Sexual behaviour among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Data from the ECHO randomized trial.

BACKGROUND: Contraceptive use has complex effects on sexual behaviour and mood, including those related to reduced concerns about unintended pregnancy, direct hormonal effects and effects on endogenous sex hormones. We set out to obtain robust evidence on the relative effects of three contraceptive methods on sex behaviours, which is important for guiding contraceptive choice and future contraceptive developments. METHODS: This is a secondary analysis of data from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) randomized trial in which 7,829 HIV-uninfected women from 12 sites in Eswatini, Kenya, South Africa and Zambia seeking contraception were randomly assigned to intramuscular depot-medroxyprogesterone acetate (DMPA-IM), the copper intrauterine device (Cu-IUD) or the levonorgestrel (LNG) implant. Data collected for 12 to 18 months using 3-monthly behavioural questionnaires that relied on recall from the preceding 3 months, were used to estimate relative risk of post-baseline sex behaviours, as well as sexual desire and menstrual bleeding between randomized groups using modified Poisson regression. RESULTS: We observed small but generally consistent effects wherein DMPA-IM users reported lower prevalence of specified high risk sexual behaviours than implant users than Cu-IUD users (the '>' and '<' symbols indicate statistically significant differences): multiple sex partners 3.6% < 4.8% < 6.2% respectively; new sex partner 3.0% < 4.0% <5.3%; coital acts 16.45, 16.65, 17.12 (DMPA-IM < Cu-IUD); unprotected sex 65% < 68%, 70%; unprotected sex past 7 days 33% <36%, 37%; sex during vaginal bleeding 7.1%, 7.1% < 8.9%; no sex acts 4.1%, 3.8%, 3.4% (DMPA-IM > Cu-IUD); partner has sex with others 10% < 11%, 11%. The one exception was having any sex partner 96.5%, 96.9% < 97.4% (DMPA-IM < Cu-IUD). Decrease in sexual desire was reported by 1.6% > 1.1% >0.5%; amenorrhoea by 49% > 41% >12% and regular menstrual pattern by 26% <35% < 87% respectively. CONCLUSIONS: These findings suggest that women assigned to DMPA-IM may have a modest decrease in libido and sexual activity relative to the implant, and the implant relative to the Cu-IUD. We found more menstrual disturbance with DMPA-IM than with the implant (and as expected, both more than the Cu-IUD). These findings are important for informing the contraceptive choices of women and policymakers and highlight the need for robust comparison of the effects of other contraceptive methods as well.

Predominance of High-Level Tetracycline-Resistant Neisseria gonorrhoeae in Kenya: Implications for Global Implementation of Doxycycline Postexposure Prophylaxis for Prevention of Sexually Transmitted Infections.

ABSTRACT: Using archived Neisseria gonorrhoeae samples from 2008 to 2012, the prevalence of tet (M) genemediating high-level tetracycline resistance in N. gonorrhoeae was 96% among 50 Kenyan women. Determining the local and national prevalence of gonococcal tetracycline resistance and surveillance of gonococcal antimicrobial resistance can inform the implementation of doxycycline postexposure prophylaxis for STI prevention.

Factors associated with HIV testing and treatment among young Black MSM and trans women in three jail systems.

Black men who have sex with men (BMSM) and transgender women (BTW) are disproportionately affected by incarceration and HIV. We assessed factors associated with HIV testing and viral suppression among 176 incarcerated BMSM and BTW in Chicago, IL; Los Angeles, CA; and Houston, TX. In multivariable logistic regression, having a sexual orientation of bisexual, heterosexual, or other vs. gay or same-gender loving was associated with higher odds of testing in custody (aOR 8.97; 95% CI 1.95 - 41.24). Binge drinking (aOR 0.19; 95% CI 0.04 - 0.92) and being unemployed prior to incarceration (aOR 0.03; 95% CI 0.00 - 0.23) were associated with lower odds of testing; participants in Los Angeles were also more likely to be tested than those in Chicago. Being housed in protective custody (aOR 3.12; 95% CI 1.09-9.59) and having a prescription for ART prior to incarceration (aOR 2.58; 95% CI 1.01-6.73) were associated with higher odds of viral suppression when adjusted for site and duration of incarceration, though the associations were not statistically significant in the full multivariable model. Future research should examine structural and process level factors that impact engagement in HIV testing and treatment among detained BMSM and BTW.

