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Chronic HIV disease is associated with a fivefold increase in albuminuria outside of sub-Saharan Africa. However, very little is known about albuminuria risk among people living with HIV (PLWH) in sub-Saharan Africa. Therefore, we conducted a cross-sectional observational HIV clinic-based study of albuminuria among 1533 adults aged 21 years or older between January 2020 and January 2021 in Gaborone, Botswana. Clinical albuminuria was defined using a sex-based albumin‒creatinine ratio (ACR) of 25-355 mg/g for females and 17-250 mg/g for males. The study population mean age was 48.5 (SD 10.3) years, and 764/1533 (49.7%) were female. The overall prevalence of albuminuria was 20.7% (95% CI 18.7%, 22.8%). A higher proportion of males were more likely to be categorized as having albuminuria than females, 25% (95% CI 22.0, 28.2) versus 16.4% (95% CI 13.8,19.2), P value < 0.001. In the final multivariate models, predictors of albuminuria differed by sex group. Larger longitudinal studies are required to evaluate the impact of albuminuria among PLWH with particular emphasis on the effect of sex on the risk of albuminuria., (© 2024. The Author(s).)

Purpose: We sought to elicit perspectives on HIV and sexually transmitted infection (STI) prevention among adolescents with recent STIs in primary care to optimize acceptability and effectiveness in designing a novel HIV/STI prevention intervention., Methods: We enrolled 13-19 year-olds with recent gonorrhea, chlamydia, trichomonas, and/or syphilis in a multimethods cross-sectional study at two primary care clinics. Participants completed surveys and interviews. We used an integrated analytic approach deductively coding data using the Integrated Behavioral Model, then inductively coding to identify themes not represented in the Integrated Behavioral Model., Results: Participants (n = 35) were 85% cisgender female, 14% cisgender male, 1% transgender female; 25% identified as lesbian, bisexual, or queer. Most (97%) identified as non-Latinx Black. None used condoms consistently, 26% were aware of pre-exposure prophylaxis (PrEP), and 31% were never HIV tested. Five key themes emerged. 1) Mental health was central to HIV prevention behavior uptake and coping with STI diagnosis. 2) Youth desired prevention counseling that allowed decisional autonomy and individualized goal setting. 3) Negative social norms around condoms and absent norms around HIV testing and PrEP limited method uptake. 4) Both confidence and concrete skills were needed to initiate prevention methods. 5) Youth desired education at the time of STI diagnosis to improve subsequent prevention decision making., Discussion: Key intervention design considerations included 1) integrating mental health assessment and referral to services, 2) promoting individualized goal setting, 4) building communication skills, 4) providing navigation and material support for PrEP uptake and HIV testing, and 5) augmenting comprehensive STI and HIV prevention education., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Food insecurity and undernutrition are related but distinct concepts contributing to poor HIV and tuberculosis outcomes. Pathways linking them with immunologic profile, which may relate to clinical outcomes, remain understudied., Methods: We analyzed data from a cohort study of 165 antiretroviral therapy (ART)-naïve adults with advanced HIV and newly diagnosed tuberculosis in Botswana from 2009 to 2013. Twenty-nine plasma biomarkers were measured pre-ART and 4 weeks post-ART initiation. We used principal components analysis (PCA) and multivariable linear regression models to assess relationships between immunological profiles and food insecurity (based on the Household Food Insecurity Access Scale), undernutrition (body mass index <18.5 kg/m 2 ), and clinical outcomes., Results: PCA identified 5 principal components with eigenvalues >1. After adjustment, food insecurity was associated with PC3 pre-ART (0.19 per increased category of severity, 95% CI: 0.02 to 0.36) and post-ART (0.24, 95% CI: 0.07 to 0.41). PC3 was driven by higher levels of IFN-α, IFN-γ, interleukin (IL)-12p40, vascular endothelial growth factor, IL-1α, and IL-8 and decreased concentrations of IL-3. Undernutrition was associated with PC5 post-ART (0.49, 95% CI: 0.16 to 0.82). PC5 was driven by higher levels of IL-8, MIP-1α, IL-6, and IL-10 and decreased concentrations in IP-10 and IFN-α. Post-ART PC3 (4.3 percentage point increased risk per increased score of 1, 95% CI: 0.3 to 8.9) and post-ART PC5 (4.8, 95% CI: 0.6 to 8.9) were associated with death in adjusted models., Discussion: We identified 2 distinct immunologic profiles associated with food insecurity, undernutrition, and clinical outcomes in patients with advanced HIV and tuberculosis. Different pathophysiologic processes may link food insecurity and undernutrition with poor outcomes in this vulnerable patient population. Future studies should assess the impact of improving food access and intake on immune function and clinical outcomes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

People living with HIV (PLWH) experience increased vulnerability to premature aging and inflammation-associated comorbidities, even when HIV replication is suppressed by antiretroviral therapy (ART). However, the factors associated with this vulnerability remain uncertain. In the general population, alterations in the N-glycans on IgGs trigger inflammation and precede the onset of aging-associated diseases. Here, we investigate the IgG N-glycans in cross-sectional and longitudinal samples from 1214 women and men, living with and without HIV. PLWH exhibit an accelerated accumulation of pro-aging-associated glycan alterations and heightened expression of senescence-associated glycan-degrading enzymes compared to controls. These alterations correlate with elevated markers of inflammation and the severity of comorbidities, potentially preceding the development of such comorbidities. Mechanistically, HIV-specific antibodies glycoengineered with these alterations exhibit a reduced ability to elicit anti-HIV Fc-mediated immune activities. These findings hold potential for the development of biomarkers and tools to identify and prevent premature aging and comorbidities in PLWH., (© 2024. The Author(s).)

Approximately one-quarter of people with HIV (PWH) in the U.S. receive coverage through the Medicare program; however, no prior real-world study has examined antiretroviral therapy (ART) gaps and adherence and associated factors in this population. This retrospective cohort analysis used 2013-2018 national Medicare fee-for-service claims data to identify all PWH initiated on a new ART regimen including protease inhibitors [PI], non-nucleoside reverse transcriptase inhibitors [NNRTIs], or integrase strand transfer inhibitors [INSTIs] between 1/1/2014 and 12/31/2017. Study outcomes included ART adherence (based on proportion of days covered [PDC]), continuous treatment gaps ranging from 1 to 6 days to ≥ 180 days, and discontinuation (continuous gap ≥ 90 days) in the 12-month follow-up period. Multivariable regressions were used to assess factors associated with ART adherence and discontinuation. The final sample included 48,627 PWH (mean age: 54.5 years, 74.4% male, 47.5% White, 89.8% disabled). Approximately 53.0% of PWH had a PDC ≥ 0.95, 30.2% had a PDC between 0.70 and < 0.95, and 16.8% had PDC < 0.70. Treatment gaps of at least ≥ 7-days (55.2%) and ≥ 30-days (26.2%) were common and 10.1% PWH discontinued treatment. Younger age, female sex, Black race, higher comorbidity score, mental health conditions, and substance use disorder were associated with higher odds of lower adherence and discontinuation (all p-values < 0.05). In conclusion, suboptimal adherence and treatment gaps in ART use were commonly observed among PWH in Medicare. Interventions and policies to mitigate barriers to adherence are urgently needed in this population to both improve their survival and increase the potential for ending the HIV epidemic in the US., (© 2023. The Author(s).)

Rates of cigarette smoking in people with HIV (PWH) are two to three times higher than in people without HIV. Nicotine is metabolized by CYP2A6 and the nicotine metabolite ratio (NMR; 3-hydroxycotinine/cotinine) is a measure of nicotine clearance. Higher NMR has been observed in PWH and is associated with lower quit rates. Efavirenz, a mainstay antiretroviral therapy (ART) globally, partially upregulates its own metabolism through CYP2A6. We hypothesized that efavirenz also upregulates nicotine metabolism by CYP2A6, resulting in a higher NMR, and switching to non-efavirenz ART would decrease the NMR, potentially leading to improved quit rates. We compared the NMR during and after efavirenz use among PWH in a longitudinal, multisite cohort. Eligibility criteria included: (i) active cigarette smoking, (ii) ART switched from efavirenz-based to non-efavirenz-based regimen, (iii) plasma available at pre- and post-ART switch, and (iv) viral suppression during study period. Plasma cotinine and 3-hydroxycotinine were measured by liquid chromatography-tandem mass spectrometry. T-tests compared the NMR on and off efavirenz. Samples were collected between 2010 and 2019 in 72 PWH. The mean NMR difference after switching to a non-efavirenz-based regimen was -0.24 (SD: 0.37, P < 0.001); 44 PWH had at least a 0.1 decrease in NMR. Effect modification by race was present; Black PWH had a larger mean decrease. Our findings suggest that previously observed higher NMR among PWH may be due to direct pharmacologic effects of ART. Assessing the effect of ART on the NMR suggests that avoiding nicotine metabolism inducers could potentially increase quit rates., (© 2023 The Authors. Clinical Pharmacology & Therapeutics © 2023 American Society for Clinical Pharmacology and Therapeutics.)

