Search

Abstract Despite antiretroviral therapy (ART), HIV persists in latently-infected cells (the HIV reservoir) which decay slowly over time. Here, leveraging >500 longitudinal samples from 67 people living with HIV (PLWH) treated during acute infection, we developed a mathematical model to predict reservoir decay from peripheral CD4 + T cells. Nonlinear generalized additive models demonstrated rapid biphasic decay of intact DNA (week 0-5: t1/2 ~ 2.83 weeks; week 5-24: t1/2 ~ 15.4 weeks) that extended out to 1 year. These estimates were ~5-fold faster than prior decay estimates among chronic treated PLWH. Defective DNA had a similar biphasic pattern, but data were more variable. Predicted intact and defective decay rates were faster for PLWH with earlier timing of ART initiation, higher initial CD4 + T cell count, and lower pre-ART viral load. In this study, we advanced our limited understanding of HIV reservoir decay at the time of ART initiation, informing future curative strategies targeting this critical time.

Abstract Background Virtual activities, hybrid work and virtual mentoring have become part of the ongoing milieu of academic medicine. As the shift to remote mentoring continues to evolve, it is now possible to adapt, refine, and improve tools to support thriving mentoring relationships that take place virtually. This study explores strategies for virtual mentoring as a cornerstone for effective training programs among senior mentors participating in an ongoing mentoring program. Methods We conducted a qualitative study among prior and current participants of an ongoing “Mentoring the Mentors” program about key strategies for optimizing virtual mentoring. Data were coded and analyzed following a thematic analysis approach. Results Respondents were mostly female (62%), white (58%), and associate (39%) or full professors (32%). We found that, with the expansion of hybrid and fully remote work, there are now fewer opportunities for informal but important chance meetings between mentors and mentees; however, virtual mentoring provides opportunities to compensate for reduced interactivity normally experienced in the workplace. The heightened need to plan and be more deliberate in the virtual sphere was woven throughout narratives and was the foundation of most recommendations. Specifically, a central obstacle for respondents was that spontaneous conversations were harder to initiate because virtual conversations are expected to have set agendas. Conclusions Developing new ways to maintain meaningful interpersonal relationships in a virtual training environment, including opportunities for serendipitous and informal engagement, is critical to the success of virtual mentoring programs.

Abstract Introduction Measuring the coverage of HIV prevention services for key populations (KPs) has consistently been a challenge for national HIV programmes. The current frameworks and measurement methods lack emphasis on effective coverage, occur infrequently, lack timeliness and limit the participation of KPs. The Effective Programme Coverage framework, which utilizes a programme science approach, provides an opportunity to assess gaps in various coverage domains and explore the underlying reasons for these gaps, in order to develop targeted solutions. We have demonstrated the application of this framework in partnership with the KP community in Nairobi, Kenya, using an expanded Polling Booth Survey (ePBS) method. Methods Data were collected between April and May 2023 among female sex workers (FSWs) and men who have sex with men (MSM) using (a) PBS, (b) bio‐behavioural survey and (c) focus group discussions. Data collection and analysis involved both KP community and non‐community researchers. Descriptive analysis was performed, and proportions were used to assess the programme coverage gaps. The data were weighted to account for the sampling design and unequal selection probabilities. Thematic analysis was conducted on the qualitative data. Results The condom programme for FSW and MSM had low availability (60.2% and 50.9%), contact (68.8% and 65.9%) and utilization (52.1% and 43.9%) coverages. The pre‐exposure prophylaxis (PrEP) programme had very low utilization coverage for FSW and MSM (4.4% and 2.8%), while antiretroviral therapy utilization coverage was higher (86.6% and 87.7%). Reasons for coverage gaps included a low peer educator‐to‐peer ratio, longer distance to the clinics, shortage of free condoms supplied by the government, experienced and anticipated side effects related to PrEP, and stigma and discrimination experienced in the facilities. Conclusions The Effective Programme Coverage framework allows programmes to assess coverage gaps and develop solutions and a research agenda targeted at specific domains of coverage with large gaps. The ePBS method works well in collecting data to understand coverage gaps rapidly and allows for the engagement of the KP community.

BackgroundAssessing HIV outcomes in key population prevention programs is a crucial component of the program cycle, as it facilitates improved planning and monitoring of anticipated results. The Joint United Nations Programme on HIV and AIDS recommends using simple, rapid methods to routinely measure granular and differentiated program outcomes for key populations. Following a program science approach, Partners for Health and Development in Africa, in partnership with the Nairobi County Government and the University of Manitoba, aims to conduct an outcome assessment using a novel, expanded polling booth survey (ePBS) method with female sex workers and men who have sex with men in Nairobi County, Kenya. ObjectiveThis study aims to (1) estimate the incidence and prevalence of HIV; (2) assess biomedical, behavioral, and structural outcomes; and (3) understand barriers contributing to gaps in access and use of available prevention and treatment services among female sex workers and men who have sex with men in Nairobi. MethodsThe novel ePBS approach employs complementary data collection methods, expanding upon the traditional polling booth survey (PBS) method by incorporating additional quantitative, qualitative, and biological data collection components and an improved sampling methodology. Quantitative methods will include (1) PBS, a group interview method in which individuals provide responses through a ballot box in an unlinked and anonymous way, and (2) a behavioral and biological survey (BBS), including a face-to-face individual interview and collection of linked biological samples. Qualitative methods will include focus group discussions. The ePBS study uses a 2-stage, population- and location-based random sampling approach involving the random selection of locations from which random participants are selected at a predetermined time on a randomly selected day. PBS data will be analyzed at the group level, and BBS data will be analyzed at an individual level. Qualitative data will be analyzed thematically. ResultsData were collected from April to May 2023. The study has enrolled 759 female sex workers (response rate: 759/769, 98.6%) and 398 men who have sex with men (response rate: 398/420, 94.7%). Data cleaning and analyses are ongoing, with a focus on assessing gaps in program coverage and inequities in program outcomes. ConclusionsThe study will generate valuable HIV outcome data to inform program improvement and policy development for Nairobi County’s key population HIV prevention program. This study served as a pilot for the novel ePBS method, which combines PBS, BBS, and focus group discussions to enhance its programmatic utility. The ePBS method holds the potential to fill an acknowledged gap for a rapid, low-cost, and simple method to routinely measure HIV outcomes within programs and inform incremental program improvements through embedded learning processes.

