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.

Perceptions of bias in HIV prevention services, happiness with social support, and anticipated PrEP stigma among Black and Latine/x sexual and gender diverse individuals.

Although pre-exposure prophylaxis (PrEP) is a highly effective preventive treatment for HIV, anticipated PrEP stigma can hinder uptake. Perceptions of bias in HIV prevention and evaluations (e.g., happiness) tied to social support among Black and Latine/x sexual and gender diverse (SGD) individuals could be important correlates of anticipated PrEP stigma. To further this line of inquiry, a national sample of 872 Black and Latine/x SGD individuals who had and had never taken PrEP (Mage = 25.1, SD = 2.8) reported how they perceived HIV prevention and how happy they were with their social support. Multivariable linear regressions revealed that greater perceptions of bias in HIV prevention services were associated with higher anticipated PrEP stigma among Black and Latine/x SGD individuals who have never taken PrEP. Greater happiness with friend support was associated with lower PrEP stigma, whereas greater happiness with family support was associated with higher PrEP stigma among individuals who have taken PrEP. Findings highlight the need for PrEP and HIV interventions to address the intersectional stigma attached to prevention and for researchers to understand how evaluations of social support may contribute to stigma among Black and Latine/x SGD individuals.

Use of Primary Care and Emergency Departments for Substance Use Treatment: The Rural and Urban Divide.

Background: Alcohol and illicit substance use remain significant public health issues in the United States. In this analysis, we assessed differences in the use of primary care and emergency departments (EDs) for treatment of substance use among rural and urban sexual minorities (SMs).Methods: Data come from the National Survey on Drug Use and Health (NSDUH, 2015-2019). Survey-weighted multivariable linear and logistic regression analyses were used to assess the relationship between sexual identity and the use of primary care settings or EDs for treatment of substance use, stratified by urbanicity of residence.Results: Among the entire sample, 7.9% reported residing in rural environments with slightly more SMs living in urban (7.3%) relative to rural (5.4%) locales. Both rural (ß=-0.20; 95% CI: -0.29, -0.10) and urban SMs (ß=-0.13; 95% CI: -0.16, -0.11) self-reported worse overall health. Urban SMs, but not rural SMs, had significantly higher odds of reporting use of primary care treatment for substance use (aOR 2.80; 95% CI: 2.13, 3.68). ED treatment for substance use was greater among both rural (aOR = 2.99; 95% CI: 1.01, 8.87) and urban SMs (aOR = 3.02; 95% CI: 2.12, 4.30) as was overall number of ED visits among both rural (ß = 0.48; 95% CI: 0.24, 0.72) and urban SMs (ß = 0.23; 95% CI: 0.19, 0.28) .Conclusion: These findings suggest increased reliance on EDs for treatment of alcohol or substance use among rural SMs. Future research should examine whether increasing culturally competent primary care services for SMs in rural areas may be a key intervention point for reducing health disparities.

CREB1 activation promotes human papillomavirus oncogene expression and cervical cancer cell transformation.

Human papillomaviruses (HPVs) infect the oral and anogenital mucosa and can cause cancer. The high-risk (HR)-HPV oncoproteins, E6 and E7, hijack cellular factors to promote cell proliferation, delay differentiation and induce genomic instability, thus predisposing infected cells to malignant transformation. cAMP response element (CRE)-binding protein 1 (CREB1) is a master transcription factor that can function as a proto-oncogene, the abnormal activity of which is associated with multiple cancers. However, little is known about the interplay between HPV and CREB1 activity in cervical cancer or the productive HPV lifecycle. We show that CREB is activated in productively infected primary keratinocytes and that CREB1 expression and phosphorylation is associated with the progression of HPV+ cervical disease. The depletion of CREB1 or inhibition of CREB1 activity results in decreased cell proliferation and reduced expression of markers of epithelial to mesenchymal transition, coupled with reduced migration in HPV+ cervical cancer cell lines. CREB1 expression is negatively regulated by the tumor suppressor microRNA, miR-203a, and CREB1 phosphorylation is controlled through the MAPK/MSK pathway. Crucially, CREB1 directly binds the viral promoter to upregulate transcription of the E6/E7 oncogenes, establishing a positive feedback loop between the HPV oncoproteins and CREB1. Our findings demonstrate the oncogenic function of CREB1 in HPV+ cervical cancer and its relationship with the HPV oncogenes.