Background: Patients with breast cancer in sub-Saharan Africa (SSA) experience a disproportionate burden of mortality. Fidelity to treatment guidelines, defined as receiving optimal dose and frequency of prescribed treatments, improves survival. We sought to identify patient factors associated with treatment fidelity and how this may differ for people with HIV (PWH) and breast cancer., Methods: We conducted a qualitative study of women who initiated outpatient treatment for stages I-III breast cancer in Botswana, with deviance sampling of high- and low-fidelity patients. One-on-one interviews were conducted using semi-structured guides informed by the Theory of Planned Behavior. The sample size was determined by thematic saturation. Transcribed interviews were double coded with an integrated analytic approach., Results: We enrolled 15 high- and 15 low-fidelity participants from August 25, 2020 to December 15, 2020, including 10 PWH (4 high, 6 low fidelity). Ninety-three percent had stage III disease. Barriers to treatment fidelity included stigma, social determinants of health (SDOH), and health system barriers. Acceptance and de-stigmatization, peer and other social support, increased knowledge and self-efficacy were identified as facilitators. The COVID-19 pandemic amplified existing socioeconomic stressors. Unique barriers and facilitators identified by PWH included intersectional stigma, and HIV and cancer care integration, respectively., Conclusion: We identified multilevel modifiable patient and health system factors associated with fidelity. The facilitators provide opportunities for leveraging existing strengths within the Botswana context to design implementation strategies to increase treatment fidelity to guideline-concordant breast cancer therapy. However, PWH experienced unique barriers, suggesting that interventions to address fidelity may need to be tailored to specific comorbidities., (© The Author(s) 2023. Published by Oxford University Press.)

Introduction: To end the HIV epidemic in Philadelphia, implementation of evidence-based practices (EBP) to increase viral suppression and retention in HIV care is critical. Managed problem solving (MAPS), an EBP for antiretroviral therapy adherence, follows a problem-solving approach to empower people living with HIV (PWH) to manage their health. To overcome barriers to care experienced by PWH in Philadelphia, the EBP was adapted to include a focus on care retention and delivery by community health workers (CHWs). The adapted intervention is MAPS+. To maximise the clinical impact and reach of the intervention, evaluation of the effectiveness and implementation of MAPS+ is necessary., Methods and Analysis: This manuscript describes the protocol for a stepped-wedge cluster-randomised type 2 hybrid effectiveness-implementation trial in 10 clinics in Philadelphia. This research incorporates innovative approaches to accomplish three objectives: (1) to evaluate the effectiveness of the CHW-led MAPS+ intervention to improve viral suppression and retention in care 1 year after the individual implementation period (N=390 participants), (2) to examine the effect of the menu of implementation strategies on reach and implementation cost and (3) to examine processes, mechanisms, and sustainment of the implementation strategies for MAPS+ (N=56 participants). Due to various factors (eg, COVID-19), protocol modifications have occurred., Ethics and Dissemination: The institutional review board (IRB) at the city of Philadelphia serves as the primary IRB; initial approval was granted on 21 December 2020. The University of Pennsylvania and Northwestern University executed reliance agreements. A safety monitoring committee comprised experts in implementation science, biostatistics and infectious diseases oversee this study. This research will offer insights into achieving the goals to end the HIV epidemic in Philadelphia as well as implementation efforts of MAPS+ and other behavioural interventions aimed at increasing medication adherence and retention in care. Dissemination will include deliverables (eg, peer-reviewed manuscripts and lay publications) to reach multiple constituents., Trial Registration Number: NCT04560621., Competing Interests: Competing interests: RSB is principal at Implementation Science & Practice. She receives royalties from Oxford University Press, consulting fees from United Behavioral Health and OptumLabs, and serves on the advisory boards for Optum Behavioral Health, AIM Youth Mental Health Foundation, and the Klingenstein Third Generation Foundation outside of the submitted work., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Chronic obstructive pulmonary disease (COPD) is one of the most common comorbid diseases among aging people with HIV (PWH) and is often mismanaged. To address this gap, we are conducting the study, "Advancing care for COPD in people living with HIV by Implementing Evidence-based management through proactive E-consults (ACHIEVE)." This intervention optimizes COPD management by promoting effective, evidence-based care and de-implementing inappropriate therapies for COPD in PWH receiving care at Veteran Affairs (VA) medical centers. Study pulmonologists are proactively supporting ID providers managing a population of PWH who have COPD, offering real-time evidence-based recommendations tailored to each patient. We are leveraging VA clinical and informatics infrastructures to communicate recommendations between the study team and clinical providers through the electronic health record (EHR) as an E-consult. If effective, ACHIEVE could serve as a model of effective, efficient COPD management among PWH receiving care in VA. This paper outlines the rationale and methodology of the ACHIEVE trial, one of a series of studies funded by the National Heart, Lung, and Blood Institute (NHLBI) within the ImPlementation REsearCh to DEvelop Interventions for People Living with HIV (PRECluDE) consortium to study chronic disease comorbidities in HIV populations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Semen is an important vector for sexual HIV-1 transmission. Although CXCR4-tropic (X4) HIV-1 may be present in semen, almost exclusively CCR5-tropic (R5) HIV-1 causes systemic infection after sexual intercourse. To identify factors that may limit sexual X4-HIV-1 transmission, we generated a seminal fluid-derived compound library and screened it for antiviral agents. We identified four adjacent fractions that blocked X4-HIV-1 but not R5-HIV-1 and found that they all contained spermine and spermidine, abundant polyamines in semen. We showed that spermine, which is present in semen at concentrations up to 14 mM, binds CXCR4 and selectively inhibits cell-free and cell-associated X4-HIV-1 infection of cell lines and primary target cells at micromolar concentrations. Our findings suggest that seminal spermine restricts sexual X4-HIV-1 transmission.

People with HIV (PWH) smoke at higher rates compared with the general population and have lower cessation rates. The primary aim of this study was to examine the impact of the COVID-19 pandemic on smoking in PWH. A survey was administered to participants in two smoking cessation trials in the United States. Mean cigarettes per day was 13.9 (SD 8.6), and participants reported they had smoked on average for 30.93 years (SD 10.4). More than half (55.7%) of participants (N = 140) reported not changing their smoking during the pandemic, while 15% reported decreasing, and 25% reported increasing their smoking. In bivariate analyses, worrying about food due to lack of money (χ 2  = 9.13, df 2, p = 0.01) and greater Covid-related worry (r s  = 0.19, p = 0.02) were significantly associated with increased smoking. Qualitative research may be needed to more clearly elucidate factors related to smoking behaviors among PWH., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Treatment management after repeated failure of antiretroviral therapy (ART) is difficult due to resistance and adherence challenges. For people who have failed non-nucleoside reverse transcriptase inhibitor-(NNRTI-) and protease inhibitor-(PI-) based regimens with no or limited resistance, remaining on PI-based ART is an option. Using data from an ART strategy trial (A5288) in low/middle-income countries which included this option, we explored whether predictors can be identified distinguishing those who experienced further virologic failure from those who achieved and maintained virologic suppression., Methods: A5288 enrolled people with confirmed HIV-1 RNA ≥ 1000 copies/mL after ≥ 24 weeks of PI-based ART and prior failure on NNRTI-based ART. This analysis focused on the 278 participants with no resistance to the PI being taken and no or limited nucleoside reverse transcriptase inhibitor (NRTI) resistance, who continued their PI with flexibility to change NRTIs. Proportional hazards models were used to evaluate predictors of virologic failure during follow-up (VF: confirmed HIV-1 RNA ≥ 1000 copies/mL at ≥ 24 weeks of follow-up)., Results: 56% of participants were female. At study entry, median age was 40 years, time on ART 7.8 years, CD4 count 169 cells/mm 3 , HIV-1 RNA 20,444 copies/mL; and 37% had NRTI resistance. The estimated proportion experiencing VF increased from 39% at week 24 to 60% at week 96. In multivariable analysis, significant predictors at study entry of VF were higher HIV-1 RNA (adjusted hazard ratio: 2.20 for ≥ 10,000 versus < 10,000 copies/mL), lower age (1.96 for < 30 versus ≥ 30 years), NRTI resistance (1.74 for present versus absent), lower CD4 count (1.73 for < 200 versus ≥ 200 cells/mm 3 ), and shorter ART duration (1.62 for < 10 versus ≥ 10 years). There was a strong trend in proportion with VF at week 96 with the number of these five risk factors that a participant had, varying from 8% for zero, to 31%, 40%, 73%, and 100% for one, two, three, and four/five. Only 13% of participants developed new NRTI or PI resistance mutations., Conclusion: A simple count of five predictors might have value for identifying risk of continued VF. Novel antiretroviral and adherence support interventions are needed to improve virologic outcomes for higher risk individuals., (© 2023. The Author(s).)

