancer (up to stage 3); five relatives nominated by these women and ten healthcare professionals (HCPs) participated in the study. Factors contributing to breast cancer (non) disclosure were explored. Data were analysed using a thematic approach. RESULTS: The analysis indicated that most of the women and family members were very reticent about breast cancer disclosure and were secretive with distant relatives and wider social networks. Whilst remaining silent about their cancer diagnosis helped women protect their identities, prevented spiritual attack, and bad advice, the need for emotional and financial support for cancer treatment triggered disclosure to close family, friends, and pastors. Some women were discouraged from persevering with conventional treatment following disclosure to their close relatives. CONCLUSIONS: Breast cancer stigma and fears around disclosure hindered women from disclosing to individuals in their social networks. Women disclosed to their close relatives for support, but this was not always safe. Health care professionals are well placed to explore women's concerns and facilitate disclosure within safe spaces to enhance engagement with breast cancer care services.

Patient-centred models of hepatitis C treatment for people who inject drugs: a multicentre, pragmatic randomised trial.

BACKGROUND: To achieve WHO targets for the elimination of hepatitis C virus (HCV) as a public threat, an increased uptake of HCV treatment among people who inject drugs (PWID) is urgently needed. Optimal HCV co-located treatment models for PWID have not yet been identified. We aimed to compare two patient-centred models of HCV care in PWID with active drug use. METHODS: We did a pragmatic randomised controlled trial at eight US cities in eight opioid treatment programmes and 15 community health centres. PWID actively injecting within 90 days of study entry were randomly assigned (1:1) to either patient navigation or modified directly observed therapy (mDOT) using computer-generated variable block sizes of 2-6 stratified by city, clinical settings, and cirrhosis status. The randomisation code was concealed, in a centralised REDCap database platform, from all investigators and research staff except for an authorised data manager at the data coordinating centre. All participants received a fixed-dose combination tablet (sofosbuvir 400 mg plus velpatasvir 100 mg) orally once daily for 12 weeks. The primary outcome was sustained virological response (SVR; determined by chart review between 70 days and 365 days after end of treatment and if unavailable, by study blood draws), and secondary outcomes were treatment initiation, adherence (measured by electronic blister packs), and treatment completion. Analyses were conducted within the modified intention-to-treat (mITT; all who initiated treatment), intention-to-treat (all who were randomised), and per-protocol populations. This trial is registered with ClinicalTrials.gov, NCT02824640. FINDINGS: Between Sept 15, 2016, and Aug 14, 2018, 1891 individuals were screened and 1136 were excluded (213 declined to participate and 923 did not meet the eligibility criteria). We randomly assigned 755 participants to patient navigation (n=379) or mDOT (n=376). In the mITT sample of participants who were randomised and initiated treatment (n=623), 226 (74% [95% CI 69-79]) of 306 participants in the mDOT group and 236 (76% [69-79]) of 317 in the patient navigation group had an SVR, with no significant difference between the groups (adjusted odds ratio [AOR] 0·97 [95% CI 0·66-1·42]; p=0·35). In the ITT sample (n=755), 226 (60% [95% CI 55-65]) of 376 participants in the mDOT group and 236 (62% [57-67]) of 379 in the patient navigation group had an SVR (AOR 0·92 [0·68-1·25]; p=0·61) and in the per-protocol sample (n=501), 226 (91% [87-94]) of 248 participants in the mDOT group and 235 (93% [89-96]) of 253 in the patient navigation group had an SVR (AOR 0·79 [0·41-1·55]; p=0·44). 306 (81%) of 376 participants in the mDOT group and 317 (84%) of 379 participants in the patient navigation group initiated treatment (AOR 0·86 [0·58-1·26]; p=0·44) and, among those, 251 (82%) participants in the mDOT group and 264 (83%) participants in the patient navigation group completed treatment (AOR 0·90 [0·58-1·39]; p=0·63). Mean daily adherence was higher in the mDOT group (78% [95% CI 75-81]) versus the patient navigation group (73% [70-77]), with a difference of 4·7% ([1·9-7·4]; p=0·0010). 421 serious adverse events were reported (217 in the mDOT group and 204 in the patient navigation group), with the most common being hospital admission (176 in the mDOT group vs 161 in the patient navigation group). INTERPRETATION: In this trial of active PWID, both models resulted in high SVR. Although adherence was significantly higher in the mDOT group versus the patient navigation group, there was no significant difference in SVR between the groups. Increases in adherence and treatment completion were associated with an increased likelihood of SVR. These results suggest that active PWID can reach high SVRs in diverse settings with either mDOT or patient navigation support. FUNDING: Patient-Centered Outcomes Research Institute, Gilead Sciences, Quest Diagnostics, Monogram Biosciences, and OraSure Technologies.