Assessment of Barriers and Facilitators to Prescribing HIV Preexposure Prophylaxis by Primary Care Providers.

ABSTRACT: HIV preexposure prophylaxis (PrEP) is a highly effective class of drugs used to prevent the transmission of HIV-1. Despite its high efficacy, the uptake of PrEP has been very low. This project sought to understand the barriers and facilitators to prescribing PrEP in a community health clinic in a Midwestern state.

Cannabis Use Frequency is Associated with PrEP Cessation and Self-reported HIV Diagnosis.

To achieve stated targets in the United States of Ending the HIV Epidemic by 2030, it is necessary to decrease rates of pre-exposure prophylaxis use (PrEP) cessation. In particular, it is key to assess PrEP use and cannabis use frequency given the recent wave of cannabis decriminalization across the U.S., particularly among sexual minority men and gender diverse (SMMGD) individuals. We used data from the baseline visit of a national study of Black and Hispanic/Latino SMMGD. Among participants reporting any lifetime cannabis use, we further assessed the association between frequency of cannabis use in the past 3 months and: (1) self-reported PrEP use, (2) recency of last PrEP dose, and (3) HIV status using adjusted regression models. Compared to those who never used cannabis, odds of PrEP cessation were higher among those who used it once or twice (aOR 3.27; 95% CI 1.38, 7.78), those who used it monthly (aOR 3.41; 95% CI 1.06, 11.01), and those who used it weekly or more frequently (aOR 2.34; 95% CI 1.06, 5.16). Similarly, those reporting cannabis use 1-2 times in the past 3 months (aOR 0.11; 95% CI 0.02, 0.58) and those reporting weekly or more frequent use (aOR 0.14; 95% CI 0.03, 0.68) were each more likely to report more recent PrEP cessation. These results suggest that cannabis users in general may be a population at elevated risk of HIV diagnosis although more research regarding these findings is needed with nationally representative populations.

Co-occurring mental health and drug use experiences among Black and Hispanic/Latino sexual and gender diverse individuals.

Black and Hispanic/Latino sexual and gender diverse individuals disproportionately experience overlapping health disparities, such as drug use and elevated depressive symptoms, which are often driven by minority stressors. We sought to better understand the interaction between drug use and mental health, as it may be fruitful in developing effective interventions to address co-occurring health disparities. In a longitudinal, 5-wave sample of 300 Black and Hispanic/Latino sexual and gender diverse (SGD) individuals collected between March 2020 and March 2022, we found a within-person association between greater than average levels of psychological distress (depression and anxiety) and more frequent extra-medical use of cannabis, inhalants, methamphetamines, and opioids over the span of two years. These associations held after adjusting for the direct, within-person association of internalized homonegativity with drug use frequency. These results suggest that psychological distress explains at least some variance in drug use among Black and Hispanic/Latino SGD individuals. This highlights the importance of interventions that focus on mental health among Black and Hispanic/Latino SGD individuals who report drug use.

Pre-exposure prophylaxis (PrEP) use, anticipated PrEP stigma, and bisexual identity among a Black and Hispanic/Latino sexual and gender diverse sample.

Black and Hispanic/Latino sexual minority men and gender diverse (SMMGD) individuals are disproportionately impacted by the HIV epidemic. Uptake and adherence to pre-exposure prophylaxis (PrEP) is suboptimal among SMMGD Black and Hispanic/Latino individuals, but most research has approached this population as homogenous (e.g., a group operationalized as men who have sex with men). Bisexual men are less likely to disclose their sexual identity and report more mental health problems than their gay counterparts, but there is less attention to the impact of different sexual identities on PrEP use over time. We utilized data from three waves of a national longitudinal study (2020-2021) to characterize Black and Hispanic/Latino SMMGD participants' PrEP use including: 1) PrEP uptake during the study; 2) consistent PrEP use across the study; and 3) discontinuation of PrEP use since study baseline. We found bisexual men were significantly less likely than gay men to be consistent PrEP users and were more likely to discontinue PrEP use over the course of the study. Of the sample who reported PrEP use across surveys, 10% initiated PrEP during the study period, 0% of whom were bisexual. Additionally, bisexual participants reported statistically significantly higher anticipated PrEP stigma relative to gay participants. These findings have implications for HIV prevention interventions. Given the differences in PrEP experiences as a function of sexual identity, researchers and clinicians should consider the disruptive role of stigma (both biphobia and anticipated PrEP stigma) in PrEP care and adherence.

