HIV-1 Incidence, Adherence, and Drug Resistance in Individuals Taking Daily Emtricitabine/Tenofovir Disoproxil Fumarate for HIV-1 Pre-Exposure Prophylaxis: Pooled Analysis From 72 Global Studies.

BACKGROUND: Oral pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir disoproxil fumarate (F/TDF) has high efficacy against HIV-1 acquisition. Seventy-two prospective studies of daily oral F/TDF PrEP were conducted to evaluate HIV-1 incidence, drug resistance, adherence, and bone and renal safety in diverse settings. METHODS: HIV-1 incidence was calculated from incident HIV-1 diagnoses after PrEP initiation and within 60 days of discontinuation. Tenofovir concentration in dried blood spots (DBS), drug resistance, and bone/renal safety indicators were evaluated in a subset of studies. RESULTS: Among 17,274 participants, there were 101 cases with new HIV-1 diagnosis (0.77 per 100 person-years; 95% CI 0.63-0.94). In 78 cases with resistance data, 18 (23%) had M184I or V, one (1.3%) had K65R, and three (3.8%) had both mutations. In 54 cases with tenofovir concentration data from DBS, 45 (83.3%), 2 (3.7%), 6 (11.1%), and 1 (1.9%) had average adherence of <2, 2-3, 4-6, and ≥7 doses/week, respectively, and the corresponding incidence was 3.9 (95% CI 2.9-5.3), 0.24 (0.060-0.95), 0.27 (0.12-0.60), and 0.054 (0.008-0.38) per 100 person-years. Adherence was low in younger participants, Hispanic/Latinx and Black participants, cisgender women, and transgender women. Bone and renal adverse event incidence rates were 0.69 and 11.8 per 100 person-years, respectively, consistent with previous reports. CONCLUSIONS: Leveraging the largest pooled analysis of global PrEP studies to date, we demonstrate that F/TDF is safe and highly effective, even with less than daily dosing, in diverse clinical settings, geographies, populations, and routes of HIV-1 exposure.

No observed bidirectional effect between tenofovir diphosphate concentrations and gender-affirming hormone concentrations among transgender persons switching from tenofovir disoproxil fumarate/emtricitabine to tenofovir alafenamide/emtricitabine for HIV pre-exposure prophylaxis.

AIMS: Many transgender and gender diverse (TGD) individuals have expressed concerns about the potential for oral pre-exposure prophylaxis to affect hormonal concentrations achieved from taking gender-affirming hormone therapy (GAHT). The purpose of this study was to understand the bidirectional effects between hormone and intraerythrocytic tenofovir diphosphate concentrations when switching from tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) to tenofovir alafenamide/emtricitabine (TAF/FTC) in TGD users/nonusers of GAHT. METHODS: The study evaluated stored blood samples and dried blood spot cards from TGD adults without HIV who took ≥12 weeks of TDF/FTC and then switched to ≥12 weeks of TAF/FTC for pre-exposure prophylaxis. RESULTS: Thirty-nine individuals met the study inclusion criteria. Regardless of sex assigned at birth and the use of GAHT, there were no significant differences in hormone concentrations when individuals taking GAHT were taking TDF/FTC and then switched to TAF/FTC. Further, there was no significant difference in intraerythrocytic tenofovir diphosphate concentrations between users and nonusers of GAHT. CONCLUSION: There are no bidirectional effects between hormone and intraerythocytic tenofovir diphosphate concentrations when switching from TDF/FTC to TAF/FTC in TGD users/nonusers of GAHT.

The impact of intimate partner violence on PrEP adherence among U.S. Cisgender women at risk for HIV.

