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Abstract Background Metabolic dysfunction associated steatotic liver disease (MASLD) is associated with increased cardiovascular disease (CVD) risk in persons with HIV (PWH). The lipidomic and metabolomic alterations contributing to this risk are poorly understood. We aimed to characterize the advanced lipoprotein and targeted metabolomic profiles in PWH and assess if the presence and severity of MASLD influence these profiles. Methods This is a cross-sectional analysis of a prospectively enrolled multicenter cohort. PWH without alcohol abuse or known liver disease underwent vibration-controlled transient elastography for controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Lipidomic and metabolomic profiling was undertaken with nuclear magnetic resonance (NMR) spectroscopy. Hepatic steatosis was defined as CAP ≥ 263 dB/m and clinically significant fibrosis (CSF) as LSM ≥ 8 kPa. Logistic regression models assessed associations between MASLD, CSF and lipidomic and metabolic parameters. Results Of 190 participants (71% cisgender male, 96% on antiretroviral therapy), 58% had MASLD and 12% CSF. Mean (SD) age was 48.9 (12.1) years and body mass index (BMI) 29.9 (6.4) kg/m2. Compared to PWH without MASLD (controls), PWH with MASLD had lower HDL-C but higher total triglyceride, VLDL-C, branched-chain amino acids, GlycA, trimethylamine N-oxide levels, Lipoprotein-Insulin Resistance and Diabetes Risk Indices. There were no significant differences in these parameters between participants with MASLD with or without CSF. In a multivariable regression analysis, MASLD was independently associated with changes in most of these parameters after adjustment for age, gender, race/ethnicity, type 2 diabetes mellitus, BMI, and lipid lowering medications use. Conclusions MASLD in PWH is independently associated with altered advanced lipoprotein and targeted metabolic profiles, indicating a higher CVD risk in this population.

Abstract Background HIV burden in the US among people who inject drugs (PWID) is driven by overlapping syndemic factors such as co-occurring health needs and environmental factors that synergize to produce worse health outcomes among PWID. This includes stigma, poverty, and limited healthcare access (e.g. medication to treat/prevent HIV and for opioid use disorder [MOUD]). Health services to address these complex needs, when they exist, are rarely located in proximity to each other or to the PWID who need them. Given the shifting drug use landscapes and geographic heterogeneity in the US, we evaluate a data-driven approach to guide the delivery of such services to PWID in local communities. Methods We used a hybrid, type I, embedded, mixed method, data-driven approach to identify and characterize viable implementation neighborhoods for the HPTN 094 complex intervention, delivering integrated MOUD and HIV treatment/prevention through a mobile unit to PWID across five US cities. Applying the PRISM framework, we triangulated geographic and observational pre-implementation phase data (epidemiological overdose and HIV surveillance data) with two years of implementation phase data (weekly ecological assessments, study protocol meetings) to characterize environmental factors that affected the viability of implementation neighborhoods over time and across diverse settings. Results Neighborhood-level drug use and geographic diversity alongside shifting socio-political factors (policing, surveillance, gentrification) differentially affected the utility of epidemiological data in identifying viable implementation neighborhoods across sites. In sites where PWID are more geographically dispersed, proximity to structural factors such as public transportation and spaces where PWID reside played a role in determining suitable implementation sites. The utility of leveraging additional data from local overdose and housing response systems to identify viable implementation neighborhoods was mixed. Conclusions Our findings suggest that data-driven approaches provide a contextually relevant pragmatic strategy to guide the real-time implementation of integrated care models to better meet the needs of PWID and help inform the scale-up of such complex interventions. This work highlights the utility of implementation science methods that attend to the impact of local community environmental factors on the implementation of complex interventions to PWID across diverse drug use, sociopolitical, and geographic landscapes in the US. Trial registration ClincalTrials.gov, Registration Number: NCT04804072 . Registered 18 February 2021.