Sexual minorities are not a homogeneous population: health disparity differences based on residence in rural versus urban settings.

INTRODUCTION: Past research has demonstrated that, separately, sexual minorities (SMs) and rural-dwelling populations are each at elevated risk for chronic diseases relative to heterosexuals and urban-dwelling populations, respectively. Little research, however, has assessed whether rural SM populations may experience even further chronic disease risk. METHODS: Data come from the US National Survey on Drug Use and Health, 2015-2019. Survey-weighted logistic regression analyses were used to assess the relationship between sexual identity and various health-associated outcomes, stratified by rural/urban status and adjusted for demographic and other risk factors. RESULTS: Urban bisexual and rural lesbian females had significantly decreased odds of having any health insurance and increased odds of asthma, chronic obstructive pulmonary disease, hepatitis, any heart disease, and STIs relative to their heterosexual counterparts, with disparities affecting bisexual women living in rural areas being largest. Urban gay males had increased odds of having health insurance relative to urban heterosexuals. Both urban gay and bisexual males also experienced increased odds for several chronic diseases, however, among rural residents increased risk was only observed for bisexual males with regards to high blood pressure. CONCLUSION: Rural-dwelling bisexual women experience elevated likelihood for physical health conditions compared to urban-dwelling bisexual women, but few other rural populations experience elevated risk. Urban gay men, meanwhile, are more likely to possess insurance but simultaneously experience worse health outcomes across several domains of diseases, suggesting lower utilization of healthcare services. Future research should strive to avoid pooling all SMs into a single risk group as we have clearly demonstrated that strong differences exist based on both sex and rural/urban status.

MicroRNA-18a targeting of the STK4/MST1 tumour suppressor is necessary for transformation in HPV positive cervical cancer.

Human papillomaviruses (HPV) are a major cause of malignancy worldwide. They are the aetiological agents of almost all cervical cancers as well as a sub-set of other anogenital and head and neck cancers. Hijacking of host cellular pathways is essential for virus pathogenesis; however, a major challenge remains to identify key host targets and to define their contribution to HPV-driven malignancy. The Hippo pathway regulates epithelial homeostasis by down-regulating the function of the transcription factor YAP. Increased YAP expression has been observed in cervical cancer but the mechanisms driving this increase remain unclear. We found significant down-regulation of the master Hippo regulatory kinase STK4 (also termed MST1) in cervical disease samples and cervical cancer cell lines compared with healthy controls. Re-introduction of STK4 inhibited the proliferation of HPV positive cervical cells and this corresponded with decreased YAP nuclear localization and decreased YAP-dependent gene expression. The HPV E6 and E7 oncoproteins maintained low STK4 expression in cervical cancer cells by upregulating the oncomiR miR-18a, which directly targeted the STK4 mRNA 3'UTR. Interestingly, miR-18a knockdown increased STK4 expression and activated the Hippo pathway, significantly reducing cervical cancer cell proliferation. Our results identify STK4 as a key cervical cancer tumour suppressor, which is targeted via miR-18a in HPV positive tumours. Our study indicates that activation of the Hippo pathway may offer a therapeutically beneficial option for cervical cancer treatment.

Substance use treatment partially mitigates association between methamphetamine use and STI risk: findings from the NSDUH cohort.