Estimated Health Outcomes and Costs of COVID-19 Prophylaxis With Monoclonal Antibodies Among Unvaccinated Household Contacts in the US.

Importance: The COVID-19 pandemic has led to more than 900 000 deaths in the US and continues to disrupt lives even as effective vaccines are available. Objective: To estimate the health outcomes and net cost of implementing postexposure prophylaxis (PEP) with monoclonal antibodies (mAbs) against household exposure to COVID-19. Design, Setting, and Participants: This study is a decision analytical model of results from a randomized clinical trial of casirivimab with imdevimab administered as subcutaneous injections to unvaccinated, SARS-CoV-2-negative household contacts of people with confirmed COVID-19 with complementary data on household demographic structure, vaccine coverage, and confirmed COVID-19 case counts. The study used US data from May 2021 for a simulated population of US individuals of all ages within low-transmission or high-transmission scenarios. Exposures: Age, sex, race, ethnicity, and COVID-19 vaccination status. Main Outcome or Measures: Symptomatic infection, hospitalization, death, and net payer cost of monoclonal antibody PEP for COVID-19. Results: In a month of transmission intensity similar to that of May 2021, a mAb PEP program reaching 50% of exposed, unvaccinated household members aged 50 years and older was estimated to avert 1820 symptomatic infections (95% uncertainty interval [UI], 1220-2454 symptomatic infections), 528 hospitalizations (95% UI, 354-724 hospitalizations), and 84 deaths (95% UI, 55-116 deaths) in a low-transmission scenario and 4834 symptomatic infections (95% UI, 3375-6257 symptomatic infections), 1404 hospitalizations (95% UI, 974-1827 hospitalizations), and 223 deaths (95% UI, 152-299 deaths) in a high-transmission scenario. Without mAb PEP, the estimated cost of hospitalizations due to COVID-19 infections from household exposure in the lower transmission scenario was $149 million (95% UI, $115-$196 million), whereas the estimated hospitalization cost in the higher transmission scenario was $400 million (95% UI, $312-$508 million). In the lower transmission scenario, mAb PEP administered to 50% of eligible contacts aged 80 years and older was estimated to have 82% probability of saving costs, but was not associated with cost savings at age thresholds of 50 years and older or 20 years and older. In contrast, in the high-transmission scenario, mAb PEP administered to 50% of eligible household contacts had estimated cost savings in 100% of simulations at the 80-year age threshold, 96% of simulations at the 50-year threshold, and 2% of simulations at the 20-year thresholds. Conclusions and Relevance: In this modeling study of a simulated US population, a mAb PEP for COVID-19 program was estimated to improve health outcomes and reduce costs. In the setting of a susceptible variant of SARS-CoV-2, health system and public health actors would have an opportunity to improve health and reduce net payer costs through COVID-19 PEP with mAbs.

ART initiation among women newly diagnosed with HIV in a contraceptive trial in sub-Saharan Africa.

Current guidelines recommend starting antiretroviral therapy (ART) as soon as possible after HIV diagnosis to reduce morbidity, mortality and onward HIV transmission. We examined factors influencing ART initiation by women who seroconverted during the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial. ECHO, conducted between 2015 and 2018, enrolled HIV-negative, sexually active women, aged 16-35 years, from four African countries. Follow-up was 12-18 months, with quarterly HIV testing. Women with incident HIV infection received extensive counselling by trial staff and referral to local facilities for HIV care. Of 304 women with ≥90 days follow-up time since HIV diagnosis, 186(61.2%) initiated ART within 90 days, 69(22.7%) initiated after 90 days, and 49(16.1%) had not initiated by the end of the study. There were no statistically significant differences in characteristics among women who initiated ART ≤90 days versus those who did not. Frequent reasons for delayed or non-initiation of ART included not feeling ready to start ART and being newly diagnosed. In a large clinical trial, ART initiation was modest within 90 days of HIV diagnosis and grew to 84% with longer observation. Despite extensive counselling on the importance of early ART initiation, personal barriers delayed some women from starting ART.