Hepatitis C Resistance-Associated Substitutions Among People Who Inject Drugs Treated With Direct-Acting Antiviral-Containing Regimens.

BACKGROUND: Resistance-associated substitutions (RASs) to HCV direct-acting antivirals (DAAs) can contribute to virologic failure and limit retreatment options. People who inject drugs (PWID) are at highest risk for transmission of resistant virus. We report on RASs at baseline and after virologic failure in DAA-naive and protease inhibitor-experienced PWID. METHODS: We sequenced the NS3/4A, NS5A, and NS5B regions from 150 PWID with genotype 1 (GT1) viruses; 128 (85.3%) GT1a, 22 (14.7%) GT1b. RESULTS: Among the 139 (92.7%) DAA-naive PWID, 85 of 139 (61.2%) had baseline RASs-67 of 139 (48.2%) in NS3 (predominantly Q80K/L); 25 of 139 (18.0%) in NS5A; and 8 of 139 (5.8%) in NS5B. Of the 11 protease inhibitor-experienced participants, 9 had baseline NS3 RASs (V36L N = 1, Q80K N = 9) and 4 had baseline NS5A RASs (M28V N = 2, H58P N = 1, A92T N = 1). Among the 11 participants who had posttreatment samples with detectable virus (7 treatment failures, 1 late relapse, 3 reinfections), 1 sofosbuvir/ledipasvir failure had a baseline H58P. Two sofosbuvir/ledipasvir-treated participants developed new NS5A mutations (Q30H, Y93H, L31M/V). Otherwise, no RASs were detected. CONCLUSIONS: Our results demonstrate RAS prevalence among DAA-naive PWID is comparable to that in the general population. Only 2 of 150 (1.3%) in our longitudinal cohort developed treatment-emergent RASs. Concern for transmission of resistant virus may therefore be minimal.

The cultural and structural influences that 'hide' information from women diagnosed with breast cancer in Ghana: an ethnography.

BACKGROUND: Socio-cultural factors may influence the uptake of breast cancer treatments. This study aimed to explore these socio-cultural influences on treatment decision-making for women in Ghana. METHOD: An ethnographic approach was adopted. Observation was conducted of women newly diagnosed with breast cancer, nominated relatives, nurses and doctors at a breast clinic in Ghana. Semi-structured interviews followed participant observation. Thematic analysis was employed. FINDINGS: Over 16 weeks (July 2017-November 2017), 31 participants were observed and 29 took part in semi-structured interviews. Three overarching themes were identified: (1) unequal power relationships; (2) Language barriers and (3) structural constraints. Following a breast cancer diagnosis, essential information necessary for treatment decision making is 'hidden' from women due to an unequal patient-provider relationship. Patients acknowledged cultural behaviours of deference to experts. Doctors deliberately misrepresented treatment information to women to encourage them to undergo surgical treatment. Structural issues such as the lack of privacy during consultations hindered quality patient engagement with decision-making. High treatment costs and the lack of resources to assist women with fertility after treatment impeded open discussions around these issues. Language barriers included a lack of terms in the local Twi language to explain cancer and its treatment. There was also an absence of appropriate information materials. CONCLUSION: Findings highlight the need for health professionals to be aware of the socio-cultural factors that limit access to quality information which is needed for informed treatment decision making. Policies that aim to provide adequate logistics; increase staffing levels; improve staff cultural awareness training and remove financial barriers are recommended.