BACKGROUND: Cisgender women account for 1 in 5 new HIV infections in the United States, yet remain under-engaged in HIV prevention. Women experiencing violence face risk for HIV due to biological and behavioral mechanisms, and barriers to prevention, such as challenges to Pre-Exposure Prophylaxis for HIV Prevention (PrEP) adherence. In this analysis, we aim to characterize intimate partner violence (IPV) among cisgender heterosexual women enrolled in a PrEP demonstration project and assess the associations with PrEP adherence. METHODS: Adherence Enhancement Guided by Individualized Texting and Drug Levels (AEGiS) was a 48-week single-arm open-label study of PrEP adherence in HIV-negative cisgender women in Southern California (N = 130) offered daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC). From 6/2016 to 10/2018, women completed a survey reporting HIV risk behavior and experiences of any IPV (past 90-days) and IPV sub-types (past-year, lifetime) and biological testing for HIV/STIs at baseline, and concentrations of tenofovir-diphosphate (TFV-DP) in dried blood spots at weeks 4, 12, 24, 36, and 48. Outcomes were TFV-DP concentrations consistent with ≥ 4 or ≥ 6 doses/week at one or multiple visits. Multivariable logistic regression models were conducted to examine associations. RESULTS: Past-90-day IPV was reported by 34.4% of participants, and past-year and lifetime subtypes reported by 11.5-41.5%, and 21.5-52.3%, respectively. Women who engaged in sex work and Black women were significantly more likely to report IPV than others. Lifetime physical IPV was negatively associated with adherence at ≥ 4 doses/week at ≥ 3 of 5 visits, while other relationships with any IPV and IPV sub-types were variable. CONCLUSION: IPV is an indication for PrEP and important indicator of HIV risk; our findings suggest that physical IPV may also negatively impact long-term PrEP adherence. CLINICAL TRIALS REGISTRATION: NCT02584140 (ClinicalTrials.gov), registered 15/10/2015.

Whole-Genome Sequencing to Predict Antimicrobial Susceptibility Profiles in Neisseria gonorrhoeae.

BACKGROUND: Neisseria gonorrhoeae is a major public health problem due to increasing incidence and antimicrobial resistance. Genetic markers of reduced susceptibility have been identified; the extent to which those are representative of global antimicrobial resistance is unknown. We evaluated the performance of whole-genome sequencing (WGS) used to predict susceptibility to ciprofloxacin and other antimicrobials using a global collection of N. gonorrhoeae isolates. METHODS: Susceptibility testing of common antimicrobials and the recently developed zolifodacin was performed using agar dilution to determine minimum inhibitory concentrations (MICs). We identified resistance alleles at loci known to contribute to antimicrobial resistance in N. gonorrhoeae from WGS data. We tested the ability of each locus to predict antimicrobial susceptibility. RESULTS: A total of 481 N. gonorrhoeae isolates, collected between 2004 and 2019 and making up 457 unique genomes, were sourced from 5 countries. All isolates with demonstrated susceptibility to ciprofloxacin (MIC ≤0.06 µg/mL) had a wild-type gyrA codon 91. Multilocus approaches were needed to predict susceptibility to other antimicrobials. All isolates were susceptible to zoliflodacin, defined by an MIC ≤0.25 µg/mL. CONCLUSIONS: Single marker prediction can be used to inform ciprofloxacin treatment of N. gonorrhoeae infection. A combination of molecular markers may be needed to determine susceptibility for other antimicrobials.

Randomized Trial of Lactin-V to Prevent Recurrence of Bacterial Vaginosis.

BACKGROUND: Bacterial vaginosis affects 15 to 50% of women of reproductive age, and recurrence is common after treatment with an antibiotic agent. The high incidence of recurrence suggests the need for new treatments to prevent recurrent bacterial vaginosis. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 2b trial to evaluate the ability of Lactobacillus crispatus CTV-05 (Lactin-V) to prevent the recurrence of bacterial vaginosis. Women 18 to 45 years of age who had received a diagnosis of bacterial vaginosis and who had completed a course of vaginal metronidazole gel as part of the eligibility requirements were randomly assigned, in a 2:1 ratio, to receive vaginally administered Lactin-V or placebo for 11 weeks; follow-up occurred through week 24. The primary outcome was the percentage of women who had a recurrence of bacterial vaginosis by week 12. RESULTS: A total of 228 women underwent randomization: 152 to the Lactin-V group and 76 to the placebo group; of these participants, 88% in the Lactin-V group and 84% in the placebo group could be evaluated for the primary outcome. In the intention-to-treat population, recurrence of bacterial vaginosis by week 12 occurred in 46 participants (30%) in the Lactin-V group and in 34 participants (45%) in the placebo group (risk ratio after multiple imputation for missing responses, 0.66; 95% confidence interval [CI], 0.44 to 0.87; P = 0.01). The risk ratio for recurrence by week 24 (also calculated with multiple imputation for missing responses) was 0.73 (95% CI, 0.54 to 0.92). At the 12-week visit, L. crispatus CTV-05 was detected in 79% of participants in the Lactin-V group. The percentage of participants who had at least one adverse event related to Lactin-V or placebo by week 24 did not differ significantly between the groups. The percentage of participants with local or systemic adverse events was similar in the two groups. CONCLUSIONS: The use of Lactin-V after treatment with vaginal metronidazole resulted in a significantly lower incidence of recurrence of bacterial vaginosis than placebo at 12 weeks. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT02766023.).