Background: Smoking contributes to significant morbidity and mortality in people with HIV. People with HIV have relatively high nicotine metabolism rates, as measured by the nicotine metabolite ratio (NMR, 3-hydroxycotinine/cotinine). A higher NMR is associated with difficulty quitting smoking. We hypothesized that HIV infection might upregulate nicotine metabolism., Setting: A retrospective study of male current smokers in the Multicenter AIDS Cohort Study who HIV seroconverted between 1985 and 1993., Methods: Eligibility included having plasma stored before and after confirmed HIV seroconversion and current tobacco use. Samples were selected from the closest available visits before (median 3.3 months) and after (median 9.4 months) seroconversion. Antiretroviral therapy use was exclusionary. Cotinine and 3-hydroxycotinine were measured using liquid chromatography-tandem mass spectrometry. We compared NMR from plasma pre-HIV and post-HIV infection using signed-rank tests. We targeted a sample size of 71 pairs to achieve 80% power to detect a 0.1 unit increase in NMR with P = 0.05., Results: We analyzed paired samples from 78 participants; the median age was 34.5 years [interquartile range (IQR 29-40 years)]. The median NMR pre-HIV and post-HIV was 0.45 (IQR 0.32-0.54) and 0.46 (IQR 0.34-0.56), respectively. The median change in NMR postseroconversion was +0.01 (IQR -0.05, +0.09), P = 0.25. Stratification of median change in NMR by timing between samples or time since HIV seroconversion did not alter this finding., Conclusions: Acquiring HIV had no measurable effect on NMR. We postulate that upregulation of the NMR may be due to direct pharmacologic effects of HIV medications or metabolic changes in response to HIV infection., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: The metabolic syndrome, a cluster of inter-related risk factors for cardiovascular diseases is highly prevalent among individuals with obesity and sedentary lifestyle. Chronic psychiatric disorders such as severe mental illness are associated with increased risk for cardiovascular diseases. We aimed to assess the prevalence and correlates of metabolic syndrome among inpatients with severe mental illness in a resource limited setting with high HIV prevalence., Methods: This was a cross-sectional study among adult inpatients at a referral psychiatric hospital in Botswana. We used convenience sampling to enrol participants available at the time of the study. The National Cholesterol Education Program Adult Treatment Panel-III (NCEP-ATP III) criteria was used to define the metabolic syndrome. Data were analysed using descriptive statistics as well as multiple logistic regression modelling., Results: A total of 137 participants were enrolled. Of these, 119 (87%) had complete data for the main analysis. The overall prevalence of metabolic syndrome was 22.6% (95% CI 15.9, 30.6) and did not differ significantly by gender or HIV status. Age was significantly associated with the risk of having the metabolic syndrome while gender, body mass index, HIV status, and days of moderate physical activity were not., Conclusion: There was a moderately high prevalence of metabolic syndrome. Thus, the management of individuals with severe mental illness in resource limited settings should include assessment of cardiovascular risk and target modifiable risk factors in this population. Consideration for the patient's age should be made when rationalizing the limited resources available for assessing metabolic syndrome among patients with severe mental illness., (© 2022. The Author(s).)

Importance: HIV self-testing (HIVST) is a promising strategy to expand the HIV care continuum, particularly among priority populations at high risk of HIV infection. However, little is known about HIVST uptake among men who have sex with men (MSM) outside of clinical trial settings., Objective: To evaluate HIVST use among urban MSM in the US who reported testing within the past 12 months., Design, Setting, and Participants: A cross-sectional study of adult MSM in the 2017 National HIV Behavioral Surveillance system, which used venue-based sampling methods to collect data related to HIV testing, receipt of prevention services, and risk factors for HIV, was conducted at 588 venues in 23 urban areas in the contiguous US and Puerto Rico. All participants were offered HIV testing. Adult cisgender MSM who reported HIV-negative or unknown HIV status and obtained HIV testing in the past 12 months were included. Data for this study were collected between June 4, 2017, and December 22, 2017, and analyzed between October 23, 2020, and August 20, 2021., Main Outcomes and Measures: Self-reported HIVST in the past year. Adjusted prevalence ratios (aPRs) using survey weights were calculated to assess factors associated with HIVST., Results: A total of 6563 MSM in 23 urban areas met inclusion criteria, of whom 506 (7.7%) individuals reported HIVST in the past year. The median age of self-testers was 29 (IQR, 25-35) years, 52.8% had completed college, and 37.9% reported non-Hispanic White race. One self-tester reported seroconverting in the prior 12 months, and an additional 10 self-testers were diagnosed with HIV during the survey. HIVST was associated with sexual orientation disclosure (aPR, 10.27; 95% CI, 3.45-30.60; P < .001), perceived discrimination against people with HIV (aPR, 1.53; 95% CI, 1.09-2.03; P = .01), younger age (aPR, 0.74; 95% CI, 0.66-0.84; P < .001), higher educational level (aPR, 1.20; 95% CI, 1.04-1.37; P = .01), and higher income levels (aPR, 1.18; 95% CI, 1.04-1.32; P = .009). No association was noted with condomless anal sex (aPR, 0.96; 95% CI, 0.88-1.06, P = .88), sexually transmitted infections (aPR, 0.96; 95% CI, 0.70-1.30; P = .77), or preexposure prophylaxis use (aPR, 0.99; 95% CI, 0.75-1.30; P = .92)., Conclusions and Relevance: In this study, HIVST was relatively uncommon in this sample of urban MSM. HIVST may not be reaching those with lower socioeconomic status or who have not disclosed their sexual identity. The findings of this study suggest that efforts to increase HIVST should focus on engaging underserved and vulnerable subgroups of MSM.

Adolescents with suboptimal medication taking may deceive caregivers about non-adherence. We conducted a 5-year longitudinal study of adolescents monitored simultaneously with both easily manipulated (e.g., self-report) and hard to manipulate (e.g., microelectronic data) strategies. Adolescents with repeatedly high adherence on the former and low adherence on the latter were invited along with their parental figures ("parents") to participate. We conducted focus groups and semi-structured interviews, separately for adolescents and parents, to elucidate drivers of discordant measures. Forty-seven adolescents and 26 parents participated in focus groups and 4 adolescents were interviewed. Adolescents described hiding pills, discarding pills, and lying. Their motivations included fear of disappointing those who care about them, desire to avoid admonishment by parents and clinic staff, and desire to avoid remedial adherence counseling. Both adolescents and parents considered negative feedback for prior poor adherence to be key motivation to hide current poor adherence from clinic staff. Providing positive feedback for truth-telling, rather than for "evidence" of excellent adherence, might help adolescent patients and their parents to develop stronger treatment alliances with each other and with clinic staff. Such alliances would allow adherence interventions to be better targeted and more fruitful in increasing adherence.

Background: Implementation mapping is a systematic, collaborative, and contextually-attentive method for developing implementation strategies. As an exemplar, we applied this method to strategy development for Managed Problem Solving Plus (MAPS+), an adapted evidence-based intervention for HIV medication adherence and care retention that will be delivered by community health workers and tested in an upcoming trial., Methods: In Step 1: Conduct Needs Assessment, we interviewed 31 stakeholders to identify determinants of MAPS+ implementation in 13 clinics serving people with HIV in Philadelphia County. In Step 2: Develop Logic Model, we used these determinants as inputs for a working logic model guided by the Consolidated Framework for Implementation Research. In Step 3: Operationalize Implementation Strategies, our team held a virtual stakeholder meeting to confirm determinants. We synthesized stakeholder feedback, then identified implementation strategies that conceptually matched to determinants using the Expert Recommendations for Implementing Change taxonomy. Next, we operationalized implementation strategies with specific examples for clinic settings. We linked strategies to behavior change theories to allow for a mechanistic understanding. We then held a second virtual stakeholder meeting to present the implementation menu for feedback and glean generalizable insights for how these strategies could be operationalized in each stakeholder's clinic. In Step 4: Protocolize Strategies, we incorporated stakeholder feedback and finalized the implementation strategy menu., Findings: Implementation mapping produced a menu of 39 strategies including revise professional roles, identify and prepare champions, use warm handoffs , and change record systems . The process of implementation mapping generated key challenges for implementation strategy development: lack of implementation strategies targeting the outer setting (i.e., sociopolitical context); tension between a one-size-fits-all and individualized approach for all clinics; conceptual confusion between facilitators and strategies; and challenges in translating the implementation science lexicon for partners., Implications: This case exemplar advances both MAPS+ implementation and implementation science methods by furthering our understanding of the use of implementation mapping to develop strategies that enhance uptake of evidence-based interventions. The implementation menu will inform MAPS+ deployment across Philadelphia in an upcoming hybrid trial. We will carry out Step 5: Test Strategies to test the effectiveness and implementation of MAPS+., Competing Interests: RSB receives royalties from Oxford University Press, currently provides consultation to United Behavioral Health, and serves on the Clinical and Scientific Advisory Board for Optum Behavioral Health. ARP has consulted on research studies funded by AbbVie, RG serves on the data and safety monitoring board for Pfizer Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hoskins, Sanchez, Hoffacker, Momplaisir, Gross, Brady, Pettit, Zentgraf, Mills, Coley and Beidas.)

Purpose: Oral cancer is the sixth most common cancer worldwide and is the seventh most common in Botswana. Lack of improvement in oral cancer survival despite the availability of multiple treatment options may be due to the high prevalence of advanced stage at presentation. We identified risk factors for presenting with oral cancer at an advanced stage to facilitate interventions to reduce mortality from oral cancers., Methods: A retrospective cohort analysis was conducted among individuals with biopsy-confirmed oral cancer at Princess Marina Hospital in Gaborone, Botswana, between 2010 and 2020. Data collected included age at diagnosis, sex, place of residence, HIV status, oral cancer stage, and oral subsite. Multivariable analyses were controlled for age, sex, district of residence, and oral subsite., Results: Of the 218 records analyzed, 79% were male, 58% were HIV-positive, the median age was 56 years (interquartile range: 47-63), and 67% presented with advanced-stage disease. Cancers from hidden oral sites were more likely to present at an advanced stage with an adjusted odds ratio (OR) of 2.98 (95% CI, 1.29 to 6.89; P = .01). Residence in socioeconomically disadvantaged districts was associated with higher likelihood (OR, 2.36; 95% CI, 1.28 to 4.39; P = .01) of advanced stage presentation compared with other districts. HIV infection was not associated with risk of advanced lesion presentation (OR, 1; 95% CI, 0.61 to 1.61; P = .97)., Conclusion: Hidden oral cancer sites and residence in districts with limited access to care were risk factors for advanced oral cancer at the time of diagnosis in Botswana. These findings support a need to increase efforts to improve access to care and increase oral cancer awareness to decrease the burden of advanced oral cancer.

