The Global Impact of Diversifying PrEP Options: Results of an International Discrete Choice Experiment of Existing and Potential PrEP Strategies with Gay and Bisexual Men (GBM) and Physicians.

To improve current and future use of existing (oral, injectable) and potential future (implants, douches) PrEP products, we must understand product preferences relative to one another, among gay and bisexual men (GBM), and physicians who prescribe PrEP. We completed an online discrete choice experiment (DCE) with separate groups of GBM and/or physicians from the U.S., South Africa, Spain, and Thailand. Participants were presented information on PrEP products, including daily pills, event-driven pills (2-1-1 regimen), injections, subdermal implants (dissolvable, removable), and rectal douches. Next, they completed a choice exercise in which they were shown ten screens, each presenting three of the aforementioned products at a time with 11 attributes for physicians and 10 attributes for GBM. For the attributes that were not constant, one level was shown per screen for each product. Participants selected the product they preferred most and rated their likelihood to select (GBM) or recommend (physicians) that product. Data were modeled using Hierarchical Bayes estimation; resulting model coefficients were used to develop attribute importance measures and product preferences. For GBM across all countries, if all aforementioned PrEP products were on the market at the same time, over 90% of GBM would use some form of PrEP; 100% of physicians would recommend at least one of the PrEP products. There were variations in product preference by country. GBM in the U.S. and Thailand preferred the injection (21.7%, 22.9%, respectively), while the dissolvable implant was preferred in South Africa and Spain (19.9%, 19.8%, respectively). In the U.S., South Africa, and Spain (where physician data were available), physicians were most likely to recommend the dissolvable implant (37.2%, 40.6%, 38.3%, respectively).

Problematic Cannabis Use Is Associated with Reduced Rectal Microbial Species Richness and Diversity Among a Pilot Sample of Young Sexual and Gender Minorities.

Compared to young heterosexual men, young sexual and gender minorities (YSGM) have elevated systemic inflammation and unique intestinal microbial profiles, influenced by HIV infection and substance use. However, links between cannabis use and microbial dysbiosis in this population have not been well described. In this pilot study, we aimed to characterize the complex interrelationships between cannabis use and microbial community structure in YSGM in relationship to HIV status. Cannabis use was assessed by self-administered Cannabis Use Disorder Identification Test (CUDIT) questionnaires and rectal microbial community alpha-diversity metrics were assessed via 16S ribosomal ribonucleic acid (rRNA) sequencing in a subset of YSGM (n = 42) in the RADAR cohort (aged 16-29) in Chicago. Multivariable regression models were used to assess the relationship between cannabis use and microbiome alpha-diversity metrics, adjusting for HIV status and other risk characteristics, including inflammation, which was evaluated by plasma levels of C-reactive protein (CRP). Problematic cannabis use, but not general use, was significantly inversely associated with microbial community richness (Adj. Beta = -8.13; 95% confidence interval [CI]: -15.68 to -0.59) and Shannon diversity (Adj. Beta = -0.04; 95% CI: -0.07 to 0.009). No significant association was observed between CUDIT score and community evenness, nor was any significant moderation observed by HIV status. We observed that problematic cannabis use was associated with reduced microbial community richness and Shannon diversity, adjusting for within population differences in inflammation and HIV status. Future research should aim to assess how cannabis use contributes to microbiome-related health factors among YSGM and if decreasing cannabis use can restore gut microbial community structure.

Syphilis Prevalence, Incidence, and Demographic Differences in a Longitudinal Study of Young Sexual and Gender Minority Adults Assigned Male at Birth.

BACKGROUND: Syphilis rates in the United States have increased. Few studies have examined syphilis incidence and prevalence prospectively among young sexual and gender minorities (YSGM). METHODS: This study of YSGM assigned male at birth comes from a Chicago-based prospective cohort at 2 visits 6 months apart (N = 882). Syphilis cases were identified through serologic test results and self-reported history. RESULTS: In this sample, 25.1% had a lifetime prevalence, and 3.3% were incident cases with a crude incidence rate of 6.76 per 100 person-years. CONCLUSIONS: Lifetime syphilis and incidence are high in this sample of YSGM relative to general population samples.