Weight change among women using intramuscular depot medroxyprogesterone acetate, a copper intrauterine device, or a levonorgestrel implant for contraception: Findings from a randomised, multicentre, open-label trial.

BACKGROUND: There is limited evidence on the impact of the use of progestin-only hormonal contraception (POC) on weight change. We conducted a secondary analysis of prospective weight change among women enrolled in the Evidence for Contraceptive options and HIV Outcomes (ECHO) trial. METHODS: The ECHO trial was conducted at 12 sites in eSwatini, Kenya, South Africa and Zambia between December 2015 and October 2018. HIV negative, women aged 16-35 years, desiring contraception, were randomised (1:1:1) to either 3-monthly intramuscular depot medroxyprogesterone acetate (DMPA-IM), levonorgestrel (LNG) implant or copper intrauterine device (IUD). Follow-up was up to 18 months. Weight (kg) was measured at baseline and study exit. Analysis was performed as intention to treat (ITT) and time on continuous contraceptive use. The primary outcome of this secondary analysis is weight change from study enrolment to the final visit at study month 12-18. The ECHO trial is registered with ClinicalTrials.gov, NCT02550067. FINDINGS: 7829 women were randomly assigned to DMPA-IM (n = 2609), copper IUD (n = 2607) or LNG implant (n = 2613). The ITT population included 7014 women 2293 DMPA-IM group, 2372 copper IUD group and 2349 LNG group) who were not lost to follow-up, pregnant on study, or missing weight data. The mean weight increased in all groups but was significantly different in magnitude: 3.5 kg (SD = 6.3), 2.4 kg (SD = 5.9) and 1.5 kg (SD = 5.7) in the DMPA-IM, LNG implant and copper IUD groups, respectively. Comparative differences between groups were (2.02 kg (95% CI, 1.68, 2.36, p < 0.001) for DMPA-IM versus copper IUD, 0.87 kg (0.53,1.20 p < 0.001) for LNG implant compared to copper IUD and 1.16 kg (0.82, 1.50, p < 0.001) for DMPA-IM compared with LNG implant. Results for continuous contraceptive use were similar. INTERPRETATION: We found differences in weight gain between POC users compared to the non-hormonal copper IUD group over 12-18 months of use. Women using POCs should be counselled about this potential side effect when choosing a contraceptive method.

Corrigendum to: 2269. HIV-Positive Individuals Who Report Being in Care Are Less Likely to Be Co-Infected With an STI; an Analysis of "Network Testing," A Service Program Offering HIV and STI Testing Services to Individual at Risk for HIV.

[This corrects the article DOI: 10.1093/ofid/ofy210.1922.].

Social-Environmental Resilience, PrEP Uptake, and Viral Suppression among Young Black Men Who Have Sex with Men and Young Black Transgender Women: the Neighborhoods and Networks (N2) Study in Chicago.

Young black men who have sex with men (YBMSM) and young black transgender women (TGW) have experienced a stark disparity in HIV prevention and care. Resilience, collective resources to adapt stressors or adversities, may improve HIV prevention and care outcomes. The present study investigated the association of resilience-based factors with PrEP uptake and viral suppression from a socioecological perspective among YBMSM and young black TGW. Data were from the baseline cycle of the Neighborhoods and Networks (N2) Study, an ongoing cohort study of 16-34-year-old YBMSM and young black TGW in Chicago (n = 324). Confidant network-level and neighborhood affiliation variables were created to measure the social-environmental context of resilience. All analyses were stratified by participants' HIV status (184 HIV-negative participants and 140 HIV-positive participants). Among HIV-negative participants, having a parental figure within an individual's confidant network was significantly associated with a greater likelihood of PrEP use. Among HIV-positive participants, confidant network members' awareness of an individual's HIV status was associated with viral suppression. Social support resources from confidant networks could improve HIV prevention and care engagement among YBMSM and young black TGW. Understanding the social and environmental contexts of resilience resource is critical for HIV prevention and care engagement.