Purpose: Optic nerve head (ONH) evaluation plays a key role in differentiating normal from glaucomatous disk. Thinning of the inferior neuroretinal rim (NRR) has been noted in early glaucoma. However, NRR thickness in different quadrants appears to depend on various factors including central retinal vessel trunk exit (CRVT) position. We evaluated ocular parameters that determined the NRR thickness in the different quadrants of normal eyes. Methods: Retrospective review of demographic and ocular data from 773 eyes of 388 subjects with normal ONH over one year was undertaken. Results: Nearly 54% were males, and the mean age was 43.2 years. The CRVT exit was central in 50% (773). The common site for noncentral CRVT was superotemporal (ST) [37%, 141/384] followed by inferotemporal (IT) [35%, 135/384]. With noncentral CRVT, the probability that the inferior, superior, nasal and temporal (ISNT) rule was not followed was 1.42 times (P < 0.001). The thinnest rim quadrant (TRQ) was mostly ST (69%) irrespective of CRVT location. The TRQ was IT in 40% when CRVT was noncentral and 82% with IT CRVT exit. With noncentral CRVT, round disks favored noncompliance [132 (54.1%), odds ratio (OR) 2.56] with the ISNT rule. The OR of noncompliance with the ISNT rule increases 1.89 times with inferonasal CRVT and 1.22 times with a unit increase in the axial length. Conclusion: TRQ was IT in IT CRVT, and noncompliance with the ISNT rule was observed with large disks, longer axial length, and noncentral CRVT. This implies that despite the ISNT rule being violated these eyes do not have optic nerve pathology and should not be subjected to unnecessary diagnostic tests.

Abstract Introduction Adherence counselling with point‐of‐care (POC) drug‐level feedback using a novel tenofovir assay may support pre‐exposure prophylaxis (PrEP) adherence; however, perceptions of urine testing and its impact on adherence are not well studied. We qualitatively examined how POC tenofovir testing was experienced by transgender women (TGW) in Uganda. Methods Within a cluster randomized trial of peer‐delivered HIV self‐testing, self‐sampling for sexually transmitted infections and PrEP among HIV‐negative TGW showing overall low PrEP prevention‐effective adherence (NCT04328025), we conducted a nested qualitative sub‐study of the urine POC assay among a random sample of 30 TGW (August 2021−February 2022). TGW interviews explored: (1) experiences with POC urine tenofovir testing and (2) perceptions of PrEP adherence counselling with drug‐level feedback. We used an inductive content analytic approach for analysis. Results Median age was 21 years (interquartile range 20–24), and 70% engaged in sex work. Four content categories describe how TGW experienced POC urine tenofovir testing: (1) Urine tenofovir testing was initially met with scepticism: Testing urine to detect PrEP initially induced anxiety, with some perceptions of being intrusive and unwarranted. With counselling, however, participants found POC testing acceptable and beneficial. (2) Alignment of urine test results and adherence behaviours: Drug‐level feedback aligned with what TGW knew about their adherence. Concurrence between pill taking and tenofovir detection in urine reinforced confidence in test accuracy. (3) Interpretation of urine tenofovir results: TGW familiar with the interpretation of oral‐fluid HIV self‐tests knew that two lines on the test device signified positivity (presence of HIV). However, two lines on the urine test strip indicated a positive result for non‐adherence (absence of tenofovir), causing confusion. Research nurses explained the difference in test interpretation to participants’ satisfaction. (4) White coat dosing: Some TGW deliberately chose not to attend scheduled clinic appointments to avoid detecting their PrEP non‐adherence during urine testing. They restarted PrEP before returning to clinic, a behaviour called “white coat dosing.” Conclusions Incorporating POC urine testing into routine PrEP adherence counselling was acceptable and potentially beneficial for TGW but required attention to context. Additional research is needed to identify effective strategies for optimizing adherence monitoring and counselling for this population.

Abstract Background Adolescent girls and young women (AGYW) account for 29% of new HIV infections in Uganda despite representing just 10% of the population. Peer support improves AGYW linkage to HIV care and medication adherence. We evaluated the feasibility and acceptability of peer delivered HIV self-tests (HIVST) and oral pre-exposure prophylaxis (PrEP) to young women in Uganda. Methods Between March and September 2021, we conducted a pilot study of 30 randomly selected young women, aged 18–24 years, who had received oral PrEP for at least three months, but had suboptimal adherence as measured by urine tenofovir testing (

BackgroundPre-Exposure Prophylaxis (PrEP) has demonstrated efficacy in preventing HIV infection. Female Bar Workers (FBWs) often act as informal sex workers, placing them at risk of HIV infection. Despite expressing interest in PrEP, FBWs face barriers to accessing public-sector clinics where PrEP is delivered. We developed a study to compare the effectiveness of workplace-based PrEP provision to standard-of-care facility-based provision for PrEP initiation, retention and adherence among FBWs.MethodsIn this double-randomized intervention study, FBWs aged 15 years and above will be screened, consented and initiated on PrEP (emtricitabine/tenofovir disoproxil), and followed for six months. Participants will be randomized at the bar level and offered PrEP at their workplace or at a health facility. Those who are initiated will be independently individually randomized to either receive or not receive an omni-channel PrEP champion intervention (support from an experienced PrEP user) to improve PrEP adherence. We expect to screen 1,205 FBWs to enroll at least 160 HIV negative women in the study. Follow-up visits will be scheduled monthly. HIV testing will be performed at baseline, month 1, 4 and 6; and TDF testing at months 2 and 6. Primary outcomes for this trial are: (1) initiation on PrEP (proportion of those offered PrEP directly observed to initiate PrEP); and (2) adherence to PrEP (detectable urine TDF drug level at 6-months post-enrollment). The primary outcomes will be analyzed using Intention-to-Treat (ITT) analyses.DiscussionUsing a randomized trial design, we will evaluate two interventions aiming to reduce barriers to uptake and retention on PrEP among FBWs, a vulnerable population at risk of HIV acquisition and onward transmission. If these interventions prove effective in promoting PrEP among FBWs, they could assist in abating the HIV epidemic in Africa.Trial registrationRegistered with German Clinical Trials Register (www.drks.de) on 29 April 2020; Registration number DRKS00018101.

The use of face masks has been widely promoted and at times mandated to prevent coronavirus disease 2019 (COVID-19). The 2023 publication of an updated Cochrane review on mask effectiveness for respiratory viruses as well as the unfolding epidemiology of COVID-19 underscore the need for an unbiased assessment of the current scientific evidence. It appears that the widespread promotion, adoption, and mandating of masking for COVID-19 were based not primarily on the strength of evidence for effectiveness but more on the imperative of decision-makers to act in the face of a novel public health emergency, with seemingly few good alternatives. Randomized clinical trials of masking for prevention of COVID-19 and other respiratory viruses have so far shown no evidence of benefit (with the possible exception of continuous use of N95 respirators by hospital workers). Observational studies provide lower-quality evidence and do not convincingly demonstrate benefit from masking or mask mandates. Unless robust new evidence emerges showing the effectiveness of masks in reducing infection or transmission risks in either trials or real-world conditions, mandates are not warranted for future epidemics of respiratory viral infections.