Barriers and facilitators to recruitment of underrepresented research participants: Perspectives of clinical research coordinators.

Background: Insufficient recruitment of groups underrepresented in medical research threatens the generalizability of research findings and compounds inequity in research and medicine. In the present study, we examined barriers and facilitators to recruitment of underrepresented research participants from the perspective of clinical research coordinators (CRCs). Methods: CRCs from one adult and one pediatric academic medical centers completed an online survey in April-May 2022. Survey topics included: participant language and translations, cultural competency training, incentives for research participation, study location, and participant research literacy. CRCs also reported their success in recruiting individuals from various backgrounds and completed an implicit bias measure. Results: Surveys were completed by 220 CRCs. CRCs indicated that recruitment is improved by having translated study materials, providing incentives to compensate participants, and reducing the number of in-person study visits. Most CRCs had completed some form of cultural competency training, but most also felt that the training either had no effect or made them feel less confident in approaching prospective participants from backgrounds different than their own. In general, CRCs reported having greater success in recruiting prospective participants from groups that are not underrepresented in research. Results of the implicit bias measure did not indicate that bias was associated with intentions to approach a prospective participant. Conclusions: CRCs identified several strategies to improve recruitment of underrepresented research participants, and CRC insights aligned with insights from research participants in previous work. Further research is needed to understand the impact of cultural competency training on recruitment of underrepresented research participants.

Inflammation Assessed by Latent Profiling is Associated with Stress and Suicidality but not Depression: Findings from the RADAR Cohort Study.

Past research has suggested that sexual and gender minorities experience elevated levels of systemic inflammation which in turn has been linked to worse mental health outcomes. Therefore, the goals of this work are to develop a better understanding of the relationship between mental health variables and inflammation among this high-risk population. Data were collected among a sample of young men who have sex with men and transgender women (YMSM/TGW, N=685) aged 16-20 at the time of enrollment. Multiplex plasma cytokine and inflammatory biomarkers were quantified. Mental health variables were self-reported and included perceived stress, depression, and suicidal ideation. Latent profile analyses (i.e., latent class analyses intended for continuous variables) were utilized to identify four unique profiles of individuals with similar inflammatory markers followed by adjusted multinomial logistic regression to estimate the association between inflammatory profiles and mental health variables. Participants experienced moderate levels of perceived stress, normal levels of depression and ten percent reported suicidal ideation in the past six months. Multinomial regression models indicated that being in the highest inflammation profile, compared to the lowest inflammation profile, was significantly associated only with increased perceived stress and suicidal ideation. In sum, we observed significant relationships between inflammation and both perceived stress and suicidal ideation, but not between inflammation and depression. Future research should continue to assess these relationships using longitudinal data as they are intricate and likely bidirectional and may be key to reducing health disparities among this population.

Analysis of the Contribution of 6-mer Seed Toxicity to HIV-1-Induced Cytopathicity.