Socio-Structural and Neighborhood Predictors of Incident Criminal Justice Involvement in a Population-Based Cohort of Young Black MSM and Transgender Women.

Black men who have sex with men (MSM) and transgender women are disproportionately affected by criminal justice involvement (CJI) and HIV. This study recruited 618 young Black MSM and transgender women in Chicago, IL, using respondent-driven sampling between 2013 and 2014. Random effects logistic regression evaluated predictors of incident CJI over 18 months of follow-up. Controlling for respondent age, gender and sexual identity, spirituality (aOR 0.56, 95% CI 0.33-0.96), and presence of a mother figure (aOR 0.41, 95% CI 0.19-0.89) were protective against CJI. Economic hardship (financial or residential instability vs. neither aOR 2.23, 95% CI 1.10-4.51), two or more past episodes of CJI vs. none (aOR 2.66, 95% CI 1.40-5.66), and substance use (marijuana use vs. none aOR 2.79, 95% CI 1.23-6.34; other drug use vs. none aOR 4.49, 95% CI 1.66-12.16) were associated with CJI during follow-up. Research to identify and leverage resilience factors that can buffer the effects of socioeconomic marginalization may increase the effectiveness of interventions to address the socio-structural factors that increase the risk for CJI among Black MSM and transgender women. Given the intersection of incarceration, HIV and other STIs, and socio-structural stressors, criminal justice settings are important venues for interventions to reduce health inequities in these populations.

Sex Partner Behavior Variation Related to Network Position of and Residential Proximity to Sex Partners Among Young Black Men Who Have Sex with Men.

This analysis examines how sex behaviors are influenced by a sex partner's network bridging position and the residential proximity between the two. The study sample consisted of 437 young black men who have sex with men (YBMSM) in Chicago and their sex partners (2013-2014). Dyadic analyses that clustered on individuals using generalized estimating equations (n = 1095 relationships) were conducted to assess the associations between different HIV-related sexual behaviors and the network position of and residential proximity to a partner. The odds of group sex was higher with partners who had high network bridging, regardless of how close they lived to one another. The odds of transactional sex was higher with partners who had high network bridging and lived in a different region of the city. Sex behaviors associated with an increased risk of HIV transmission were associated with the network structural position of and residential proximity to partners among YBMSM.

The Motivational PrEP Cascade Guides Interpretation of Early PrEP Linkage to Care for Young Black Men Who Have Sex With Men: The Case of Chicago's PrEPLine.

Pre-exposure prophylaxis (PrEP) uptake remains low among Black men who have sex with men (BMSM). PrEPLine, launched in August 2015, based in Chicago, was designed to support PrEP linkage among BMSM. PrEPLine moves clients through the Motivational PrEP Cascade, addresses barriers, and tracks outcomes. Study findings suggest that three variables (i.e., being gay/same gender loving, living more than 15 miles from a clinic location, rescheduling an appointment) demonstrated a significant positive association with initiating PrEP. A subanalysis of BMSM found that two variables (i.e., living on the West Side of Chicago relative to those living on the South Side, and among those living in communities with a higher rate of poverty [more than 30%], relative to those living in communities with a lower rate of poverty [less than 20%]) demonstrated a significant negative association with initiating PrEP.

A modeling framework to inform preexposure prophylaxis initiation and retention scale-up in the context of 'Getting to Zero' initiatives.

OBJECTIVE(S): 'Getting to Zero' (GTZ) initiatives aim to eliminate new HIV infections over a projected time frame. Increased preexposure prophylaxis (PrEP) uptake among populations with the highest HIV incidence, such as young Black MSM, is necessary to accomplish this aim. Agent-based network models (ABNMs) can help guide policymakers on strategies to increase PrEP uptake. DESIGN: Effective PrEP implementation requires a model that incorporates the dynamics of interventions and dynamic feedbacks across multiple levels including virus, host, behavior, networks, and population. ABNMs are a powerful tool to incorporate these processes. METHODS: An ABNM, designed for and parameterized using data for young Black MSM in Illinois, was used to compare the impact of PrEP initiation and retention interventions on HIV incidence after 10 years, consistent with GTZ timelines. Initiation interventions selected individuals in serodiscordant partnerships, or in critical sexual network positions, and compared with a controlled setting where PrEP initiators were randomly selected. Retention interventions increased the mean duration of PrEP use. A combination intervention modeled concurrent increases in PrEP initiation and retention. RESULTS: Selecting HIV-negative individuals for PrEP initiation in serodiscordant partnerships resulted in the largest HIV incidence declines, relative to other interventions. For a given PrEP uptake level, distributing effort between increasing PrEP initiation and retention in combination was approximately as effective as increasing only one exclusively. CONCLUSION: Simulation results indicate that expanded PrEP interventions alone may not accomplish GTZ goals within a decade, and integrated scale-up of PrEP, antiretroviral therapy, and other interventions might be necessary.