Background: Managed problem solving (MAPS) is an evidence-based intervention that can boost HIV medication adherence and increase viral suppression, but it is not widely used in community clinics. Deploying community health workers to deliver MAPS could facilitate broader implementation, in support of the Ending the HIV Epidemic (EHE) initiative's goal of reducing new HIV infections in the US by 90% by 2030., Setting: Ryan White-funded clinics in Philadelphia, 1 of 48 US counties prioritized in the EHE., Methods: Semistructured stakeholder interviews were conducted with 13 clinics and 4 stakeholder groups: prescribing clinicians, nonprescribing clinical team members (eg, medical case managers), clinic administrators, and policymakers. Interviews were based on the Consolidated Framework for Implementation Research and investigated perceived barriers to and facilitators of MAPS delivery by community health workers. Rapid qualitative analytic techniques were used to synthesize interview data and identify key categories along an implementation pathway. Core determinants (ie, barriers and facilitators) of MAPS implementation were grouped within each category., Results: Stakeholders were receptive to CHW-delivered MAPS and offered critical information on potential implementation determinants including preferences for identification and referral of patients, and the importance of integration and communication within the care team., Conclusions: This study elucidates insights regarding barriers and facilitators to delivering an evidence-based behavioral intervention in clinics serving people with HIV (PWH) and extends a rapid qualitative approach to HIV care that rigorously incorporates stakeholder data into the development of implementation strategies. It also offers insights for national implementation efforts associated with EHE., Competing Interests: This publication was made possible in part through an Ending the HIV Epidemic Supplement from the Penn Center for AIDS Research (CFAR; P30 045088; funding provided for R.S.B. (project director), F.M., R.G., C.H., K.Z. and A.R.P.) and the Penn CFAR ISPHERE Scientific Working Group, and support from the Penn Mental Health AIDS Research Center (P30 MH 097488; funding for R.G.). Dr. Beidas receives royalties from Oxford University Press. R.S.B. has provided consultation to the Camden Coalition of Healthcare Providers and currently provides consultation to United Behavioral Health. R.S.B. serves on the Clinical and Scientific Advisory Board for Optum Behavioral Health. A.R.P. has consulted on research studies funded by AbbVie, unrelated to the topic of this manuscript. R.G. serves on the data and safety monitoring board for Pfizer drug company, unrelated to the current work. A.LS. and K.H. were received funding from the National Institute of Mental Health Training Fellowship (T32 MH109433; Mandell/Beidas MPIs). The remaining authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second-line protease inhibitor (PI)-based antiretroviral therapy (ART) from 10 low- and middle-income countries (LMICs). Participants resistant to lopinavir (LPV) and/or multiple nucleotide reverse transcriptase inhibitors started on third-line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) and/or etravirine (ETR) according to their resistance profiles. At 48 weeks, 87% of these participants achieved HIV-1 RNA ≤200 copies/ml. We report here long-term outcomes over 144 weeks., Methods: Study participants were enrolled from 2013 to 2015, prior to the availability of dolutegravir in LMICs. "Extended Follow-up" of the study started after the last participant enrolled had reached 48 weeks and included participants still on antiretroviral (ARV) regimens containing RAL, DRV/r and/or ETR at that time. RAL, DRV/r and ETR were provided for an additional 96 weeks (giving total follow-up of ≥144 weeks), with HIV-1 RNA measured at 48 and 96 weeks and CD4 count at 96 weeks after entry into Extended Follow-up. Proportion of participants with HIV-1 RNA ≤200 copies/ml was estimated every 24 weeks, using imputation if necessary to handle the different measurement schedule in Extended Follow-up; mean CD4 count changes were estimated using loess regression., Results and Discussion: Of 257 participants (38% females), at study entry, median CD4 count was 179 cells/mm 3 , and HIV-1 RNA was 4.6 log 10 copies/ml. Median follow-up was 168 weeks (IQR: 156-204); 15 (6%) participants were lost to follow-up and 9 (4%) died. 27/246 (11%), 26/246 (11%) and 13/92 (14%) of participants who started RAL, DRV/r and ETR, respectively, discontinued these drugs; only three due to adverse events. 87%, 86%, 83% and 80% of the participants had HIV-1 RNA ≤200 copies/ml at weeks 48, 96, 144 and 168 (95% CI at week 168: 74-85%), respectively. Mean increase from study entry in CD4 count at week 168 was 265 cells/mm 3 (95% CI 247-283)., Conclusions: Third-line regimens comprising of RAL, DRV/r and/or ETR were very well tolerated and had high rates of durable virologic suppression among PLWH in LMICs who were failing on second-line PI-based ART prior to the availability of dolutegravir., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Purpose: Patients who are HIV-positive and have breast cancer have worse overall survival (OS) compared with patients who are HIV-negative. Pathologic complete response (pCR) and relative dose intensity (RDI) of chemotherapy are associated with survival. We assessed whether pCR and RDI rates were lower for patients who are HIV-positive and received neoadjuvant chemotherapy (NACT)., Methods: This was a prospective cohort analysis of patients initiating NACT in Botswana (February 2017 to September 2019). Primary outcomes were pCR and RDI; secondary outcomes were OS and toxicity. HIV status and zidovudine (ZDV) treatment were stratification factors. Multivariable analysis was used to control for confounding., Results: In total, 26 of 110 enrolled individuals were HIV-positive. In univariable analysis, HIV-positive (odds ratio [OR] = 0.2; P = .048) and RDI < 0.85 (OR = 0.30; P = .025) were associated with pCR. In multivariable analysis, the magnitude of association decreased for HIV-positive (OR = 0.28; P = .11), but RDI < 0.85 remained independently associated with pCR (OR = 0.32; P = .035). Patients who are HIV-positive had significantly lower mean RDI, and those on ZDV had significantly lower RDI. Ninety-one (83%) were stage III with 2-year OS significantly worse for patients who are HIV-positive (58% v 74%). Hazard ratio for all-cause mortality was 2.68 (95% CI, 1.17 to 6.13; P = .028) in patients who are HIV-positive compared with patients who are HIV-negative. Toxicity rates were similar despite patients who are HIV-positive receiving significantly lower dose intensity chemotherapy., Conclusion: Patients who are HIV-positive and have breast cancer in Botswana have lower pCR rates and also receive lower dose intensity therapy, which may contribute to worse OS. Patients who are HIV-positive on ZDV-containing regimens received even lower dose intensity of NACT. Administering optimal dose intensity in patients who are HIV-positive remains a challenge, and targeted interventions that address modifiable risk factors are needed to improve therapy delivery and outcomes., Competing Interests: Robert GrossConsulting or Advisory Role: PfizerResearch Funding: Merck (Inst) Lawrence N. ShulmanResearch Funding: Celgene (Inst), Independence Blue Cross (Inst) Surbhi GroverHonoraria: Varian Medical SystemsConsulting or Advisory Role: GenesisCareResearch Funding: Varian Medical Systems Angela DeMicheleResearch Funding: Pfizer (Inst), Genentech (Inst), Calithera Biosciences (Inst), Novartis (Inst)No other potential conflicts of interest were reported.