Utilizing patient perception of group treatment in exploring medication adherence, social support, and quality of life outcomes in people who inject drugs with hepatitis C.

People who inject drugs (PWID) have a high prevalence of hepatitis C virus (HCV). Group treatment is a practical option for addressing barriers to treatment in this population. Prior research on group treatment has resulted in mixed conclusions about its effectiveness in addressing barriers to treatment. A patient's perception of the group environment may help to explain this variability. This study sought to explore the association between indicators of group treatment environment and improved outcomes in HCV-infected PWID. This secondary analysis of a randomized controlled trial exploring different models of treatment for HCV in a PWID population consisted of 42 participants randomized to the group treatment branch of the trial. Independent variables consisted of group sessions attended and group climate constructs of engagement, conflict, and avoidance. Dependent variables consisted of medication adherence, social support, and health-related quality of life. The study implemented generalized estimating equations to assess associations with the outcomes at the end of treatment. Factors indicative of group treatment environment were related to medication adherence and other barriers to health for HCV-infected PWID: social support and health-related quality of life. Perceptions of conflict or avoidance were associated with worse outcomes, while increased session attendance was generally associated with better outcomes. The study attests to the importance of examining group environment factors during treatment interventions. Although preliminary, the study provides specific indicators of treatment success for HCV-infected PWID and practical implications to improve patients' health outcomes and better tailor treatment to the patient.

Hepatitis C Virus Direct-Acting Antiviral Treatment Adherence Patterns and Sustained Viral Response Among People Who Inject Drugs Treated in Opioid Agonist Therapy Programs.

BACKGROUND: Adequate medication adherence is critical for achieving sustained viral response (SVR) of hepatitis C virus (HCV) among people who inject drugs (PWID). However, it is less known which patterns of direct-acting antiviral (DAA) treatment adherence are associated with SVR in this population or what factors are associated with each pattern. METHODS: The randomized 3-arm PREVAIL study used electronic blister packs to obtain daily time frame adherence data in opiate agonist therapy program settings. Exact logistic regressions were applied to test the associations between SVR and 6 types of treatment adherence patterns. RESULTS: Of the 113 participants treated with combination DAAs, 109 (96.5%) achieved SVR. SVR was significantly associated with all pattern parameters except for number of switches between adherent and missed days: total adherent daily doses (exact adjusted odds ratio [AOR] = 1.12; 95% confidence interval [CI] = 1.04-1.22), percent total doses (1.09; 1.03-1.16), days on treatment (1.16; 1.05-1.32), maximum consecutive adherent days (1.34; 1.06-2.04), and maximum consecutive nonadherent days (0.85; .74-.95 = 0.003). SVR was significantly associated with total adherent doses in the first 2 months of treatment, it was not in the last month. While alcohol intoxication was significantly associated with frequent switches, drug use was not associated with any adherence pattern. CONCLUSIONS: Consistent maintenance of adequate total dose adherence over the entire course of HCV treatment is important in achieving SVR among PWID. Additional integrative addiction and medical care may be warranted for treating PWID who experience alcohol intoxication.

High HCV cure rates among people who inject drugs and have suboptimal adherence: A patient-centered approach to HCV models of care.