OBJECTIVES/GOALS: Contingency management (CM), wherein patients earn prizes for behavior change, is the gold-standard for reducing stimulant misuseand has been shown to improve medication adherence.We aim to describe the feasibility, acceptability, and effectiveness of CM to reduce stimulant use and optimize ART adherence in Women’s HIV primary care. METHODS/STUDY POPULATION: Using the ADAPT-ITT model for adapting evidence-based HIV interventions, we implemented the CoMBostudy at the Ward 86 Women’s Clinic at San Francisco General Hospital. Inclusion criteria are (1) adult age women with HIV, (2) suboptimal ART adherence, (3) stimulant use disorder with goal of reduced-use. Participants receive weekly CM for 12 weeks with escalating incentives for point-of-care urine testing negative for stimulants and positive for tenofovir ART. We use mixed methods to evaluate feasibility and acceptability ofCoMBowith quantitative process measures, sequential explanatory in-depth interviews with participants and staff, and effectiveness by proportion of point-of-care urine tests without stimulants and with tenofovir. RESULTS/ANTICIPATED RESULTS: CoMBoStudy enrollment began in September 2023; n=10 participants have enrolled with an additional n=20 planned.We will report feasibility and acceptability using:1) the number of women with HIV, stimulant use disorder, and suboptimal ART adherence enrolled vs. recruited, 2) the number and proportion of CM sessions attended/missed, 3) cost per participant, and 4) participant-reported facilitators and barriers to CM engagement. We will report preliminary effectiveness based on: 1) proportion of POC tests negative for stimulants, positive for ART, and 2)trend in self-reported stimulant use assessed weekly during CM. DISCUSSION/SIGNIFICANCE: Women with comorbid HIV and stimulant use disorder have demonstrated poor outcomes including reduced ART adherence and faster progression to AIDS. This work aims to expand access to evidence-based treatment for stimulant use disorder for women with HIV and share key opportunities and challenges for doing so in the women’s health HIV primary setting.

Background Postacute sequelae of COVID‐19 (PASC) and HIV are both associated with reduced exercise capacity, but whether SARS‐CoV‐2 or PASC are associated with exercise capacity among people with HIV (PWH) is unknown. We hypothesized that PWH with PASC would have reduced exercise capacity from chronotropic incompetence. Methods and Results We conducted cross‐sectional cardiopulmonary exercise testing within a COVID recovery cohort that included PWH with and without prior SARS‐CoV‐2 infection and people without HIV with prior SARS‐CoV‐2 infection (controls). We evaluated associations of HIV, SARS‐CoV‐2, and PASC with exercise capacity (peak oxygen consumption) and chronotropy (adjusted heart rate reserve). We included 83 participants (median age, 54 years; 35% women; 37 PWH): 23 out of 37 (62%) PWH and all 46 controls had prior SARS‐CoV‐2 infection, and 11 out of 23 (48%) PWH and 28 out of 46 (61%) without HIV had PASC. Peak oxygen consumption was reduced among PWH versus controls (80% predicted versus 99%, P=0.005), a difference of 5.5 mL/kg per minute (95% CI, 2.7–8.2; P

Abstract Introduction Adolescent girls and young women (AGYW) face barriers that jeopardize their prevention‐effective use of daily oral pre‐exposure prophylaxis (PrEP). We sought to understand factors that influence AGYW's prolonged breaks in PrEP use, and their decisions to re‐initiate or discontinue using PrEP in the context of a community‐based adherence support intervention. Methods In‐depth interviews (IDIs) were conducted between December 2019 and April 2021 with purposively selected AGYW (aged 16–25) enrolled in the Community PrEP Study (CPS) in Buffalo City Metro Health District, Eastern Cape Province, South Africa. AGYW were offered monthly PrEP for 24 months at two community‐based study sites. Interview guides were informed by the Information‐Motivation‐Behavioural Skills Model, and data were analysed using illustrative code reports and a case analysis. Results A total of 603 participants were enrolled and initiated on PrEP in the parent study. Fifty‐three IDIs were conducted with 50 CPS participants. Findings revealed that external factors (e.g. local movement, school holidays and medication side‐effects) and social conflicts (e.g. discretion and partner mistrust) directly influenced breaks in PrEP usage. A decrease in one's self‐perception of HIV risk prolonged the duration of these “PrEP breaks.” Once PrEP refill visits were missed, some AGYW delayed returning for refills out of fear of being scolded by study staff. The differences between those participants who eventually re‐initiated PrEP and those who disengaged from PrEP use can be attributed to social support and encouragement, level of familiarity with PrEP, risk perceptions, self‐initiated discussions with staff and diminishing side effects. Conclusions Despite implementing a community‐based PrEP delivery platform and behavioural intervention that included support for daily oral PrEP adherence and disclosure, participants struggled with consistent daily oral PrEP use. Unpredictable life events, including local movement and schooling schedules, in addition to being judged for their perceived behaviours, pose a challenge for consistent pill pick‐up for AGYW and habit formation. Long‐acting injectable PrEP may mitigate a number of these external barriers. Interventions that integrate long‐term planning skills, how to navigate existing social judgements and how to access sources of social support may further improve habit formation for PrEP use, regardless of its formulation.

Abstract Introduction Novel point‐of‐care assays which measure urine tenofovir (TFV) concentrations may have a role in improving adherence monitoring for people living with HIV (PLHIV) receiving antiretroviral therapy (ART). However, further studies of their diagnostic accuracy, and whether results are associated with viraemia and drug resistance, are needed to guide their use, particularly in the context of the global dolutegravir rollout. Methods We conducted a cross‐sectional evaluation among PLHIV receiving first‐line ART containing tenofovir disoproxil fumarate at enrolment into a randomized trial in two South African public sector clinics. We calculated the diagnostic accuracy of the Abbott point‐of‐care immunoassay to detect urine TFV compared to liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). We evaluated the association between point‐of‐care urine TFV results and self‐reported adherence, viraemia ≥1000 copies/ml and HIV drug resistance, among people receiving either efavirenz or dolutegravir‐based ART. Results Between August 2020 and March 2022, we enrolled 124 participants. The median age was 39 (IQR 34–45) years, 55% were women, 74 (59.7%) were receiving efavirenz and 50 (40.3%) dolutegravir. The sensitivity and specificity of the immunoassay to detect urine TFV ≥1500 ng/ml compared to LC‐MS/MS were 96.1% (95% CI 90.0−98.8) and 95.2% (75.3−100.0), respectively. Urine TFV results were associated with short (p

Acquired ectropion uveae (AEU) is a common sequela to various inflammatory and ischemic conditions, though it is not well recognized. There is a paucity of literature describing AEU. So here, we present five cases where we documented ectropion uveae following chronic inflammation. Patients with ectropion uveae following chronic inflammation and ischemia were retrospectively reviewed. Their medical records and clinical findings were analyzed. Five patients of various ages were found to have AEU, of which 1 was post trabeculectomy with phacoemulsification and posterior chamber intraocular lens, 1 following neovascular glaucoma (NVG), 1 following uveitic glaucoma, and 2 following iridocorneal endothelial syndrome. Patients with NVG and uveitic glaucoma also had undergone glaucoma filtration surgeries. AEU may be seen secondary to inflammatory and ischemic processes and should be looked for carefully as they may cause progressive glaucoma.

