Glenn-Milo Santos

Decreases in Community Viral Load Are Accompanied by Reductions in New HIV Infections in San Francisco

Background At the individual level, higher HIV viral load predicts sexual transmission risk. We evaluated San Franciscos community viral load (CVL) as a population level marker of HIV transmission risk. We hypothesized that the decrease in CVL in San Francisco from 2004–2008, corresponding with increased rates of HIV testing, antiretroviral therapy (ART) coverage and effectiveness, and population-level virologic suppression, would be associated with a reduction in new HIV infections. Methodology/Principal Findings We used San Franciscos HIV/AIDS surveillance system to examine the trends in CVL. Mean CVL was calculated as the mean of the most recent viral load of all reported HIV-positive individuals in a particular community. Total CVL was defined as the sum of the most recent viral loads of all HIV-positive individuals in a particular community. We used Poisson models with robust standard errors to assess the relationships between the mean and total CVL and the primary outcome: annual numbers of newly diagnosed HIV cases. Both mean and total CVL decreased from 2004–2008 and were accompanied by decreases in new HIV diagnoses from 798 (2004) to 434 (2008). The mean (p = 0.003) and total CVL (p = 0.002) were significantly associated with new HIV cases from 2004–2008. Conclusions/Significance Reductions in CVL are associated with decreased HIV infections. Results suggest that wide-scale ART could reduce HIV transmission at the population level. Because CVL is temporally upstream of new HIV infections, jurisdictions should consider adding CVL to routine HIV surveillance to track the epidemic, allocate resources, and to evaluate the effectiveness of HIV prevention and treatment efforts.

Amphetamine-group substances and HIV.

Amphetamine-group substances are used worldwide and are more prevalent than either cocaine or opioids. We reviewed published reports about amphetamine-group substances and did a meta-analysis of randomised controlled trials of behavioural interventions for their use. Most research was done in developed countries. Many, but not all, studies show an association between amphetamine-group substance use and risk of HIV infection. Much use of amphetamine-group substances is non-injection and is associated with increased HIV risk, particularly in men who have sex with men. The structural, social, interpersonal, and personal factors that link to amphetamine-group substance use and HIV risk are poorly understood. 13 studies, with a cumulative sample size of 1997 individuals, qualified for the meta-analysis. Overall, high-intensity behavioural interventions were moderately effective in reducing use of amphetamine-group substances (effect size 0.28, 95% CI 0.13-0.44). We did not find conclusive evidence that behavioural interventions as a group are more effective than are passive or minium treatment for reduction of amphetamine-group substance use or sexual risk behaviours. The search for effective, scalable, and sustainable interventions for amphetamine-group substance use, including pharmacotherapies, should be supported and encouraged.

Sexual Stigma, Criminalization, Investment, and Access to HIV Services Among Men Who Have Sex with Men Worldwide

Abstract Globally, HIV disproportionately affects men who have sex with men (MSM). This study explored associations between access to HIV services and (1) individual-level perceived sexual stigma; (2) country-level criminalization of homosexuality; and (3) country-level investment in HIV services for MSM. 3,340 MSM completed an online survey assessing access to HIV services. MSM from over 115 countries were categorized according to criminalization of homosexuality policy and investment in HIV services targeting MSM. Lower access to condoms, lubricants, and HIV testing were each associated with greater perceived sexual stigma, existence of homosexuality criminalization policies, and less investment in HIV services. Lower access to HIV treatment was associated with greater perceived sexual stigma and criminalization. Criminalization of homosexuality and low investment in HIV services were both associated with greater perceived sexual stigma. Efforts to prevent and treat HIV among MSM should be coupled with structural interventions to reduce stigma, overturn homosexuality criminalization policies, and increase investment in MSM-specific HIV services.ResumenGlobalmente, el VIH afecta desproporcionadamente a los HSH. Este estudio exploró las asociaciones entre el acceso a servicios para el VIH y (1) la percepción del estigma sexual a nivel individual; (2) la criminalización de la homosexualidad en cada país; y (3) el nivel de inversión financiera por país en servicios para el VIH dirigidos a HSH. Un total de 3,340 HSH completaron una encuesta a través del internet sobre el acceso a servicios para el VIH. HSH de más de 115 países fueron clasificados según las legislaciones sobre la criminalización de la homosexualidad y el nivel de inversión en servicios para el VIH dirigido a HSH. Un menor acceso a condones, lubricantes y pruebas del VIH fueron asociados con una mayor percepción del estigma sexual, la existencia de legislación sobre la criminalización de la homosexualidad y menos inversión en servicios para el VIH. Menos acceso a tratamientos para el VIH, fue asociado con una mayor percepción de estigma sexual y la criminalización de la homosexualidad. A su vez, la criminalización de la homosexualidad y la baja inversión en servicios para el VIH, fueron asociados con una mayor percepción del estigma sexual. Los esfuerzos para prevenir y tratar el VIH entre HSH necesitan ser ligados a intervenciones estructurales para reducir el estigma, reformar legislaciones de criminalización de la homosexualidad y aumentar las inversiones en los servicios para el VIH específicamente diseñados para HSH.