BACKGROUND: Though people who inject drugs (PWID) make up the majority of the hepatitis C virus (HCV) epidemic, concerns about adherence often exclude PWID from receiving direct-acting antiviral (DAA) medication. The most effective models of HCV care to promote sustained virologic response (SVR) and high adherence need to be evaluated. METHODS: We conducted a prospective cohort study in three opioid treatment programs (OTPs) in the Bronx, NY. Participants, in collaboration with providers, chose one of three models of onsite care: directly observed therapy (mDOT), group treatment (GT), or self-administered individual treatment (SIT).  SVR12, daily adherence, and participant characteristics were compared between groups. RESULTS: Of 61 participants, the majority were male (62%) and Latino (67%), with a mean age of 53 (SD 9). Participants received DAAs via one of three models of care: mDOT (21%), GT (25%), or SIT (54%). The majority (59%) used illicit drugs during treatment. Overall, SVR12 was 98% with no differences between models of care: mDOT (100%), GT (100%), and SIT (97%) (p = 1.0). Overall, daily adherence was 73% (SD 16); 86% among those who chose mDOT compared to 71% among those who chose GT (p<0.01) and 73% among those who chose SIT (p<0.01). CONCLUSION: Despite ongoing illicit drug use and suboptimal adherence, SVR12 was high among PWID treated onsite at an OTP using any one of three models of care. Shared decision making in real world settings may be key to choosing the appropriate model of care for PWID.

Rates of perfect self-reported adherence to direct-acting antiviral therapy and its correlates among people who inject drugs on medications for opioid use disorder: The PREVAIL study.

Adequate adherence to direct-acting antivirals (DAAs) for hepatitis C virus (HCV) is critical to attaining sustained virologic response (SVR). In this PREVAIL study's secondary analyses, we explored the association between self-reported and objective DAAs adherence among a sample of people who inject drugs (PWID) receiving medications for opioid use disorder (MOUD) (N = 147). Self-reported adherence was recoded 3 times during treatment (weeks 4, 8 and 12) using a visual analog scale (VAS), whereas objective adherence was collected continuously during treatment using electronic blister packs. Participants who reported being perfectly adherent had significantly higher blister pack adherence in each period (weeks 4, 8 and 12; ps < .05) and over the 12-week study (p < .001) compared to those who reported being non-perfectly adherent. Whites were more likely to report perfect adherence (91.7%) than Blacks (48.7%), Latinos (52.2%) and other (75.0%) race groups. Participants who reported recent use of cocaine (63.9%) or polysubstance use (60.0%) and those who had a positive result for cocaine (62.8%) were more likely to be non-perfectly adherent, although none of these factors were associated with blister pack adherence. This study showed that the VAS could serve as a reliable option for assessing DAAs adherence among PWID on MOUD. The implementation of VAS may be an ideal option for monitoring adherence among PWID on MOUD, especially in clinical settings with limited resources. PWID on MOUD who are Black or other races than White, as well as those who report recent cocaine or polysubstance use may require additional support to maintain optimal DAA adherence.

Factors and HCV treatment outcomes associated with smoking among people who inject drugs on opioid agonist treatment: secondary analysis of the PREVAIL randomized clinical trial.

BACKGROUND: Cigarette smoking has emerged as a leading cause of mortality among people with hepatitis C virus (HCV). People who inject drugs (PWID) represent the largest group of adults infected with HCV in the US. However, cigarette smoking remains virtually unexplored among this population. This study aimed at (1) determining prevalence and correlates of cigarette smoking among HCV-infected PWID enrolled in opiate agonist treatment programs; (2) exploring the association of smoking with HCV treatment outcomes including adherence, treatment completion and sustained virologic response (SVR); and 3) exploring whether cigarette smoking decreased after HCV treatment. METHODS: Participants were 150 HCV-infected PWID enrolled in a randomized clinical trial primarily designed to test three intensive models of HCV care. Assessments included sociodemographics, presence of chronic health and psychiatric comorbidities, prior and current drug use, quality of life, and HCV treatment outcomes. RESULTS: The majority of the patients (84%) were current cigarette smokers at baseline. There was a high prevalence of psychiatric and medical comorbidities in the overall sample of PWID. Alcohol and cocaine use were identified as correlates of cigarette smoking. Smoking status did not influence HCV treatment outcomes including adherence, treatment completion and SVR. HCV treatment was not associated with decreased cigarette smoking. CONCLUSIONS: The present study showed high prevalence of cigarette smoking among this population as well as identified correlates of smoking, namely alcohol and cocaine use. Cigarette smoking was not associated with HCV treatment outcomes. Given the detrimental effects that cigarette smoking and other co-occurring, substance use behaviors have on HCV-infected individuals' health, it is imperative that clinicians treating HCV also target smoking, especially among PWID. The high prevalence of cigarette smoking among PWID will contribute to growing morbidity and mortality among this population even if cured of HCV. Tailored smoking cessation interventions for PWID along with HCV treatment may need to be put into clinical practice. TRIAL REGISTRATION: NCT01857245 . Registered May 20, 2013.

