Safety, Efficacy, and Pharmacokinetics of Combination SARS-CoV-2 Neutralizing Monoclonal Antibodies BMS-986414 (C135-LS) and BMS-986413 (C144-LS) Administered Subcutaneously in Non-Hospitalized Persons with COVID-19 in a Phase 2 Trial.

Background: Outpatient COVID-19 monoclonal antibody (mAb) treatment via subcutaneous delivery, if effective, overcomes the logistical burdens of intravenous administration. Methods: ACTIV-2/A5401 was a randomized, masked placebo-controlled platform trial where participants with COVID-19 at low risk for progression were randomized 1:1 to subcutaneously administered BMS-986414 (C135-LS) 200 mg, plus BMS-986413 (C144-LS) 200 mg, (BMS mAbs), or placebo. Coprimary outcomes were time to symptom improvement through 28 days; nasopharyngeal SARS-CoV-2 RNA below the lower limit of quantification (LLoQ) on days 3, 7, or 14; and treatment-emergent grade 3 or higher adverse events (TEAEs) through 28 days. Results: A total of 211 participants (105 BMS mAbs and 106 placebo) initiated study product. Time to symptom improvement favored the active therapy but was not significant (median 8 vs 10 days, P=0.19). There was no significant difference in the proportion with SARS-CoV-2 RNA

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.

Ingestible sensor system for measuring, monitoring and enhancing adherence to antiretroviral therapy: An open-label, usual care-controlled, randomised trial.

BACKGROUND: Co-encapsulated antiretrovirals (ARVs) with ingestible sensor (IS) has the capacity to monitor adherence in real-time using a sensor patch, a mobile device, and supporting software. We evaluated the acceptability, effectiveness, and sustainability of the IS system with real-time text reminders. METHODS: Participants were recruited from HIV clinics in Los Angeles and were randomised 1:1 to IS or usual care (UC) group. Adherence to ARVs (primary outcome) was measured by IS system (IS group only), plasma ARV concentration, and self-report. IS-measured adherence was clustered by group-based trajectory model and was validated by ARV concentration summarized by integrated pharmacokinetic adherence measure (IPAM) score. HIV RNA viral load (VL) was compared between IS and UC group. FINDINGS: A total of 112 (IS = 54, UC = 58) participants who completed baseline with at least one follow-up data collection were included in analyses. Overall satisfaction rate for the IS system was >90%. The IPAM score was higher (0.018, 95% CI: -0.098-0.134, p = 0.75) and VL decayed faster (-0.020, 95% CI: -0.042-0.002, p = 0.08) in the IS group compared with the UC group. The ingestible sensor system was well tolerated by study participants. INTERPRETATION: The IS system was well accepted by participants and its use was associated with improved adherence and lower HIV RNA VL. The findings provide a potentially effective strategy for improving adherence. FUNDING: This work was supported by grant R01-MH110056 from the National Institute of Mental Health (NIMH)/National Institutes of Health (NIH). Y. Wang was in part supported by the NIMH/NIH award T32MH080634. E. Daar was in part supported by the National Center for Advancing Translational Sciences through UCLACTSI Grant UL1TR001881. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Randomized Trial of Individualized Texting for Adherence Building (iTAB) Plus Motivational Interviewing for PrEP Adherence in Transgender Individuals: The iM-PrEPT Study.