Gender-Based Violence and Post-traumatic Stress Disorder Symptoms Predict HIV PrEP Uptake and Persistence Failure Among Transgender and Non-binary Persons Participating in a PrEP Demonstration Project in Southern California.

Gender-based violence (GBV) against transgender and nonbinary (TGNB) persons is a pervasive public health issue. GBV has been linked to mental health problems such as depression and posttraumatic stress disorder (PTSD), as well has risk for HIV seroconversion and HIV treatment nonadherence. However, the impact of GBV on HIV pre-exposure prophylaxis (PrEP) use among TGNB persons has yet to be investigated. In the current study we assessed longitudinal PrEP persistence data from dried blood spots (DBS) collected from 172 racially and ethnically diverse TGNB participants during a 48-week PrEP demonstration project in Southern California from June 2017 to September 2020. Participants were categorized into three levels of PrEP uptake and persistence based on their PrEP levels at the start and end of the study: low-low, high-low, and high-high. Individual-, social-, and structural-level variables were then entered into multinomial logistic regression models to predict levels of PrEP uptake and persistence based on hypotheses informed by syndemic and minority stress theories. The models demonstrated that experience of GBV predicted significantly lower odds of PrEP uptake and persistence and greater PTSD symptoms predicted significantly greater odds of early PrEP discontinuation. Higher levels of coping skills, already being on PrEP at baseline, and being in a steady relationship were associated with greater odds of PrEP uptake and persistence. Implications for future GBV research, advocacy, interventions, and much needed structural changes focused on improving the health and safety of TGNB individuals are discussed.

Impact of (recurrent) bacterial vaginosis on quality of life and the need for accessible alternative treatments.

BACKGROUND: Bacterial vaginosis (BV) is one of the most common vaginal dysbiosis in women aged 15-44 years old. METHODS: We administered a cross-sectional, single timepoint survey to women ages 18 years or older and who have had bacterial vaginosis (BV). Women completed an anonymous online survey evaluating the impact of BV on their quality of life, how effective different types of treatments were and the amount of self-diagnosed vs. provider diagnosed BV episodes they had. RESULTS: 62 participants completed the anonymous online survey. With a self-reported median number of BV episodes in the past year was 4 (IQR 1-7). Among these women 69.8% reported BV had a negative impact on their sexual health, 67.7% on their physical health, 74.6% on their mental health. More than half of the respondents had used probiotics with oral Lactobacillus sp. (53.2%), mainly by oral route, and over a third had used vaginal boric acid (37.1%). Most women were unaware of Lactobacillus crispatus. Lactobacillus probiotics were more likely to be tried by women who were negatively impacted by BV for overall quality of life (p = 0.033), sexual health (p = 0.002), and mental health (p = 0.006) while boric acid use was more likely to be used by women who were negatively impacted by BV for their sexual health (p = 0.008). CONCLUSIONS: BV is associated with negative quality of life and the women most impacted are seeking alternative treatments such as probiotics (Lactobacillus) and boric acid. There needs to be improvements in BV treatment that include alternative therapy options that have demonstrated efficacy with standardized composition, formulation and dosage.

Efficacy of Daily Text Messaging to Support Adherence to HIV Pre-Exposure Prophylaxis (PrEP) among Stimulant-Using Men Who Have Sex with Men.