Syndemic conditions associated with increased HIV risk in a global sample of men who have sex with men

Objective We evaluated the relationship among syndemic conditions (defined as a cluster of interconnected psychosocial health conditions), sexual behaviours and self-reported HIV infection in a global sample of men who have sex with men (MSM). Methods We used generalised estimating equations logistic regression models with robust SEs to assess the relationships among cumulative number of syndemic conditions—including depression, substance use, violence, sexual stigma and homelessness—and unprotected anal intercourse (UAI) and HIV infection, while accounting for clustering within-country in a global cross-sectional survey of 3934 MSM across 151 countries. Results We observed parallel, significant dose–response associations between the number of syndemic conditions and UAI, as well as number of syndemic conditions and HIV infection. Compared with participants without syndemics, the adjusted OR (aOR) for UAI among those with 1, 2 and 3 or more syndemic conditions were 1.44 (Bonferroni-adjusted 95% CI 1.23 to 1.68), 1.89 (1.51 to 2.36) and 2.03 (1.43 to 2.89), respectively. Compared with participants without syndemics, the aOR for HIV infection among those with 1, 2 and 3 or more syndemic conditions were 1.67 (1.24 to 2.26), 2.02 (1.44 to 2.85) and 2.35 (1.31 to 4.21), respectively. Conclusions This analysis provides evidence of intertwining syndemics that may operate synergistically to increase HIV risk among MSM globally. To curb HIV effectively and advance the health of MSM, multiple conditions must be addressed concurrently using multi-level approaches that target both individual and structural risk factors.

Access to Basic HIV-Related Services and PrEP Acceptability among Men Who Have Sex with Men Worldwide:: Barriers, Facilitators, and Implications for Combination Prevention

Introduction. Men who have sex with men (MSM) are disproportionately impacted by HIV globally. Easily accessible combination HIV prevention strategies, tailored to the needs of MSM, are needed to effectively address the AIDS pandemic. Methods and Materials. We conducted a cross-sectional study among MSM (n = 3748) from 145 countries from April to August 2012. Using multivariable random effects models, we examined factors associated with acceptability of preexposure prophylaxis (PrEP) and access to condoms, lubricants, HIV testing, and HIV treatment. Results. Condoms and lubricants were accessible to 35% and 22% of all respondents, respectively. HIV testing was accessible to 35% of HIV-negative respondents. Forty-three percent of all HIV-positive respondents reported that antiretroviral therapy was easily accessible. Homophobia, outness, and service provider stigma were significantly associated with reduced access to services. Conversely, community engagement, connection to gay community, and comfort with service providers were associated with increased access. PrEP acceptability was associated with lower PrEP-related stigma, less knowledge about PrEP, less outness, higher service provider stigma, and having experienced violence for being MSM. Conclusions. Ensuring HIV service access among MSM will be critical in maximizing the potential effectiveness of combination approaches, especially given the interdependence of both basic and newer interventions like PrEP. Barriers and facilitators of HIV service access for MSM should be better understood and addressed.

Prevalence and correlates of substance use among trans*female youth ages 16–24 years in the San Francisco Bay Area