BACKGROUND: Transgender and nonbinary individuals at risk for HIV may benefit from adherence support for pre-exposure prophylaxis. METHODS: Between June 2017 and September 2020, 255 transgender and nonbinary individuals received daily oral tenofovir disoproxil fumarate/emtricitabine for 48 weeks randomized 1:1 to receive individualized Texting for Adherence Building (iTAB) or iTAB plus motivational interviewing (iTAB + MI) through phone for nonadherence. The primary end point was dried blood spot tenofovir diphosphate concentrations at weeks 12 and 48 (or last on-drug study visit) ≥1246 fmol/punch consistent with ≥7 doses/week (ie, near-perfect adherence). Secondary outcomes included dried blood spot tenofovir diphosphate concentrations ≥719 fmol/punch consistent with ≥4 doses/week (ie, adequate adherence) and self-reported adherence by daily text messages. RESULTS: Adherence for the outcome ≥1246 fmol/punch and ≥719 fmol/punch, respectively, was 49.1% and 57.9% for transgender men, 37.7% and 47.2% for nonbinary individuals, and 31.0% and 44.1% for transgender women. No difference was seen in iTAB + MI compared with iTAB alone by drug levels except where it approached significance in transgender women for the outcome of ≥719 fmol/punch in the iTAB + MI group compared with iTAB only (52% versus 35.7%, P = 0.065). There was a significant difference in self-reported daily dose adherence in the iTAB + MI group compared with iTAB alone (57.9% of days versus 46.4%, P = 0.009). In transgender women, the mean percentage of daily doses taken was 58.5% with iTAB + MI and 37.3% with iTAB alone ( P < 0.001). CONCLUSIONS: In addition to automated approaches to adherence promotion, phone-based MI triggered by repeatedly missing doses may improve pre-exposure prophylaxis adherence among transgender women.

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.

Sexually transmitted infections among participants in an HIV PrEP adherence trial.

BACKGROUND: HIV PrEP effectiveness is highly dependent on adherence. High STI incidence has been reported among PrEP users. We assessed the relationship between STI incidence (CT, NG, and syphilis) and PrEP adherence. METHODS: We performed a subanalysis of a controlled, open-label, two-arm, randomized clinical demonstration project of a text-message based adherence intervention. Participants had 48 weeks of follow-up and had STI testing every 12 or 24 weeks. PrEP adherence was measured at week 48 using intracellular tenofovir-diphosphate drug concentrations. We calculated incidence rate ratios for STIs among those adherent as compared with those not adherent to PrEP. RESULTS: Of the 381 assessed for CT, NG and syphilis at one or more follow-up visits, there were 16 cases of syphilis or 5.0 per 100 person years (95% CI: 2.6, 7.5); 63 cases of NG or 26.3 per 100 person years (95% CI: 19.8, 32.8); and 81 cases of CT or 36.3 per 100 person years (95% CI: 28.4, 44.2). We found no association between adequate PrEP adherence and STI incidence (aIRR: 0.97 95% CI: 0.67, 1.40). CONCLUSIONS: We found that the incidence of STIs was not significantly different between those adherent to PrEP and those non-adherent. Further research is needed to assess how PrEP use may impact STIs over time.

Pre-Exposure Prophylaxis Perspectives, Sociodemographic Characteristics, and HIV Risk Profiles of Cisgender Women Seeking and Initiating PrEP in a US Demonstration Project.

Little information is known about the cisgender women who seek and initiate pre-exposure prophylaxis (PrEP) for HIV prevention in the United States. Adherence Enhancement Guided by Individualized Texting and Drug Levels was a 48-week single-arm open-label demonstration study of daily oral tenofovir disoproxil fumaratel emtricitabine (TDF/FTC) in cisgender women ≥ 18 years old at risk for HIV. Participants were surveyed at screening and enrollment about sociodemographics, HIV risk perception and behaviors, and PrEP perspectives and aggregated into three risk groups according to HIV sexual risk behavior: being in a serodiscordant partnership (SD), engaging in sex work (SW), and having partners with unknown HIV status at risk for HIV (UP). One hundred sixty-seven women presented for screening with n = 31 screen failures. Of the 162 women completing enrollment, mean age was 40 (standard deviation 11), with 41% non-Hispanic Black, 22% non-Hispanic White, and 19% Latina. Compared with those who screened ineligible, enrolled participants were more likely to have heard of PrEP, had higher HIV risk perception, and reported higher perceived PrEP efficacy. Sixty-four women (47%) were categorized as SD, 21 (15%) as SW, and 51 (38%) as UP. The SW were more likely to report higher levels of drinking and drug use (p = 0.002) and history of intimate partner violence in the past year (p < 0.001) compared with SD and UP. Among cisgender women enrolled, there were significant differences between the three risk groups by demographics, HIV risk behavior, and PrEP perspectives, suggesting that interventions to successfully implement PrEP in US women may need to be tailored by HIV risk group. Clinical Trial Registration number: NCT02584140.