BACKGROUND: In recent years, both methamphetamine use and STIs have been on the rise in the USA. In this analysis, we sought to ascertain whether the risk of STIs and HIV among methamphetamine users was moderated on the basis of participation in substance use treatment programmes. METHODS: Data came from the National Survey on Drug Use and Health, 2015-2019. Among adult participants, survey-weighted logistic regression analyses were used to assess the relationship between past year methamphetamine use and risk of HIV and STIs, stratified by methamphetamine treatment utilisation and adjusted for demographic and other risk factors. RESULTS: Among participants in the analytic sample (n=210 392), 1862 (0.9%) reported past year methamphetamine use, 566 (0.3%) reported receiving treatment for its use, 5471 (2.6%) tested positive for any STI in the past year and 395 (0.2%) for HIV ever in their lifetime. Past year methamphetamine use was associated with increased risk of STIs among those who did not receive treatment (adjusted OR=3.628; 95% CI 2.75 to 4.92). Significant moderation was also present between past-year methamphetamine use, risk of STI, and substance use treatment. CONCLUSION: In this analysis, we demonstrated a strong relationship between methamphetamine use and risk of STIs that differed based on receipt of substance use treatment. These findings suggested that integrated STI and substance use treatment programmes may yield substantial public health benefits.

Sexual minorities are at elevated risk of cardiovascular disease from a younger age than heterosexuals.

Cardiovascular disease is the leading cause of death worldwide. In this study, we assessed factors related to cardiovascular disease risk and outcomes among sexual minorities (SM). Data from multiple waves of the PATH study were used in this analysis. Multivariable regression models were used to assess the association between sexual identity and: tobacco or e-cigarette use, adverse cardiovascular events, and age at first diagnosis of adverse cardiovascular disease events. In our sample (N = 23,205), 1,660 (7.15%) participants identified as SM. SM men, relative to heterosexual men, are more likely to be diagnosed with high blood pressure (aRR = 1.27; 95% CI 1.10, 1.47), high cholesterol (aRR = 1.32; 95% CI: 1.12, 1.55), congestive heart failure (aRR = 2.29; 95% CI 1.13, 4.65), stroke (aRR = 2.39; 95% CI: 1.14, 5.04), heart attack (aRR = 2.40; 95% CI 1.42, 4.04), and other heart conditions (aRR = 1.52; 95% CI: 1.06, 2.18). Although no simple differences were observed among SM women compared to heterosexual women, SM women were more likely to be diagnosed at a younger age for high blood pressure (aRR = -0.69; 95% CI - 1.08, - 0.29), high cholesterol (aRR = -0.77; 95% CI - 1.15, - 0.38), stroke (aRR = - 1.04; 95% CI - 1.94, - 0.13), and heart attack (aRR = - 1.26; 95% CI - 2.42, - 0.10). SM men were only diagnosed at a younger age for stroke (aRR = - 1.18; 95% CI - 2.06, - 0.30). Compared to heterosexuals, sexual minorities are at higher risk for cardiovascular disease, more likely to develop cardiovascular disease at an earlier age, and more likely to use tobacco products. Future research should focus on decreasing cardiovascular risk among sexual minorities including reducing tobacco use and stress. Screening recommendations for sexual minority populations should also be reviewed in light of a growing body of literature suggesting elevated risk from a young age.

Substance Use and Healthcare Utilization Across the Pre-Exposure Prophylaxis (PrEP) Care Cascade among Black and Latino Men Who Have Sex with Men.

Background: Despite the documented efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention, large disparities in uptake and adherence exist among Black and Latino/Hispanic men who have sex with men (BLMSM). Limited data exists among BLMSM on the impact of substance use at different stages of the PrEP Care Cascade. We examined the ways substance (alcohol, cannabis, other drug) use is related to PrEP experiences across the PrEP Care Cascade (PrEP aware/no use; PrEP use/discontinuation; PrEP use/adherent).Methods: We utilized data from a national sample of 908 BLMSM (Mage = 25.17, range: 18-29), collected between February and October 2020.Results: We found that heavier alcohol use, more other drug (e.g., cocaine) use, more participant healthcare utilization, and higher number of partners across all measures of substance use were separately associated with a lower likelihood of being aware of PrEP. These same factors were also associated with a higher likelihood of PrEP adherence. Conversely, only cannabis use was associated with discontinuation of PrEP use.Conclusions: While we confirm some earlier findings (i.e., alcohol use is associated with both PrEP discontinuation and PrEP use), we newly identify cannabis as a barrier to the adherence of PrEP. Our findings highlight the need for improved PrEP interventions to increase awareness among BLMSM with substance use who are among the most at-risk for HIV infection.