Abstract Background Strategies to support adherence are constrained by the lack of tools to objectively monitor medication intake in low-resource settings. Pharmacologic measures are objective, but pharmacy refill data is more accessible and cost-efficient. This study compared short-term and long-term efavirenz (EFV) drug levels with pharmacy refill adherence data (PRA) and evaluated their ability to predict viral suppression among people living with HIV in Nigeria. Methods Paired hair and dried blood spot (DBS) samples were obtained from 91 adults living with HIV receiving 600 mg EFV-based antiretroviral therapy (ART) and EFV concentrations were measured via validated methods using liquid-chromatography-mass-spectrometry. PRA was estimated from pharmacy records, based on the number of days a patient collected medication before or after the scheduled pick-up date. PRA was categorized into ≤ 74%, 75–94% and ≥ 95%, defined as poor, medium and high adherence, respectively. HIV viral loads closest to the hair sampling time (within 6 months) were also abstracted. Receiver Operating Characteristics (ROC) curve analyses compared the ability of adherence metrics to predict viral suppression. Results Based on PRA, 81% of participants had high adherence while 11% and 8% had medium and poor adherence, respectively. The median (IQR) EFV concentrations were 6.85 ng/mg (4.56–10.93) for hair and 1495.6 ng/ml (1050.7–2365.8) for DBS. Of the three measures of adherence, hair EFV concentration had the highest Area Under Curve (AUC) to predict viral suppression. Correlations between EFV concentrations in DBS and hair with PRA were positive (r = 0.12, P = 0.27 and r = 0.21, P = 0.05, respectively) but not strong. Conclusions EFV concentrations in hair were the strongest predictor of viral suppression and only weakly correlated with pharmacy refill adherence data in Nigeria. This study suggests that resource-limited settings may benefit from objective adherence metrics to monitor and support adherence.

Abstract Background Women in Africa face disproportionate risk of human immunodeficiency virus (HIV) acquisition, accounting for more than half of new infections in Africa and similarly face a disproportionate burden of sexually transmitted infections (STIs). Very high STI prevalence is being observed globally, especially among people taking pre-exposure prophylaxis (PrEP) for HIV prevention. Doxycycline post-exposure prophylaxis (dPEP) has been proposed as an STI prevention strategy to reduce chlamydia, syphilis, and possibly gonorrhea, and trials are ongoing among cisgender men who have sex with men (MSM) and transgender women who are taking PrEP in high-income settings. We designed and describe here the first open-label trial to determine the effectiveness of dPEP to reduce STI incidence among cisgender women. Methods We are conducting an open-label 1:1 randomized trial of dPEP versus standard of care (STI screening and treatment and risk-reduction counseling without dPEP) among 446 Kenyan women aged ≥ 18 and ≤ 30 years old women taking PrEP. Women are followed for 12 months, with quarterly STI testing, treatment, and adherence counseling. The primary trial outcome will be the combined incidence of Chlamydia trachomatis, Neisseria gonorrhoeae, and Treponema pallidum, compared between the randomized groups. We will also assess dPEP acceptability, tolerability, safety, impact on sexual behavior, adherence, and occurrence of antimicrobial resistance (AMR) in N. gonorrhoeae and C. trachomatis isolates. Finally, we will estimate cost per incident STI case and complications averted accounting for nonadherence and benefits relative AMR or side effects. Discussion The results of this trial may have immediate implications for the global epidemic of STIs and sexual health. If effective, dPEP could put STI prevention into women’s hands. While dPEP may be able to prevent STIs, it carries important risks that could counter its benefits; global debate about the balance of these potential risks and benefits requires data to inform policy and implementation and our study aims to fill this gap. Trial registration ClinicalTrials.gov NCT04050540 .

Abstract Background Nearly 50% of men living with HIV in many countries are unaware of their HIV status; men also have lower uptake of HIV treatment and pre-exposure prophylaxis (PrEP). In SSA, highly mobile men such as those working in fishing communities alongside Lake Victoria have low uptake of HIV testing and low rates of linkage to HIV treatment and PrEP, despite increasing availability of these services. HIV self-testing (HIVST) kits hold promise for overcoming barriers to HIV testing and linkage to services for HIV-positive and HIV-negative men. We describe here a protocol for an HIV status-neutral, social network-based approach to promote HIV testing, linkage to care and prevention, and better health outcomes, including adherence, in fishermen around Lake Victoria. Methods Utilizing beach management unit (BMU) registries of fishermen operating in three Lake Victoria fishing communities in Siaya County, Kenya, we completed a census and social network mapping to identify close social networks of men. Network clusters identified by a socially-central lead (“promotor”) and selected to ensure maximal separation between treatment and control will be randomized. Promotors in both arms will receive basic HIV training; intervention promotors are further trained in HIVST to distribute kits to their cluster, while control promotors will distribute to their cluster vouchers for free HIVST at nearby clinics. We will test whether these promoters can enhance linkage to ART and PrEP after self-testing, thereby addressing a key limitation of HIVST. We will also measure 6- and 12-month viral load in those living with HIV and PrEP adherence among those without HIV via urine tenofovir levels as objective markers of adherence. Discussion This study has the potential to improve HIV health and promote HIV prevention among a hard to reach, at-risk, and highly mobile population of men in Western Kenya—a critical population in Kenya’s HIV prevention and treatment program. Further, if successful, this innovative social networks-based model could be scaled at the regional level to address HIV prevention and care among similarly at-risk populations of men in eastern Africa and inland fisheries settings across the continent. Trial registration Self-Test Strategies and Linkage Incentives to Improve ART and PrEP Uptake in Men, registered on February 26, 2021, registration # NCT04772469 .