Abstract Background Persons with opioid use disorders who inject drugs (PWID) in the United States (US) face multiple and intertwining health risks. These include interference with consistent access, linkage, and retention to health care including medication for opioid use disorder (MOUD), HIV prevention using pre-exposure prophylaxis (PrEP), and testing and treatment for sexually transmitted infections (STIs). Most services, when available, including those that address substance misuse, HIV prevention, and STIs, are often provided in multiple locations that may be difficult to access, which further challenges sustained health for PWID. HPTN 094 (INTEGRA) is a study designed to test the efficacy of an integrated, “whole-person” strategy that provides integrated HIV prevention including antiretroviral therapy (ART), PrEP, MOUD, and STI testing and treatment from a mobile health delivery unit (“mobile unit”) with peer navigation compared to peer navigation alone to access these services at brick and mortar locations. Methods HPTN 094 (INTEGRA) is a two-arm, randomized controlled trial in 5 US cities where approximately 400 PWID without HIV are assigned either to an experimental condition that delivers 26 weeks of “one-stop” integrated health services combined with peer navigation and delivered in a mobile unit or to an active control condition using peer navigation only for 26 weeks to the same set of services delivered in community settings. The primary outcomes include being alive and retained in MOUD and PrEP at 26 weeks post-randomization. Secondary outcomes measure the durability of intervention effects at 52 weeks following randomization. Discussion This trial responds to a need for evidence on using a “whole-person” strategy for delivering integrated HIV prevention and substance use treatment, while testing the use of a mobile unit that meets out-of-treatment PWID wherever they might be and links them to care systems and/or harm reduction services. Findings will be important in guiding policy for engaging PWID in HIV prevention or care, substance use treatment, and STI testing and treatment by addressing the intertwined epidemics of addiction and HIV among those who have many physical and geographic barriers to access care. Trial registration ClinicalTrials.gov NCT04804072 . Registered on 18 March 2021.

Abstract Introduction Social 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. Methods We 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. Results Of 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. Conclusion TW 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.

Summary: Background: Despite high rates of HIV transmission among men who have sex with men (MSM) in Lima, Peru, limited data exist on the sexual network characteristics or risk factors for secondary HIV transmission among MSM with uncontrolled HIV infection. We report the frequency of serodiscordant, condomless anal intercourse (CAI) and associated sexual network characteristics among MSM in Lima with detectable HIV viremia and compare to those with undetectable viremia. Methods: This cross-sectional analysis includes MSM who tested positive for HIV-1 during screening for a trial of partner management and STI control (June 2022–January 2023). Participants were tested for HIV, gonorrhoea, chlamydia, and syphilis, and completed questionnaires on their demographic characteristics, sexual identity and behaviour, sexual network structures and engagement in HIV care. Findings: Of 665 MSM, 153 (23%) had detectable (>200 copies/mL) viremia. 75% (499/662) of men living with HIV were previously diagnosed, with 94% (n = 469/499) reporting that they were on ART, and 93% (n = 436/469) virally suppressed. 96% (n = 147/153) of men with detectable viremia reported serodiscordant CAI with at least one of their last three sexual partners, and 74% (n = 106/144) reported the same with all three of their recent partners. In contrast, 62% (n = 302/489) of men with undetectable viral load reported serodiscordant CAI with all of their last three partners (p

Background: Integrase inhibitor (INSTI) use has been associated with greater weight gain (WG) among people living with HIV (PLWH), but it is unclear how this effect compares in magnitude to traditional risk factors for WG. We assessed the population attributable fractions (PAFs) of modifiable lifestyle factors and INSTI regimens in PLWH who experienced a ≥5% WG over follow-up. Methods: In an observational cohort study from 2007 to 2019 at Modena HIV Metabolic Clinic, Italy, ART-experienced but INSTI-naive PLWH were grouped as INSTI-switchers vs non-INSTI. Groups were matched for sex, age, baseline BMI and follow-up duration. Significant WG was defined as an increase of ≥5% from 1st visit weight over follow-up. PAFs and 95% CIs were estimated to quantify the proportion of the outcome that could be avoided if the risk factors were not present. Results: 118 PLWH switched to INSTI and 163 remained on current ART. Of 281 PLWH (74.3% males), mean follow-up was 4.2 years, age 50.3 years, median time since HIV diagnosis 17.8 years, CD4 cell count 630 cells/µL at baseline. PAF for weight gain was the greatest for high BMI (45%, 95% CI: 27–59, p