Background: Men who have sex with men (MSM) who use stimulants are at increased risk for HIV infection. Adherence to pre-exposure prophylaxis (PrEP) reduces the risk of HIV infection. We evaluated the efficacy of the individualized Texting for Adherence Building (iTAB) intervention for PrEP adherence compared to standard of care (SoC) among 119 MSM who use stimulants (cocaine, methamphetamine and/or other amphetamine) from the California Collaborative Treatment Group 595 randomized control trial.Method: Three ordered levels of PrEP adherence (non-adherence, adequate adherence, and near-perfect adherence) were compared between intervention arms across study visits (weeks 12 and 48) using ordinal logistic regressions.Results: The effect of intervention arm was not significant in the final model; however, there was a 38% decrease in odds (OR = 0.62, p=.023) of having near-perfect adherence (versus non-adherence or adequate adherence) at week 48 compared to week 12, indicating a significant effect of time. In a follow-up analysis examining week 48 only, logistic regression examining PrEP adherence showed that receiving iTAB (compared to SoC) trended toward higher odds of near-perfect adherence relative to adequate adherence (OR = 2.48, p=.061). Higher HIV knowledge resulted in higher odds (OR = 1.72, p=.020) of near-perfect adherence (versus non-adherence or adequate adherence).Conclusion: HIV knowledge may influence PrEP adherence, and most notably, the iTAB intervention may support near-perfect adherence relative to adequate adherence.

Low incidence and prevalence of hepatitis C in two cohorts of HIV pre-exposure prophylaxis adherence interventions in men who have sex with men in Southern California.

HIV pre-exposure prophylaxis (PrEP) has been associated with incident hepatitis C virus (HCV) infection in men who have sex with men (MSM) due to decreased condom use. We examined rates of HCV among MSM and transgender women at high-risk of HIV on PrEP in Southern California using data from two trials (NCT01761643 and NCT01781806). Five of 599 participants (0.84%, 95% CI, 0.27-1.93) had HCV antibodies detected at entry. Factors associated with HCV seropositivity included being older (p = .002) and lower education level (p < .001). HCV-positive participants had no reported cases of sexually transmitted infection (rectal, urethral or pharyngeal gonorrhoea and/or chlamydia) at entry while HCV-negative participants had a prevalence of 18% (95% CI, 15%-21%). There were no significant differences in substance use and sexual risk behaviour between HCV-positive and HCV-negative participants 1-3 months prior to entry. Among early PrEP adopters, incident HCV did not occur despite ongoing condomless intercourse. Screening intervals for HCV in MSM on PrEP should be led by a risk behaviour assessment.

Facilitators of PrEP Persistence among Black and Latinx Transgender Women in a PrEP Demonstration Project in Southern California.

Black and Latinx transgender women in the United States (U.S.) are at disproportionately high risk for HIV. Although HIV pre-exposure prophylaxis (PrEP) reduces the risk of HIV infection, uptake and persistence (i.e., ability to continue taking PrEP over time) can be a challenge for Black and Latinx transgender women due to myriad social and structural forces. In this qualitative study, we present unique data on the facilitators of PrEP persistence from Black and Latinx transgender women who initiated PrEP and exhibited varying levels of persistence during a demonstration project in Southern California. PrEP persistence was assessed by collecting quantitative intracellular tenofovir-diphosphate (TFV-DP) levels on dried blood spot (DBS) samples collected at weeks 12 and 48. Informed by the socioecological framework, we conducted and analyzed interviews using qualitative content analysis to determine themes on the facilitators of PrEP persistence. Individual-level facilitators included the use of reminders, having high individual-level HIV risk perception, feeling empowered to take PrEP, and reporting having improved peace of mind and mental health because of taking PrEP. Interpersonal/Community-level facilitators included feeling motivation to prevent HIV in the community, motivation to prevent HIV in the context of sex work, and having high community-level risk perception. Structural-level facilitators included having positive experiences in affirming healthcare settings and having PrEP visits combined with other gender-related healthcare visits. Interventions aiming to increase PrEP uptake and persistence among Black and Latinx transgender women in the U.S. should harness the multiple levels of support exhibited by those who were able to start and persist on PrEP in the face of the myriad social and structural barriers.

Results from a Pre-exposure Prophylaxis Demonstration Project for At-risk Cisgender Women in the United States.