Prescription Opioid Use in a Population-Based Sample of Young Black Men Who Have Sex with Men: A Longitudinal Cohort Study.

Background: Prescription opioid use (POU) among young adults is increasing. This represents a major public health concern due to the increased risks of opioid use misuse and opioid-related overdose. Limited research has examined the POU among young black men who have sex with men (YBMSM), a diverse group experiencing continued increases in HIV incidence over the past decade. Objective: This study aims to examine the prevalence and both the individual and network characteristics of POU among YBMSM. Methods: Data were from a longitudinal cohort study of 16-29 year old YBMSM (N = 514) between 2013 and 2016 in Chicago. Bivariate and multivariable associations were estimated using general estimating equations (GEE). Results: Approximately 4.2% of YBMSM reported POU in the past 12 months with a cumulative incidence rate of 4.1% over the 18-month follow-up period. YBMSM having criminal justice involvements, experiencing violence, or using any illicit drug other than marijuana in the past 12 months were more likely to report POU in the past 12 months. The presence of a mother figure, however, was associated with a decreased risk of POU in the past 12 months, while engaging in condomless anal sex with their named sexual partners was associated with an increased risk of POU in the past 12 months. Conclusions: This is one of the first studies to describe POU among a population-based sample of YBMSM. The high incidence rate of POU among YBMSM is alarming, and it underscores the need for further analysis on POU among this key population.

Correlates of Durable Viral Suppression (DVS) Among Criminal Justice-involved (CJI) Black Men Living with HIV in Louisiana.

Durable viral suppression (DVS) is needed to reduce HIV transmission risk and prevent new HIV infections. We examined changes in viral suppression and correlates of DVS among 97 criminal justice-involved (CJI) Black men living with HIV in Louisiana enrolled in a linkage, re-engagement, and retention in care intervention. Most participants (75%) were Black men who have sex with men. Forty-four percent (44%) were virally suppressed at baseline and only 20% had achieved DVS over a 12-month period. Multinomial logistic regression analyses showed that compared with DVS participants, those with no viral suppression (NVS) and some viral suppression (SVS) were more likely to have lived with HIV for a longer period of time and were less likely to be adherent at baseline. Medication adherence was critical for DVS among this sample of CJI Black men living with HIV who represent a high priority population for HIV care and treatment interventions.

2269. HIV-Positive Individuals Who Report Being in Care Are Less Likely to Be Co-Infected With an STI; an Analysis of "Network Testing," A Service Program Offering HIV and STI Testing Services to Individual at Risk for HIV.