Long COVID (LongC) is associated with a myriad of symptoms including cognitive impairment. We reported at the beginning of the COVID-19 pandemic that neuronal-enriched or L1CAM+ extracellular vesicles (nEVs) from people with LongC contained proteins associated with Alzheimer’s disease (AD). Since that time, a subset of people with prior COVID infection continue to report neurological problems more than three months after infection. Blood markers to better characterize LongC are elusive. To further identify neuronal proteins associated with LongC, we maximized the number of nEVs isolated from plasma by developing a hybrid EV Microfluidic Affinity Purification (EV-MAP) technique. We isolated nEVs from people with LongC and neurological complaints, AD, and HIV infection with mild cognitive impairment. Using the OLINK platform that assesses 384 neurological proteins, we identified 11 significant proteins increased in LongC and 2 decreased (BST1, GGT1). Fourteen proteins were increased in AD and forty proteins associated with HIV cognitive impairment were elevated with one decreased (IVD). One common protein (BST1) was decreased in LongC and increased in HIV. Six proteins (MIF, ENO1, MESD, NUDT5, TNFSF14 and FYB1) were expressed in both LongC and AD and no proteins were common to HIV and AD. This study begins to identify differences and similarities in the neuronal response to LongC versus AD and HIV infection.

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.

Syndemic psychosocial and reproductive factors affecting women's retention in HIV care remain understudied. We analyzed correlates of non-retention in a cohort of women with HIV in Brazil from 2000‒2015. Participants self-reported exposure to physical/sexual violence, illicit drug use, adolescent pregnancy, or induced abortion. Lifetime history of these psychosocial stressors were used to create a syndemic score based on the presence or absence of these conditions. All dichotomous variables were summed (range 0 to 4), with greater scores indicating more syndemic factors experienced. Logistic regression models identified predictors of non-retention, defined as < 2 HIV viral load or CD4 results within the first year of enrollment. Of 915 women, non-retention was observed for 18%. Prevalence of syndemic factors was adolescent pregnancy (53.2%), physical/sexual violence (38.3%), induced abortion (27.3%), and illicit drug use (17.2%); 41.2% experienced ≥ 2 syndemic conditions. Syndemic scores of 2 and 3 were associated with non-retention, as well as low education, years with HIV and seroprevalent syphilis. Psychosocial and reproductive syndemics can limit women's retention in HIV care. Syphilis infection predicted non-retention and could be explored as a syndemic factor in future studies.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in persons with HIV (PWH) (HIV-NAFLD). It is unknown if HIV-NAFLD is associated with impairment in health-related quality of life (HRQOL). We examined HRQOL in PWH with and without NAFLD, compared HRQOL in HIV- versus primary NAFLD, and determined factors associated with HRQOL in these groups. Prospectively enrolled 200 PWH and 474 participants with primary NAFLD completed the Rand SF-36 assessment which measures 8 domains of HRQOL. Individual domain scores were used to create composite physical and mental component summary scores. Univariate and multivariate analyses determined variables associated with HRQOL in PWH and in HIV- and primary NAFLD. In PWH, 48% had HIV-NAFLD, 10.2% had clinically significant fibrosis, 99.5% were on antiretroviral therapy, and 96.5% had HIV RNA

Abstract Background Social 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). Methods In 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. Results Among 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. Conclusions Findings compare social support, perceived social norms, and discussion patterns of Peruvian MSM and trans women, offering insight into social contexts and sexual behaviors. Trial registration The parent study from which this analysis was derived was registered at ClinicalTrials.gov (Identifier: NCT03010020 ) on January 4, 2017.

