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INTRODUCTION: Oral pre-exposure prophylaxis (PrEP) for HIV-1 infection is over 99% effective in protecting against HIV acquisition when used consistently and appropriately. However, PrEP uptake and persistent use remains suboptimal, with a substantial gap in utilization among key populations who could most benefit from PrEP. In Latin America specifically, there is poor understanding of barriers to PrEP uptake and persistence among transgender (trans) women. METHODS: In April-May 2018, we conducted qualitative interviews lasting 25-45 min as part of an end-of-project evaluation of TransPrEP, a pilot RCT that examined the impact of a social network-based peer support intervention on PrEP adherence among trans women in Lima, Peru. Participants in the qualitative evaluation, all adult trans women, included individuals who either (1) screened eligible to participate in the TransPrEP pilot, but opted not to enroll (n = 8), (2) enrolled, but later withdrew (n = 6), (3) were still actively enrolled at the time of interview and/or successfully completed the study (n = 16), or (4) were study staff (n = 4). Interviews were audio recorded and transcribed verbatim. Codebook development followed an immersion/crystallization approach, and coding was completed using Dedoose. RESULTS: Evaluation participants had a mean age of 28.2 years (range 19-47). When describing experiences taking PrEP, participant narratives highlighted side effects that spanned three domains: physical side effects, such as prolonged symptoms of gastrointestinal distress or somnolence; economic challenges, including lost income due to inability to work; and social concerns, including interpersonal conflicts due to HIV-related stigma. Participants described PrEP use within a broader context of social and economic marginalization, with a focus on daily survival, and how PrEP side effects negatively contributed to these stressors. Persistence was, in some cases, supported through the interventions educational workshops. CONCLUSION: This research highlights the ways that physical, economic, and social side effects of PrEP can impact acceptability and persistence among trans women in Peru, amplifying and layering onto existing stressors including economic precarity. Understanding the unique experiences of trans women taking PrEP is crucial to informing tailored interventions to improve uptake and persistence.

BackgroundCisgender women represent over half of people living with HIV globally. However, current research efforts toward a cure for HIV focus predominantly on cisgender men. The under-representation of women in HIV cure clinical studies is particularly problematic given data suggesting that sex-dependent phenotypes limit scientific discovery.ObjectiveWe aimed to generate considerations to increase the meaningful involvement of women in HIV cure-related research.Materials and methodsWe conducted in-depth interviews with biomedical researchers and community members to better understand factors that could increase the meaningful involvement of women in HIV cure clinical trials. Participants were affiliated with academia, industry, community advisory boards, and community-based organizations, and were identified using listings from the AIDS Clinical Trials Group and the Martin Delaney Collaboratories. We used conventional content analysis to analyze the qualitative data.ResultsWe recruited 27 participants, of whom 11 were biomedical researchers and 16 were community members. Participants included 25 cisgender women, 1 transgender woman, and 1 cisgender man. Key considerations emerged, including the need to ensure that HIV cure studies reflect HIV epidemiologic trends and having accurate representation by sex and gender in HIV cure research. To increase the meaningful involvement of women, recommendations included instituting intentional enrollment goals, frequent and mandatory reporting on enrollment, and incentives for sites to enroll women. Additional themes included the need for agency and self-determination, attention to lived experiences, trauma and healing, and adequate support for women (e.g. logistical, psychosocial, mental, emotional, and physical). Participants noted that women would be willing to participate in HIV cure trials, related procedures (e.g. biopsies), and analytical treatment interruptions. They also expressed a desired for women-centered and holistic clinical trial designs that account for intersectionality.ConclusionsOur empirical inquiry extends recent calls to action to increase diversity of people involved in HIV cure research. Redressing the under-inclusion of women in HIV cure research is an urgent imperative. The entire field must mobilize and reform to achieve this goal. Meaningfully involving women across the gender spectrum in HIV cure research is needed to ensure that interventions are safe, effective, scalable, and acceptable for all people with HIV.

OBJECTIVES: Gender-affirming hormonal therapies (GAHT) and HIV increase cardiovascular risk for transgender women (TW), yet there is a paucity of data quantifying cardiometabolic changes following GAHT initiation, particularly among TW with HIV. METHODS: The Féminas study enrolled TW from October 2016 to March 2017 in Lima, Peru. Participants reported sexual activity that was high risk for HIV acquisition or transmission. All were tested for HIV/ sexually transmitted infection and were given access to GAHT (oestradiol valerate and spironolactone), HIV pre-exposure prophylaxis (PrEP) or antiretroviral therapy (ART) for 12 months. Biomarker measurement was done on stored serum, whereas fasting glucose and lipids were measured in real time. RESULTS: In all, 170 TW (32 with HIV, 138 without HIV) had median age 27 years and 70% prior GAHT use. At baseline, PCSK9, sCD14, sCD163, IL-6, sTNFRI/II, CRP and EN-RAGE levels were significantly higher in TW with HIV than in TW without HIV. High-density lipoprotein and total cholesterol were lower and insulin and glucose parameters were similar. All TW with HIV started ART, but only five achieved virological suppression at any time. No TW without HIV initiated PrEP. Over 6 months, all participants initiated GAHT and had worsening insulin, glucose and HOMA-IR. Large d-dimer decreases also occurred. Similar changes occurred in TW with and without HIV. CONCLUSIONS: In this unique cohort of TW, GAHT decreased d-dimer but worsened insulin sensitivity. Because PrEP uptake and ART adherence were very low, observed effects are primarily attributed to GAHT use. Further study is needed to better understand cardiometabolic changes in TW by HIV serostatus.