The human papillomavirus oncoproteins: a review of the host pathways targeted on the road to transformation.

Persistent infection with high-risk human papillomaviruses (HR-HPVs) is the causal factor in over 99 % of cervical cancer cases, and a significant proportion of oropharyngeal and anogenital cancers. The key drivers of HPV-mediated transformation are the oncoproteins E5, E6 and E7. Together, they act to prolong cell-cycle progression, delay differentiation and inhibit apoptosis in the host keratinocyte cell in order to generate an environment permissive for viral replication. The oncoproteins also have key roles in mediating evasion of the host immune response, enabling infection to persist. Moreover, prolonged infection within the cellular environment established by the HR-HPV oncoproteins can lead to the acquisition of host genetic mutations, eventually culminating in transformation to malignancy. In this review, we outline the many ways in which the HR-HPV oncoproteins manipulate the host cellular environment, focusing on how these activities can contribute to carcinogenesis.

Autocrine STAT3 activation in HPV positive cervical cancer through a virus-driven Rac1-NFκB-IL-6 signalling axis.

Persistent human papillomavirus (HPV) infection is the leading cause of cervical cancer. Although the fundamental link between HPV infection and oncogenesis is established, the specific mechanisms of virus-mediated transformation are not fully understood. We previously demonstrated that the HPV encoded E6 protein increases the activity of the proto-oncogenic transcription factor STAT3 in primary human keratinocytes; however, the molecular basis for STAT3 activation in cervical cancer remains unclear. Here, we show that STAT3 phosphorylation in HPV positive cervical cancer cells is mediated primarily via autocrine activation by the pro-inflammatory cytokine Interleukin 6 (IL-6). Antibody-mediated blockade of IL-6 signalling in HPV positive cells inhibits STAT3 phosphorylation, whereas both recombinant IL-6 and conditioned media from HPV positive cells leads to increased STAT3 phosphorylation within HPV negative cervical cancer cells. Interestingly, we demonstrate that activation of the transcription factor NFκB, involving the small GTPase Rac1, is required for IL-6 production and subsequent STAT3 activation. Our data provides new insights into the molecular re-wiring of cancer cells by HPV E6. We reveal that activation of an IL-6 signalling axis drives the autocrine and paracrine phosphorylation of STAT3 within HPV positive cervical cancers cells and that activation of this pathway is essential for cervical cancer cell proliferation and survival. Greater understanding of this pathway provides a potential opportunity for the use of existing clinically approved drugs for the treatment of HPV-mediated cervical cancer.

Molecular screening in a longitudinal cohort of young men who have sex with men and young transgender women: associations with focus on the emerging sexually transmitted pathogen Mycoplasma genitalium.

OBJECTIVES: This investigation sought to characterise risk factors associated with acquisition of traditional and emerging agents of sexually transmitted infection (STI) in a cohort of young men who have sex with men and transgender women. METHODS: 917 participants provided urine and rectal swab submissions assessed by transcription-mediated amplification (TMA)-based assays for Chlamydia trachomatis and Neisseria gonorrhoeae and by off-label TMA-based Trichomonas vaginalis and Mycoplasma genitalium testing. A subset provided specimens at 6-month and 12-month follow-up visits. RESULTS: Prevalence of M. genitalium from rectal and urine specimens (21.7% and 8.9%, respectively) exceeded that of C. trachomatis (8.8% and 1.6%) and other STI agents. Black participants yielded higher prevalence of M. genitalium (30.6%) than non-black participants (17.0%; χ²=22.39; p<0.0001). M. genitalium prevalence from rectal specimens was 41.5% in HIV-positive participants vs 16.3% in HIV-negative participants (χ²=57.72; p<0.0001). Participant age, gender identity, condomless insertive anal/vaginal sexual practice and condomless receptive anal sexual practice were not associated with rectal C. trachomatis (p≥0.10), N. gonorrhoeae (p≥0.29), T. vaginalis (p≥0.18) or M. genitalium (p≥0.20) detection. While prevalence of T. vaginalis was calculated at ≤1.0%, baseline rectal and urine screening status was predictive of detection/non-detection at follow-up. A non-reactive M. genitalium baseline rectal or urine screening result was less predictive of non-reactive follow-up versus C. trachomatis, N. gonorrhoeae and T. vaginalis. CONCLUSIONS: Rectal M. genitalium detection is associated with black race and HIV seropositivity. Baseline M. genitalium infection influences subsequent detection of the organism.