BackgroundTransgender women (TW) are at increased risk for both human immunodeficiency virus (HIV) and cardiovascular disease (CVD). Antiretroviral therapy-treated HIV has been associated with a two-fold increased risk of CVD, potentially due to dysregulated Toll-like receptor (TLR)-induced immune activation. Use of estrogens in feminizing hormone therapy (FHT) may enhance inflammatory responses and the risk of cardiovascular mortality in TW. Despite this, the immunomodulatory effects of estrogen use in TW with HIV have been inadequately explored.MethodsAs an in vitro model for FHT, cryopreserved PBMCs (cryoPBMCs) from HIV negative (HIV-), HIV+ ART-suppressed (HIV+SP), and HIV+ ART-unsuppressed (HIV+USP) cisgender men were cultured overnight in the presence of 17-β estradiol or 17-α ethinylestradiol with and without the TLR4 agonist LPS or the TLR8 agonist ssPolyU. Monocyte activation (CD69, HLA-DR, CD38) was assessed by flow cytometry. Cytokine levels (IL-6, TNF-α, IL-1β, and IL-10) were measured in cell culture supernatants by Legendplex. Levels of phosphorylated TLR signaling molecules (JNK, MAPK p38) were assessed by Phosflow. Plasma levels of immune activation biomarkers (LPS-binding protein, monocyte activation markers sCD14 and sCD163, and inflammatory molecules IL-6 and TNF-α receptor I) were measured by ELISA.ResultsPBMCs from people with HIV (PWH) produced greater levels of inflammatory cytokines following exposure to LPS or ssPolyU compared to levels from cells of HIV- individuals. While estrogen exposure alone induced mild changes in immune activation, LPS-induced TLR4 activation was elevated with estrogen in cisgender men (CM) with HIV, increasing monocyte activation and inflammatory cytokine production (IL-6, TNF-α). Interestingly, testosterone inhibited LPS-induced cytokine production in CM regardless of HIV status. Plasma markers of immune activation and microbial translocation (e.g., sCD14, sCD163, LPS-binding protein) were generally higher in PWH compared to HIV- CM, and these markers were positively associated with in vitro responsiveness to estrogen and LPS in CM with HIV.ConclusionsOur in vitro data suggest that estrogen exposure may enhance innate immune activation in PWH. Further examination is needed to fully understand the complex interactions of FHT, HIV, and CVD in TW, and determine optimal FHT regimens or supplementary treatments aimed at reducing excess immune activation.

Abstract Plasma biomarkers that reflect energy balance disorders in people living with HIV (PLWH) remain limited. Growth differentiation factor 15 (GDF15) abundance in plasma of mice and humans induces negative energy balance but also becomes highly elevated in obesity and other metabolic diseases. We sought to compare plasma GDF15 levels in PLWH and HIV‐negative persons and mouse models expressing the HIV accessory protein Vpr (that recapitulate HIV‐associated metabolic disorders) and determine their relationship to metabolic parameters. We measured liver Gdf15 mRNA levels and plasma GDF15 levels in male Vpr mice and littermate controls. In parallel, we analyzed plasma GDF15 levels in 18 male PLWH on stable, long‐term antiretroviral therapy and 13 HIV‐negative men (6 healthy controls and 7 with metabolic syndrome). Plasma GDF15 levels were correlated with anthropometric and immune cell parameters in humans. Gene expression analysis of Vpr mouse liver demonstrated elevated Gdf15 mRNA. Plasma GDF15 levels were also higher in Vpr mouse models. Levels of plasma GDF15 in PLWH were greater than in both HIV‐negative groups and correlated positively with the CD4/CD8 T cell ratio in PLWH. Plasma GDF15 levels correlated positively with age in the HIV‐negative subjects but not in PLWH. Since GDF15 levels predict fatty liver disease and energy balance disorders, further studies are warranted to determine the effect of GDF15 in mediating the metabolic disturbances that occur in Vpr mice and PLWH.

Abstract Background Dyslipidemia often accompanies human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART). Lipid abnormalities likely contribute to increased cardiometabolic disease among people with HIV (PWH). Here, we expand our previous findings on changes in the lipidome following ART initiation, and associations among lipid species, including ceramides (CER), diacylglycerols (DAG), and triacylglycerols (TAG), with immune activation. Methods Concentrations and fatty acid composition of plasma lipids (~ 1300 species) were measured by differential mobility spectroscopy in samples from 35 treatment-naïve PWH pre- and post-initiation of ART (raltegravir (RAL)/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)); lipidomes were compared to those found in demographically similar HIV-uninfected individuals (n = 13). Results Compared to people without HIV, 37.1% of all lipid species measured were altered in PWH at baseline, and 31.8% of lipid species were altered following 48 weeks of ART. Concentrations of lipid classes were also altered in PWH; diacylglycerols (DAGs) and triacylglycerols (TAGs) were increased at baseline, and DAGs remained increased after 48 weeks of ART. Lipids previously linked to cardiovascular disease (CVD) and diabetes were enriched in PWH pre- and post ART, and were related to immune activation and insulin resistance scores. Polyunsaturated fatty acid (PUFA)-containing lipids were lower in PWH compared to levels in controls, and were inversely related to levels of inflammatory biomarkers. Conclusions HIV infection and ART initiation both induce cardiometabolic changes to the composition of the plasma lipidome. These alterations are associated with inflammatory biomarkers, and may directly contribute to elevated CVD risk and diabetes. Trial registration This study is registered with Clinicaltrials.gov ( NCT00660972 ). Registered April 16, 2008.