BackgroundSelf-collection of specimens at home and their return by mail might help reduce some of the barriers to HIV and bacterial sexually transmitted infection (STI) screening encountered by gay, bisexual, and other men who have sex with men (GBMSM). To evaluate the benefits and challenges of bringing this approach to scale, researchers are increasingly requesting GBMSM to return self-collected specimens as part of web-based sexual health studies. Testing self-collected hair samples for preexposure prophylaxis drug levels may also be a viable option to identify GBMSM who face adherence difficulties and offer them support. ObjectiveProject Caboodle! sought to evaluate the acceptability and feasibility of self-collecting at home and returning by mail 5 specimens (a finger-stick blood sample, a pharyngeal swab, a rectal swab, a urine specimen, and a hair sample) among 100 sexually active GBMSM in the United States aged between 18 and 34 years. In this manuscript, we aimed to describe the key lessons learned from our study’s implementation and to present recommendations offered by participants to maximize the rates of self-collected specimen return. MethodsFollowing the specimen self-collection phase, a subset of 25 participants (11 who returned all 5 specimens, 4 who returned between 1 and 4 specimens, and 10 who did not return any specimens) was selected for in-depth interviews conducted via a videoconferencing platform. During the session, a semistructured interview guide was used to discuss the factors influencing decisions regarding returning self-collected specimens for laboratory processing. The transcripts were analyzed using template analysis. ResultsUniversity branding of web-based and physical materials instilled a sense of trust in participants and increased their confidence in the test results. Shipping the specimen self-collection box in plain unmarked packaging promoted discretion during transit and on its receipt. Using different colored bags with matching color-coded instructions to self-collect each type of specimen minimized the potential for confusion. Participants recommended including prerecorded instructional videos to supplement the written instructions, providing information on the importance of triple-site bacterial STI testing, and adding a reminder of the types of testing that would and would not be conducted on hair samples. Participants also suggested tailoring the specimen self-collection box to include only the tests that they might be interested in completing at that time, adding real-time videoconferencing to the beginning of the study to introduce the research team, and sending personalized reminders following the delivery of the specimen self-collection box. ConclusionsOur results offer valuable insights into aspects that facilitated participant engagement in self-collected specimen return, as well as areas for potential improvement to maximize return rates. Our findings can help guide the design of future large-scale studies and public health programs for home-based HIV, bacterial STI, and preexposure prophylaxis adherence testing. International Registered Report Identifier (IRRID)RR2-10.2196/13647

Summary: Background: Isoniazid preventive therapy (IPT) initiation during pregnancy was associated with increased incidence of adverse pregnancy outcomes in the TB APPRISE trial. Effects of in utero IPT exposure on infant growth are unknown. Methods: This post-hoc analysis used data from the TB APPRISE trial, a multicentre, double-blind, placebo-controlled trial, which randomised women to 28-week IPT starting in pregnancy (pregnancy-IPT) or postpartum week 12 (postpartum-IPT) in eight countries with high tuberculosis prevalence. Participants were enrolled between August 2014 and April 2016. Based on modified intent-to-treat analyses, we analysed only live-born babies who had at least one follow-up after birth and compared time to infant growth faltering between arms to 12 weeks and 48 weeks postpartum in overall and sex-stratified multivariable Cox proportional hazards regression. Factors adjusted in the final models include sex of infant, mother's baseline BMI, age in years, ART regimen, viral load, CD4 count, education, and household food insecurity. Results: Among 898 HIV-exposed uninfected (HEU) infants, 447 (49.8%) were females. Infants in pregnancy-IPT had a 1.47-fold higher risk of becoming underweight by 12 weeks (aHR 1.47 [95% CI: 1.06, 2.03]) than infants in the postpartum-IPT; increased risk persisted to 48 weeks postpartum (aHR 1.34 [95% CI: 1.01, 1.78]). Maternal IPT timing was not associated with stunting or wasting. In sex-stratified analyses, male infants in the pregnancy-IPT arm experienced an increased risk of low birth weight (LBW) (aRR 2.04 [95% CI: 1.16, 3.68), preterm birth (aRR 1.81 [95% CI: 1.04, 3.21]) and becoming underweight by 12 weeks (aHR 2.02 [95% CI: 1.29, 3.18]) and 48 weeks (aHR 1.82 [95% CI: 1.23, 2.69]). Maternal IPT timing did not influence growth in female infants. Interpretation: Maternal IPT during pregnancy was associated with an increased risk of LBW, preterm birth, and becoming underweight among HEU infants, particularly male infants. These data add to prior TB APPRISE data, suggesting that IPT during pregnancy impacts infant growth, which could inform management, and warrants further examination of mechanisms. Funding: The TB APPRISE study Supported by the National Institutes of Health (NIH) (award numbers, UM1AI068632 [IMPAACT LOC], UM1AI068616 [IMPAACT SDMC], and UM1AI106716 [IMPAACT LC]) through the National Institute of Allergy and Infectious Diseases, with cofunding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (contract number, HHSN275201800001I) and the National Institute of Mental Health.

Introduction: Human mobility is a critical aspect of existence and survival, but may compromise care engagement among people living with HIV (PLHIV). We examined the association between various forms of human mobility with retention in HIV care and antiretroviral treatment (ART) interruptions. Methods: In a cohort of adult PLHIV in Kenya and Uganda, we collected surveys in 2016 about past 6-month travel and lifetime migration histories, including reasons and locations, and engagement in HIV care defined as (1) discontinuation of care, and (2) history of a treatment interruption among those who remained in care. We estimated associations between mobility and these care engagement outcomes via logistic regression, adjusted for sex, prior mobility, age, region, marital status, household wealth, and education. Results: Among 1081 participants, 56 (5%) reported having discontinued care; among those in care, 104 (10%) reported treatment interruption. Past-year migration was associated with a higher risk of discontinuation of care (adjusted odds ratio [aOR] 1.98, 95% CI 1.08–3.63). In sex-stratified models, the association was somewhat attenuated in women, but remained robust among men. Past-year migration was associated with reduced odds of having a treatment interruption among men (aOR 0.51, 95% CI 0.34–0.77) but not among women (aOR 2.67, 95% CI 0.78, 9.16). Travel in the past 6 months was not associated with discontinuation of care or treatment interruptions. Conclusions: We observed both negative and protective effects of recent migration on care engagement and ART use that were most pronounced among men in this cohort. Migration can break ties to ongoing care, but for men, who have more agency in the decision to migrate, may foster new care and treatment strategies. Strategies that enable health facilities to support individuals throughout the process of transferring care could alleviate the risk of care disengagement.