HIV-1 (HIV) infects CD4+ T cells, the gradual depletion of which can lead to AIDS in the absence of antiretroviral therapy (ART). Some cells, however, survive HIV infection and persist as part of the latently infected reservoir that causes recurrent viremia after ART cessation. Improved understanding of the mechanisms of HIV-mediated cell death could lead to a way to clear the latent reservoir. Death induced by survival gene elimination (DISE), an RNA interference (RNAi)-based mechanism, kills cells through short RNAs (sRNAs) with toxic 6-mer seeds (positions 2 to 7 of sRNA). These toxic seeds target the 3' untranslated region (UTR) of mRNAs, decreasing the expression of hundreds of genes critical for cell survival. In most cells under normal conditions, highly expressed cell-encoded nontoxic microRNAs (miRNAs) block access of toxic sRNAs to the RNA-induced silencing complex (RISC) that mediates RNAi, promoting cell survival. HIV has been shown to inhibit the biogenesis of host miRNAs in multiple ways. We now report that HIV infection of cells deficient in miRNA expression or function results in enhanced RISC loading of an HIV-encoded miRNA HIV-miR-TAR-3p, which can kill cells by DISE through a noncanonical (positions 3 to 8) 6-mer seed. In addition, cellular RISC-bound sRNAs shift to lower seed viability. This also occurs after latent HIV provirus reactivation in J-Lat cells, suggesting independence of permissiveness of cells to viral infection. More precise targeting of the balance between protective and cytotoxic sRNAs could provide new avenues to explore novel cell death mechanisms that could be used to kill latent HIV. IMPORTANCE Several mechanisms by which initial HIV infection is cytotoxic to infected cells have been reported and involve various forms of cell death. Characterizing the mechanisms underlying the long-term survival of certain T cells that become persistent provirus reservoirs is critical to developing a cure. We recently discovered death induced by survival gene elimination (DISE), an RNAi-based mechanism of cell death whereby toxic short RNAs (sRNAs) containing 6-mer seed sequences (exerting 6-mer seed toxicity) targeting essential survival genes are loaded into RNA-induced silencing complex (RISC) complexes, resulting in inescapable cell death. We now report that HIV infection in cells with low miRNA expression causes a shift of mostly cellular RISC-bound sRNAs to more toxic seeds. This could prime cells to DISE and is further enhanced by the viral microRNA (miRNA) HIV-miR-TAR-3p, which carries a toxic noncanonical 6-mer seed. Our data provide multiple new avenues to explore novel cell death mechanisms that could be used to kill latent HIV.

HIV-1 infected humanized DRAGA mice develop HIV-specific antibodies despite lack of canonical germinal centers in secondary lymphoid tissues.

A major barrier in the use of humanized mice as models of HIV-1 (HIV) infection is the inadequate generation of virus-specific antibody responses. Humanized DRAGA (hDRAGA) mice generate antigen-specific class switched antibodies to several pathogens, but whether they do so in HIV infection and the extent to which their secondary lymphoid tissues (sLT) support germinal center responses is unknown. hDRAGA mice were evaluated for their ability to support HIV replication, generate virus-specific antibody responses, develop splenocyte subsets, and organize sLT architecture. hDRAGA mice supported persistent HIV replication and developed modest levels of gp41-specific human IgM and IgG. Spleens from uninfected and HIV infected hDRAGA mice contained differentiated B and CD4+ T cell subsets including germinal center (GC) B cells and T follicular helper cells (TFH); relative expansions of TFH and CD8+ T cells, but not GC B cells, occurred in HIV-infected hDRAGA mice compared to uninfected animals. Immunofluorescent staining of spleen and mesenteric lymph node sections demonstrated atypical morphology. Most CD4+ and CD8+ T cells resided within CD20hi areas. CD20hi areas lacked canonical germinal centers, as defined by staining for IgD-Ki67+cells. No human follicular dendritic cells (FDC) were detected. Mouse FDC were distributed broadly throughout both CD20hi and CD20lo regions of sLT. HIV RNA particles were detected by in situ hybridization within CD20+ areas and some co-localized with mouse FDC. Viral RNA+ cells were more concentrated within CD20hi compared to CD20lo areas of sLT, but differences were diminished in spleen and eliminated in mesenteric lymph nodes when adjusted for CD4+ cell frequency. Thus, hDRAGA mice recapitulated multiple aspects of HIV pathogenesis including HIV replication, relative expansions in TFH and CD8+ T cells, and modest HIV-specific antibody production. Nevertheless, classical germinal center morphology in sLT was not observed, which may account for the inefficient expansion of GC B cells and generation of low titer human antibody responses to HIV-1 in this model.

Follicular regulatory T cells eliminate HIV-1-infected follicular helper T cells in an IL-2 concentration dependent manner.