Background: Treatment with integrase strand transfer inhibitors (INSTIs) has been associated with excess weight gain, however the long-term effect of INSTI-based regimens on adipose tissue (AT) compartments remains unknown. Objectives: To evaluate the effect of switching to an INSTI on visceral (VAT) and subcutaneous (SAT) AT in virologically-suppressed adults with HIV. Methods: We performed a retrospective observational cohort study of ART experienced adults referred to the metabolic Clinic of the University of Modena and Reggio Emilia who had ≥2 assessments of body composition by abdominal computed tomography. An interrupted time series model with mixed-effect model incorporated was used to calculate VAT and SAT change rate, adjusting for smoking status, use of alcohol, and physical activity. Results: A total of 698 patients were included: 156 who switched to an INSTI-based regimen and 542 who did not. After switch to INSTI, mean SAT area increased approximately 3-fold (before 0.27 vs after 0.73 cm2/month; p = 0.011), and VAT area 7-fold (0.18 vs 1.30 cm2/month; p

Background Antiretroviral therapy (ART) is associated with gain in quantity of fat and muscle, but the impact on quality is less understood. The objective of this study was to compare fat and muscle density among people with HIV (PWH) on stable raltegravir (RAL), atazanavir with ritonavir (ATV/r), or darunavir with ritonavir (DRV/r), and explore implications on muscle function. Methods Participants from the Modena HIV Metabolic Clinic taking RAL, ATV/r, or DRV/r with at least 1 computed tomography (CT) scan were included. CT scans were reanalyzed for area and density of truncal fat and musculature. Multivariate models explored the effect of ART on fat and muscle density. Results One hundred six participants were receiving ATV/r, 48 DRV/r, and 141 RAL. In multivariate models (reference ATV/r), only DRV/r was associated with greater subcutaneous (SAT) and visceral adipose tissue (VAT) area, lower lateralis muscle density (more fat), and greater lateralis intermuscular fat area. Compared to ATV/r, RAL was independently associated with less psoas intermuscular fat area. Among all, greater paraspinal muscle density correlated with better physical function. No associations between ART group and physical function were seen among men; DRV/r was associated with stronger grip strength among women. Conclusion DRV/r was associated with greater fat area and lower density of both fat and muscle, and RAL with less intermuscular psoas fat. Higher density psoas and paraspinal musculature were associated with better physical function, suggesting potential clinical relevance of these findings.

Abstract Background Condomless anal intercourse (CAI) appears to be increasing among men who have sex with men (MSM) globally, and is reported to be as high as 70% in recent studies in Peru. To improve understanding of the evolving context of CAI among MSM in Peru, we studied associations between partner type, substance use, and condomless anal intercourse (CAI) in locations where MSM commonly report having sexual encounters. Methods In a 2017 cross-sectional study of rectal STI screening and HIV prevention, a convenience sample of MSM recruited from community venues in Lima completed a survey of demographic characteristics and sexual risk behavior with their three most recent partners. Generalized estimating equations estimated correlations of CAI with location of last sexual contact, participant substance use prior to sex, and negotiation of condom use before or during sex. The network data integration application, Cytoscape, mapped intersections of partner type, sexual orientation, substance use, and CAI by four types of locations where sex occurred: 1) Home, 2) Hotel, 3) Sauna or Internet Cabin, and 4) Public Spaces. Results Of 447 MSM (median age 27 years), 76.9% reported CAI with ≥1 of their last three partners. Participants reported sex with casual partners most commonly in homes (64.6%) and hotels (60.4%), and with anonymous partners most often in saunas/Internet cabins (57.5%) and public spaces (52.6%). CAI was less commonly reported in hotels (aPR, 95% CI: 0.85, 0.75–0.97) compared to homes. Participants who used marijuana before sex at home were more likely to report CAI than MSM who did not use marijuana (1.36, 1.01–1.92). Partner alcohol use before sex was associated with CAI in saunas/Internet cabins (3.17, 1.45–6.91) and public spaces (2.65, 1.41–4.98). In the sexual network maps, almost all MSM who used drugs prior to their sexual encounters used drugs with more than one of their last three partners. Conclusions CAI was common and associated with different risk factors, like partner type and substance use, based on location where sex occurred. Novel combination HIV, STI, and substance use prevention interventions must consider how the social environments of MSM influence condom use and other sexual risk behaviors. Trial registration ClinicalTrials.gov Identifier NCT03010020, January 4, 2017.