BACKGROUND Substance use is highly prevalent among transgender (trans*) females and has been associated with negative health outcomes, including HIV infection. Little is known about psychosocial risk factors that may influence the onset of substance use among trans*female youth, which can contribute to health disparities during adulthood. METHODS We conducted a secondary data analysis of a study on HIV risk and resilience among trans*female youth (N=292). Prevalence of substance use was assessed and multivariable logistic regression models were used to examine the relationship between posttraumatic stress disorder (PTSD), psychological distress, gender-related discrimination, parental drug or alcohol problems (PDAP) and multiple substance use outcomes. RESULTS Most (69%) of the trans*female youth reported recent drug use. In multivariable analyses, those with PTSD had increased odds of drug use [AOR=1.94 (95% CI=1.09-3.44)]. Those who experienced gender-related discrimination had increased odds of drug use [AOR=2.28 (95% CI=1.17-4.44)], drug use concurrent with sex [AOR=2.35 (95% CI=1.11-4.98)] and use of multiple drugs [AOR=3.24 (95% CI=1.52-6.88)]. Those with psychological distress had increased odds of using multiple heavy drugs [AOR=2.27 (95% CI=1.01-5.12)]. Those with PDAP had increased odds of drugs use [AOR=2.62 (95% CI=1.43-4.82)], drug use concurrent with sex [AOR=2.01 (95% CI, 1.15-3.51)] and use of multiple drugs [AOR=2.10 (95% CI=1.22-3.62)]. CONCLUSIONS Substance use is highly prevalent among trans*female youth and was significantly associated with psychosocial risk factors. In order to effectively address substance use among trans*female youth, efforts must address coping related to gender-based discrimination and trauma. Furthermore, structural level interventions aiming to reduce stigma and gender-identity discrimination might also be effective.

Nonrandomized Intervention Study of Naloxone Coprescription for Primary Care Patients Receiving Long-Term Opioid Therapy for Pain