BACKGROUND: Alcohol-induced blackouts have been associated concurrently and prospectively with alcohol-related harm. Although rates of heavy drinking among military samples tend to be comparable or higher than rates among civilian samples, the prevalence and correlates of blackout in the military population are understudied. METHODS: Veterans (N = 241, 29% female, 39% Black) reported on their alcohol consumption and mental health as part of a larger health-related study among veterans. In this secondary analysis, we tested theoretically and empirically informed predictors (gender, drinking quantity, and other drug use) and consequences [depression, posttraumatic stress disorder (PTSD)] of alcohol-induced blackout. Given the diversity of the sample, potential roles of racial/ethnic discrimination and drinking to cope in alcohol-induced blackout were also tested. RESULTS: Past-year prevalence of alcohol-induced blackout was 53% among veterans who drank alcohol and 68% among those who screened positive for hazardous drinking. Everyday experience of racial discrimination was the strongest concurrent predictor of alcohol-induced blackout. Drinking quantity and use of other drugs were significant correlates only in bivariate models. Controlling for gender, race, drinking quantity, other drug use, and discrimination, blackout frequency was significantly associated with symptoms of depression, but not symptoms of PTSD. Both blackout and racial discrimination were associated with drinking to cope. CONCLUSIONS: The prevalence and correlates of alcohol-induced blackout among veterans are largely consistent with those documented in civilian and young adult populations. Among racially diverse groups, racial discrimination may be more strongly associated with mental health symptoms than alcohol consumption or acute alcohol consequences such as blackout.

IntroductionSocial networks contribute to normative reinforcement of HIV prevention strategies, knowledge sharing, and social capital, but little research has characterized the social networks of transgender women (TW) in Latin America. We conducted a mixed methods analysis of three network clusters of TW in Lima, Peru, to evaluate network composition, types of support exchanged, and patterns of communication.MethodsWe recruited TW residing in or affiliated with three "casas trans" (houses shared among TW) in Lima between April-May 2018. Eligible participants were 18 or older, self-reported HIV-negative, and reported recent intercourse with a cis-male partner. Participants completed demographic questionnaires, social network interviews, and semi-structured interviews to assess egocentric network structures, support exchanged, and communication patterns. Quantitative and qualitative data were analyzed using Stata v14.1 and Atlas.ti, respectively.ResultsOf 20 TW, median age was 26 years and 100% reported involvement in commercial sex work. Respondents identified 161 individuals they interacted with in the past month (alters), of whom 33% were TW and 52% family members. 70% of respondents reported receiving emotional support from family, while 30% received financial support and instrumental support from family. Of the 13 (65%) respondents who nominated someone as a source of HIV prevention support (HPS), the majority (69%) nominated other TW. In a GEE regression analysis adjusted for respondent education and region of birth, being a family member was associated with lower likelihood of providing financial support (aOR 0.21, CI 0.08-0.54), instrumental support (aOR 0.16, CI 0.06-0.39), and HPS (aOR 0.18, CI 0.05-0.64). In qualitative interviews, most respondents identified a cis-female family member as their most trusted and closest network member, but other TW were more often considered sources of day-to-day support, including HPS.ConclusionTW have diverse social networks where other TW are key sources of knowledge sharing and support, and family members may also represent important and influential components. Within these complex networks, TW may selectively solicit and provide support from different network alters according to specific contexts and needs. HIV prevention messaging could consider incorporating network-based interventions with TW community input and outreach efforts for supportive family members.

Transgender women's (TW) social networks may facilitate HIV prevention information dissemination and normative reinforcement. We conducted a qualitative study of social networks among 20 TW affiliated with 3 "casas trans" (houses shared among TW) in Lima, Peru, using diffusion of innovations theory to investigate community-level HIV prevention norms. Participants completed demographic questionnaires, social network interviews, and semistructured in-depth interviews. Median age was 26 and all participants engaged in sex work. Interviews revealed high HIV prevention knowledge and positive attitudes, but low engagement in HIV prevention. Respondents primarily discussed HIV prevention with other TW. Network members' opinions about pre-exposure prophylaxis (PrEP) frequently influenced respondents' personal beliefs, including mistrust of healthcare personnel, concern that PrEP efficacy was unproven, fear of adverse effects, and frustration regarding difficulty accessing PrEP. Patterns of influence in TW networks may be leveraged to improve uptake of HIV prevention tools, including PrEP.