Declines in Depressive Symptoms Among People who Inject Drugs Treated With Direct-Acting Antivirals While on Opioid Agonist Therapy.

BACKGROUND: Hepatitis C virus (HCV) frequently co-occurs with symptoms of depression, which are aggravated on interferon-based regimens. However, it is unknown whether HCV treatment with direct-acting antivirals (DAAs) has effects on depressive symptoms among people who inject drugs (PWID). In this study, we examined changes in depressive symptoms during and after HCV treatment among PWID on opioid agonist therapies (OATs). METHODS: Participants were 141 PWID who achieved sustained viral response after on-site HCV treatment at 3 OAT programs.Depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II) at baseline, every 4 weeks during treatment, and 12 and 24 weeks after treatment completion. Current diagnosis of depression or other psychiatric diagnoses were obtained through chart review. Use of illicit drugs was measured by urine toxicology screening. Alcohol use was measured using the Addiction Severity Index-Lite. RESULTS: Of the 141 PWID infected with HCV, 24.1% had severe, 9.9% had moderate, 15.6% had mild, and 50.4% had minimal levels of depression as per BDI-II scores at baseline. HCV treatment was significantly associated with reductions in depressive symptoms that persisted long term, regardless of symptom severity (P < .001) or presence of depression (P ≤ .01) or other psychiatric diagnoses (P ≤ .01) at baseline. Concurrent drug use (P ≤ .001) or hazardous alcohol drinking (P ≤ .001) did not interfere with reductions in depressive symptoms. CONCLUSIONS: Depressive symptoms are highly prevalent among HCV-infected PWID. HCV treatment was associated with sustained reductions in depressive symptoms. HCV therapy with DAAs may have important implications for PWID that go beyond HCV cure.

Low Adherence Achieves High HCV Cure Rates Among People Who Inject Drugs Treated With Direct-Acting Antiviral Agents.

We measured hepatitis C virus (HCV) adherence via electronic blister packs for 145 people who inject drugs treated on-site in a methadone program. The overall sustained virologic response (SVR) rate was 96% (95% CI, 91%-98%), and overall daily adherence was 78% (95% CI, 76%-81%). Participants who achieved at least 50% adherence had an overall SVR rate of 99%, with each 5% adherence interval >50% achieving at least 90% adherence. Suboptimal adherence may still lead to cure in the direct-acting antiviral era.

Artificial Intelligence Platform Demonstrates High Adherence in Patients Receiving Fixed-Dose Ledipasvir and Sofosbuvir: A Pilot Study.

This study evaluated health outcomes among people who inject drugs who are infected with hepatitis C virus using an artificial intelligence platform. Mean (SD) cumulative adherence (visual confirmation of administration) was 91.3% (10.5%). Most subjects (88.2%) achieved ≥80% adherence to treatment, and 88.2% (15 of 17) achieved a sustained virologic response.

A Phylogenetic Analysis of Hepatitis C Virus Transmission, Relapse, and Reinfection Among People Who Inject Drugs Receiving Opioid Agonist Therapy.