Purpose: To study the correlation between choroidal thickness (CT) and IOP control in primary angle-closure glaucoma (PACG). Methods: In total, 61 patients (102 eyes) with PACG underwent subfoveal CT (SFCT) scanning using enhanced depth imaging–optical coherence tomography. The subjects with PACG were further grouped as controlled IOP (≤21 mm Hg on maximal medical therapy) and uncontrolled IOP (>21 mm Hg on maximal medical therapy). The average CT of the PACG eyes was calculated and compared between both groups. A correlation analysis was done between CT and intereye difference in CT with the disease parameters. Results: The mean CT was 274.38 ± 42.10 μm in 102 PACG eyes. SFCT was significantly increased in the uncontrolled IOP group as compared with the controlled IOP group. The mean SFCT was 245.57 ± 62.10 μm in the controlled group and 294.46 ± 51.05 μm in the uncontrolled group (P < 0.01). Factors associated with a thicker choroid were younger age, high IOP, and higher optic nerve head cupping (P < 0.001). Neither the visual field-mean deviation (VF-MD) nor pattern standard deviation (PSD) was found to be associated with overall CT. The intereye asymmetry between CT was significantly associated with poor VF-MD and PSD. Conclusion: PACG eyes with thicker choroid may be a risk factor for poor IOP control on medical anti-glaucoma therapy. Thicker choroid as compared to the fellow eye is a poor prognostic sign and these eyes should be monitored closely.

Objective measures of adherence for antiretrovirals used as pre-exposure prophylaxis (PrEP) are critical for improving preventative efficacy in both clinical trials and real-world application. Current objective adherence measures either reflect only recent behavior (eg days for plasma or urine) or cumulative behavior (eg months for dried blood spots). Here, we measured the accumulation of the antiretroviral drug maraviroc (MVC) in hair strands by infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) to evaluate adherence behavior longitudinally at high temporal resolution. An MSI threshold for classifying daily adherence was established using clinical samples from healthy volunteers following directly observed dosing of 1 to 7 doses MVC/week. We then used the benchmarked MSI assay to classify adherence to MVC-based PrEP regimens in hair samples collected throughout the 48-week HPTN069/ACTGA5305 study. We found that only ~32% of investigated hair samples collected during the study's active dosing period showed consistent daily PrEP adherence throughout a retrospective period of 30 days, and also found that profiles of daily individual adherence from MSI hair analysis could identify when patients were and were not taking study drug. The assessment of adherence from MSI hair strand analysis was 62% lower than adherence classified using paired plasma samples, the latter of which may be influenced by white-coat adherence. These findings demonstrate the ability of MSI hair analysis to examine daily variability of adherence behavior over a longer-term measurement and offer the potential for longitudinal comparison with risk behavior to target patient-specific adherence interventions and improve outcomes.

Abstract Background Strategies to control coronavirus 2019 disease (COVID-19) have often been based on preliminary and limited data and have tended to be slow to evolve as new evidence emerges. Yet knowledge about COVID-19 has grown exponentially, and the expanding rollout of vaccines presents further opportunity to reassess the response to the pandemic more broadly. Main text We review the latest evidence concerning 10 key COVID-19 policy and strategic areas, specifically addressing: 1) the expansion of equitable vaccine distribution, 2) the need to ease restrictions as hospitalization and mortality rates eventually fall, 3) the advantages of emphasizing educational and harm reduction approaches over coercive and punitive measures, 4) the need to encourage outdoor activities, 5) the imperative to reopen schools, 6) the far-reaching and long-term economic and psychosocial consequences of sustained lockdowns, 7) the excessive focus on surface disinfection and other ineffective measures, 8) the importance of reassessing testing policies and practices, 9) the need for increasing access to outpatient therapies and prophylactics, and 10) the necessity to better prepare for future pandemics. Conclusions While remarkably effective vaccines have engendered great hope, some widely held assumptions underlying current policy approaches call for an evidence-based reassessment. COVID-19 will require ongoing mitigation for the foreseeable future as it transforms from a pandemic into an endemic infection, but maintaining a constant state of emergency is not viable. A more realistic public health approach is to adjust current mitigation goals to be more data-driven and to minimize unintended harms associated with unfocused or ineffective control efforts. Based on the latest evidence, we therefore present recommendations for refining 10 key policy areas, and for applying lessons learned from COVID-19 to prevent and prepare for future pandemics.

Web-based HIV and sexually transmitted infection (STI) prevention studies are increasingly requesting gay, bisexual, and other men who have sex with men (GBMSM) to return self-collected specimens for laboratory processing. Some studies have solicited self-collected extragenital swabs for gonorrhea and chlamydia testing, but to date, none have solicited self-collected hair samples for pre-exposure prophylaxis (PrEP) adherence testing. Project Caboodle! offered 100 racially/ethnically diverse GBMSM aged 18 to 34 years residing across the United States a choice to self-collect at home and return by mail any of the following: a finger-stick blood sample (for HIV testing), a pharyngeal swab, a rectal swab and a urine specimen (for gonorrhea and chlamydia testing), and a hair sample (to visually assess its adequacy for PrEP drug level testing). Despite not incentivizing specimen return, 51% mailed back at least one type of specimen within 6 weeks (1% returned three specimens, 11% returned four specimens and 39% returned all five specimens). The majority of returned specimens were adequate for laboratory processing. Significantly more participants without a college education ( p = .0003) and those who were working full-time or part-time ( p = .0070) did not return any specimens. In addition, lower levels of HIV-related knowledge ( p = .0390), STI-related knowledge ( p = .0162), concern about contracting HIV ( p = .0484), and concern about contracting STIs ( p = .0108) were observed among participants who did not return any specimens. Self-collection of specimens holds promise as a remote monitoring strategy that could supplement testing in clinical settings, but a better understanding of why some GBMSM may choose to fully, partially, or not engage in this approach is warranted.