In the United States, the opioid analgesic overdose death rate increased from 1.4 to 5.4 per 100000 adults from 1999 to 2011 (1). Efforts to manage this increase in mortality have focused on modifying the prescribing practices of providers (2). Mandated urine testing, pain agreements, and inspections of prescription drug monitoring program data have become standard practice, yet few data support a link between such interventions and reduced opioid-related morbidity or mortality. In fact, whereas opioid analgesic deaths have recently plateaued, heroin use and overdose deaths have skyrocketed, suggesting possible unintended consequences of opioid stewardship initiatives (3, 4). Many communities have used the targeted distribution of naloxone, the short-acting opioid antagonist, to address opioid-related mortality (5). Provision of naloxone to those likely to witness or experience an opioid overdose, principally illicit drug users, has been associated with substantial reductions in community-level opioid overdose mortality relative to communities that did not implement naloxone distribution (6). Other observational and ecologic analyses have demonstrated marked reductions in opioid overdose mortality in communities that distributed naloxone, including Chicago, Illinois (7); New York City (8); and Scotland (9). A meta-analysis demonstrated a higher likelihood of survival in overdose situations when naloxone was administered by laypersons (10). Naloxone distribution to heroin users is remarkably cost-effective (11). In San Francisco, California, implementation and expansion of a targeted naloxone distribution program were temporally associated with a decline in heroin overdose deaths from as high as 180 per year to as few as 10 through 2012. The number of deaths attributed to opioid analgesics, however, exceeded 100 annually from 2010 to 2012 (12). Most of these decedents had received primary care in safety-net clinics, and most had received long-term opioid therapy for pain. However, literature to support naloxone prescribing to this population is limited to early descriptive analyses (13) and anecdotal reports (14). At U.S. Army Fort Bragg, overdoses seen in the emergency department (ED) declined from 8 per month to 0 after naloxone coprescription was started (14, 15); this finding suggests that naloxone prescription may have affected the overdose event rate by influencing patient and/or provider behavior, rather than simply being available as a reversal agent. These results are consistent with some data indicating that heroin users who receive naloxone reduce heroin use (16). In response to these data, we developed and coordinated a standardized naloxone coprescribing program at primary care clinics in a safety-net system in San Francisco. To inform the larger-scale implementation of naloxone prescribing for patients prescribed opioid medications, we assessed the feasibility of introducing and scaling up naloxone coprescribing in these primary care clinics and conducted analyses to assess the association of naloxone coprescribing with ED use and prescribed opioid dose. Methods Naloxone for Opioid Safety Evaluation (NOSE) staff coordinated the clinical program and conducted the evaluation. The study was approved by the Committee on Human Research of the University of California, San Francisco (CHR#13-11168). Clinical Program The clinical program was implemented in a rolling fashion from February 2013 to April 2014 at 6 clinics where patients had died of opioid overdose from 2010 to 2012. All clinics accepted only publicly insured or uninsured patients, and 2 were resident training sites. Onsite leaders were selected, and a consistent protocol was implemented across sites, beginning with training in naloxone prescribing for providers (physicians, nurse practitioners, and physician assistants) and staff (see Appendix and Appendix Table 1, for implementation plan and process outcomes). Training covered rationale and indications for prescribing naloxone (anyone who uses opioids long term or is otherwise at risk for witnessing or experiencing an opioid overdose), language to approach patients (for example, use such phrases as bad reaction instead of overdose), naloxone formulations, and pharmacy/payer coverage. Additionally, providers and staff were trained on how to educate patients on naloxone use, how to assemble the intranasal device (the U.S. Food and Drug Administration has since approved a device requiring no assembly [17]), and ensuring that caretakers know how and when to administer naloxone (Appendix Figure 1). Appendix Figure 1. Checklist for clinic staff to train patients receiving naloxone. CPR = cardiopulmonary resuscitation. Appendix Table 1. Implementation Plan and Process Outcomes for Naloxone Coprescribing at Safety-Net Clinics Initial training was provided to all sites approximately 30 days preceding initiation of naloxone coprescription; after initiation, additional training was provided and at least 1 reminder e-mail was sent to providers (Appendix Figure 2). Because most providers opted to prescribe the intranasal formulation of naloxone and the mucosal atomization device was not readily available from pharmacies, clinics could order the device and patient brochures (Appendix Figure 3) in zipper-seal plastic bags from the clinic systems central pharmacy. NOSE staff assisted with any logistic problems, and a clinical pharmacist educated any pharmacies that encountered problems ordering, dispensing, or billing for naloxone (Appendix Figure 4). Appendix Figure 2. E-mail template to remind providers about naloxone prescribing. ECW = eClinicalWorks; LCR = lifetime clinical record. Appendix Figure 3. Naloxone for opioid safety patient brochure. Appendix Figure 3. Continued. Appendix Figure 4. Informational sheet for pharmacists on ordering, dispensing, counseling, and billing for naloxone. Data Sources and Data Abstraction Feasibility was assessed through chart reviews of all patients receiving long-term opioid therapy by prescription. Patients receiving sufficient opioids to take at least 1 pill daily for more than 3 months were added to a pain management registry (PMR) by staff at each clinic. This list was downloaded every 3 months during the intervention period, and a merged list of 3138 patients with demographic data was generated in March 2015. A manual chart review was conducted to determine whether patients were valid PMR entrantCs during the study period and to collect the following data: 1) opioid type, dose, quantity per 30 days, and date prescribed at 2 clinic visits (the visit closest to the baseline date [start of naloxone coprescribing at the given clinic or the date the patient was added to the PMR, whichever was later] and the last visit at the clinic before chart review [that is, follow-up date]); 2) the date of initial naloxone prescription; and 3) dates of all ED visits at the county hospital and opioid-relatedness. The ED visits were coded as opioid-related in accordance with documentation for establishing drug-relatedness of ED visits from the Drug Abuse Warning Network (18). Visits were opioid-related if the documenting physician considered them to be primarily due to an adverse event from an opioid or to opioid-seeking behavior; a subset of visits was coded as oversedation if the assessment was an opioid poisoning or other complication attributed by the documenting physician to opioid-induced sedation. Staff reviewing charts included a physician who trained other staff and reviewed uncertain cases; 62.5% of charts were independently assessed by at least 2 reviewers (see Appendix for details). Death information was extracted from the California Electronic Death Record System on 14 July 2015. Feasibility Analysis We assessed bivariate relationships between all demographic and clinical characteristics presented in Table 1 and the receipt of naloxone during the study period using chi-square, Fisher exact (for comparisons with cell sizes <5), and Wilcoxon rank-sum tests. Morphine equivalent daily dose in milligrams (MEQ) was calculated for each patient at baseline and subsequent follow-up dates by using standard conversion ratios from the literature (19, 20). Table 1. Demographic and Clinical Characteristics of PMR Patients, by Receipt of Naloxone Prescription We fit a normal-logistic regression model, with random effects for providers, to assess both patient- and provider-level predictors of naloxone prescription. All baseline patient characteristics assessed in bivariate analyses were included in the model, except for opioid type; the latter was excluded because relevant elements of formulations (such as presence of acetaminophen or duration of action) do not necessarily correspond to opioid type. Only baseline history of any opioid-related ED visit was included in the model because this category of visit was hypothesized to be most relevant to naloxone prescribing. The model also included provider type (attending physician or fellow, resident physician, or other provider) and the size of each providers panel of PMR patients, while controlling for time in days from 1 February 2013 (the earliest program initiation date) to patient baseline date, as well as time between the baseline and follow-up visit dates. To characterize residual differences among providers in naloxone prescription rates, we calculated the odds ratio for the difference between the 25th and 75th percentile values of the random provider effect. A descriptive summary of the PMR panel size, number of patients prescribed naloxone, and percentage of patients prescribed naloxone per provider is presented in Appendix Table 2. Appendix Table 2. Provider-Level Data on Total Number of Patients, Number of Patients Prescribed Naloxone, and Percentage of Patients Prescribed Naloxone Analysis of ED Use In our prespecified plan to assess the association of naloxone receipt with opioid-related ED visits, numbers of opioid-rela