BACKGROUND: Understanding hepatitis C virus (HCV) transmission among people who inject drugs (PWID) is essential for HCV elimination. We aimed to differentiate reinfections from treatment failures and to identify transmission linkages and associated factors in a cohort of PWID receiving opioid agonist therapy (OAT). METHODS: We analyzed baseline and follow-up specimens from 150 PWID from 3 OAT clinics in the Bronx, New York. Next-generation sequencing data from the hypervariable region 1 of HCV were analyzed using Global Hepatitis Outbreak and Surveillance Technology. RESULTS: There were 3 transmission linkages between study participants. Sustained virologic response (SVR) was not achieved in 9 participants: 7 had follow-up specimens with similar sequences to baseline, and 2 died. In 4 additional participants, SVR was achieved but the participants were viremic at later follow-up: 2 were reinfected with different strains, 1 had a late treatment failure, and 1 was transiently viremic 17 months after treatment. All transmission linkages were from the same OAT clinic and involved spousal or common-law partnerships. CONCLUSION: This study highlights the use of next-generation sequencing as an important tool for identifying viral transmission and to help distinguish relapse and reinfection among PWID. Results reinforce the need for harm reduction interventions among couples and those who report ongoing risk factors after SVR.

Low Hepatitis C Reinfection Following Direct-acting Antiviral Therapy Among People Who Inject Drugs on Opioid Agonist Therapy.

BACKGROUND: Direct-acting antiviral (DAA) therapy is highly effective in people who inject drugs (PWID); however, rates, specific injection behaviors, and social determinants associated with hepatitis C virus (HCV) reinfection following DAA therapy among PWID on opioid agonist therapy (OAT) are poorly understood. METHODS: PREVAIL was a randomized controlled trial that assessed models of HCV care for 150 PWID on OAT. Those who achieved sustained virologic response (SVR) (n = 141; 94%) were eligible for this extension study. Interviews and assessments of recurrent HCV viremia occurred at 6-month intervals for up to 24 months following PREVAIL. We used survival analysis to analyze variables associated with time to reinfection. RESULTS: Of 141 who achieved SVR, 114 had a least 1 visit in the extension study (62% male; mean age, 52 years). Injection drug use (IDU) was reported by 19% (n = 22) in the extension study. HCV reinfection was observed in 3 participants. Over 246 person-years of follow-up, the incidence of reinfection was 1.22/100 person-years (95% CI, 0.25-3.57). All reinfections occurred among participants reporting ongoing IDU. The incidence of reinfection in participants reporting ongoing IDU (41 person-years of follow-up) was 7.4/100 person-years (95% CI, 1.5-21.6). Reinfection was associated with reporting ongoing IDU in the follow-up period (P < .001), a lack confidence in the ability to avoid contracting HCV (P < .001), homelessness (P = .002), and living with a PWID (P = .007). CONCLUSIONS: HCV reinfection was low overall, but more common among people with ongoing IDU following DAA therapy on OAT, as well as those who were not confident in the ability to avoid contracting HCV, homeless, or living with a PWID. Interventions to mediate these risk factors following HCV therapy are warranted.

Cost-effectiveness of Hepatitis C Virus Treatment Models for People Who Inject Drugs in Opioid Agonist Treatment Programs.

BACKGROUND: Many people who inject drugs in the United States have chronic hepatitis C virus (HCV). On-site treatment in opiate agonist treatment (OAT) programs addresses HCV treatment barriers, but few evidence-based models exist. METHODS: We evaluated the cost-effectiveness of HCV treatment models for OAT patients using data from a randomized trial conducted in Bronx, New York. We used a decision analytic model to compare self-administered individual treatment (SIT), group treatment (GT), directly observed therapy (DOT), and no intervention for a simulated cohort with the same demographic characteristics of trial participants. We projected long-term outcomes using an established model of HCV disease progression and treatment (hepatitis C cost-effectiveness model: HEP-CE). Incremental cost-effectiveness ratios (ICERs) are reported in 2016 US$/quality-adjusted life years (QALY), discounted 3% annually, from the healthcare sector and societal perspectives. RESULTS: For those assigned to SIT, we projected 89% would ever achieve a sustained viral response (SVR), with 7.21 QALYs and a $245 500 lifetime cost, compared to 22% achieving SVR, with 5.49 QALYs and a $161 300 lifetime cost, with no intervention. GT was more efficient than SIT, resulting in 0.33 additional QALYs and a $14 100 lower lifetime cost per person, with an ICER of $34 300/QALY, compared to no intervention. DOT was slightly more effective and costly than GT, with an ICER > $100 000/QALY, compared to GT. In probabilistic sensitivity analyses, GT and DOT were preferred in 91% of simulations at a threshold of <$100 000/QALY; conclusions were similar from the societal perspective. CONCLUSIONS: All models were associated with high rates of achieving SVR, compared to standard care. GT and DOT treatment models should be considered as cost-effective alternatives to SIT.