CD36 is a multifunctional scavenger receptor and lipid transporter implicated in metabolic and inflammatory pathologies, as well as cancer progression. CD36 is known to be expressed by adipocytes and monocytes/macrophages, but its expression by T cells is not clearly established. We found that CD4 and CD8 T cells in adipose tissue and liver of humans, monkeys, and mice upregulated CD36 expression (ranging from ~5–40% CD36+), whereas little to no CD36 was expressed by T cells in blood, spleen, and lymph nodes. CD36 was expressed predominantly by resting CD38-, HLA.DR-, and PD-1- adipose tissue T cells in monkeys, and increased during high-fat feeding in mice. Adipose tissue and liver promote a distinct phenotype in resident T cells characterized by CD36 upregulation.

Background: Reduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis. Methods: Six PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors. Shotgun sequencing on stool before, after last FMT, and 20 weeks thereafter was performed. Inflammation and gut permeability biomarkers were measured. Results: Median age at week 0 was 39 years, CD4+ T cell count 496 cells/mm3, HIV RNA levels

Background: Lipid profiles are altered by HIV infection and antiretroviral therapy (ART). Among HIV-uninfected (HIV-) populations the concentrations of various lipid classes (ie, lysophosphatidylcholine, LPC) and their saturated (SaFA), monounsaturated (MUFA), and polyunsaturated fatty acid (PUFA) composition are related to cardiometabolic disease risk. Associations between changes in the lipidome and immune activation in HIV-infected (HIV+) individuals beginning ART have not been described. Methods: Plasma lipid concentrations and their fatty acid composition were measured by differential mobility spectroscopy in samples from 35 treatment-naive HIV+ participants beginning raltegravir (RAL)-based ART and from HIV- individuals (N=13) matched for age and sex. Results: The levels of SaFA, including palmitic (16:0) and stearic (18:0) acid were enriched in HIV+ participants (pre- and post-ART), and SaFA levels were often positively correlated with levels of immune activation (ie, IL-6, sCD14, and TNFR1) at baseline and week 48. Levels of PUFAs (including 18:3, 20:4, and 20:5) were lower in HIV+ participants at baseline compared to levels in HIV- participants (P

Abstract Background Syphilis infection has recently resurfaced as a significant public health problem. Although there has been a tremendous amount of research on the epidemiology of syphilis, there has been limited work done to synthesize the extensive body of research and systematically estimate patterns of disease within high-risk groups in the Americas. The purpose of this systematic review and meta-analysis is to (1) summarize recent patterns of syphilis infection in North and South America among four high-risk groups (MSM, transgender women, sex workers, and incarcerated individuals) from 1980 to 2016, (2) identify and differentiate regional geographic epidemiologic characteristics, and (3) compare the epidemics of the economically developed countries of North America from the developing countries and public health systems of Latin America and the Caribbean. Methods/design Primary studies reporting syphilis prevalence and/or incidence in at least one of the four high-risk groups will be identified from Medline/PubMed, Embase, Lilacs, SciELO, The Cochrane Library, Web of Science, Scopus, ProQuest, CINAHL, Clase, and Periódica, as well as “gray” literature sources (conference abstracts, country reports, etc.). Studies published from 1980 through 2016 will be included. Data will be extracted from studies meeting inclusion and exclusion criteria and a random effects meta-analysis of prevalence and incidence estimates will be conducted. Heterogeneity, risk of bias, and publication bias will be assessed. Pooled prevalence and incidence estimates will be calculated for comparisons based on geographic region, risk factors, and time period. Discussion Our systematic review and meta-analysis aims to contribute to an improved understanding of global epidemiologic patterns of syphilis infection in most-at-risk populations. Through systematic classification of the existing literature, and comparison of disease patterns across regional, temporal and socio-behavioral differences, we hope to improve public health surveillance and improve efforts to control the spread of disease across the Americas. Systematic review registration PROSPERO CRD42016047306.