Background: People with HIV (PWH) smoke tobacco at much higher rates than the general population. Previous research has shown that PWH have faster nicotine metabolism than HIV-uninfected individuals, which may underlie this disparity, but the cause is unknown. We investigated whether higher nicotine metabolite ratio (NMR; 3-hydroxycotinine:cotinine), a validated biomarker of nicotine metabolism through CYP2A6, was associated with antiretroviral use among HIV-infected smokers., Methods: We conducted a retrospective cohort study of HIV-positive smokers in the University of Pennsylvania Center for AIDS Research cohort. We compared the NMR before viral suppression (>10,000 copies/mL) and after viral suppression on antiretroviral therapy (<200 copies/mL). We used mixed-effects linear regression to analyze the change in NMR after viral suppression and assessed for effect modification by efavirenz use., Results: Eighty-nine individuals were included in the study. We observed effect modification by efavirenz use (interaction term for efavirenz use, P < 0.001). Among those on nonefavirenz regimens, the mean NMR increased by 0.14 (95% confidence interval: 0.05 to 0.23, P = 0.002). Among those on efavirenz-containing regimens, the mean NMR increased by 0.53 (95% confidence interval: 0.39-0.66, P < 0.001)., Conclusions: We observed a clinically and statistically significant increase in NMR after viral suppression among smokers with HIV, which more than doubled among those on efavirenz-based regimens. Higher NMR among HIV-positive smokers on antiretroviral therapy may help explain the higher rates of tobacco use and lower quit rates among PWH in care. These findings suggest that regimen choice and other modifiable factors may be targets for future attempts to increase success rates for tobacco cessation among PWH., Competing Interests: R.F.T. has consulted for Quinn Emanuel and Ethismos Research on topics unrelated to this work. R.A.S. has received free medication and placebo supply from Pfizer for past cessation trials and has provided consultation to Pfizer, GlaxoSmithKline, and Curaleaf. R.L.A. has an investigator-initiated grant from Novo Nordisk, Inc., for a study unrelated to this work. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Youth account for a disproportionate number of new HIV infections; however, pre-exposure prophylaxis (PrEP) use is limited. We evaluated PrEP counselling rates among non-Hispanic Black youth in the United States after a bacterial sexually transmitted infection (STI) diagnosis., Methods: We conducted a retrospective cohort study of Black youth receiving care at two academically affiliated clinics in Philadelphia between June 2014 and June 2019. We compared PrEP counselling for youth who received primary care services versus those who did not receive primary care services, all of whom met PrEP eligibility criteria due to STI diagnosis per U.S. Centers for Disease Control and Prevention clinical practice guidelines. Two logistic regression models for receipt of PrEP counselling were fit: Model 1 focused on sexual and gender minority (SGM) status and Model 2 on rectal STIs with both models adjusted for patient- and healthcare-level factors., Results: Four hundred and sixteen patients met PrEP eligibility criteria due to STI based on sex assigned at birth and sexual partners. Thirty patients (7%) had documentation of PrEP counselling. Receipt of primary care services was not significantly associated with receipt of PrEP counselling in either Model 1 (adjusted OR (aOR) 0.10 [95% CI 0.01, 0.99]) or Model 2 (aOR 0.52 [95% CI 0.10, 2.77]). Receipt of PrEP counselling was significantly associated with later calendar years of STI diagnosis (aOR 6.80 [95% CI 1.64, 29.3]), assigned male sex at birth (aOR 26.2 [95% CI 3.46, 198]) and SGM identity (aOR 317 [95% CI 39.9, 2521]) in Model 1 and later calendar years of diagnosis (aOR 3.46 [95% CI 1.25, 9.58]), assigned male sex at birth (aOR 18.6 [95% CI 3.88, 89.3]) and rectal STI diagnosis (aOR 28.0 [95% CI 8.07, 97.5]) in Model 2. Fourteen patients (3%) started PrEP during the observation period; 12/14 (86%) were SGM primary care patients assigned male sex at birth., Conclusions: PrEP counselling and uptake among U.S. non-Hispanic Black youth remain disproportionately low despite recent STI diagnosis. These findings support the need for robust investment in PrEP-inclusive sexual health services that are widely implemented and culturally tailored to Black youth, particularly cisgender heterosexual females., (© 2022 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Evidence on the impact of human immunodeficiency virus (HIV) drug resistance on regimens following treatment failure is varied and inconclusive. Differential medication adherence may explain this variation. We aimed to test the association between drug resistance at first-line antiretroviral therapy (ART) switch and adherence to and virologic failure on subsequent ART. We conducted a secondary analysis of data from an open-labeled randomized trial of second-line ART (ACTG A5234). ART susceptibility was determined from study entry plasma using the Stanford Drug Resistance database version 8.7. Adherence was measured with microelectronic monitors. Three adherence variables and rates of virologic failure (HIV-1 RNA ≥1000 copies/mL) on second-line ART were compared between participants with and without resistance at first-line ART failure. Of 214 participants switching to second-line ART with baseline resistance results, 113 (53%) were men, mean age was 39 years (standard deviation 10.3), and 37 (17%) had susceptible virus at study entry. Cumulative genotypic susceptibility score (cGSS) was inversely associated with adherence, adjusted odds ratio (aOR) 0.15, 95% confidence interval (CI) (0.05-0.40), p  < 0.001. The aOR of virologic failure for a one-unit increase in cGSS was 1.72, 95% CI (1.22-2.41), p  < 0.001. Participants switched to second-line ART without resistance displayed inferior adherence and had higher rates of virologic failure. Therefore, these individuals warrant additional adherence interventions to help them achieve virologic success. Clinical Trial Registration number: NCT00608569.

Background: Tobacco use is approximately three times more common in people living with HIV (PLWH) than the general population. Moreover, current behavioral and pharmacological smoking cessation interventions are less effective for PLWH, highlighting a need for novel ways to optimize tobacco cessation treatments in this group. Prior research indicates that personalized treatment based on the nicotine metabolite ratio (NMR), a biomarker of nicotine metabolism, and augmenting smoking cessation medication adherence may improve cessation treatment for PLWH., Methods: In this 2 × 2 factorial design trial, 488 smokers with HIV receive 12 weeks of smoking cessation medication along with randomization to 1) tailor the smoking cessation drug to their metabolism or not, and 2) provide additional counseling on smoking cessation medication adherence or not. Those randomized to the pharmacogenetic optimization arm receive varenicline or the nicotine patch based on their NMR (varenicline for fast metabolizers and the nicotine patch for slow metabolizers) and those in the control arm receive varenicline. Those randomized to the experimental adherence counseling arm receive Managed Problem Solving (MAPS) targeting their smoking cessation medication and those in the control arm receive standard counseling., Conclusion: PLWH on suppressive antiretroviral therapy who smoke lose more life-years due to tobacco use than to their HIV infection, and have lower response rates to current evidence-based treatments for smoking cessation. Both the NMR tailoring and MAPS interventions have the potential to optimize treatments for tobacco use among this population. If effective, this trial may demonstrate ways to further improve long-term health outcomes for PLWH., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Addressing tobacco use among HIV+ smokers is a priority. Lack of knowledge about how HIV+ smokers respond to tobacco use treatments limits our ability to effectively treat this population of smokers. Using data from 2 clinical trials that provided 12 weeks of varenicline and behavioral counseling, 1 with smokers with HIV (n = 89) and 1 with smokers without HIV (n = 179), we used mixed logistic regression modeling to compare point-prevalence abstinence rates and adherence to the initial target quit date (TQD) and Cox regression for repeated outcomes to evaluate lapse and recovery dynamics between the groups. Sixty percent of HIV- smokers refrained from smoking at the TQD while only 33% of HIV+ smokers did (odds ratio [OR] = 0.32, 95% CI [0.18, 0.56], p < .001). The point-prevalence abstinence rates at Week 12 were 31% (HIV-) and 28% (HIV+; OR = 0.7, 95% CI [0.42, 1.16], p = .16) and the point prevalence abstinence rates at Week 24 were 22% (HIV-) and 15% (HIV+; OR = 0.87, 95% CI [0.49, 1.57], p = .65). Although there was no interaction between HIV status and lapse risk, χ2(3) < 1, there was a significant interaction for the recovery model, (χ2(3) = 20.4, p < 0.001): as the number of events increased, the time to the next recovery became longer among smokers with HIV, compared to smokers without HIV. Although HIV+ smokers were treated effectively with varenicline, compared to HIV- smokers, they showed significantly lower initial cessation at the TQD and took increasingly longer to recover following lapses. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Despite access to nationally supplied antiretroviral treatment, viral load suppression rates remain suboptimal in the Dominican Republic. Counseling and support services are available but mainly targeted to those identified as having the most need. At Clínica de Familia La Romana (CFLR) in La Romana, all patients undergo a structured baseline interview including exploration of expected barriers to care. We conducted a retrospective cohort study of a random sample of patients at CFLR with treatment initiation between 1 January 2015 and 1 December 2017 to determine if self-identified barriers to HIV care predict viral load suppression. Viral load suppression occurred in 63% of the 203 patients evaluated. Lack of food ( n = 19) was significantly associated with lack of viral suppression (OR 3.0, 95% CI 1.14-7.87). Nondisclosure of HIV status ( n = 24) showed evidence for a protective effect (OR 0.33; 95% CI 0.11-1.0). Further steps should be taken to address food insecurity as well as to understand associated barriers to care among individuals with food insecurity.

Objective: To evaluate associations between hair antiretroviral hair concentrations as an objective, cumulative adherence metric, with self-reported adherence and virologic outcomes., Design: Analysis of cohort A of the ACTG-A5288 study. These patients in resource-limited settings were failing second-line protease inhibitor-based antiretroviral therapy (ART) but were susceptible to at least one nucleoside reverse transcriptase inhibitor (NRTI) and their protease inhibitor, and continued taking their protease inhibitor-based regimen., Methods: Antiretroviral hair concentrations in participants taking two NRTIs with boosted atazanavir (n = 69) or lopinavir (n = 112) were analyzed at weeks 12, 24, 36 and 48 using liquid-chromatography--tandem-mass-spectrometry assays. Participants' self-reported percentage of doses taken in the previous month; virologic failure was confirmed HIV-1 RNA at least 1000 copies/ml at week 24 or 48., Results: From 181 participants with hair samples (61% women, median age: 39 years; CD4+ cell count: 167 cells/μl; HIV-1 RNA: 18 648 copies/ml), 91 (50%) experienced virologic failure at either visit. At 24 weeks, median hair concentrations were 2.95 [interquartile range (IQR) 0.49-4.60] ng/mg for atazanavir, 2.64 (IQR 0.73--7.16) for lopinavir, and 0.44 (IQR 0.11--0.76) for ritonavir. Plasma HIV-1 RNA demonstrated inverse correlations with hair levels (rs -0.46 to -0.74) at weeks 24 and 48. Weaker associations were seen with self-reported adherence (rs -0.03 to -0.24). Decreasing hair concentrations were significantly associated with virologic failure, the hazard ratio (95% CI) for ATV, LPV, and RTV were 0.69 (0.56-0.86), 0.77 (0.68-0.87), and 0.12 (0.06-0.27), respectively., Conclusion: Protease inhibitor hair concentrations showed stronger associations with subsequent virologic outcomes than self-reported adherence in this cohort. Hair adherence measures could identify individuals at risk of second-line treatment failure in need of interventions., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Rapid and efficient biological sample preparation and pretreatment are crucial for highly sensitive, reliable and reproducible molecular detection of infectious diseases. Herein, we report a self-powered, integrated sample concentrator (SPISC) for rapid plasma separation, pathogen lysis, nucleic acid trapping and enrichment at the point of care. The proposed sample concentrator uses a combination of gravitational sedimentation of blood cells and capillary force for rapid, self-powered plasma separation. The pathogens (e.g., HIV virus) in separated plasma were directly lysed and pathogen nucleic acid was enriched by an integrated, flow-through FTA® membrane in the concentrator, enabling highly efficient nucleic acid preparation. The FTA® membrane of the SPISC is easy to store and transport at room temperature without need for uninterrupted cold chain, which is crucial for point of care sampling in resource-limited settings. The platform has been successfully applied to detect HIV virus in blood samples. Our experiments show that the sample concentrator can achieve a plasma separation efficiency as high as 95% and a detection sensitivity as low as 10 copies per 200 μL blood (∼100 copies per mL plasma) with variability less than 7%. The sample concentrator described is fully compatible with downstream nucleic acid detection and has great potential for early diagnostics, monitoring and management of infectious diseases at the point of care.