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.

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.

Barriers and Facilitators to PrEP Initiation and Adherence Among Transgender and Gender Non-Binary Individuals in Southern California.

While transgender and gender non-binary (trans/nb) individuals are disproportionately affected by HIV, pre-exposure prophylaxis (PrEP) uptake remains low in this underserved population. We conducted four focus groups with 37 trans/nb individuals in San Diego and Los Angeles to assess barriers and facilitators of PrEP usage. Transcripts were coded for qualitative themes. Although overall PrEP awareness was high, participants reported limited knowledge and misinformation about PrEP. Barriers to PrEP use included: structural access (e.g., discrimination from health care providers, lack of trans-inclusive services, financial barriers), mental health struggles limiting ability to access PrEP, and concerns about potential side effects, drug-drug interactions with hormone therapy, and lack of other STI protection. Facilitators of PrEP usage included: increased PrEP availability, prior experience taking daily medications, and motivation to have active and healthy lives without fear of contracting HIV. Addressing both structural and psychosocial/behavioral factors in trans-affirming health care environments is crucial to designing inclusive, effective PrEP interventions.

Real-Time and Wireless Assessment of Adherence to Antiretroviral Therapy With Co-Encapsulated Ingestion Sensor in HIV-Infected Patients: A Pilot Study.

Adherence with antiretroviral therapy is important for preventing disease progression and HIV transmission. The co-encapsulated pill sensor system sends a signal through a cutaneous patch and allows real-time monitoring of pill ingestion. A 16-week pilot study used a sensor system in 15 HIV-infected individuals with real-time monitoring of pill-taking with a personalized short message system text. System acceptability was assessed by survey at weeks 4, 8, 12, and 16. Follow-up occurred in 80% of subjects through 8 weeks. The system effectively collected measures of pill ingestion, which triggered text message reminders. Only 2 of 14 participants stated that co-encapsulated pills were "unable to take" or "poorly tolerated." At least 75% of respondents stated at each visit that the patch was very or somewhat comfortable. With regard to text message reminders, only 10-15% of the participants at any visit did not find the messages to be helpful. Larger studies will define the utility of this system to assess antiretroviral adherence relative to standard measures.

Characteristics of a cohort of high-risk men who have sex with men on pre-exposure prophylaxis reporting transgender sexual partners.

Transgender people continue to be at high-risk for HIV acquisition, but little is known about the characteristics of their sexual partners. To address this gap, we examined sociodemographic and sexual characteristics of cisgender men who have sex with men (MSM) on pre-exposure prophylaxis (PrEP) reporting transgender sexual partners.A cohort of 392 MSM in southern California in a randomized clinical trial for PrEP adherence were followed from 2013 to 2016. Multivariable generalized estimating equation and logistic models identified characteristics of MSM reporting transgender sexual partners and PrEP adherence.Only 14 (4%) MSM reported having transgender sexual partners. MSM were more likely to report transgender partners if they were African American, had incident chlamydia, reported injection drug-using sexual partners, or received items for sex. Most associations remained significant in the multivariable model: African American (adjusted odds ratio [AOR] 11.20, P = .01), incident chlamydia (AOR 3.71, P = .04), and receiving items for sex (AOR 5.29, P = .04). There were no significant differences in PrEP adherence between MSM reporting transgender partners and their counterpart.MSM who report transgender sexual partners share characteristics associated with individuals with high HIV prevalence. Identifying this group distinct from larger cohorts of MSM could offer new HIV prevention opportunities for this group of MSM and the transgender community.

Recent HIV Risk Behavior and Partnership Type Predict HIV Pre-Exposure Prophylaxis Adherence in Men Who Have Sex with Men.