Background: Incomplete immune reconstitution may occur despite successful antiretroviral therapy (ART). Gut-associated lymphoid tissue (GALT) fibrosis may contribute via local CD4+ T lymphocyte depletion, intestinal barrier disruption, microbial translocation, and immune activation. Methods: In a cross-sectional analysis, we measured circulating fibrosis biomarker levels on cryopreserved plasma from adult HIV-infected (HIV+) SCOPE study participants on suppressive ART who also had fibrosis quantification on recto-sigmoid biopsies. Relationships among biomarker levels, clinical and demographic variables, GALT lymphoid aggregate (LA) collagen deposition, and LA CD4+ T lymphocyte density were analyzed using simple regression. Biomarker levels were also compared to levels in HIV+ viremic SCOPE participants and a convenience sample of HIV-uninfected (HIV-) samples. Results: HIV+ aviremic participants (n=39) were 92% male and 41% non-white, with median age 48 years, CD4+ T lymphocyte count 277 cells/mm3, and 17 years since HIV diagnosis. Most biomarkers were lower in HIV− (n=36) vs HIV+ aviremic individuals, although CXCL4 levels were higher. HIV+ viremic individuals (N=18) had higher median TGF-ß3, CIC-C1Q, and TIMP-1 (P

Background: HIV infection and antiretroviral therapy (ART) have both been linked to dyslipidemia and increased cardiovascular disease (CVD) risk. Alterations in the composition of saturated (SaFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids are related to inflammation and CVD progression in HIV-uninfected (HIV–) populations. The relationships among the lipidome and markers of monocyte and immune activation in HIV-infected (HIV+) individuals are not well understood.Methods: Concentrations of serum lipids and their fatty acid composition were measured by direct infusion-tandem mass spectrometry in samples from 20 ART-treated HIV+ individuals and 20 HIV– individuals.Results: HIV+ individuals had increased levels of free fatty acids (FFAs) with enrichment of SaFAs, including palmitic acid (16:0) and stearic acid (18:0), and these levels were directly associated with markers of monocyte (CD40, HLA-DR, TLR4, CD36) and serum inflammation (LBP, CRP). PUFA levels were reduced significantly in HIV+ individuals, and many individual PUFA species levels were inversely related to markers of monocyte activation, such as tissue factor, TLR4, CD69, and SR-A. Also in HIV+ individuals, the composition of lysophosphatidylcholine (LPC) was enriched for SaFAs; LPC species containing SaFAs were directly associated with IL-6 levels and monocyte activation. We similarly observed direct relationships between levels of SaFAs and inflammation in HIV uninfected individuals. Further, SaFA exposure altered monocyte subset phenotypes and inflammatory cytokine production in vitro.Conclusions: The lipidome is altered in ART-treated HIV infection, and may contribute to inflammation and CVD progression. Detailed lipidomic analyses may better assess CVD risk in both HIV+ and HIV– individuals than does traditional lipid profiling.

Objectives: HIV-infected women are at increased risk of human papillomavirus (HPV) infection. Time trends in annual prevalences of cervical high-risk human papillomavirus (HR-HPV) genotypes among a non-vaccinated, HIV-infected female cohort in urban Brazil were assessed for the period 2006–2012. Methods: Cervical specimens were collected for HPV genotyping yearly between January 2006 and December 2012 in a cross-sectional analysis of participants aged ≥18 years enrolled in the Women's HIV Cohort at Fiocruz in Rio de Janeiro, Brazil. Age-adjusted generalized estimating equation models with an exchangeable matrix were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for annual HPV positivity (reference year: 2006). Results: Among the 590 participants, the median age across all study years ranged from 35.5 to 40.0 years. The prevalence of any HR-HPV was ≥53% every year; prevalences of HR-HPV 16, 58, 59, and 68 were ≥24% in at least 1 year. The odds of HPV 16 and 68 decreased in 2012. HPV 58 prevalence followed a U-shape, beginning and ending at >20%. HPV 59 prevalence followed a linear trend, with increased odds in 2012 (OR 16.0, 95% CI 3.8–67.3; Bonferroni-adjusted p-value