Sexual and gender politics inform relational expectations surrounding sexual experiences of Peruvian transgender women (TW) and men who have sex with men (MSM). We used the framework of sexual role strain, or incongruence between preferred sexual role and actual sexual practices, to explore potential conflicts between personally articulated identities and externally defined norms of gender and sexuality and its potential to increase HIV/STI risk. Cross-sectional individual- and dyad-level data from 766 TW and MSM in Lima, Peru were used to assess the partnership contexts within which insertive anal intercourse was practiced despite receptive role preference (receptive role strain), and receptive anal intercourse practiced despite insertive role preference (insertive role strain). Sexual role strain for TW was more common with non-primary partners, while for MSM it occurred more frequently in the context of a primary partnership. Receptive role strain was more prevalent for TW with unknown HIV status (reference: without HIV) or pre-sex drug use (reference: no pre-sex drug use). For homosexual MSM, receptive role strain was more prevalent during condomless anal intercourse (reference: condom-protected) and with receptive or versatile partners (reference: insertive). Among heterosexual or bisexual MSM, insertive role strain was more prevalent with insertive or versatile partners (reference: receptive), and less prevalent with casual partners (reference: primary). Our findings suggest TW and MSM experience different vulnerabilities during sexual role negotiation with different partner-types. Future studies should explore the impact of sexual role strain on condom use agency, HIV/STI risk, and discordances between public and private presentations of gender and sexual orientation.

To inform culturally relevant HIV prevention interventions, we explore the complexity of sex work among Peruvian transgender women. In 2015, we conducted twenty in-depth interviews and demographic surveys with transgender women in Lima, Peru to examine how transgender women enact individual- and community-level resistance strategies within a context of pervasive marginalization. Although 40% self-identified as "sex workers," 70% recently exchanged sex for money. Participants described nuanced risk-benefit analyses surrounding paid sexual encounters. Classification of clients as "risky" or "rewarding" incorporated issues of health, violence, and pleasure. Interviews highlighted context-informed decision-making (rejecting disrespectful clients, asserting condom use with specific partner types) demonstrating that motivations were not limited to HIV prevention or economic renumeration, but considered safety, health, attraction, gender validation, hygiene, and convenience. These findings underscore the complex risk assessments employed by Peruvian trans women. These individual-level decision-making and context-specific health promotion strategies represent critical frameworks for HIV prevention efforts.

BackgroundSocial networks, norms, and discussions about sexual health may inform sexual practices, influencing risk of human immunodeficiency virus (HIV) or sexually transmitted infection (STI) acquisition. To better understand social networks of Peruvian men who have sex with men (MSM) and transgender women (trans women), we examined key social network members (SNMs), participant perceptions of these network members' opinions toward sexual health behaviors, and associations between network member characteristics and condomless anal intercourse (CAI).MethodsIn a 2017 cross-sectional study, a convenience sample of 565 MSM and trans women with HIV-negative or unknown serostatus was asked to identify three close SNMs; describe discussions about HIV and STI prevention with each; and report perceived opinions of condom use, HIV/STI testing, and partner notification of STIs. Generalized estimating equations evaluated relationships between SNM characteristics, opinions, and discussions and participant-reported CAI.ResultsAmong participants who identified as MSM, 42.3% of key SNMs were perceived to identify as gay. MSM "never" discussed HIV and STI prevention concerns with 42.4% of heterosexual SNMs, but discussed them "at least once weekly" with 16.9 and 16.6% of gay- and bisexual- identifying SNMs, respectively. Among participants who identified as trans women, 28.2% of key SNMs were perceived as heterosexual; 25.9%, as bisexual; 24.7%, as transgender; and 21.2%, as gay. Trans women discussed HIV/STI prevention least with cis-gender heterosexual network members (40.2% "never") and most with transgender network members (27.1% "at least once weekly"). Participants perceived most of their close social network to be completely in favor of condom use (71.2% MSM SNMs, 61.5% trans women SNMs) and HIV/STI testing (73.1% MSM SNMs, 75.6% trans women SNMs), but described less support for partner STI notification (33.4% MSM SNMs, 37.4% trans women SNMs). Most participants reported CAI with at least one of their past three sexual partners (77.5% MSM, 62.8% trans women). SNM characteristics were not significantly associated with participant-reported frequency of CAI.ConclusionsFindings compare social support, perceived social norms, and discussion patterns of Peruvian MSM and trans women, offering insight into social contexts and sexual behaviors.Trial registrationThe parent study from which this analysis was derived was registered at ClinicalTrials.gov (Identifier: NCT03010020 ) on January 4, 2017.

Sexual communication with partners informs risk assessment and sexual practices. We evaluated participant, partner, and network factors associated with communication about condom use and HIV serostatus and explored their relationships with condomless anal intercourse (CAI) among 446 men who have sex with men (MSM) and 122 transgender women (TW) in Lima, Peru. Generalized estimating equations assessed contextual influences on communication and practices with recent sexual partners. More frequent HIV communication was reported by MSM who: identified as heterosexual, compared to bisexual or gay; characterized partnerships as stable, compared to casual, anonymous, or commercial; or discussed HIV/STIs with close social contacts (p

We conducted a pilot randomized controlled trial of a social network-based intervention to promote PrEP adherence among transgender women (TW) in Lima, Peru. We enrolled 89 TW from six social networks and cluster-randomized them 1:1 to standard of care (n = 44) or the TransPrEP intervention (n = 45). Core workshops discussed strategies to support PrEP adherence and defined group adherence objectives. Maintenance workshops discussed participants' experiences taking PrEP and collective adherence goals. At 3-month follow-up, we evaluated 40 participants and obtained 29 hair samples for tenofovir level measurements. Though no significant differences were observed, 36.4% (4/11) of participants of TransPrEP participants and 10.0% (1/10) of control participants had tenofovir levels > 0.023 ng/mg, consistent with ≥ 4 doses per week. 81.8% (9/11) of intervention and 40.0% (4/10) of control participants had any detectable tenofovir in their hair. Pilot assessment of our network-based intervention suggested a trend towards improved PrEP adherence, measured objectively, for TW in Peru.