Follicular helper CD4+ T cells (TFH) are highly permissive to HIV and major foci of virus expression in both untreated and treated infection. Follicular regulatory CD4+ T cells (TFR) limit TFH numbers and function in vitro and in vivo. We evaluated the hypothesis that TFR suppress HIV replication in TFH using a well-established model of ex vivo HIV infection that employs tonsil cells from HIV uninfected individuals spinoculated with CXCR4- and CCR5-tropic HIV-GFP reporter viruses. Both CXCR4 and CCR5-tropic HIV replication were reduced in TFH cultured with TFR as compared to controls. Blocking antibodies to CD39, CTLA-4, IL-10, and TGF-beta failed to reverse suppression of HIV replication by TFR, and there were no sex differences in TFR suppressive activity. TFR reduced viability of TFH and even more so reduced HIV infected TFH as assessed by total and integrated HIV DNA. Exogenous IL-2 enhanced TFH viability and particularly numbers of GFP+ TFH in a concentration dependent manner. TFR reduced productively infected TFH at low and moderate IL-2 concentrations, and this was associated with decreases in extracellular IL-2. Both IL-2 expressing cells and larger numbers of FoxP3+CD4+ cells were detected in follicles and germinal centers of lymph nodes of people living with HIV. TFR may deplete TFH in vivo through restriction of IL-2 and thereby contribute to decay of HIV expressing cells in B cell follicles during HIV infection.

Preferences Among Physicians and Men Who Have Sex with Men (MSM) for a Long-Acting, Removable Implant for HIV Prevention: A Discrete Choice Study.

A longer acting, removable implant for HIV prevention has the potential to improve uptake of HIV pre-exposure prophylaxis (PrEP) by removing the need for daily adherence to an oral tablet, reducing potential side effects, and eliminating concerns about residual drug following injections. To end the HIV epidemic, we must understand the needs and preferences of groups most affected by HIV (e.g., men who have sex with men; MSM), and the physicians who prescribe PrEP to them. This article describes a discrete choice experiment to estimate the preference share for the implant within a competitive context of other PrEP products (including the oral tablet, dissolvable implant, and injection) and evaluate the impact of potential implant attributes. Physicians who had prescribed oral PrEP (n = 75) and MSM at risk for HIV (n = 175) completed a web-based survey that prompted decision-making about PrEP product preferences. The findings from both physicians and MSM demonstrated that the removable implant could capture a meaningful portion of the preference share, making it feasible to advance in the development pipeline as an important addition to the biomedical HIV prevention toolkit. Among MSM, specifically, the cost of treatment was the most important attribute impacting product preference. Our findings inform implant developers and future payers (e.g., commercial manufacturers, insurance companies) about specific device attributes that will likely affect MSM's willingness to use and physicians' willingness to prescribe this HIV prevention strategy.

Gut dysbiosis and inflammatory blood markers precede HIV with limited changes after early seroconversion.

BACKGROUND: Alterations in the gut microbiome have been associated with HIV infection, but the relative impact of HIV versus other factors on the gut microbiome has been difficult to determine in cross-sectional studies. METHODS: To address this, we examined the gut microbiome, serum metabolome, and cytokines longitudinally within 27 individuals before and during acute HIV using samples collected from several ongoing cohort studies. Matched control participants (n=28) from the same cohort studies without HIV but at similar behavioral risk were used for comparison. FINDINGS: We identified few changes in the microbiome during acute HIV infection, but did find alterations in serum metabolites involving secondary bile acid (lithocholate sulfate, glycocholenate sulfate) and amino acid metabolism (3-methyl-2-oxovalerate, serine, cysteine, N-acetylputrescine). Greater microbiome differences, including decreased Bacteroides spp and increased Megasphaera elsdenii, were seen when comparing pre-HIV infection visits to matched at-risk controls. Those who acquired HIV also had elevated inflammatory cytokines (TNF-α, B cell activating factor, IL-8) and bioactive lipids (palmitoyl-sphingosine-phosphoethanolamide and glycerophosphoinositol) prior to HIV acquisition compared to matched controls. INTERPRETATION: Longitudinal sampling identified pre-existing microbiome differences in participants with acute HIV compared to matched control participants observed over the same period. These data highlight the importance of increasing understanding of the role of the microbiome in HIV susceptibility. FUNDING: This work was supported by NIH/NIAID (K08AI124979; P30AI117943), NIH/NIDA (U01DA036267; U01DA036939; U01DA036926; U24DA044554), and NIH/NIMH (P30MH058107; R34MH105272).

mTOR regulation of metabolism limits LPS-induced monocyte inflammatory and procoagulant responses.