Background. Increasing body mass index (BMI) is generally associated with loss of metabolic health, although some obese individuals remain metabolically healthy. Among nonobese men, HIV infection has been associated with a lower prevalence of metabolic health. Methods. We conducted a cross-sectional analysis of 470 HIV-infected and 368 HIV-uninfected men enrolled in the Multicenter AIDS Cohort Study Cardiovascular substudy. Circulating biomarker levels were compared by BMI category and by HIV serostatus. Poisson regression with robust variance determined associations between metabolic health and circulating inflammatory biomarker levels after adjusting for factors previously associated with metabolic health. Results. HIV-infected men were younger and less likely to be obese. Among HIV-infected, normal weight metabolically healthy men (compared to unhealthy) had significantly lower circulating levels of interleukin- (IL-) 6, soluble tumor necrosis factor receptors (sTNFR) I and II, and homeostatic model assessment of insulin resistance (HOMA-IR), higher adiponectin, less visceral fat, and more subcutaneous fat. Among HIV-uninfected normal weight men and obese men (regardless of HIV serostatus), metabolic health was associated only with higher levels of adiponectin, less visceral fat, and lower HOMA-IR values. In multivariate analyses restricted to HIV-infected men, lower hs-CRP, sTNFRI, sTNFRII, and HOMA-IR and higher adiponectin levels were associated with metabolic health. Additional adjustment for visceral adiposity did not alter results. Conclusions. Among HIV-infected normal weight men, metabolic health was associated with less systemic inflammation, a relationship that, among normal weight men, was unique to HIV+ men and did not exist among obese men of either HIV serostatus.

OBJECTIVES:Arachidonic acid metabolites (eicosanoids) reflect oxidative stress and vascular health and have been associated with anthropometric measures and sex differences in cross-sectional analyses of HIV-infected (HIV+) persons. Telmisartan is an angiotensin receptor blocker and PPAR-γ agonist with potential anti-inflammatory and metabolic benefits. We assessed telmisartan's effects on urine eicosanoids among HIV+ adults with central adiposity on suppressive antiretroviral therapy enrolled in a prospective clinical trial. METHODS:Thirty-five HIV+ adults (15 women; 20 men) completed 24 weeks of open-label oral telmisartan 40mg daily. Lumbar computed tomography quantified visceral (VAT) and subcutaneous (SAT) abdominal adipose tissue. Urine F2-isoprostane (F2-IsoP), prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane B2 (TxB-M) were quantified at baseline and 24 weeks using gas/liquid chromatography-mass spectroscopy. Mann-Whitney-U tests compared sub-group differences; Spearman's rho assessed correlations between clinical factors and eicosanoid levels. RESULTS:Median PGE-M increased on telmisartan (p5% VAT (+3.7 ng/mg cr, p5% SAT (+1.7 ng/mg cr, p = 0.04). Median baseline F2-IsoP and TxB-M were slightly higher in women (both between-group p = 0.08) and did not change on telmisartan. CONCLUSIONS:Urine PGE-M increased with 24 weeks of telmisartan in virally suppressed, HIV+ adults with central adiposity. Associations with favorable fat redistribution suggest increased PGE-M may reflect a beneficial response.

BACKGROUND:Lower muscle density on computed tomography (CT) provides a measure of fatty infiltration of muscle, an aspect of muscle quality that has been associated with metabolic abnormalities, weakness, decreased mobility, and increased fracture risk in older adults. We assessed the cross-sectional relationship between HIV serostatus, age, thigh muscle attenuation, and thigh muscle cross-sectional area (CSA). METHODS:Mean CT-quantified Hounsfield units (HU) of the thigh muscle bundle and CSA were evaluated in 368 HIV-infected and 145 HIV-uninfected men enrolled in the Multicenter AIDS Cohort Study (MACS) Cardiovascular Substudy using multivariable linear regression. Models all were adjusted for HIV serostatus, age, race, and body mass index (BMI); each model was further adjusted for covariates that differed by HIV serostatus, including insulin resistance, hepatitis C, malignancy, smoking, alcohol use, and self-reported limitation in physical activity. RESULTS:HIV-infected men had greater thigh muscle CSA (p