To improve understanding of factors associated with intimate partner violence (IPV) and explore its role in sexually transmitted infection (STI) acquisition, we analyzed partnership-level correlates of IPV among men who have sex with men (MSM) and transgender women (TW) in Peru. In a 2017 cross-sectional study of rectal STI screening and HIV prevention, MSM/TW completed a sociobehavioral survey addressing demographic characteristics, sexual risk behaviors, and substance use, and were tested for rectal gonorrhea and chlamydia, syphilis, and HIV. Generalized estimating equations estimated individual- and partner-level correlates of IPV. Of 576 participants (median age, 27 years), 7.9% (36/456) of MSM and 15.0% (18/120) of TW reported IPV with ≥ 1 of their last three partners. MSM/TW reporting IPV were more likely to meet criteria for an alcohol use disorder (74.1%) than participants reporting no IPV (56.7%; p

Limited data exists on intimate partner violence (IPV) among transgender women (TW), though global trends suggest IPV is associated with HIV risk in this population. We describe the prevalence of verbal, physical, and/or sexual violence as well as participant- and partner-level correlates of IPV among TW in Lima, Peru. Among 389 respondents, 15.2% reported IPV with one or more of their last three sexual partners: 9.2% verbal, 8.2% physical, and 2.3% sexual violence. Physical and verbal violence were more common with stable partners (aPR 3.46, 95% CI 1.17-10.25, aPR 2.46, 95% CI 1.14-5.28, respectively). Physical violence was associated with condomless receptive anal intercourse (cRAI) (aPR 2.22, 95% CI 1.19-4.13) and partner alcohol use (aPR 4.38, 95% CI 1.56-12.33) while verbal violence correlated with participant inebriation (aPR 4.86, 95% CI 1.63-14.46). Our results link IPV with stable partnerships, alcohol use, and cRAI, suggesting TW in Peru may benefit from multidimensional IPV prevention strategies to foster supportive relationships and reduce HIV transmission.

BackgroundStigma differentially influences HIV and STI care among MSM, especially regarding partner notification practices. Recognizing the heterogeneous behaviors/identities within the category "MSM," we used mixed-methods to assess sexual risk behaviors among men who have sex with men only (MSMO) and behaviorally bisexual MSM (MSMW) with HIV and/or other STIs.MethodsMSMO/MSMW recently diagnosed (

ObjectiveWhile men who have sex with men (MSM) are disproportionately affected by Peru's overlapping HIV and STI epidemics, there are few data on how partnership-level and network-level factors affect STI transmission in Peru. We explored partnership-level and network-level factors associated with gonorrhoea/chlamydia (Neisseria gonorrhoeae and/or Chlamydia trachomatis (NG/CT)) and/or syphilis infection among MSM in Peru.MethodsWe present the results of a cross-sectional secondary analysis of MSM (n=898) tested for syphilis and NG/CT infection as part of the screening process for two STI control trials in Lima, Peru. Participants completed questionnaires on demographics, sexual identity and role, characteristics of their three most recent sexual partners (partner sexual orientation, gender, role, partnership type, partner-specific sexual acts) and 30-day sexual network characteristics (number of sexual partners, partnership types, frequency of anal/vaginal intercourse). Participants were tested for syphilis and urethral, rectal and oropharyngeal NG/CT. Differences in network characteristics were analysed with χ2 and Kruskal-Wallis tests.ResultsApproximately 38.9% of participants had a new STI diagnosis (syphilis (rapid plasma reagin ≥16): 10.6%; NG/CT: 22.9%; syphilis-NG/CT coinfection: 5.4%). Condomless anal intercourse (CAI) was not significantly associated with an STI diagnosis. Gay-identified participants with exclusively homosexual networks had a higher prevalence of STIs (47.4%) than gay-identified MSM with only heterosexual/bisexual partners (34.6%, p=0.04), despite reporting fewer sexual partners (any partners: 2, 1-4 vs 3, 2-6; p=0.001; casual partners: 1, 0-3 vs 2, 1-4; p=0.001) and more stable partnerships (1, 0-1 vs 0, 0-1; p=0.003) in the last month.ConclusionsNetwork size and the number of casual sexual partners were associated with NG/CT infection among MSM in Peru. Despite reporting fewer sexual risk behaviours (smaller network size, more stable partnerships, less CAI), MSM with homosexual-only sexual networks had a higher prevalence of NG/CT and syphilis. These findings suggest network composition among MSM in Peru plays an important role in the risk for STI acquisition.