BACKGROUND: Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is effective for reducing human immunodeficiency virus (HIV) acquisition among cisgender women. We report results from the first US observational open-label demonstration project of pre-exposure prophylaxis (PrEP) among at-risk cisgender women. METHODS: Adherence Enhancement Guided by Individualized Texting and Drug Levels was a 48-week, single-arm, open-label demonstration study of daily oral TDF/FTC in cisgender women ≥18 years old at risk for HIV. Adherence was supported using 2-way text messaging and titrated adherence counseling based on rapid-turnaround tenofovir diphosphate concentrations from dried blood spots. Study visits occurred at baseline, weeks 4 and 12, and quarterly through week 48. Outcomes included TDF/FTC adherence, retention, and persistence. RESULTS: From June 2016 to October 2018, 136 cisgender women enrolled (mean age, 40 years (standard deviation, 11); 38% non-Hispanic Black and 19% Latina). At 48 weeks, 84 (62%) participants were retained and 62 (46%) remained on PrEP. More than one-third (12/31) of those on study but off PrEP throughout the study discontinued TDF/FTC because of side effects, and 1 adverse event led to study discontinuation. Of 120 participants with drug concentrations measured, 67 (56%) had at least 1 concentration consistent with 6 doses/week; 22 (18%) had consistent ≥6 doses/week across all study visits attended. There were no incident HIV infections and 4 incident bacterial sexually transmitted infections. CONCLUSION: Adequate PrEP adherence for protective drug concentrations was not achieved for most study participants. More work needs to be done to fully explicate the reasons for nonadherence and low retention in cisgender women.

Resistance-Guided Treatment of Gonorrhea: A Prospective Clinical Study.

BACKGROUND: Novel treatment strategies to slow the continued emergence and spread of antimicrobial resistance in Neisseria gonorrhoeae are urgently needed. A molecular assay that predicts in vitro ciprofloxacin susceptibility is now available but has not been systematically studied in human infections. METHODS: Using a genotypic polymerase chain reaction assay to determine the status of the N. gonorrhoeae gyrase subunit A serine 91 codon, we conducted a multisite prospective clinical study of the efficacy of a single oral dose of ciprofloxacin 500 mg in patients with culture-positive gonorrhea. Follow-up specimens for culture were collected to determine microbiological cure 5-10 days post-treatment. RESULTS: Of the 106 subjects possessing culture-positive infections with wild-type gyrA serine N. gonorrhoeae genotype, the efficacy of single-dose oral ciprofloxacin treatment in the per-protocol population was 100% (95% 1-sided confidence interval, 97.5-100%). CONCLUSIONS: Resistance-guided treatment of N. gonorrhoeae infections with single-dose oral ciprofloxacin was highly efficacious. The widespread introduction and scale-up of gyrA serine 91 genotyping in N. gonorrhoeae infections could have substantial medical and public health benefits in settings where the majority of gonococcal infections are ciprofloxacin susceptible. CLINICAL TRIALS REGISTRATION: NCT02961751.

Multilevel Barriers to HIV PrEP Uptake and Adherence Among Black and Hispanic/Latinx Transgender Women in Southern California.

Black and Hispanic/Latinx transgender women in the United States (U.S.) are disproportionately affected by HIV. Pre-exposure prophylaxis (PrEP) reduces risk of HIV infection but PrEP uptake remains low among Black and Hispanic/Latinx transgender women. Between July 2018 and August 2019, we conducted individual interviews with 30 Black and Hispanic/Latinx transgender women who were prescribed PrEP through a PrEP demonstration project and 10 healthcare providers who provide PrEP services to transgender women in Los Angeles and San Diego, California. The interviews assessed general attitudes, experiences, and beliefs about PrEP as well as individual-, interpersonal-, community-, and structural-level barriers to PrEP uptake and adherence. PrEP adherence was assessed by collecting quantitative intracellular tenofovir-diphosphate (TFV-DP) levels in retrospect on batched, banked dried blood spot (DBS) samples. We utilized qualitative content analysis to identify themes from the interviews. Findings indicated the presence of individual-level barriers including cost concerns, mental health issues, substance use, and concerns about PrEP side effects including hormone interaction. Interpersonal-level barriers included the influence of intimate/romantic partners and the impact of patient-provider communication. Community-level barriers consisted of experiencing stigma and negative community opinions about PrEP use as well as having negative experiences in healthcare settings. Structural-level barriers included unreliable transportation, employment, and housing insecurity. Interventions aiming to increase PrEP uptake and adherence among Black and Hispanic/Latinx transgender women in the U.S. should employ a multilevel approach to addressing the needs of transgender women, especially the structural barriers that have greatly limited the use of PrEP.