Sexual Positioning Practices and Anal Human Papillomavirus Infection Among Young Men Who Have Sex with Men and Transgender Women-Chicago, Illinois, 2016-2018.

BACKGROUND: Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States; men who have sex with men (MSM) have higher prevalence of infection and related disease compared with other men. We assessed whether differences in HPV acquisition exist among MSM according to their sexual positioning practices, as well as self-reported receipt of HPV vaccination. METHODS: We enrolled young MSM and transgender women aged 18 to 26 years in Chicago, IL (N = 666). Participants self-reported their history of HPV vaccination and submitted self-collected anal swab specimens for type-specific HPV detection using an L1-consensus PCR assay. Multivariable logistic regression analyses were used to assess relationships between sexual positioning practices and detection of any HPV or quadrivalent HPV vaccine (4vHPV) types by vaccination status, defined as self-reported receipt of ≥1 HPV vaccine dose versus none. RESULTS: Among 666 participants, 400 (60.1%) had any anal HPV, and 146 (21.9%) had a 4vHPV type. Among vaccinated participants, 18, 36, and 177 reported exclusively insertive, exclusively receptive, or both sexual positioning practices, respectively. Compared with participants reporting exclusively insertive anal sex, odds of any HPV were significantly higher among participants engaging exclusively in receptive anal sex (adjusted odds ratio [aOR], 5.90; 95% confidence interval [CI], 2.52-13.78), as well as those engaging in both (aOR, 3.32; 95% CI, 1.71-6.44). Vaccinated participants, compared with unvaccinated participants, had lower odds of 4vHPV-type HPV regardless of sexual positioning practices (aOR, 0.56; 95% CI, 0.34-0.92). CONCLUSIONS: Adult men and transgender women who practice anal receptive sex have high prevalence of infection with any HPV. Routine vaccination of all adolescents is expected to reduce HPV-related disease incidence among adult MSM and transgender women as vaccinated cohorts age.

Substance Use Predicts Sustained Viral Suppression in a Community Cohort of Sexual and Gender Minority Youth Living with HIV.

Retention in care and sustained viral suppression are integral outcomes in the care continuum for people living with HIV (PLWH) and HIV prevention; however, less is known about how substance use predicts sustained viral suppression over time. This study seeks to examine the predictive effects of substance use on sustained viral suppression in a sample of cisgender sexual minority men and gender minority PLWH (n = 163) drawn from a longitudinal sample in the Chicago area collected 2015-2019. Using data from 3 visits separated by 6 months, participants were coded persistently detectable, inconsistently virally suppressed, and consistently virally suppressed (< 40 copies/mL at all visits). Multinomial logistic regressions were utilized. About 40% of participants had sustained viral suppression. In multinomial logistic regressions, CUDIT-R predicted persistent detectable status and stimulant use was associated with inconsistent viral suppression. Substance use may create challenges in achieving sustained viral suppression, which has important implications for care and prevention.

RESUMEN: Retención en el cuidado de la salud y supresión viral sostenida son resultados integrales en la cascada del tratamiento de VIH para personas viviendo con el virus del SIDA (PVVS) y prevención del VIH. Sin embargo, no se sabe mucho acerca de cómo el uso de substancias predice la supresión viral sostenida a través del tiempo. Este estudio busca examinar los efectos predictivos del uso de substancias en la supresión viral sostenida en una muestra de minoría de hombres cisgéneros y minorías de género PVVS (n = 163) basada en una muestra longitudinal en la región de Chicago obtenida en 2015­2019. Utilizando datos de 3 visitas con un intervalo de 6 meses, participantes fueron identificados como detectables persistentemente, inconsistentemente viralmente suprimido, y consistentemente viralmente suprimido (< 40 copias/mL en todas las visitas). Regresión logística multinomial fue utilizada. Cerca de 40% de los participantes tenían supresión viral sostenida. En regresión logística multinomial, CUDIT-R predicho status detectable persistente y uso de estimulantes fueron asociados a la supresión viral inconsistente. Uso de substancias crean desafíos para lograr la supresión viral sostenida, lo que tiene importante trascendencia para el cuidado y prevención.