Translocated lipopolysaccharide (LPS) activates monocytes via TLR4 and is hypothesized to increase cardiovascular disease risk in persons living with HIV. We tested whether mTOR activity supports LPS-stimulated monocyte production of pro-inflammatory cytokines and tissue factor (TF), as it propels the inflammatory response in several immune cell types besides monocytes. However, multi-omics analyses here demonstrate that mTOR activates a metabolic pathway that limits abundance of these gene products in monocytes. Treatment of primary human monocytes with catalytic mTOR inhibitors (mTORi) increased LPS-induced polyfunctional responses, including production of IL-1ß, IL-6, and the pro-coagulant, TF. NF-κB-driven transcriptional activity is enhanced with LPS stimulation after mTORi treatment to increase expression of F3 (TF). Moreover, intracellular NAD+ availability is restricted due to decreased salvage pathway synthesis. These results document mTOR-mediated restraint of the LPS-induced transcriptional response in monocytes and a metabolic mechanism informing strategies to reverse enhanced risk of coagulopathy in pro-inflammatory states.

COVID-19 symptom severity predicts neutralizing antibody activity in a community-based serological study.

Serological testing for SARS-CoV-2 IgG antibodies is used to assess their presence in blood samples from exposed individuals and provides a measure of the magnitude of immune response to infection. The measurement of neutralizing antibodies (NAbs) in particular provides information about the severity of prior infection and level of protective immunity against re-infection. Much of the work investigating the association between prior infection severity and NAb levels has been conducted among clinical populations, and less is known about this relationship in the general population. Accordingly, we utilize data from a large (n = 790) community-based cohort of unvaccinated, seropositive participants. We analyzed the association between NAb response, measured via surrogate virus neutralization assay, with patterns of symptoms and household exposure. Our results indicate no detectable NAb activity in 63.8% of the seropositive participants (n = 504). Those with detectable NAb levels demonstrated a positive relationship between NAb activity and both self-reported previous symptom severity and household exposure. These findings are significant in light of recent concerns about degree of protective immunity conferred by prior infection or vaccination, and we highlight the value of community-based research for investigating variation in immune response.

Preservation of lymphocyte functional fitness in perinatally-infected and treated HIV+ pediatric patients displaying sub-optimal viral control.

Background: Host-pathogen dynamics associated with HIV infection are quite distinct in children versus adults. We interrogated the functional fitness of the lymphocyte responses in two cohorts of perinatally infected HIV+ pediatric subjects with early anti-retroviral therapy (ART) initiation but divergent patterns of virologic control. We hypothesized that sub-optimal viral control would compromise immune functional fitness. Methods: The immune responses in the two HIV+ cohorts (n = 6 in each cohort) were benchmarked against the responses measured in age-range matched, uninfected healthy control subjects (n = 11) by utilizing tests for normality, and comparison [the Kruskal-Wallis test, and the two-tailed Mann-Whitney U test (where appropriate)]. Lymphocyte responses were examined by intra-cellular cytokine secretion, degranulation assays as well as phosflow. A subset of these data were further queried by an automated clustering algorithm. Finally, we evaluated the humoral immune responses to four childhood vaccines in all three cohorts. Results: We demonstrate that contrary to expectations pediatric HIV+ patients with sub-optimal viral control display no significant deficits in immune functional fitness. In fact, the patients that display better virologic control lack functional Gag-specific T cell responses and compared to healthy controls they display signaling deficits and an enrichment of mitogen-stimulated CD3 negative and positive lymphocyte clusters with suppressed cytokine production. Conclusions: These results highlight the immune resilience in HIV+ children on ART with sub-optimal viral control. With respect to HIV+ children on ART with better viral control, our data suggest that this cohort might potentially benefit from targeted interventions that might mitigate cell-mediated immune functional quiescence.

Low Levels of Neutralizing Antibodies After Natural Infection With Severe Acute Respiratory Syndrome Coronavirus 2 in a Community-Based Serological Study.