RESUMEN: Las mujeres transexuales negras e hispanas/latinx en los Estados Unidos (EE. UU.) se ven afectadas de manera desproporcionada por el VIH. La profilaxis previa a la exposición (PrEP) reduce el riesgo de infección por VIH, pero la aceptación sigue siendo baja entre las mujeres transgénero negras e hispanas/latinx. Entre julio de 2018 y agosto de 2019, realizamos entrevistas individuales con 30 mujeres transgénero negras e hispanas/latinx a las que se les recetó PrEP a través de un proyecto de demostración de PrEP y a 10 proveedores de atención médica que brindan servicios de PrEP a mujeres transgénero en Los Ángeles y San Diego, California. Las entrevistas evaluaron las actitudes, experiencias y creencias generales sobre PrEP, así como las barreras a nivel individual, interpersonal, comunitario y estructural para la aceptación y la adherencia. La adherencia a PrEP se evaluó mediante la recolección de niveles intracelulares cuantitativos de difosfato de tenofovir (TFV-DP) en retrospectiva en muestras de manchas de sangre seca (DBS) acumuladas y almacenadas. Utilizamos análisis de contenido cualitativo para identificar temas de las entrevistas. Los hallazgos indicaron la presencia de barreras a nivel individual, incluidas preocupaciones de costos, problemas de salud mental, uso de sustancias y preocupaciones sobre los efectos secundarios de PrEP, incluida la interacción hormonal. Las barreras a nivel interpersonal incluyeron la influencia de las parejas íntimas/románticas y el impacto de la comunicación entre el paciente y el proveedor. Las barreras a nivel de la comunidad consistieron en experimentar estigma y opiniones negativas de la comunidad sobre el uso de PrEP, así como tener experiencias negativas en entornos de atención médica. Las barreras a nivel estructural incluían transporte poco confiable, así como inseguridad en el empleo y la vivienda. Las intervenciones destinadas a aumentar la aceptación y el cumplimiento de PrEP entre las mujeres transgénero negras e hispanas/latinx en los EE. UU. deben emplear un enfoque multinivel para abordar las necesidades de las mujeres transgénero, especialmente las barreras estructurales que han limitado en gran medida el uso de PrEP.

"PrEP"ing for a PrEP demonstration project: understanding PrEP knowledge and attitudes among cisgender women.

BACKGROUND: Prior to implementing a pre-exposure prophylaxis (PrEP) demonstration study, we sought to explore cisgender women's experiences with HIV prevention, PrEP knowledge and attitudes, and anticipated barriers and facilitators for PrEP uptake and adherence in Southern California. METHODS: Three focus groups were held with cisgender women of mixed HIV serostatus in San Diego and Los Angeles between November 2015 and January 2016. Women were recruited through local testing sites, community-based organizations, and social media. Focus groups were audio-recorded and transcripts were analyzed using thematic analysis. RESULTS: Twenty-two women participated in focus groups, with median age 44 (IQR 30-53) and 6 identifying as non-Hispanic Black, 7 non-Hispanic White, 8 Latina and 1 mixed race. Despite limited prior PrEP knowledge and no PrEP experience, participants expressed interest in taking PrEP. Anticipated benefits were freedom from worry about HIV and control over sexual health; however, these were tempered by concerns including the possibility of increased HIV risk behaviors and potential side effects. Cisgender women reported potential barriers to PrEP uptake and adherence barriers, like competing priorities and poor PrEP access. Conversely, PrEP facilitators included utilizing practical tools such as phone apps and pill boxes as well as receiving encouragement from loved ones and support from other cisgender women on PrEP, women living with HIV and their medical providers. CONCLUSIONS: Although PrEP awareness was low, participants recognized the importance of PrEP and ways to facilitate adherence. Exploring perspectives of cisgender women is integral to developing effective interventions to support PrEP uptake and adherence for women at elevated risk for HIV.

Effect of Cannabis Use on Human Immunodeficiency Virus DNA During Suppressive Antiretroviral Therapy.

Cannabis use is frequent among people living with human immunodeficiency virus (HIV) and is associated with reduced systemic inflammation. We observed a faster HIV DNA decay during antiretroviral therapy among cannabis users, compared to those with no drug use. No cannabis effect was observed on cellular HIV RNA transcription.

Sexually Transmitted Infections in Pregnancy and Reproductive Health: Proceedings of the STAR Sexually Transmitted Infection Clinical Trial Group Programmatic Meeting.