BACKGROUND: The prevalence of STIs among people living with HIV (PLWH) has implications for HIV treatment as prevention and community efforts to stop the spread of HIV. We explored the factors associated with HIV/STI co-infection in HIV-positive individuals. METHODS: We analyzed data from our "Network Testing" service program, which was designed to expand HIV/STI testing services to high-risk individuals including gay, bisexual, and other men who have sex with men (MSM) in Chicago's South side, a high HIV prevalent area. This program provides incentivized testing to participants and up to six referred individuals within their social network. The prevalence of selected STIs, including syphilis, gonorrhea, or chlamydia infection, among HIV-positive individuals was evaluated. Bivariate and multivariable logistic regression analyses were used to assess sociodemographic, testing history, and risk factors significantly associated with HIV/STI co-infection. RESULTS: Of the 295 HIV-positive individuals, 110 (37%) tested positive for at least one STI, with 90 (32%) testing positive for syphilis, 23 (16%) for gonorrhea, and 12 (8%) for chlamydia. The median age was 27 years old and 91% of clients were MSM. In multivariable analyses, individuals who reported being in care were less likely to be co-infected (adjusted odds ratio [aOR] 0.45, 95% confidence interval 0.23-0.90). Additionally, participants who reported having a previous STI test were more likely to be co-infected (aOR=6.10, 95% CI: 1.87-19.90). We found no association with co-infection and other risk factors including multiple partners and condomless sex. CONCLUSION: The high STI prevalence among HIV-positive individuals suggests: 1) a continued need for regular STI testing and treatment among PLWH to reduce the likelihood of HIV transmission to others; and 2) the receipt of HIV care serves as an important opportunity to provide comprehensive services including STI testing/treatment. DISCLOSURES: R. Issema, CDC FOA PS15-1502: Employee of Grant Recipient and Employee, Grant recipient. CDC FOA PS17-1704: Employee of Grant Recipient, Grant recipient. T. Songster, CDC FOA 15-1502: Employee of the grant recipient, Grant recipient. CDC FOA 17-1704: Employee of grant recipient, Grant recipient. M. Edgar, CDC FOA PS15-1502: Employee of Grant Recipient, Grant recipient. B. Davis, CDC FOA PS15-1502: Employee of Grant Recipient, Grant recipient. T. Lee, CDC FOA PS15-1502: Employee of Grant Recipient, Grant recipient. J. Harris, CDC FOA PS15-1502: Employee of Grant Recipient, Grant recipient. T. Cleveland, CDC FOA PS15-1502: Employee of Grant Recipient, Grant recipient. H. Chancler, CDC FOA PS15-1502: Employee of Grant Recipient, Grant recipient. J. Schneider, CDC FOA PS15-1502: Grant Investigator, Grant recipient. CDC FOA PS17-1704: Grant Investigator, Grant recipient. Chicago Department of Public Health A2 HIV Prevention and Testing Grant: Grant Investigator, Grant recipient.

Polarized axonal surface expression of neuronal KCNQ potassium channels is regulated by calmodulin interaction with KCNQ2 subunit.

KCNQ potassium channels composed of KCNQ2 and KCNQ3 subunits give rise to the M-current, a slow-activating and non-inactivating voltage-dependent potassium current that limits repetitive firing of action potentials. KCNQ channels are enriched at the surface of axons and axonal initial segments, the sites for action potential generation and modulation. Their enrichment at the axonal surface is impaired by mutations in KCNQ2 carboxy-terminal tail that cause benign familial neonatal convulsion and myokymia, suggesting that their correct surface distribution and density at the axon is crucial for control of neuronal excitability. However, the molecular mechanisms responsible for regulating enrichment of KCNQ channels at the neuronal axon remain elusive. Here, we show that enrichment of KCNQ channels at the axonal surface of dissociated rat hippocampal cultured neurons is regulated by ubiquitous calcium sensor calmodulin. Using immunocytochemistry and the cluster of differentiation 4 (CD4) membrane protein as a trafficking reporter, we demonstrate that fusion of KCNQ2 carboxy-terminal tail is sufficient to target CD4 protein to the axonal surface whereas inhibition of calmodulin binding to KCNQ2 abolishes axonal surface expression of CD4 fusion proteins by retaining them in the endoplasmic reticulum. Disruption of calmodulin binding to KCNQ2 also impairs enrichment of heteromeric KCNQ2/KCNQ3 channels at the axonal surface by blocking their trafficking from the endoplasmic reticulum to the axon. Consistently, hippocampal neuronal excitability is dampened by transient expression of wild-type KCNQ2 but not mutant KCNQ2 deficient in calmodulin binding. Furthermore, coexpression of mutant calmodulin, which can interact with KCNQ2/KCNQ3 channels but not calcium, reduces but does not abolish their enrichment at the axonal surface, suggesting that apo calmodulin but not calcium-bound calmodulin is necessary for their preferential targeting to the axonal surface. These findings collectively reveal calmodulin as a critical player that modulates trafficking and enrichment of KCNQ channels at the neuronal axon.