Men who have sex with men (MSM) reporting higher HIV risk behavior over time are often more adherent to pre-exposure prophylaxis (PrEP), but it is unclear if recent risk behavior and partnership type affect long-term PrEP adherence. HIV-negative MSM and transgender women completing the 48-week randomized study TAPIR (Daily Text Messages to Support Adherence to PrEP in At-Risk for HIV Individuals) were included. At baseline and weeks 24 and 48, a modified Calculated Risk (mCalcR) Score estimated the likelihood of HIV seroconversion over 1 year based on reported condomless anal sex acts in the last month and current sexually transmitted infection. mCalcR scores were categorized as low, moderate, and high/very high risk. Partnership type was classified as no partner/single HIV-negative partner (no/single-), single HIV-positive partner (single+), or multiple partners of any serostatus (multi) in the past 3 months. PrEP adherence was measured by intracellular tenofovir-diphosphate (TFV-DP) levels. Among 313 individuals, there was no difference in mCalcR category from baseline to week 48. There was a significant change in partnership type, with no/single partnerships increasing from 0.5% to 9%. Participants with moderate and high/very risk had higher TFV-DP levels than the low-risk group. No/single participants had lower TFV-DP levels than those reporting single+ or multi. Although there was a shift toward lower-risk partnerships, HIV risk category remained stable over time. Individuals with riskier behaviors and partnerships had higher PrEP drug levels, suggesting continued motivation for and adherence to PrEP.

Predictors of Long-Term HIV Pre-exposure Prophylaxis Adherence After Study Participation in Men Who Have Sex With Men.

BACKGROUND: Efficacy of HIV pre-exposure prophylaxis (PrEP) among men who have sex with men is well documented in randomized trials. After trial completion, participants are challenged with acquiring PrEP on their own and remaining adherent. METHODS: This was a follow-up study of the TAPIR randomized controlled multicenter PrEP trial. Participants were contacted after their last TAPIR visit (ie, after study-provided PrEP was discontinued) to attend observational posttrial visits 24 and 48 weeks later. Adherence during TAPIR and posttrial visits was estimated by dried blood spot intracellular tenofovir diphosphate levels (adequate adherence defined as tenofovir diphosphate levels >719 fmol/punch). Binary logistic regression analysis assessed predictors of completing posttrial visits and PrEP adherence among participants completing ≥1 visit. RESULTS: Of 395 TAPIR participants who were on PrEP as part of the TAPIR trial for a median of 597 days (range 3-757 days), 122 (31%) completed ≥1 posttrial visit (57% of University of California San Diego participants completed posttrial visits, whereas this was 13% or lower for other study sites). Among participants who completed ≥1 posttrial visit, 57% had adequate adherence posttrial. Significant predictors of adequate adherence posttrial were less problematic substance use, higher risk behavior, and adequate adherence in year 1 of TAPIR. CONCLUSION: More than half of PrEP users followed after trial completion had successfully acquired PrEP and showed adequate adherence. Additional adherence monitoring and intervention measures may be needed for those with low PrEP adherence and problematic substance use during the first year of trial.

Effect of Vitamin D Supplementation on Bone Turnover Markers During HIV Pre-Exposure Prophylaxis Using Tenofovir Disoproxil Fumarate-Emtricitabine in Men Who Have Sex with Men.