BackgroundHIV pretreatment drug resistance (PDR) to NNRTIs in persons initiating ART is increasing in Mexico.ObjectivesTo compare HIV PDR in eight sub-regions of Mexico.Patients and methodsA large PDR survey was implemented in Mexico (September 2017-March 2018) across eight sub-regions. All larger clinics (which provide ART to 90% of all initiators) were included, allocating sample size using the probability-proportional-to-size method. Both antiretroviral-naive and prior antiretroviral-exposed persons were included. HIV PDR levels were estimated from pol Sanger sequences obtained at a WHO-designated laboratory.ResultsA total of 2006 participants were enrolled from 74 clinics. PDR to NNRTIs was higher than to other drug classes (P

Laparoscopic surgery is safe in pregnancy, but is not without risk. Inadvertent uterine perforation of the gravid uterus is a rare complication. Three pregnant women had inadvertent uterine perforation during laparoscopic surgery. All patients were counseled regarding the risks of an "incidental fetoscopy" and elected to continue the pregnancy. Two delivered after preterm premature rupture of membranes at 32 and 36 weeks' gestation, and one twin pregnancy delivered at 30 weeks due to preeclampsia. Surgical planning of the gravid patient undergoing laparoscopic surgery should include demarcation of the most superior aspect of the uterine fundus, either via physical examination or, if not conclusive, via preoperative or intraoperative ultrasound.

HIV and other sexually transmitted infections (STIs) continue to affect men who have sex with men (MSM) and transgender women (TW) in Peru at disproportionately high rates. The ineffectiveness of traditional prevention strategies may be due to the disconnect between health promotion messages and community-level understandings of sexual cultures. We conducted 15 workshops with MSM and TW to develop a community-based sexual health intervention. Intervention development consisted of focus groups and scenic improvisation to identify sexual scripts for an HIV prevention telenovela, or Spanish soap opera. Workshops were stratified by self-reported socioeconomic status, sexual orientation, and gender identity: (1) low-income MSM (n = 9); (2) middle/high-income MSM (n = 6); and (3) TW (n = 8). Employing a conceptual model based on sexual scripts and critical consciousness theories, this paper reports on three themes identified during the telenovela-development process as participants sought to "rescript" social and sexual stereotypes associated with HIV-related vulnerability: (1) management of MSM and TW social identities at the intersection of socioeconomic status, sexuality, and gender performance; (2) social constructions of gender and/or sexual role and perceived and actual HIV/STI risk(s) within sexual partnership interactions; and (3) idealized and actual sexual scripts in the negotiation of safer sex practices between MSM/TW and their partners. These findings are key to reframing existing prevention strategies that fail to effectively engage poorly defined "high-risk populations." Leveraging community-based expertise, the results provide an alternative to the static transfer of information through expert-patient interactions in didactic sessions commonly used in HIV prevention interventions among MSM and TW.

The Lulun Project incorporated a social marketing strategy that accompanied a randomized controlled trial (RCT) of a food-based intervention that introduced eggs into the complementary feeding diet of Ecuadorian infants. This strategy was designed to promote behaviour change, in this case, egg consumption, through voluntary prosocial behaviour, empowerment, and brand loyalty. A three-phase social marketing strategy (design, campaigns, and evaluation) contributed to our successful RTC by applying techniques drawn from marketing, publicity, design, and communications. To develop the strategy, we conducted (a) market research focused on culturally based norms, values, and local expectations; (b) a situational assessment based on the four Ps of social marketing (people, product, place, and price); and (c) fostered a creative process to develop the project's brand and communication plan. The strategy combined a communication plan, brand, and activities that were implemented in four campaigns: outreach, recruitment, promotion, and closing. Our evaluation showed that the social marketing strategy was instrumental in promoting the RCT's objectives and responding to unforeseen events and community concerns regarding the RCT. The strategy resulted in high compliance, low attrition, and infant feeding policy change, including Ecuador's Ministry of Public Health new complementary feeding guidelines for introducing eggs early in complementary feeding. Use of social marketing techniques, like those in our study, could be key for scaling up this food-based intervention-or others like it-in Ecuador and beyond.

BackgroundImmunodysregulation polyendocrinopathy enteropathy x-linked (IPEX) syndrome is a monogenic autoimmune disease caused by FOXP3 mutations. Because it is a rare disease, the natural history and response to treatments, including allogeneic hematopoietic stem cell transplantation (HSCT) and immunosuppression (IS), have not been thoroughly examined.ObjectiveThis analysis sought to evaluate disease onset, progression, and long-term outcome of the 2 main treatments in long-term IPEX survivors.MethodsClinical histories of 96 patients with a genetically proven IPEX syndrome were collected from 38 institutions worldwide and retrospectively analyzed. To investigate possible factors suitable to predict the outcome, an organ involvement (OI) scoring system was developed.ResultsWe confirm neonatal onset with enteropathy, type 1 diabetes, and eczema. In addition, we found less common manifestations in delayed onset patients or during disease evolution. There is no correlation between the site of mutation and the disease course or outcome, and the same genotype can present with variable phenotypes. HSCT patients (n = 58) had a median follow-up of 2.7 years (range, 1 week-15 years). Patients receiving chronic IS (n = 34) had a median follow-up of 4 years (range, 2 months-25 years). The overall survival after HSCT was 73.2% (95% CI, 59.4-83.0) and after IS was 65.1% (95% CI, 62.8-95.8). The pretreatment OI score was the only significant predictor of overall survival after transplant (P = .035) but not under IS.ConclusionsPatients receiving chronic IS were hampered by disease recurrence or complications, impacting long-term disease-free survival. When performed in patients with a low OI score, HSCT resulted in disease resolution with better quality of life, independent of age, donor source, or conditioning regimen.