BACKGROUND: Confidence in natural immunity after infection with severe acute respiratory syndrome coronavirus 2 is one reason for vaccine hesitancy. METHODS: We measured antibody-mediated neutralization of spike protein-ACE2 receptor binding in a large community-based sample of seropositive individuals who differed in severity of infection (N = 790). RESULTS: A total of 39.8% of infections were asymptomatic, 46.5% were symptomatic with no clinical care, 13.8% were symptomatic with clinical care, and 3.7% required hospitalization. Moderate/high neutralizing activity was present after 41.3% of clinically managed infections, in comparison with 7.9% of symptomatic and 1.9% of asymptomatic infections. CONCLUSIONS: Prior coronavirus disease 2019 infection does not guarantee a high level of antibody-mediated protection against reinfection in the general population.

Does body mass index explain the apparent anti-inflammatory effects of cannabis use? Results From a cohort study of sexual and gender minority youth.

BACKGROUND: Cannabis use has been linked to lower systemic inflammation, but the pathways connecting cannabis use and systemic inflammation are unclear. Here we investigate whether body mass index (BMI) accounts for the association between cannabis use and systemic inflammation in a cohort of sexual and gender minority youth assigned male at birth (n = 712). METHODS: Substance use was assessed across six biannual visits. Cannabis use was measured using the Cannabis Use Disorders Identification Test-Revised (CUDIT-R) and urine screening for tetrahydrocannabinol (THC). At the final visit, BMI was measured, and a plasma sample was collected to measure biomarkers of systemic inflammation: C-reactive protein (CRP), interleukin-6, interleukin-1ß, and tumor necrosis factor-α. Inflammatory markers were log2-transformed. Age, gender, race/ethnicity, education, HIV status, cigarette use, alcohol use, and polydrug use were included as covariates. RESULTS: In models including all covariates except BMI, greater cumulative CUDIT-R score was associated with lower CRP (ß = -0.14; 95% CI: -0.22,-0.05) and lower interleukin-6 (ß = -0.12; 95% CI: -0.21,-0.04). These associations were attenuated when BMI was added to the model. Mediation analyses revealed an indirect effect of cumulative CUDIT-R score on CRP (ß = -0.08; 95% CI: -0.12,-0.05) and interleukin-6 (ß = -0.08; 95% CI: -0.12,-0.05), mediated by BMI. Models using urine THC or self-reported frequency to operationalize cannabis use produced similar results. We found no clear evidence that HIV status moderates these associations. CONCLUSIONS: These results suggest that BMI may partially account for the apparent anti-inflammatory effects of cannabis use. Research on the mechanisms linking cannabis use, adiposity, and inflammation may uncover promising intervention targets.

Geographic disparities in COVID-19 case rates are not reflected in seropositivity rates using a neighborhood survey in Chicago.

To date, COVID-19 case rates are disproportionately higher in Black and Latinx communities across the US, leading to more hospitalizations, and deaths in those communities. These differences in case rates are evident in comparisons of Chicago neighborhoods with differing race and/or ethnicities of their residents. Disparities could be due to neighborhoods with more adverse health outcomes associated with poverty and other social determinants of health experiencing higher prevalence of SARS-CoV-2 infection or due to greater morbidity and mortality resulting from equivalent SARS-CoV-2 infection prevalence. We surveyed five pairs of adjacent ZIP codes in Chicago with disparate COVID-19 case rates for highly specific and quantitative serologic evidence of any prior infection by SARS-CoV-2 to compare with their disparate COVID-19 case rates. Dried blood spot samples were self-collected at home by internet-recruited participants in summer 2020, shortly after Chicago's first wave of the COVID-19 pandemic. Pairs of neighboring ZIP codes with very different COVID-19 case rates had similar seropositivity rates for anti-SARS-CoV-2 receptor binding domain IgG antibodies. Overall, these findings of comparable exposure to SARS-CoV-2 across neighborhoods with very disparate COVID-19 case rates are consistent with social determinants of health, and the co-morbidities related to them, driving differences in COVID-19 rates across neighborhoods.