Intensive Models of Hepatitis C Care for People Who Inject Drugs Receiving Opioid Agonist Therapy: A Randomized Controlled Trial.

Background: Many people who inject drugs (PWID) are denied treatment for hepatitis C virus (HCV) infection, even if they are receiving opioid agonist therapy (OAT). Research suggests that HCV in PWID may be treated effectively, but optimal models of care for promoting adherence and sustained virologic response (SVR) have not been evaluated in the direct-acting antiviral (DAA) era. Objective: To determine whether directly observed therapy (DOT) and group treatment (GT) are more effective than self-administered individual treatment (SIT) in promoting adherence and achieving SVR among PWID receiving OAT. Design: Three-group, randomized controlled trial conducted from October 2013 to April 2017. (ClinicalTrials.gov: NCT01857245). Setting: Three OAT programs in Bronx, New York. Participants: Persons aged 18 years and older with genotype 1 HCV infection who were willing to receive HCV therapy on site in the OAT program. Of 190 persons screened, 158 were randomly assigned to a study group and 150 initiated treatment: DOT (n = 51), GT (n = 48), and SIT (n = 51). Intervention: 2 intensive interventions (DOT and GT) and 1 control condition (SIT). Measurements: Primary: adherence, measured by using electronic blister packs. Secondary: HCV treatment completion and SVR 12 weeks after treatment completion. Results: Mean age was 51 years; 65% of participants had positive results on urine drug testing during the 6 months before treatment, and 75% reported ever injecting drugs. Overall adherence, estimated from mixed-effects models using the daily timeframe, was 78% (95% CI, 75% to 81%) and was greater among participants randomly assigned to DOT (86% [CI, 80% to 92%]) than those assigned to SIT (75% [CI, 70% to 81%]; difference, 11% [CI, 5% to 18%]; Bonferroni-corrected P = 0.001). No significant difference in adherence was observed between participants randomly assigned to GT (80% [CI, 74% to 86%]) and those assigned to SIT (difference, 4.7% [CI, -2% to 11%]; Bonferroni-corrected P = 0.29). The HCV treatment completion rate was 97%, with no differences among groups (P = 0.53). Overall SVR was 94% (CI, 89% to 97%); the SVR rate was 98% in the DOT group, 94% in the GT group, and 90% in the SIT group (P = 0.152). Limitation: These findings may not be generalizable to PWID not enrolled in OAT programs. Conclusion: All models of onsite HCV care delivered to PWID in OAT programs resulted in high SVR, despite ongoing drug use. Directly observed therapy was associated with greater adherence than SIT. Primary Funding Source: National Institute on Drug Abuse and Gilead Sciences.

Physical activity modifies genetic susceptibility to obesity in postmenopausal women.