Psychological reactance is an aversive response to perceived threats against personal agency. For adolescents receiving HIV treatment in Botswana, we utilized a two-question, medication-specific reactance tool to assess whether: (1) verbal reminders to take medicines made adolescents want to avoid taking them, and, (2) whether adolescents felt anger when reminded to take medicines. Reactant adolescents had 2.05-fold (95% CI 1.23, 3.41) greater odds of treatment failure than non-reactant adolescents (p = 0.03). Adjusted risk of treatment failure was 14% (95% CI 3%, 28%) greater for each point elevation in reactance score (p = 0.016). Autonomy over medication-taking did not modify the association between reactance and treatment failure. Psychological reactance may be a useful interventional target for improving adolescent adherence.

Rationale: People with HIV (PWH) smoke cigarettes at much higher rates than the general population and evidence-based cessation methods are less effective, putting PWH at greater risk for negative health outcomes. It is critical to identify the factors that underlie this health disparity. Delay discounting-the decline in the value of a reward when it is delayed-may explain this disparity., Objectives: This study aimed to (1) compare delay discounting between adult smokers with HIV and without HIV and (2) evaluate whether acute smoking abstinence disproportionately increases delay discounting among smokers with HIV., Methods: This sub-study was part of a larger study (NCT03169101) examining predictors of smoking cessation outcomes among smokers with HIV (n = 34) and smokers without HIV (n = 46) at two counterbalanced laboratory sessions (once smoking-as-usual and once following 24-h biochemically confirmed abstinence) then again, after 8 weeks of smoking cessation treatment., Results: There were no significant differences in delay discounting rates between HIV status groups (p = 0.49) or within-subject abstinence effects (p = 0.70). However, smokers without HIV exhibited a significant increase in delay discounting following smoking cessation treatment compared to baseline (p = 0.02), whereas the change among smokers with HIV did not reach statistical significance (p = 0.09)., Conclusions: These findings do not support differences in delay discounting as a reason for the lower success rates of HIV+ smokers at quitting. Although delay discounting may not explain the disparity in smoking rates between people with and without HIV, future work should focus on additional correlates of higher smoking rates and lower quit rates among people with HIV.

The effects of mental health comorbidities and social support on the HIV pre-exposure prophylaxis (PrEP) care continuum are unknown. We conducted a cross-sectional study of men and transgender individuals, ≥ 18 years-old, with ≥ 2 male or transgender partners, or recent condomless anal intercourse. Surveys assessed demographics, mental health treatment, depressive symptomatology, social support, and PrEP-related social contacts. Logistic regression assessed associations between these factors and PrEP uptake and persistence. Participants (n = 247) were 89% cis-male and 46% African-American. Median age was 27 (IQR:23-33). Thirty-seven percent had ever used PrEP, of whom 18% discontinued use. High depressive symptomology was identified in 11% and 9% were receiving mental health treatment. There were no significant associations between depressive symptoms or mental health treatment on the odds of PrEP uptake or discontinuation. Each additional PrEP contact conferred a greater odds of uptake (aOR:1.24, 95% CI: 1.09-1.42). Network-level targets may produce fruitful interventions to increase PrEP uptake.

The use of antiretroviral therapy for people with HIV (PWH) has improved life expectancy. However, PWH now lose more life-years to tobacco use than to HIV infection. Unfortunately, PWH smoke at higher rates and have more difficulty maintaining abstinence than the general population, compounding their risk for chronic disease. In this Commentary, we describe a United States National Cancer Institute-led initiative to address the relative lack of research focused on developing, testing, and implementing smoking cessation interventions for PWH. This initiative supports seven clinical trials designed to systematically test and/or develop and test adaptations of evidence-based smoking cessation interventions for PWH (eg, combination of behavioral and pharmacological). We summarize each project, including setting/recruitment sites, inclusion/exclusion criteria, interventions being tested, and outcomes. This initiative provides critical opportunities for collaboration and data harmonization across projects. The knowledge gained will inform strategies to assist PWH to promote and maintain abstinence, and ensure that these efforts are adaptable and scalable, thereby addressing one of the major threats to the health of PWH. Reducing smoking behavior may be particularly important during the COVID-19 pandemic given that smokers who become infected with SARS-CoV-2 may be at risk for more severe disease., Implications: This Commentary describes a National Cancer Institute-led initiative to advance the science and practice of treating tobacco use among PWH, which is now responsible for more life years lost than HIV. We describe the scope of the problem, the objectives of the initiative, and a summary of the seven funded studies. Harmonization of data across projects will provide information related to treatment mediators and moderators that was not previously possible. Stakeholders interested in tobacco cessation, including researchers, clinicians and public health officials, should be aware of this initiative and the evidence-base it will generate to advance tobacco treatment among this high-risk population., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

GPR15 is a G protein-coupled receptor (GPCR) proposed to play a role in mucosal immunity that also serves as a major entry cofactor for HIV-2 and simian immunodeficiency virus (SIV). To discover novel endogenous GPR15 ligands, we screened a hemofiltrate (HF)-derived peptide library for inhibitors of GPR15-mediated SIV infection. Our approach identified a C-terminal fragment of cystatin C (CysC95-146) that specifically inhibits GPR15-dependent HIV-1, HIV-2, and SIV infection. In contrast, GPR15L, the chemokine ligand of GPR15, failed to inhibit virus infection. We found that cystatin C fragments preventing GPR15-mediated viral entry do not interfere with GPR15L signaling and are generated by proteases activated at sites of inflammation. The antiretroviral activity of CysC95-146 was confirmed in primary CD4 + T cells and is conserved in simian hosts of SIV infection. Thus, we identified a potent endogenous inhibitor of GPR15-mediated HIV and SIV infection that does not interfere with the physiological function of this GPCR., Competing Interests: The authors declare no competing interest., (Copyright © 2021 the Author(s). Published by PNAS.)

Introduction: PLWHA who smoke have shown lower cessation rates within placebo-controlled randomized trials of varenicline. Adherence and rate of nicotine metabolism may be associated with quit rates in such clinical trials., Methods: This secondary analysis of a randomized placebo-controlled trial of varenicline for smoking among PLWHA (N = 179) examined the relationship between varenicline adherence (pill count, ≥80% of pills), nicotine metabolism (based on the nicotine metabolite ratio; NMR) and end-of-treatment smoking cessation (self-reported 7-day point prevalence abstinence, confirmed with carbon monoxide of ≤ 8 ppm, at the end of treatment; EOT)., Results: Combining varenicline and placebo arms, greater adherence (OR = 1.011, 95% CI:1.00-1.02, p = 0.051) and faster nicotine metabolism (OR = 3.08, 95% CI:1.01-9.37, p = 0.047) were related to higher quit rates. In separate models, adherence (OR = 1.009, 95% CI:1.004-1.01, p < 0.001) and nicotine metabolism rate (OR = 2.04, 95% CI:1.19-3.49, p = 0.009) interacted with treatment arm to effect quit rates. The quit rate for varenicline vs. placebo was higher for both non-adherent (19% vs. 5%; χ 2 [1] = 2.80, p = 0.09) and adherent (35% vs. 15%; χ 2 [1] = 6.51, p = 0.01) participants, but the difference between treatment arms was statistically significant only for adherent participants. Likewise, among slow metabolizers (NMR < 0.31), the varenicline quit rate was not significantly higher vs. placebo (14% vs. 5%; χ 2 [1] = 1.17, p = 0.28) but, among fast metabolizers (NMR ≥ 0.31), the quit rate for varenicline was significantly higher vs. placebo (33% vs. 14%; χ 2 [1] = 4.43, p = 0.04)., Conclusions: Increasing varenicline adherence and ensuring that fast nicotine metabolizers receive varenicline may increase quit rates for PLWHA., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Despite reductions in smoking rates in the general population, little is known about recent smoking trends among people living with HIV (PLWH). We compared the risk for smoking and temporal trends in smoking among PLWH and the general population in the Philadelphia metropolitan area between 2009 and 2014. We used weighted logistic regression to assess the relation between HIV and smoking, and examined temporal smoking trends. The adjusted odds ratio (OR) for smoking comparing PLWH to the general population was 1.80 (95% CI 1.55-2.09) after adjusting for socio-economic, demographic, and mental health diagnosis variables. Smoking prevalence decreased in both the PLWH and general populations during the study period, and we did not observe a significant difference in rates of decline between groups (P = 0.54). Despite overall progress in smoking cessation, a disparity persisted in smoking rates between PLWH and the general population, with and without adjustment for socio-economic, demographic, and mental health variables. Further research is needed to understand the mechanisms linking HIV and tobacco use in order to inform public health efforts to reduce smoking among PLWH.