Transgender women (TW) represent a vulnerable population at increased risk for HIV infection in Peru. A mixed-methods study with 48 TW and 19 healthcare professionals was conducted between January and February 2015 to explore barriers and facilitators to implementing a model of care that integrates HIV services with gender-affirmative medical care (i.e., hormone therapy) in Lima, Peru. Perceived acceptability of the integrated care model was high among TW and healthcare professionals alike. Barriers included stigma, lack of provider training or Peruvian guidelines regarding optimal TW care, and service delivery obstacles (e.g., legal documents, spatial placement of clinics, hours of operation). The hiring of TW staff was identified as a key facilitator for engagement in health care. Working in partnership with local TW and healthcare provider organizations is critical to overcoming existing barriers to successful implementation of an integrated HIV services and gender-affirmative medical care model for this key population in Peru.

BackgroundThe CXCR4-CXCL12 axis plays an important role in the chronic lymphocytic leukemia (CLL)-microenvironment interaction. Overexpression of CXCR4 has been reported in different hematological malignancies including CLL. Binding of the pro-survival chemokine CXCL12 with its cognate receptor CXCR4 induces cell migration. CXCL12/CXCR4 signaling axis promotes cell survival and proliferation and may contribute to the tropism of leukemia cells towards lymphoid tissues and bone marrow. Therefore, we hypothesized that targeting CXCR4 with an IgG1 antibody, PF-06747143, may constitute an effective therapeutic approach for CLL.MethodsPatient-derived primary CLL-B cells were assessed for cytotoxicity in an in vitro model of CLL microenvironment. PF-06747143 was analyzed for cell death induction and for its potential to interfere with the chemokine CXCL12-induced mechanisms, including migration and F-actin polymerization. PF-06747143 in vivo efficacy was determined in a CLL murine xenograft tumor model.ResultsPF-06747143, a novel-humanized IgG1 CXCR4 antagonist antibody, induced cell death of patient-derived primary CLL-B cells, in presence or absence of stromal cells. Moreover, cell death induction by the antibody was independent of CLL high-risk prognostic markers. The cell death mechanism was dependent on CXCR4 expression, required antibody bivalency, involved reactive oxygen species production, and did not require caspase activation, all characteristics reminiscent of programmed cell death (PCD). PF-06747143 also induced potent B-CLL cytotoxicity via Fc-driven antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity activity (CDC). PF-06747143 had significant combinatorial effect with standard of care (SOC) agents in B-CLL treatment, including rituximab, fludarabine (F-ara-A), ibrutinib, and bendamustine. In a CLL xenograft model, PF-06747143 decreased tumor burden and improved survival as a monotherapy, and in combination with bendamustine.ConclusionsWe show evidence that PF-06747143 has biological activity in CLL primary cells, supporting a rationale for evaluation of PF-06747143 for the treatment of CLL patients.

IntroductionIn Peru, transgender women (TW) experience unique vulnerabilities for HIV infection due to factors that limit access to, and quality of, HIV prevention, treatment and care services. Yet, despite recent advances in understanding factors associated with HIV vulnerability among TW globally, limited scholarship has examined how Peruvian TW cope with this reality and how existing community-level resilience strategies are enacted despite pervasive social and economic exclusion facing the community. Addressing this need, our study applies the understanding of social capital as a social determinant of health and examines its relationship to HIV vulnerabilities to TW in Peru.MethodsUsing qualitative methodology to provide an in-depth portrait, we assessed (1) intersections between social marginalization, social capital and HIV vulnerabilities; and (2) community-level resilience strategies employed by TW to buffer against social marginalization and to link to needed HIV-related services in Peru. Between January and February 2015, 48 TW participated (mean age = 29, range = 18-44) in this study that included focus group discussions and demographic surveys. Analyses were guided by an immersion crystallization approach and all coding was conducted using Dedoose Version 6.1.18.ResultsThemes associated with HIV vulnerability included experiences of multilevel stigma and limited occupational opportunities that placed TW at risk for, and limited their engagement with, existing HIV services. Emergent resiliency-based strategies included peer-to-peer and intergenerational knowledge sharing, supportive clinical services (e.g. group-based clinic attendance) and emotional support through social cohesion (i.e. feeling part of a community).ConclusionThis study highlights the importance of TW communities as support structures that create and deploy social resiliency-based strategies aimed at deterring and mitigating the impact of social vulnerabilities to discrimination, marginalization and HIV risk for individual TW in Peru. Public health strategies seeking to provide HIV prevention, treatment and care for this population will benefit from recognizing existing social capital within TW communities and incorporating its strengths within HIV prevention interventions. At the intersection of HIV vulnerabilities and collective agency, dimensions of bridging and bonding social capital emerged as resiliency strategies used by TW to access needed healthcare services in Peru. Fostering TW solidarity and peer support are key components to ensure acceptability and sustainability of HIV prevention and promotion efforts.

Risk perception and health behaviors result from individual-level factors influenced by specific partnership contexts. We explored individual- and partner-level factors associated with partner-specific perceptions of HIV/STI risk among 372 HIV/STI-positive MSM and transgender women (TW) in Lima, Peru. Generalized estimating equations explored participants' perception of their three most recent partner(s) as a likely source of their HIV/STI diagnosis. Homosexual/gay (PR = 2.07; 95 % CI 1.19-3.61) or transgender (PR = 2.84; 95 % CI 1.48-5.44) partners were more likely to be considered a source of infection than heterosexual partners. Compared to heterosexual respondents, gay and TW respondents were less likely to associate their partner with HIV/STI infection, suggesting a cultural link between gay or TW identity and perceived HIV/STI risk. Our findings demonstrate a need for health promotion messages tailored to high-risk MSM partnerships addressing how perceived HIV/STI risk aligns or conflicts with actual transmission risks in sexual partnerships and networks.