OBJECTIVE: We conducted a gene-environment interaction study to evaluate whether the association of body mass index (BMI) associated meta genome-wide association study single-nucleotide polymorphisms (SNPs) (as a genetic risk score) and BMI is modified by physical activity and age. METHODS: In 8,206 women of European ancestry from the Women's Health Initiative (WHI), we used linear regression to examine main effects of the 95 SNP BMI genetic risk score (GRS) and physical activity on BMI, and evaluated whether genetic associations are modified by physical activity (two-way interaction) and age (three-way interaction). RESULTS: We found evidence for modification of the BMI GRS-BMI association according to both physical activity and age. We observed a significant two-way interaction of BMI GRS × physical activity in the crude model (P interaction = 0.05), where a smaller effect of the BMI GRS on BMI with increasing physical activity. The beta coefficient was 0.05 (standard error [SE] = 0.02, P = 0.01) for the high-activity group compared with beta = 0.13 (SE = 0.02, P = 4.8 × 10) for the sedentary group. The three-way interaction was statistically significant (adjusted P interaction = 0.01). Notably, in the 70+ age group, the BMI GRS-BMI association was attenuated and no longer significant in the high-activity group; the beta coefficient for the 70+ high-activity group was relatively small and nonsignificant (beta = 0.02, SE = 0.03, P = 0.58) compared with 70+ sedentary group (beta = 0.17, SE = 0.03, P = 2.5 × 10). CONCLUSION: Our study suggests that physical activity attenuates the influence of genetic predisposition to obesity, and this effect is more profound in the oldest age group.

Rationale, design, and methodology of a trial evaluating three models of care for HCV treatment among injection drug users on opioid agonist therapy.

BACKGROUND: People who inject drugs (PWID) constitute 60% of the approximately 5 million people in the U.S. infected with hepatitis C virus (HCV). Treatment of PWID is complex due to addiction, mental illness, poverty, homelessness, lack of positive social support, poor adherence-related skills, low motivation and knowledge, and poor access to and trust in the health care system. New direct-acting antiviral medications are available for HCV with high cure rates and few side effects. The life expectancy and economic benefits of new HCV treatments will not be realized unless we determine optimal models of care for the majority of HCV-infected patients. The purpose of this study is to evaluate the effectiveness of directly observed therapy and group treatment compared with self-administered individual treatment in a large, urban opioid agonist therapy clinic setting in the Bronx, New York. METHODS/DESIGN: In this randomized controlled trial 150 PWID with chronic HCV were recruited from opioid agonist treatment (OAT) clinics and randomized to one of three models of onsite HCV treatment in OAT: 1) modified directly observed therapy; 2) group treatment; or 3) control - self-administered individual treatment. Participants were age 18 or older, HCV genotype 1, English or Spanish speaking, treatment naïve (or treatment experienced after 12/3/14), willing to receive HCV treatment onsite, receiving methadone or buprenorphine at the medication window at least once per week, and able to provide informed consent. Outcomes of interest include adherence (as measured by self-report and electronic blister packs), HCV treatment completion, sustained virologic response, drug resistance, and cost-effectiveness. DISCUSSION: This paper describes the design and rationale of a randomized controlled trial comparing three models of care for HCV therapy delivered in an opioid agonist treatment program. Our trial will be critical to rigorously identify models of care that result in high adherence and cure rates. Use of blister pack technology will help us determine the role of adherence in successful cure of HCV. Moreover, the trial methodology outlined here can serve as a template for the development of future programs and studies among HCV-infected drug users receiving opioid agonist therapy, as well as the cost-effectiveness of such programs. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov ( NCT01857245 ). Trial registration was obtained prospectively on May 20th, 2013.

Navigating condom use and HIV status disclosure with partners met online: a qualitative pilot study with gay and bisexual men from Craigslist.org.

We conducted face-to-face semi-structured interviews with 50 men recruited from the New York City men-seeking-men section of Craigslist.org. Participants discussed their favorite venues for meeting sex partners (n = 28 said the Internet), and we focused on these men's responses to probes regarding decisions around condom use and HIV status disclosure with online partners. A majority indicated they set a priori rules for themselves to always use condoms, and they cited the Internet as their favorite venue in part because it helped them sort for like-minded partners. Participants indicated that having in-person conversations around condom use and HIV was often difficult, and that the Internet was a convenient medium to facilitate the process. Notable differences were observed in how HIV-positive and HIV-negative men navigated serostatus disclosure-HIV-negative men were less subtle in starting the conversation. Finally, participants described a common narrative around distrust with online partners, which is one reason why they consistently use condoms. These data suggest that features which allow men to easily indicate, and filter for, condom use preferences should be built into (or maintained on) profile-based sexual networking sites and sexual bulletin board sites.