HIV treatment cascade among transgender women in a San Francisco respondent driven sampling study

Objective Male-to-female transgender women (transwomen) have a disproportionate burden of HIV. We sought to estimate HIV treatment cascade indicators among transwomen in San Francisco. Methods We conducted a respondent driven sampling (RDS) study of 314 transwomen from August to December 2010. The study tested participants for HIV and collected self-reported data on linkage and access to care, viral load and antiretroviral treatment (ART). We derived population-based estimates and 95% CIs of cascade indicators using sampling weights based on established RDS methods. We conducted RDS-weighted logistic regression analyses to evaluate correlates of being on ART and being virologically suppressed (viral load ≤200 copies/mL). Results The RDS-weighted population-based estimate of HIV prevalence was 39% (95% CI 32% to 48%) among transwomen tested for HIV. Among HIV-positive transwomen, 77% (95% CI 70% to 93%) reported being linked to care within 3 months of diagnosis and 87% (95% CI 76% to 98%) accessed care in the past 6 months. In addition, 65% (95% CI 54% to 75%) were on ART, and less than half (44%; 95% CI 21% to 58%) were virologically suppressed. Housing instability was associated with lower odds of being on ART and being virologically suppressed. Conclusions We observed a high prevalence of HIV in our population-based estimates of transwomen in San Francisco, coupled with modest ART use and low virological suppression rates, indicating high potential for forward transmission. Poor HIV treatment outcomes were consistently associated with housing instability. These data suggest that multi-level efforts, including efforts to address housing insecurity, are urgently needed to ameliorate disparities in HIV clinical outcomes among transwomen and reduce secondary HIV transmission to their partners.

Dose-response associations between number and frequency of substance use and high-risk sexual behaviors among HIV-negative substance-using men who have sex with men (SUMSM) in San Francisco.

Abstract: We evaluated the relationship between frequency and number of substances used and HIV risk [ie, serodiscordant unprotected anal intercourse (SDUAI)] among 3173 HIV-negative substance-using MSM. Compared with nonusers, the adjusted odds ratio (AOR) for SDUAI among episodic and at least weekly users, respectively, was 3.31 [95% confidence interval (CI), 2.55 to 4.28] and 5.46 (95% CI, 3.80 to 7.84) for methamphetamine, 1.86 (95% CI, 1.51 to 2.29) and 3.13 (95% CI, 2.12 to 4.63) for cocaine, and 2.08 (95% CI, 1.68 to 2.56) and 2.54 (95% CI, 1.85 to 3.48) for poppers. Heavy alcohol drinkers reported more SDUAI than moderate drinkers [AOR, 1.90 (95% CI, 1.43 to 2.51)]. Compared with nonusers, AORs for using 1, 2, and ≥3 substances were 16.81 (95% CI, 12.25 to 23.08), 27.31 (95% CI, 18.93 to 39.39), and 46.38 (95% CI, 30.65 to 70.19), respectively. High-risk sexual behaviors were strongly associated with frequency and number of substances used.

Brief overdose education is sufficient for naloxone distribution to opioid users

BACKGROUND While drug users are frequently equipped with naloxone for lay opioid overdose reversal, the amount of education needed to ensure knowledge of indications and administration is unknown. METHODS We administered four instruments, assessing comfort and knowledge around opioid overdose and naloxone administration, to opioid users receiving naloxone for the first time (N=60) and upon returning for a refill (N=54) at community distribution programs. Participants completed the instruments prior to receiving naloxone; first-time recipients repeated the instruments immediately after the standardized 5-10min education. RESULTS Comfort with recognition of, response to, and administration of naloxone for an overdose event significantly increased after brief education among first-time recipients (p<0.05). Knowledge of appropriate responses to opioid overdose was high across all assessments; 96% of participants could identify at least one acceptable action to assess and one acceptable action to care for an opioid overdose. Facility with naloxone administration was high across all assessments and significantly increased for intranasal administration after education for first-time recipients (p<0.001). First-time recipients (before and after education) and refillers demonstrated a high level of knowledge on the Brief Overdose Recognition and Response Assessment, correctly identifying a mean of 13.7 out of 16 overdose scenarios. CONCLUSIONS Opioid users seeking naloxone in San Francisco have a high level of baseline knowledge around recognizing and responding to opioid overdose and those returning for refills retain that knowledge. Brief education is sufficient to improve comfort and facility in recognizing and managing overdose.