Abstract Background The risk of tuberculosis (TB) is high among people with HIV (PWH). Heavy alcohol drinking independently increases TB risk and approximately 25% of PWH globally engage in heavy drinking. While isoniazid (INH) preventive therapy decreases TB incidence and mortality among PWH, heavy drinking during INH is associated with liver toxicity and poor adherence. Interventions are, therefore, urgently needed to decrease alcohol use and improve adherence to INH in this population in settings with high prevalence of HIV and TB like Uganda. Methods The Drinkers’ Intervention to Prevent TB (DIPT) study is a 2×2 factorial randomized controlled trial among HIV/TB co-infected adults (≥18 years) who engage in heavy alcohol drinking and live in Uganda. The trial will allocate 680 participants with a 1:1:1:1 individual randomization to receive 6 months of INH and one of the following interventions: (1) no incentives (control), (2) financial incentives contingent on low alcohol use, (3) financial incentives contingent on high adherence to INH, and (4) escalating financial incentives for both decreasing alcohol use and increasing adherence to INH. Incentives will be in the form of escalating lottery-based monetary rewards. Participants will attend monthly visits to refill isoniazid medications, undergo liver toxicity monitoring, and, except for controls, determine eligibility for prizes. We will estimate (a) the effect of incentives contingent on low alcohol use on reduction in heavy drinking, measured via a long-term objective and self-reported metric of alcohol use, at 3- and 6-month study visits, and (b) the effect of incentives contingent on high adherence to INH, measured as >90% pill-taking days by medication event monitoring system cap opening. We will use qualitative methods to explore the mechanisms of any influence of financial incentives on HIV virologic suppression. Discussion This study will provide new information on low-cost strategies to both reduce alcohol use and increase INH adherence among people with HIV and TB infection who engage in heavy drinking in low-income countries with high HIV and TB prevalence. Trial registration ClinicalTrials.gov NCT03492216 . Registered on April 10, 2018

Abstract Background Treatment monitoring of drug-resistant tuberculosis (DR-TB) in resource-limited settings is challenging. We developed a multi-analyte assay for eleven anti-TB drugs in small hair samples as an objective metric of drug exposure. Methods Small hair samples were collected from participants at various timepoints during directly observed RR-TB treatment at an inpatient tertiary referral facility in South Africa (DR-TB cohort). We assessed qualitative determination (i.e., detection above limit of detection) of bedaquiline, linezolid, clofazimine, pretomanid, levofloxacin, moxifloxacin, pyrazinamide, isoniazid, ethambutol, ethionamide, and prothionamide in an LC-MS/MS index panel assay against a reference standard of inpatient treatment records. Because treatment regimens prior to hospitalization were not available, we also analyzed specificity (for all drugs except isoniazid) using an external cohort of HIV-positive patients treated for latent TB infection with daily isoniazid (HIV/LTBI cohort) in Uganda. Results Among the 57 DR-TB patients (58% with pre-XDR/XDR-TB; 70% HIV-positive) contributing analyzable hair samples, the sensitivity of the investigational assay was 94% or higher for all drugs except ethionamide (58.5, 95% confidence interval [CI], 40.7–99.9). Assay specificity was low across all tested analytes within the DR-TB cohort; conversely, assay specificity was 100% for all drugs in the HIV/LTBI cohort. Conclusions Hair drug concentrations reflect long-term exposure, and multiple successive regimens commonly employed in DR-TB treatment may result in apparent false-positive qualitative and falsely elevated quantitative hair drug levels when prior treatment histories within the hair growth window are not known.

Purpose: The purpose of this study is to assess the effect of dexmedetomidine on intraocular pressure (IOP) as an additive in peribulbar injections in glaucoma surgeries. Methods: A prospective, randomized, double-blind, parallel assignment interventional study was conducted for patients undergoing glaucoma surgeries at a tertiary eye care hospital in North India. Patients were randomized to two groups, Dexmed group and Placebo group. In the Dexmed group, dexmedetomidine (0.4 μg/kg body weight) was given as an additive along with peribulbar block. The primary outcome was change in IOP pre- and postperibulbar injections (IOP before the block, and after 5 and 15 min of the block). Secondary outcome measures were onset of block, adverse effects (bradycardia, hypotension, respiratory depression, and level 4 sedation), and surgeon satisfaction. Results: A total of 104 patients were randomized, 52 each in the Dexmed group and Placebo group. The percentage decrease in IOP was significantly more in the Dexmed group than in the Placebo group both at 5 and 15 min' post block (P < 0.05). At 5 min, the mean percent decrease in IOP in Dexmed group was -10.48, whereas it was 2.85 in the Placebo group. At 15 min, the mean percent decrease in IOP was -22.59 and -9.42 in the Dexmed and Placebo group, respectively. There was no significant difference between the two groups in the onset of block and adverse effects. Surgeon satisfaction was significantly greater in the Dexmed group than the Placebo group (P < 0.05). Conclusion: Dexmedetomidine lowers IOP significantly in patients undergoing glaucoma surgeries with safe hemodynamic changes and sedative effect.

Abstract Background Increasing numbers of young people living with HIV (YPLWH) have unaddressed mental health challenges. Such challenges are associated with poor antiretroviral therapy (ART) adherence and high mortality. Few evidence-based mental health interventions exist to improve HIV outcomes among YPLWH. Methods This pilot group treatment trial individually randomized YPLWH from two clinical sites in Tanzania, evaluated acceptability, feasibility, and preliminary effectiveness of a mental health intervention, Sauti ya Vijana (SYV; The Voice of Youth), was compared to the local standard-of-care (SOC) for improving ART adherence and virologic suppression. Enrolled YPLWH were 12–24 years of age and responded to mental health and stigma questionnaires, self-reported adherence, objective adherence measures (ART concentration in hair), and HIV RNA at baseline and 6-months (post-intervention). Feasibility and acceptability were evaluated, and potential effectiveness was assessed by comparing outcomes between arms using mixed effects modeling. Results Between June 2016 and July 2017, 128 YPLWH enrolled; 105 were randomized and 93 (55 in SYV) followed-up at 6-months and were thereby included in this analysis. Mean age was 18.1 years; 51% were female; and 84% were HIV-infected perinatally. Attendance to intervention sessions was 86%; 6-month follow-up was 88%, and fidelity to the protocol approached 100%. Exploratory analyses of effectiveness demonstrated self-reported adherence improved by 7.3 percentage points (95% CI: 2.2, 12.3); and the pooled standard deviation for all ART concentration values increased by 0.17 units (95% CI: − 0.52, 0.85) in the SYV arm compared to SOC. Virologic suppression rates (HIV RNA

Objectives: The aim was to fully characterize the plasma and urine washout pharmacokinetics of tenofovir (TFV) in adults following 6 weeks of controlled levels of tenofovir disoproxil fumarate (TDF) adherence, in order to inform the utility of clinic-based adherence testing. Design: This was a three-arm, randomized, open-label study in adult volunteers. Participants were randomized to receive TDF 300 mg/emtricitabine (FTC) 200 mg as (1) 7 doses/week (perfect adherence), (2) 4 doses/week (moderate adherence), or (3) 2 doses/week (low adherence). Plasma and urine samples were collected regularly during the 6-week dosing phase and for 4 weeks following drug cessation. Results: Twenty-eight adults were included in this analysis. Median (range) age was 33 (20–49) years. No differences in TFV pharmacokinetic parameters during the washout were observed across the study arms. Small differences in TFV plasma concentrations occurred across arms between 4 and 10 h post-dose. The cumulative amount of TFV excreted in urine was not different at 24 h post-dose, but at 148 h it was 24.8 mg, 21.0 mg, and 17.2 mg for the perfect, moderate, and low adherence arms, respectively (p = 0.043). Conclusions: Among adults with different TDF adherence patterns, relative differences in plasma concentrations and cumulative urine extraction of TFV were minor following cessation. TFV measurement in plasma or urine is more indicative of last drug ingestion, rather than prior dose patterns.