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC) reduces bone mineral density in HIV-uninfected men who have sex with men (MSM). We hypothesized that PrEP with TDF-FTC would increase bone turnover markers (BTMs) at week 24 and that vitamin D supplementation from weeks 24 to 48 would blunt this increase. Participants were from a cohort of 398 MSM and transgender women who received daily TDF-FTC for PrEP. At week 24, a prospective intervention group initiated vitamin D3 4,000 IU daily. Concurrent controls were selected from the cohort who took ≤400 IU/day of vitamin D3 matched by age, race, and body mass index. The primary endpoint was the change in procollagen-I N-terminal propeptide (P1NP) from weeks 24 to 48. Paired t-tests were used to compare changes in BTMs between intervention and controls. Among 48 intervention-control pairs, median age was 33 years. At baseline, 68.9% of the intervention group and 77.3% of controls were vitamin D sufficient (≥20 ng/mL, p = .94). P1NP, C-telopeptide, parathyroid hormone (PTH), and 25-OH vitamin D3 did not increase significantly at week 24. P1NP fell by a mean ± SD of -27.6 ± 49.9 pg/mL from weeks 24 to 48 with vitamin D and -2.5 ± 40.2 pg/mL in controls (p = .01). There were no significant between-group differences in the weeks 24-48 change in C-telopeptide, PTH, or 25-OH vitamin D3. Vitamin D3 supplementation with 4,000 IU/day resulted in a significant reduction in the BTM P1NP compared with controls, suggesting that this intervention has potential to improve bone health during PrEP.

Sexual Risk Compensation in a Pre-exposure Prophylaxis Demonstration Study Among Individuals at Risk of HIV.

BACKGROUND: A public health concern regarding HIV pre-exposure prophylaxis (PrEP) is sexual risk compensation (ie, increased unsafe sex among PrEP users that may undermine prevention efforts). METHODS: This demonstration study (NCT#01761643; initiated in 2013) included 398 men who have sex with men who initiated PrEP and were followed over 48 weeks at 4 sites in Southern California. Wilcoxon signed-rank tests compared previous 30-day number of sex partners and condomless insertive anal sex and receptive anal sex (CIAS and CRAS, respectively) acts at weeks 4, 12, 24, 36, and 48 to baseline. At 2 sites, PrEP users were also compared with a lagged, comparison group of 99 men who have sex with men who did not receive PrEP over 24 weeks using linear regression models, adjusting for age, race/ethnicity, education, and respective baseline scores. Logistic regression compared week 24 sexually transmitted infection (STI) rates. RESULTS: Over 48 weeks in the PrEP group, there were significant decreases in the number of unknown HIV status sex partners and increases in CRAS at all study visits; there was no consistent change in number of HIV+ sex partners or CIAS. Among participants at 2 sites, there were no significant differences between PrEP and non-PrEP users in change in number of partners, CIAS, CRAS, or STI rates at week 24. CONCLUSIONS: Among early adopters of PrEP, there is some evidence for sexual risk compensation. Results support current guidelines of regular STI screening and behavioral risk reduction and adherence counseling with the provision of PrEP.

Two-drug regimens for treatment of naïve HIV-1 infection and as maintenance therapy.

As people live longer with HIV infection, there has been a resurgence of interest in challenging the use of three-drug therapy, including two nucleoside reverse transcriptase inhibitors plus a third drug, as initial treatment of HIV infection or for maintenance therapy in virologically suppressed individuals. Although initial studies showed poor efficacy and/or substantial toxicity, more recent regimens have held greater promise. The SWORD-1 and -2 studies were pivotal trials of dolutegravir plus rilpivirine as maintenance therapy in virologically suppressed patients with no history of drug resistance, leading to the US Food and Drug Administration's approval of the regimen as a small, single tablet. More recently, the GEMINI-1 and -2 studies demonstrated that dolutegravir plus lamivudine is as safe and effective as the same regimen when combined with tenofovir disoproxil fumarate in treatment-naïve individuals. Together, these and other studies of novel two-drug regimens offer the potential for improved tolerability and simplicity, as well as a reduction in cost. We will review historical and recent trials of two-drug therapy for the treatment of HIV-1 infection.

Substance Use and Adherence to HIV Preexposure Prophylaxis for Men Who Have Sex with Men1.