Conjoint Analysis of User Acceptability of Sustained Long-Acting Pre-Exposure Prophylaxis for HIV.

Long-acting delivery modalities of HIV pre-exposure prophylaxis (PrEP), such as subdermal implants, are in development. To facilitate end-user uptake and sustained use, it is critical to understand potential consumers' and physician prescribers' preferences about, interest in, and relative importance of different implant features. The ordered identification of these key attributes allows implant developers to incorporate this feedback into product design, which theoretically improves acceptability, feasibility, and user experience with the device. In this study, n = 75 PrEP-prescribing physicians and n = 143 men having sex with men (MSM) at risk for HIV completed web-based surveys that directly compared the importance of eight to nine different implant features, respectively. Conjoint analysis determined the importance of these features, relative to each other. Implants presented in the study were well received, with a majority of physicians and MSM indicating that they were likely to recommend or use them. The implant was perceived as unique, reliable, and convenient, as well as able to deliver better compliance. The attributes most critical to the adoption of the implant among physicians and MSM were (1) the chance of becoming infected with HIV while on implant treatment, (2) the length of protection and size of the implant, and (3) the side effect advantages over current PrEP oral pill treatment. Some concerns about the implant included side effects and the product's safety (among MSM) and the cost or insurance coverage level for the implant (both physicians and MSM). There was also some resistance to the implantation procedure itself.

Forecasting HIV-1 Genetic Cluster Growth in Illinois,United States.

BACKGROUND: HIV intervention activities directed toward both those most likely to transmit and their HIV-negative partners have the potential to substantially disrupt HIV transmission. Using HIV sequence data to construct molecular transmission clusters can reveal individuals whose viruses are connected. The utility of various cluster prioritization schemes measuring cluster growth have been demonstrated using surveillance data in New York City and across the United States, by the Centers for Disease Control and Prevention (CDC). METHODS: We examined clustering and cluster growth prioritization schemes using Illinois HIV sequence data that include cases from Chicago, a large urban center with high HIV prevalence, to compare their ability to predict future cluster growth. RESULTS: We found that past cluster growth was a far better predictor of future cluster growth than cluster membership alone but found no substantive difference between the schemes used by CDC and the relative cluster growth scheme previously used in New York City (NYC). Focusing on individuals selected simultaneously by both the CDC and the NYC schemes did not provide additional improvements. CONCLUSION: Growth-based prioritization schemes can easily be automated in HIV surveillance tools and can be used by health departments to identify and respond to clusters where HIV transmission may be actively occurring.

Traumatic events and mental health: The amplifying effects of pre-trauma systemic inflammation.

BACKGROUND: Traumatic experiences are strongly predictive of adverse mental health outcomes. Experimental studies have demonstrated that systemic inflammation can increase reactivity to threatening stimuli. It is not known whether naturally occurring inflammation amplifies the impact of traumatic experiences on mental health. Here we test whether incident traumatic events are more predictive of adverse mental health outcomes for individuals with greater pre-trauma systemic inflammation in a racially and ethnically diverse cohort study of youth assigned male at birth who identify as sexual or gender minorities (ages 16-29, n = 518), a group at high risk for trauma exposure. METHODS: Measures of inflammation, depression symptom severity, and perceived stress were measured at baseline. One year later, depression symptom severity and perceived stress were measured again, and participants reported the traumatic events they had experienced in the intervening year. RESULTS: In a model adjusted for baseline depression symptom severity and other key covariates, we found that higher baseline levels of interleukin-1ß amplified the effect of incident trauma exposure on depression symptom severity at follow-up (ß = 0.234, SE = 0.080, P = 0.004). In a model adjusted for baseline perceived stress and other key covariates, we found that higher baseline scores on a multi-marker inflammatory index amplified the effect of incident trauma exposure on perceived stress at follow-up (ß = 0.243, SE = 0.083, P = 0.003). CONCLUSIONS: These findings suggest that greater pre-trauma inflammation may predict poorer mental health following trauma exposure. Understanding how inflammation interacts with trauma to shape mental health may generate novel insights for preventing and treating the debilitating psychological consequences of trauma.