Prior sexually transmitted infections (STIs) are associated with higher rates of subsequent human immunodeficiency virus (HIV) infection, but the influence of prior STIs on perceived vulnerability to HIV remains unclear. We aimed to assess this relationship, hypothesizing that a prior STI diagnosis is associated with higher self-assessed vulnerability to HIV. We performed a cross-sectional study of men and transgender individuals who have sex with men screening for HIV prevention trials in Philadelphia. An unadjusted regression analysis found no significant association between prior STI and HIV risk perception ( p  = 0.71) or HIV anxiety ( p  = 0.32). Multivariate logistic regression models that controlled for predetermined potential cofounders known to impact HIV risk-such as condom use, preexposure prophylaxis use, and demographics-also failed to show statistically significant associations between prior STI and HIV risk perception ( p  = 0.87) or HIV anxiety ( p  = 0.10). Furthermore, there was no effect modification by HIV preventive behaviors on the relationship between prior STI and HIV vulnerability. These data suggest that a gap exists between how clinicians may attribute individual HIV risk and how individuals view their own vulnerability at a given moment in time. Future research should focus on the dynamic relationship between perceived HIV vulnerability, STI diagnosis, and adoption of preventive behavior to determine better, individualized targets for HIV prevention interventions.

Background: Human immunodeficiency virus (HIV) drug resistance profiles are needed to optimize individual patient management and to develop treatment guidelines. Resistance profiles are not well defined among individuals on failing second-line antiretroviral therapy (ART) in low- and middle-income countries (LMIC)., Methods: Resistance genotypes were performed during screening for enrollment into a trial of third-line ART (AIDS Clinical Trials Group protocol 5288). Prior exposure to both nucleoside reverse transcriptase inhibitors (NRTIs) and non-NRTIs and confirmed virologic failure on a protease inhibitor-containing regimen were required. Associations of drug resistance with sex, age, treatment history, plasma HIV RNA, nadir CD4+T-cell count, HIV subtype, and country were investigated., Results: Plasma HIV genotypes were analyzed for 653 screened candidates; most had resistance (508 of 653; 78%) to 1 or more drugs. Genotypes from 133 (20%) showed resistance to at least 1 drug in a drug class, from 206 (32%) showed resistance to at least 1 drug in 2 drug classes, and from 169 (26%) showed resistance to at least 1 drug in all 3 commonly available drug classes. Susceptibility to at least 1 second-line regimen was preserved in 59%, as were susceptibility to etravirine (78%) and darunavir/ritonavir (97%). Susceptibility to a second-line regimen was significantly higher among women, younger individuals, those with higher nadir CD4+ T-cell counts, and those who had received lopinavir/ritonavir, but was lower among prior nevirapine recipients., Conclusions: Highly divergent HIV drug resistance profiles were observed among candidates screened for third-line ART in LMIC, ranging from no resistance to resistance to 3 drug classes. These findings underscore the need for access to resistance testing and newer antiretrovirals for the optimal management of third-line ART in LMIC., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Purpose: This study aimed to determine if disclosure of HIV status to adolescents impacted their medication adherence and how medication autonomy might explain observed effects., Methods: Three hundred adolescents on HIV treatment using electronic medication monitors were followed for 24 months while undergoing routine care. One hundred six of the adolescents were HIV disclosure-naïve and HIV status disclosure in this group was assessed quarterly. Analyses included data from the 75 adolescents who experienced disclosure during the study providing adherence and autonomy data both predisclosure and postdisclosure. Segmented generalized estimating equations were used to examine the trend of adherence and autonomy predisclosure and postdisclosure. Covariates assessed include age at disclosure, sex, and orphan status., Results: Median age at study entry was 12.2 years (interquartile range 11.6-12.9). Incident disclosure occurred in 75 (71%) of the adolescents at a median age of 13.1 years (interquartile range 12.5-13.9). Adherence decreased by 11% (95% confidence interval [CI] 7-15, p < .001) during the predisclosure period and by 22% (95% CI 9-36, p = .001) during the postdisclosure period. Adolescents' autonomy over their medication-taking increased over time, but disclosure did not impact the rate of increase in measured medication-taking autonomy. On a scale of 1-4 assessing autonomy (1 = receiving directly observed therapy and 4 = taking medicines mostly without supervision), autonomy increased by an average of .03 units/month (95% CI .02-.03, p < .001) predisclosure and by .05 units/month (95% CI -.01 to .11, p = .42) postdisclosure., Conclusions: The findings suggest that, among perinatally HIV infected adolescents, HIV status disclosure may adversely impact treatment adherence. Postdisclosure support to HIV infected adolescents should be intensified., (Copyright © 2020 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Quitting smoking among people living with HIV/AIDS (PLWHA) is a priority. However, PLWHA and clinicians working with PLWHA are reluctant to use tobacco use treatments out of concern that smoking cessation can diminish anti-retroviral therapy (ART) adherence and quality of life (QoL) and increase psychiatric symptoms. This secondary analysis from a placebo-controlled varenicline trial for tobacco dependence among PLWHA ( N  = 179) examined if smoking cessation at the end of treatment (EOT) was associated with changes in ART adherence, QoL, anxiety and depression symptoms, and varenicline side effects. ART adherence was not affected by smoking cessation ( p  > 0.05), remaining ≥98% for all participants. Across 8 QoL subscales, 7 remained unchanged over time across smokers and abstainers; side effects were not associated with cessation. Controlling for baseline smoking rate, adherence to varenicline/placebo and counseling, and treatment arm, participants who had quit smoking at EOT reported a significant reduction in depression ( β  = -1.657, 95% CI: -2.893, -0.422, p  = .009) and anxiety ( β  = -1.434, 95% CI: -2.812, -0.56, p  = .041) and increased life satisfaction ( β  = 0.88, 95% CI: 0.21, 3.275, p  = .027). When PLWHA quit smoking they may not experience adverse clinical outcomes including ART non-adherence and may experience beneficial psychological effects, supporting the use of FDA-approved smoking cessation treatments among PLWHA.

Background: Sex differences in studies of antiretroviral (ART) drug exposure and treatment outcomes support the hypothesis that some ART combinations may not be well tolerated in women. We evaluated disparities in outcomes between men and women participating in ACTG A5288, an interventional strategy trial for individuals failing a protease inhibitor-based second-line ART regimen in low- and middle-income countries., Methods: Participants were assigned to one of 4 cohorts (A-D) based on resistance profiles and ART history. Cohort A had no lopinavir/ritonavir (LPV/r) resistance and stayed on their second-line regimen, and cohorts B, C, and D had increasing resistance and accessed novel ART regimens. In this secondary analysis, we evaluated sex differences in the primary endpoint, HIV-1 RNA ≤200 copies/mL at week 48; confirmed virologic failure ≥1000 copies/mL (VF); and clinical outcomes and adverse events (intent-to-treat)., Results: Women made up 258/545 (47%) of the study population. More women than men were assigned to cohort A. Median follow-up was 72 weeks. Fewer women than men had HIV-1 RNA ≤200 copies/mL at week 48: 39% vs. 49% in cohort A and 83% vs. 89% in cohorts B, C, and D combined. More women experienced VF, grade ≥3 signs and symptoms, but similar grade ≥3 diagnoses or laboratory abnormalities., Conclusions: More women than men entered the study with a resistance profile suggesting that their second-line regimen could have been effective in maintaining virologic suppression. The more frequent occurrence of grade ≥3 signs and symptoms in women suggests that tolerability issues were under recognized in women on protease inhibitor-based therapy.