STAT3 activation by E6 is essential for the differentiation-dependent HPV18 life cycle.

Human papillomaviruses (HPV) activate a number of host factors to control their differentiation-dependent life cycles. The transcription factor signal transducer and activator of transcription (STAT)-3 is important for cell cycle progression and cell survival in response to cytokines and growth factors. STAT3 requires phosphorylation on Ser727, in addition to phosphorylation on Tyr705 to be transcriptionally active. In this study, we show that STAT3 is essential for the HPV life cycle in undifferentiated and differentiated keratinocytes. Primary human keratinocytes containing high-risk HPV18 genomes display enhanced STAT3 phosphorylation compared to normal keratinocytes. Expression of the E6 oncoprotein is sufficient to induce the dual phosphorylation of STAT3 at Ser727 and Tyr705 by a mechanism requiring Janus kinases and members of the MAPK family. E6-mediated activation of STAT3 induces the transcription of STAT3 responsive genes including cyclin D1 and Bcl-xL. Silencing of STAT3 protein expression by siRNA or inhibition of STAT3 activation by small molecule inhibitors, or by expression of dominant negative STAT3 phosphorylation site mutants, results in blockade of cell cycle progression. Loss of active STAT3 impairs HPV gene expression and prevents episome maintenance in undifferentiated keratinocytes and upon differentiation, lack of active STAT3 abolishes virus genome amplification and late gene expression. Organotypic raft cultures of HPV18 containing keratinocytes expressing a phosphorylation site STAT3 mutant display a profound reduction in suprabasal hyperplasia, which correlates with a loss of cyclin B1 expression and increased differentiation. Finally, increased STAT3 expression and phosphorylation is observed in HPV positive cervical disease biopsies compared to control samples, highlighting a role for STAT3 activation in cervical carcinogenesis. In summary, our data provides evidence of a critical role for STAT3 in the HPV18 life cycle.

Comprehensive Molecular Screening in a Cohort of Young Men Who Have Sex With Men and Transgender Women: Effect of Additive Rectal Specimen Source Collection and Analyte Testing.

BACKGROUND: This study's purposes were to characterize detection rates of several sexually transmitted infection (STI) agents and describe the effect additional specimen source and analyte screening has on STI detection within a cohort of young men who have sex with men and transgender women. METHODS: Within a 16-month interval, 1966 encounters involved dual urine and rectal swab submissions assessed by commercial transcription-mediated amplification-based assays for Chlamydia trachomatis and Neisseria gonorrhoeae and by off-label transcription-mediated amplification-based Trichomonas vaginalis and Mycoplasma genitalium testing. Identification of STI carriers used algorithms involving Food and Drug Administration-cleared screening methods, laboratory-modified testing for extraurogenital C. trachomatis and N. gonorrhoeae, and laboratory-developed tests for T. vaginalis and M. genitalium. RESULTS: Food and Drug Administration-indicated urine C. trachomatis and N. gonorrhoeae screening revealed 39 encounters (2.0%) yielding one or both agents. Via C. trachomatis and N. gonorrhoeae screening that included rectal swab analysis, 264 encounters (13.4%) yielded evidence of either (140 C. trachomatis, 88 N. gonorrhoeae) or both (36 participants) infections. Detection rates for C. trachomatis and N. gonorrhoeae were 1.4% and 0.6% for urine screening and 8.2% and 6.2% for rectal screening, respectively. Off-label screening identified 413 additional encounters with STI (5 T. vaginalis, 396 M. genitalium, 12 with both). Of these identifications, 82.1% were generated from analysis of rectal swabs (4 participants with T. vaginalis, 323 participants with M. genitalium, 12 with both). Overall detection rates of T. vaginalis (0.2% urine, 1.3% rectal) and M. genitalium (9.1% urine, 21.5% rectal) were variable. CONCLUSIONS: Additive analyte testing, including extraurogenital collections, contributes to comprehensive STI screening within a high-risk demographic.