12 research outputs found
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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
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Sexually transmitted infections among participants in an HIV PrEP adherence trial.
BackgroundHIV 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.MethodsWe 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.ResultsOf 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).ConclusionsWe 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
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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
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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
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Trajectories and Predictors of Longitudinal Preexposure Prophylaxis Adherence Among Men Who Have Sex With Men.
BackgroundAdherence 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.MethodsIn 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.ResultsGMM 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.ConclusionsThis 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 registrationNCT01761643
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Trajectories and Predictors of Longitudinal Preexposure Prophylaxis Adherence Among Men Who Have Sex With Men.
BackgroundAdherence 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.MethodsIn 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.ResultsGMM 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.ConclusionsThis 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 registrationNCT01761643
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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
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
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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
BackgroundOutpatient COVID-19 monoclonal antibody (mAb) treatment via subcutaneous delivery, if effective, overcomes the logistical burdens of intravenous administration.MethodsACTIV-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.ResultsA 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 ConclusionsWhile safe, the BMS mAbs delivered subcutaneously were not effective at treating COVID-19 at low risk for progression. The lack of clinically significant activity may relate to the pharmacokinetics of subcutaneous administration of mAbs