IntroductionWe sought to determine the relationship between the degree of stomach herniation by antenatal sonography and neonatal outcomes in fetuses with isolated left-sided congenital diaphragmatic hernia (CDH).Materials and methodsWe retrospectively reviewed neonatal medical records and antenatal sonography of fetuses with isolated left CDH cared for at a single institution (2000-2012). Fetal stomach position was classified on sonography as follows: intra-abdominal, anterior left chest, mid-to-posterior left chest, or retrocardiac (right chest).ResultsNinety fetuses were included with 70% surviving to neonatal discharge. Stomach position was intra-abdominal in 14% (n = 13), anterior left chest in 19% (n = 17), mid-to-posterior left chest in 41% (n = 37), and retrocardiac in 26% (n = 23). Increasingly abnormal stomach position was linearly associated with an increased odds of death (OR 4.8, 95% CI 2.1-10.9), extracorporeal membrane oxygenation (ECMO; OR 5.6, 95% CI 1.9-16.7), nonprimary diaphragmatic repair (OR 2.7, 95% CI 1.4-5.5), prolonged mechanical ventilation (OR 5.9, 95% CI 2.3-15.6), and prolonged respiratory support (OR 4.0, 95% CI 1.6-9.9). All fetuses with intra-abdominal stomach position survived without substantial respiratory morbidity or need for ECMO.DiscussionFetal stomach position is strongly associated with neonatal outcomes in isolated left CDH. This objective tool may allow for accurate prognostication in a variety of clinical settings.

BackgroundNew strategies to support partner notification (PN) are critical for STD control and require detailed understanding of how specific individual and partnership characteristics guide notification decisions.MethodsFrom 2011 to 2012, 397 MSM and TW recently diagnosed with HIV, syphilis, or another STD completed a survey on anticipated notification of recent sexual partners and associated factors. Qualitative interviews were conducted with a subset of participants to provide further depth to quantitative findings. Prevalence ratios and generalized estimating equation (GEE) models were used to analyze participant- and partner-level factors associated with anticipated PN.ResultsAmong all partners reported, 52.5% were described as "Very Likely" or "Somewhat Likely" to be notified. Anticipated notification was more likely for main partners than casual (adjusted Prevalence Ratio [aPR], 95% CI: 0.63, 0.54-0.75) or commercial (aPR, 95% CI: 0.44, 0.31-0.62) partners. Other factors associated with likely notification included perception of the partner as an STD source (aPR, 95% CI: 1.27, 1.10-1.48) and anticipated future sexual contact with the partner (aPR, 95% CI: 1.30, 1.11-1.52). An HIV diagnosis was associated with a lower likelihood of notification than non-HIV STDs (aPR: 0.68, 0.55-0.86). Qualitative discussion of the barriers and incentives to PN reflected a similar differentiation of anticipated notification according to partnership type and type of HIV/STD diagnosis.DiscussionDetailed attention to how partnership characteristics guide notification outcomes is essential to the development of new PN strategies. By accurately and thoroughly assessing the diversity of partnership interactions among individuals with HIV/STD, new notification techniques can be tailored to partner-specific circumstances.

Previous analyses of partner notification (PN) have addressed individual, interpersonal, social, and structural issues influencing PN outcomes but have paid less attention to the conceptual framework of PN itself. We conducted 18 individual interviews and 8 group discussions, in a two-stage qualitative research process, to explore the meanings and contexts of PN for sexually transmitted infections (STI) among men who have sex with men (MSM) and men who have sex with men and women (MSMW) in Lima, Peru. Participants described PN as the open disclosure of private, potentially stigmatizing information that could strengthen or disrupt a partnership, structured by the tension between concealment and revelation. In addition to informing partners of an STI diagnosis, the act of PN was believed to reveal other potentially stigmatizing information related to sexual identity and practices such as homosexuality, promiscuity, and HIV co-infection. In this context, the potential development of visible, biological STI symptoms represented a risk for disruption of the boundary between secrecy and disclosure that could result in involuntary disclosure of STI status. To address the conflict between concealment and disclosure, participants cited efforts to "manejar la situacion" (manage the situation) by controlling the biological risks of STI exposure without openly disclosing STI status. We use this concept of "managing the situation" as a practical and theoretical framework for comprehensive Partner Management for HIV/STI control systems among MSM in Latin America.