Objective: To determine whether regulatory variations in the heme oxygenase-1 (HO-1) promoter (GT) n dinucleotide repeat length could identify unique population genetic risks for neurocognitive impairment (NCI) in persons living with HIV (PLWH), we genotyped 528 neurocognitively assessed PLWH of European American and African American descent and linked genotypes to cognitive status., Methods: In this cross-sectional study of PLWH (the CNS HIV Antiretroviral Therapy Effect Research cohort), we determined HO-1 (GT) n repeat lengths in 276 African Americans and 252 European Americans. Using validated criteria for HIV-associated NCI (HIV NCI), we found associations between allele length genotypes and HIV NCI and between genotypes and plasma markers of monocyte activation and inflammation. For comparison of HO-1 (GT) n allele frequencies with another population of African ancestry, we determined HO-1 (GT) n allele lengths in African PLWH from Botswana (n = 428)., Results: PLWH with short HO-1 (GT) n alleles had a lower risk for HIV NCI (OR = 0.63, 95% CI: 0.42-0.94). People of African ancestry had a lower prevalence of short alleles and higher prevalence of long alleles compared with European Americans, and in subgroup analyses, the protective effect of the short allele was observed in African Americans and not in European Americans., Conclusions: Our study identified the short HO-1 (GT) n allele as partially protective against developing HIV NCI. It further suggests that this clinical protective effect is particularly relevant in persons of African ancestry, where the lower prevalence of short HO-1 (GT) n alleles may limit induction of HO-1 expression in response to inflammation and oxidative stress. Therapeutic strategies that enhance HO-1 expression may decrease HIV-associated neuroinflammation and limit HIV NCI., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Rationale: Barriers to smoking cessation, including negative affect and cognitive dysfunction, may contribute to high smoking rates among people living with HIV/AIDS (PLWH). Varenicline may help PLWH quit smoking by improving mood and cognition, yet this has not been explored., Objectives: The goal of this study was to evaluate the effect of varenicline on mood and cognition among PLWH enrolled in a smoking cessation clinical trial., Methods: In this secondary analysis of a varenicline trial (NCT01710137), we assessed mood (depression, anxiety) and cognition (attention, working memory) at weeks 0 (baseline), 1, 3, and 12 (end-of-treatment, EOT). Primary outcomes were changes in mood and cognition from baseline to EOT. Secondarily, mood and cognition were evaluated as predictors of biochemically confirmed 7-day point-prevalence abstinence at EOT., Results: Overall, 173 subjects (87 varenicline, 86 placebo) were included. At EOT, varenicline reduced anxiety (P < 0.001), vs. placebo (P = 0.31; interaction P = 0.05). Across both treatment arms, reductions in anxiety from baseline to EOT were associated with a higher likelihood of abstinence (OR = 1.3, 95% CI 1.1 to 1.6, P = 0.01). There were no significant treatment by time interactions for cognition or depression., Conclusions: These data suggest that varenicline operates, at least in part, by reducing anxiety. Anxiety should be an intervention target for smokers with HIV interested in quitting.

Introduction: With medical advances, the life expectancy of people living with HIV/AIDS (PLWHA) has improved; however, tobacco use remains a prominent risk for mortality. Although studies have examined the efficacy of varenicline for treating smoking among PLWHA, the relationship between varenicline adherence and cessation and correlates of varenicline adherence remain under-studied., Methods: We conducted secondary analyses from a randomized placebo-controlled trial of varenicline for smoking among PLWHA, using data from participants who received varenicline (N = 89). The relationship between varenicline adherence (based on pill count) and end-of-treatment smoking cessation was assessed, as were correlates of varenicline adherence., Results: Those who were abstinent took an average of 137.1 pills (SD = 39.3), or 83% of pills prescribed, vs. 105.3 pills (SD = 64.1), or 64%, for those who were smoking (OR = 1.01, 95% CI: 1.001-1.021, p = 0.03); 52/89 (58%) participants were adherent based on taking ≥80% of pills. The quit rate for adherent participants was 35% (18/52) vs. 19% (7/37) for non-adherent participants. Adherent participants were older, smoked fewer cigarettes each day, started smoking at an older age, and had lower baseline creatinine vs. non-adherent participants (p < 0.05). There was a significant time-by-group interaction effect for anxiety (F[1,72] = 6.24, p = 0.02), depression (F[1,72] = 4.2, p = 0.04), and insomnia (F[1,72] = 7.73, p = 0.007), indicating that adherent participants had less depression, anxiety, and insomnia during the initial weeks of treatment, vs. non-adherent participants., Conclusions: Our findings underscore the importance of varenicline adherence for determining cessation and highlight the role of early changes in anxiety, depression, and insomnia determining varenicline adherence., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: The aim of the study was to characterize perceived social support for young men and transgender women who have sex with men (YM/TWSM) taking HIV pre-exposure prophylaxis (PrEP)., Methods: Mixed-methods study of HIV-negative YM/TWSM of color prescribed oral PrEP. Participants completed egocentric network inventories characterizing their social support networks and identifying PrEP adherence support figures. A subset (n = 31) completed semistructured interviews exploring adherence support and qualities of PrEP support figures. We calculated proportions of role types (e.g., family), individuals disclosed to regarding PrEP use, and PrEP-supportive individuals within each participant network. Interviews were analyzed using an inductive approach., Results: Participants (n = 50) were predominately African American men who have sex with men. Median age was 22 years (interquartile range: 20-23). Biologic family were the most common support figures, reported by 75% of participants (mean family proportion .37 [standard deviation (SD): .31]), followed by 67% reporting friends (mean friend proportion .38 [SD: .36]). Most network members were aware (mean disclosed proportion .74 [SD: .31]) and supportive (mean supportive proportion .87 [SD: .28]) of the participants' PrEP use. Nearly all (98%) participants identified ≥1 figure who provided adherence support; more often friends (48%) than family (36%). Participants characterized support as instrumental (e.g., transportation); emotional (e.g., affection); and social interaction (e.g., taking medication together). Key characteristics of PrEP support figures included closeness, dependability, and homophily (alikeness) with respect to sexual orientation., Conclusions: Although most YM/TWSM identified family in their support networks, friends were most often cited as PrEP adherence support figures. Interventions to increase PrEP adherence should consider integrated social network and family-based approaches., (Copyright © 2019 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

The negative impacts of stress on antiretroviral therapy (ART) adherence and the many stressors faced by people returning from incarceration support the need for stress reduction interventions for this population. We hypothesized that 37 returning citizens living with HIV and substance use problems randomized to a 12-session weekly yoga intervention would experience improved ART adherence, lower viral loads, and lower heart rate and blood pressure as compared to 36 people randomized to treatment as usual (TAU). We found that ART adherence increased for yoga participants and decreased for TAU participants. There were no significant changes for viral load, heart rate, or blood pressure. The lack of statistically significant effects may be due to a small sample size and enrollment of people largely in HIV treatment. Studies with larger sample sizes and participants exhibiting low ART adherence are warranted to better understand yoga's impact.

HIV-positive people are at increased risk for malignancies associated with human papillomavirus (HPV) infection, including oropharyngeal squamous cell carcinoma (OPSCC). The purpose of this study was to determine whether cancer treatment disparities exist between HIV-positive and HIV-negative people with OPSCC. We conducted a retrospective cohort study comparing OPSCC treatment adequacy and treatment outcomes in HIV-positive and HIV-negative people in the post-antiretroviral therapy era. Treatment adequacy was determined by measuring two primary endpoints associated with OPSCC survival: time to therapy and total radiation dose. Treatment outcomes were assessed by measuring disease-free and overall survival. We identified a total of 37 HIV-positive and 149 HIV-negative people with OPSCC. HIV-positive people experienced a median delay of 10 days from time of OPSCC diagnosis to start of therapy compared with HIV-negative people [hazard ratio (HR) 0.61, 95% confidence interval (CI) 0.38-0.98]. Total post-radiation dose in HIV-positive people was lower than that in HIV-negative people [58.5 Gray (Gy) versus 64.4 Gy, p  = .04]. HIV-positive people also experienced greater hazards for disease recurrence (HR 3.43, 95% CI 1.39-8.46) and death (HR 4.21, 95% CI 1.29-13.80) compared with HIV-negative people. In conclusion, we detected a clinically important delay in time to therapy as well as worse disease-free and overall survival in HIV-positive people with OPSCC compared with their HIV-negative counterparts. These findings are relevant to understanding how HIV-positive people are diagnosed and undergo therapy for HPV-associated malignancies and highlight the need to address cancer treatment disparities in this group.

We aimed to discover barriers and facilitators of HIV pre-exposure prophylaxis (PrEP) adherence in young men and transgender women of color who have sex with men (YMSM/TW). Short-term and sustained adherence were measured by urine tenofovir concentration and pharmacy refills, respectively. Optimal adherence was defined as having both urine tenofovir concentration consistent with dose ingestion within 48 h and pharmacy refills consistent with ≥ 4 doses per week use. Participants completed semi-structured interviews exploring adherence barriers and facilitators. Participants (n = 31) were primarily African-American (68%), mean age 22 years (SD: 1.8), and 48% had optimal adherence. Adherence barriers included stigma, health systems inaccessibility, side effects, competing stressors, and low HIV risk perception. Facilitators included social support, health system accessibility, reminders/routines, high HIV risk perception, and personal agency. Our findings identify targets for intervention to improve PrEP adherence in these populations, including augmenting health activation and improving accuracy of HIV risk perception.

We examine the effect of the Undetectables Intervention (UI) on viral loads among socially vulnerable HIV-positive clients. The UI utilized a toolkit that included financial incentives, graphic novels, and community-based case management services. A pre-post repeated measures analysis (n = 502) through 4 years examined longitudinal effects of the intervention. Logistic models regressed social determinants on viral loads. Finally, in-depth qualitative interviews (n = 30) examined how UI shaped adherence. The proportion of virally suppressed time-points increased 15% (from 67 to 82% pre to post-enrollment, p < 0.0001). The proportion of the sample virally suppressed at all time-points increased by 23% (from 39 to 62% pre to post-enrollment, p < 0.0001). African Americans and the homeless were the most likely to be unsuppressed at baseline, but, along with substance users, benefitted the most from UI. The intervention shaped adherence through two pathways, by: (1) establishing worth around adherence, and (2) increasing motivation to become suppressed, and maintain adherence.