The goal of the STAR Sexually Transmitted Infection Clinical Trial Group (STI CTG) Programmatic meeting on Sexually Transmitted Infections (STIs) in Pregnancy and Reproductive Health in April 2018 was to review the latest research and develop recommendations to improve prevention and management of STIs during pregnancy. Experts from academia, government, nonprofit, and industry discussed the burden of STIs during pregnancy; the impact of STIs on adverse pregnancy and birth outcomes; interventions that work to reduce STIs in pregnancy, and the evidence, policy, and technology needed to improve STI care during pregnancy. Key points of the meeting are as follows: (i) alternative treatments and therapies for use during pregnancy are needed; (ii) further research into the relationship between the vaginal microbiome and STIs during pregnancy should be supported; (iii) more research to determine whether STI tests function equally well in pregnant as nonpregnant women is needed; (iv) development of new lower cost, rapid point-of-care testing assays could allow for expanded STI screening globally; (v) policies should be implemented that create standard screening and treatment practices globally; (vi) federal funding should be increased for STI testing and treatment initiatives supported by the Centers for Disease Control and Prevention (CDC), the Centers of Excellence in STI Treatment, public STD clinics, and the President's Emergency Plan for AIDS Relief (PEPFAR).

Greater Levels of Self-Reported Adherence to Pre-Exposure Prophylaxis (PrEP) are Associated with Increased Condomless Sex Among Men Who Have Sex with Men.

The effectiveness of pre-exposure prophylaxis (PrEP) against HIV acquisition depends on treatment adherence; however, within-person associations between levels of PrEP adherence and engagement in condomless sex have not been well studied. In the context of a demonstration project, 372 men who have sex with men received once-daily PrEP and completed six study visits over 48 weeks. Two-part growth mixture modeling was used to examine the longitudinal trajectory of condomless anal intercourse (CAI) and self-reports of PrEP adherence, controlling for relevant covariates. Over time, greater PrEP adherence was contemporaneously associated with both a higher likelihood of engaging in any CAI and with a greater number of CAI acts. Substance use was also associated with a higher likelihood of engaging in CAI. Contemporaneous associations between self-reported PrEP adherence and CAI suggest that adherence behaviors may be motivated by the desire to mitigate risk of HIV infection; however, exact directionality is unknown.

RESUMEN: La eficacia de la profilaxis Pre-exposición (PrEP) contra la adquisición del VIH depende de la adherencia al tratamiento; sin embargo, las asociaciones dentro de la persona entre los niveles de adherencia a PrEP y la participación en el sexo sin condón no han sido bien estudiadas. En un proyecto de demostración, 372 hombres que tienen relaciones sexuales con hombres recibieron PrEP diariamente y completaron seis visitas de estudio durante 48 semanas. El modelado de mezclas de crecimiento en dos partes se utilizó para examinar la trayectoria longitudinal de las relaciones sexuales anales sin condonación (CAI) y los autoinformes de adherencia a PrEP, controlando las covariables pertinentes. Con el tiempo, una mayor adherencia a PrEP se asoció a la misma vez con una mayor probabilidad de participar en cualquier CAI y tambien con un mayor número de CAI. El consumo de sustancias también se asoció con una mayor probabilidad de participar en CAI. Las asociaciones contemporáneas entre la adherencia a PrEP autoinformada y CAI sugieren que los comportamientos de adherencia pueden estar motivados por el deseo de mitigar el riesgo de infección por el VIH; sin embargo, se desconoce la direccionalidad exacta.

Syndemics and the PrEP Cascade: Results from a Sample of Young Latino Men Who Have Sex with Men.

Young Latino men who have sex with men (MSM) are a highly vulnerable population for HIV infection. Pre-exposure prophylaxis (PrEP) is a novel biomedical HIV prevention tool that may aid in reducing the disparity in HIV incidence among Latino MSM. However, PrEP use is disproportionally low among Latino MSM and, therefore, identifying barriers along the PrEP continuum of care (the "PrEP cascade") would provide insight into how to best deploy PrEP interventions. Syndemics theory is a prominent framework employed in HIV prevention; however, to date, no known studies have applied this theory to PrEP. Thus, the aim of the current study was to explore the association between syndemics and the PrEP cascade, including the degree to which psychosocial and structural syndemic constructs are related to the PrEP cascade. Participants were 151 young Latino MSM (M age = 24 years; SD = 3) residing in San Diego, California, who completed a battery of online self-report measures. Results indicated high levels of syndemic indicators and varying levels of engagement across the PrEP cascade. As syndemic indicators increased, the odds of engagement across the PrEP cascade were significantly lowered. Psychosocial and structural syndemic factors accounted for unique variance in the PrEP cascade. Results highlight the need for combination interventions that address both psychosocial and structural barriers to PrEP use and persistence among young Latino MSM.