The effectiveness of oral HIV preexposure prophylaxis (PrEP) strongly depends on maintaining adherence. We investigated the association between substance use and PrEP adherence, as well as incident sexually transmitted infections (STIs) in a high-risk cohort of 394 participants (391 men who have sex with men and 3 transgender women) who were enrolled in a PrEP demonstration project. We assessed baseline and ongoing substance use over a 48-week period for stimulants and nonstimulant substances and for each substance separately. We measured PrEP adherence by using dried blood spots to obtain levels of tenofovir diphosphate. No differences in these levels were found between substance users and nonsubstance users. Baseline stimulant use was strongly associated (odds ratio 3.4; p<0.001) with incident STIs during the study. Thus, PrEP adherence was not decreased by substance use. Because substance users had increased rates of STIs, indicating higher-risk behavior, they might be excellent candidates for PrEP.

Trajectories and Predictors of Longitudinal Preexposure Prophylaxis Adherence Among Men Who Have Sex With Men.

Background: Adherence is necessary for efficacy of preexposure prophylaxis (PrEP), and text-messaging methods are promising tools for both adherence assessment and support. Although PrEP adherence is variable, little research has examined patterns of variability or factors associated with longitudinal use. Methods: In the context of a randomized controlled trial of text-messaging versus standard of care for PrEP adherence, 181 men who have sex with men received once-daily tenofovir disoproxil fumarate/emtricitabine and daily adherence texts for 48 weeks. Growth mixture modeling (GMM) was used to identify subgroups of individuals with similar trajectories of text-reported adherence. Between-group differences in pharmacologic measures of adherence (ie, tenofovir diphosphate and emtricitabine triphosphate levels), as well as predictors and study-end attitudes associated with group membership, were examined. Results: GMM identified 4 trajectories of text-reported adherence. Classes with higher text-reported adherence had higher drug concentrations. Younger age and minority race were associated with lower adherence, and individuals in classes with lower adherence had greater baseline levels of depression, substance use concerns, and sexual risk. Differences in study satisfaction were also associated with adherence. Conclusions: This study supports the use of text-reported PrEP adherence. Identifying factors associated with less-than-optimal adherence may aid clinicians in anticipating at-risk patients requiring augmented intervention. Clinical trials registration: NCT01761643.

Effect of rectal douching/enema on rectal gonorrhoea and chlamydia among a cohort of men who have sex with men on HIV pre-exposure prophylaxis.

OBJECTIVES: Rectal douching/enema (RD) is a common practice among men who have sex with men (MSM) in preparation for sex. RD can break down the rectal mucosal barrier and potentially affect the rectal microbiome. The objective of this study was to understand if RD is associated with acquiring rectal infections (RI) with rectal gonorrhoea (NG) and/or chlamydia (CT). METHODS: From 2013 to 2015, 395 adult HIV-uninfected MSM were enrolled in a randomised controlled study for pre-exposure prophylaxis (PrEP) adherence with routine sexual risk survey and testing. Using data from this cohort, baseline differences by RI were assessed using Pearson's χ² and Wilcoxon-Mann-Whitney test. Association between RD and RI was modelled using multivariable logistic regression adjusted for potential confounders (sexual behaviour, substance use and age) selected a priori. Effect modification by number of male partners and sensitivity analysis to rule out reverse causality were also conducted. RESULTS: Of 395 participants, 261 (66%) performed RD and 133 (33%) had at least one NG/CT RI over 48 weeks. Number of condomless anal receptive sex (med: 4, p<0.001), male partners (med:6, p<0.001) and substance use (any of methamphetamine/hallucinogens/dissociative/poppers) (p<0.001) were associated with increased odds of RI. Controlling for potential confounders, odds of prevalent RI were 3.59 (p<0.001, 95% CI 1.90 to 6.78) and incident RI 3.87 (p=0.001, 95% CI 1.78 to 8.39) when douching weekly or more compared with not douching. MSM with more than six male partners had 5.34 (p=0.002, 95% CI 1.87 to 15.31) increased odds of RI when douching weekly or more compared with not douching. CONCLUSION: Rectal hygiene with RD is a common practice (66%) among HIV-uninfected MSM on PrEP in this study, which increases the odds of acquiring rectal NG and/or CT independent of sexual risk behaviour, substance use and other factors. This suggests interventional approaches targeting rectal hygiene products and practices could reduce sexually transmitted infections.