ObjectiveCongenital diaphragmatic hernia (CDH) results in morbidity and death from lung hypoplasia and persistent pulmonary hypertension (PH). We sought to define the relationship between fetal ultrasound markers of severity in CDH and the time to resolution of neonatal PH.Study designWe conducted a retrospective study of fetuses with an antenatal ultrasound scan and left-sided CDH cared for at the University of California San Francisco (2002-2012). Fetal liver position was classified on ultrasound scan as abdominal (entire liver within the abdomen) or thoracic (any portion of the liver within the thorax). Fetal stomach position was classified from least to most aberrant: abdominal, anterior left chest, mid-posterior left chest, or retrocardiac (right chest). Lung-to-head ratio (LHR) was determined from available scans at 20-29 weeks of gestational age (GA). Routine neonatal echocardiograms were performed weekly for up to 6 weeks or until PH resolved or until discharge. PH was assessed by echocardiogram with the use of a hierarchy of ductus arteriosus level shunt, interventricular septal position, and tricuspid regurgitant jet velocity. Days to PH-free survival was defined as the age at which pulmonary artery pressure was estimated to be

Pyramidal neurons in layers 2/3 and 5 of primary somatosensory cortex (S1) exhibit somewhat modest synaptic plasticity after whisker input deprivation. Whether neurons involved at earlier steps of sensory processing show more or less plasticity has not yet been examined. Here, we used longitudinal in vivo two-photon microscopy to investigate dendritic spine dynamics in apical tufts of GFP-expressing layer 4 (L4) pyramidal neurons of the vibrissal (barrel) S1 after unilateral whisker trimming. First, we characterize the molecular, anatomical, and electrophysiological properties of identified L4 neurons in Ebf2-Cre transgenic mice. Next, we show that input deprivation results in a substantial (∼50%) increase in the rate of dendritic spine loss, acutely (4-8 d) after whisker trimming. This robust synaptic plasticity in L4 suggests that primary thalamic recipient pyramidal neurons in S1 may be particularly sensitive to changes in sensory experience. Ebf2-Cre mice thus provide a useful tool for future assessment of initial steps of sensory processing in S1.

BackgroundPartnership type is an important factor associated with unprotected anal intercourse (UAI) and subsequent risk for HIV and sexually transmitted infections (STI). We examined the association of partnership type with UAI among men who have sex with men (MSM) and male-to-female transgender women (TGW) in Lima, Peru, recently diagnosed with HIV and/or STI.MethodsWe report data from a cross-sectional analysis of MSM and TGW recently diagnosed with HIV and/or STI in Lima, Peru between 2011 and 2012. We surveyed participants regarding UAI with up to their three most recent sexual partners according to partner type. Multivariable Generalized Estimate Equating (GEE) models with Poisson distribution were used to estimate prevalence ratios (PR) for UAI according to partner type.ResultsAmong 339 MSM and TGW recently diagnosed with HIV and/or STI (mean age: 30.6 years, SD 9.0), 65.5% self-identified as homosexual/gay, 16.0% as bisexual, 15.2% as male-to-female transgender, and 3.3% as heterosexual. Participants provided information on 893 recent male or TGW partners with whom they had engaged in insertive or receptive anal intercourse: 28.9% stable partners, 56.4% non-stable/non-transactional partners (i.e. casual or anonymous), and 14.7% transactional partners (i.e. transactional sex client or sex worker). Unprotected anal intercourse was reported with 41.3% of all partners. In multivariable analysis, factors associated with UAI included partnership type (non-stable/non-transactional partner APR 0.73, [95% CI 0.59-0.91], transactional partner APR 0.53 [0.36-0.78], p10 encounters APR 1.43 [1.06-1.92], p10 sexual encounters, suggesting UAI is more prevalent in partnerships with a greater degree of interpersonal commitment. Further research assessing partner-level factors and behavior is critical for improving HIV and/or STI prevention efforts among Peruvian MSM and TGW.

We assessed the potential impact of Internet partner notification among men who have sex with men and transgender women in Peru recently diagnosed as having sexually transmitted disease. Use of Internet partner notification was anticipated for 55.9% of recent partners, including 43.0% of partners not currently expected to be notified, a 20.6% increase in anticipated notification outcomes.

BackgroundFurther research is necessary to understand the factors contributing to the high prevalence of HIV/STIs among men who have sex with men (MSM) in Peru. We compared HIV/STI prevalence and risk factors between two non-probability samples of MSM, one passively enrolled from an STI clinic and the other actively enrolled from community venues surrounding the clinic in Lima, Peru.MethodsA total of 560 self-identified MSM were enrolled between May-December, 2007. 438 subjects enrolled from a municipal STI clinic and 122 subjects enrolled during community outreach visits. All participants underwent screening for HIV, syphilis, HSV-2, gonorrhoea, and chlamydia and completed a survey assessing their history of HIV/STIs, prior HIV testing, and sexual behavior.ResultsHIV prevalence was significantly higher among MSM enrolled from the clinic, with previously undiagnosed HIV identified in 9.1% compared with 2.6% of community participants. 15.4 % of all MSM screened were infected with ≥ 1 curable STI, 7.4% with early syphilis (RPR ≥ 1:16) and 5.5% with urethral gonorrhoea and/or chlamydia. No significant differences between populations were reported in prevalence of STIs, number of male sex partners, history of unprotected anal intercourse, or alcohol and/or drug use prior to sex. Exchange of sex for money or goods was reported by 33.5% of MSM enrolled from the clinic and 21.2% of MSM from the community (p = 0.01).ConclusionsOur data demonstrate that the prevalence of HIV and STIs, including syphilis, gonorrhoea, and chlamydia are extremely high among MSM enrolled from both clinic and community venues in urban Peru. New strategies are needed to address differences in HIV/STI epidemiology between clinic- and community-enrolled samples of MSM.