Early Antiretroviral Therapy Is Associated with Lower HIV DNA Molecular Diversity and Lower Inflammation in Cerebrospinal Fluid but Does Not Prevent the Establishment of Compartmentalized HIV DNA Populations.

Even when antiretroviral therapy (ART) is started early after infection, HIV DNA might persist in the central nervous system (CNS), possibly contributing to inflammation, brain damage and neurocognitive impairment. Paired blood and cerebrospinal fluid (CSF) were collected from 16 HIV-infected individuals on suppressive ART: 9 participants started ART <4 months of the estimated date of infection (EDI) ("early ART"), and 7 participants started ART >14 months after EDI ("late ART"). For each participant, neurocognitive functioning was measured by Global Deficit Score (GDS). HIV DNA levels were measured in peripheral blood mononuclear cells (PBMCs) and CSF cell pellets by droplet digital (dd)PCR. Soluble markers of inflammation (sCD163, IL-6, MCP-1, TNF-α) and neuronal damage (neurofilament light [NFL]) were measured in blood and CSF supernatant by immunoassays. HIV-1 partial C2V3 env deep sequencing data (Roche 454) were obtained for 8 paired PBMC and CSF specimens and used for phylogenetic and compartmentalization analysis. Median exposure to ART at the time of sampling was 2.6 years (IQR: 2.2-3.7) and did not differ between groups. We observed that early ART was significantly associated with lower molecular diversity of HIV DNA in CSF (p<0.05), and lower IL-6 levels in CSF (p = 0.02), but no difference for GDS, NFL, or HIV DNA detectability compared to late ART. Compartmentalization of HIV DNA populations between CSF and blood was detected in 6 out of 8 participants with available paired HIV DNA sequences (2 from early and 4 from late ART group). Phylogenetic analysis confirmed the presence of monophyletic HIV DNA populations within the CSF in 7 participants, and the same population was repeatedly sampled over a 5 months period in one participant with longitudinal sampling. Such compartmentalized provirus in the CNS needs to be considered for the design of future eradication strategies and might contribute to the neuropathogenesis of HIV.

Self-initiated continuation of and adherence to HIV pre-exposure prophylaxis (PrEP) after PrEP demonstration project roll-off in men who have sex with men: associations with risky decision making, impulsivity/disinhibition, and sensation seeking.

The objective of this study was to examine differences in the levels of risky decision making and other frontal system behavior constructs in relation to self-initiated continuance of HIV pre-exposure prophylaxis (PrEP) and PrEP adherence outcomes among men who have sex with men (MSM) following completion of a clinical PrEP trial. At the last PrEP trial visit, study provided PrEP was discontinued and participants were navigated to the community for PrEP continuation. In this cross-sectional analysis, 84/187 (45%) MSM who completed a prospective observational post-PrEP trial follow-up visit at the University of California San Diego were included. PrEP adherence was measured using dried blood spot tenofovir diphosphate (TFV-DP) levels. Risky decision making was assessed using the Iowa Gambling Task (IGT) and the Balloon Analogue Risk Task (BART), while impulsivity/disinhibition, sensation seeking, and substance use were assessed via standardized self-report questionnaires. A total of 58/84 (69%) of MSM who completed the 12-month post-study visit continued PrEP. Of those, n = 46 (79%) reached TFV-DP levels associated with adequate adherence. Individuals who elected to continue PrEP 12 months post-trial had riskier decision making on BART, but less impulsivity/disinhibition compared to individuals who did not continue PrEP. Neither risky decision making nor impulsivity/disinhibition/sensation seeking nor substance use correlated with PrEP adherence. Our findings suggest that those with risky decision making may have greater insight into their HIV risks, and therefore be more likely to continue to use PrEP. However, elevated impulsivity/disinhibition, indicative of greater neurobehavioral alterations, was negatively associated with PrEP continuance and is a potential target for future interventions to help people link to PrEP.