Introduction Substantial improvements in viral suppression among people living with HIV (PLHIV) are needed to end the HIV epidemic, requiring extensive scale-up of low-cost HIV monitoring services. Point-of-care (POC) tests for monitoring antiretroviral therapy (ART) adherence and viral load (VL) may be efficient and effective tools for real-time clinical decision making. We aim to evaluate the effects of a combined intervention of POC ART adherence and VL testing compared with standard-of-care on ART adherence, viral suppression and retention at 6 and 18 months post-ART initiation among PLHIV.Methods and analysis Simplifying TREAtment and Monitoring for HIV (STREAM HIV) is a two-arm, open-label, randomised controlled superiority trial of POC urine tenofovir (POC TFV) and VL monitoring in PLHIV. We aim to enrol 540 PLHIV initiating a first-line ART regimen at a public HIV clinic in South Africa. Participants will be randomised 1:1 to the intervention or control arm. Intervention arm participants will receive monthly POC TFV testing for the first 5 months and POC VL testing at months 6 and 12. Intervention arm participants will also receive reflex POC TFV testing if viraemic and reflex HIV drug resistance testing for those with viraemia and detectable TFV. Control arm participants will receive standard-of-care, including laboratory-based VL testing at months 6 and 12. Primary outcomes include ART adherence (TFV-diphosphate concentration) at 6 months and viral suppression and retention at 18 months. Secondary outcomes include viral suppression and retention at 6 months, TFV-diphosphate concentration at 18 months, cost and cost-effectiveness of the intervention and acceptability of the intervention among PLHIV and healthcare workers.Ethics and dissemination STREAM HIV has received ethical approval from the University of Washington Institutional Review Board (STUDY00007544), University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC/00000833/2019) and Division of AIDS Regulatory Support Center (38509). Findings will be disseminated at international conferences and in peer-reviewed journals.Trial registration number NCT04341779.

Summary: We describe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific T cell responses, soluble markers of inflammation, and antibody levels and neutralization capacity longitudinally in 70 individuals with PCR-confirmed SARS-CoV-2 infection. Participants represent a spectrum of illness and recovery, including some with persistent viral shedding in saliva and many experiencing post-acute sequelae of SARS-CoV-2 infection (PASC). T cell responses remain stable for up to 9 months. Whereas the magnitude of early CD4+ T cell immune responses correlates with severity of initial infection, pre-existing lung disease is independently associated with higher long-term SARS-CoV-2-specific CD8+ T cell responses. Among participants with PASC 4 months following coronavirus disease 2019 (COVID-19) symptom onset, we observe a lower frequency of CD8+ T cells expressing CD107a, a marker of degranulation, in response to Nucleocapsid (N) peptide pool stimulation, and a more rapid decline in the frequency of N-specific interferon-γ-producing CD8+ T cells. Neutralizing antibody levels strongly correlate with SARS-CoV-2-specific CD4+ T cell responses.

BackgroundOral pre-exposure prophylaxis (PrEP) is highly effective for HIV prevention, but data are limited on HIV incidence among PrEP users in generalized epidemic settings, particularly outside of selected risk groups. We performed a population-based PrEP study in rural Kenya and Uganda and sought to evaluate both changes in HIV incidence and clinical and virologic outcomes following seroconversion on PrEP.Methods and findingsDuring population-level HIV testing of individuals ≥15 years in 16 communities in the Sustainable East Africa Research in Community Health (SEARCH) study (NCT01864603), we offered universal access to PrEP with enhanced counseling for persons at elevated HIV risk (based on serodifferent partnership, machine learning-based risk score, or self-identified HIV risk). We offered rapid or same-day PrEP initiation and flexible service delivery with follow-up visits at facilities or community-based sites at 4, 12, and every 12 weeks up to week 144. Among participants with incident HIV infection after PrEP initiation, we offered same-day antiretroviral therapy (ART) initiation and analyzed HIV RNA, tenofovir hair concentrations, drug resistance, and viral suppression (ConclusionsPopulation-level offer of PrEP with rapid start and flexible service delivery was associated with 74% lower HIV incidence among PrEP initiators compared to matched recent controls prior to PrEP availability. HIV infections were significantly lower among women who started PrEP. Universal HIV testing with linkage to treatment and prevention, including PrEP, is a promising approach to accelerate reductions in new infections in generalized epidemic settings.Trial registrationClinicalTrials.gov NCT01864603.

Abstract Introduction: Trainees and investigators from underrepresented minority (URM) backgrounds face unique challenges to establishing successful careers in clinical and translational research. Structured training for mentors is an important mechanism to increase the diversity of the research workforce. This article presents data from an evaluation of the University of California, San Francisco (UCSF) Center for AIDS Research (CFAR) Mentoring the Mentors program aimed at improving mentors’ competency in working with diverse mentees in HIV research. Methods: Mentors from around the USA who had in one of seven separate 2-day training workshops conducted from 2013 to 2020 were invited to participate in an online evaluation survey of their experiences with the training and their subsequent mentoring activities. Results: There was a high response rate (80%) among the 226 mentors invited to complete the survey. The 180 respondents were diverse in demographics, professional disciplines, and geographic distribution. Quantitative and qualitative data indicate a lasting positive impact of the training, with sustained improvements documented on a validated measure of self-appraised mentoring competency. Respondents also endorsed high interest in future, follow-up training with continued focus on topics related to mentoring in the context of diversity. Conclusion: The evaluation of the UCSF CFAR Mentoring the Mentors program showed lasting impact in improving mentoring practices, coupled with high interest in continued in-depth training in areas focused on diversity, equity, and inclusion.

The population with HIV is aging and has unique health needs. We present findings from an evaluation of the geriatric-HIV program, Golden Compass, at San Francisco General Hospital. We used the implementation science framework, RE-AIM ( Reach, Effectiveness, Adoption, Implementation, Maintenance ) to guide the evaluation and used quantitative and qualitative methods to assess RE-AIM dimensions. From January 2017 to June 2018, 198 adults age ≥50 years participated in the program, with an estimated reach of 17%. Providers and patients indicated high acceptability of the program and were satisfied with clinics and classes. Colocation of services, specific pharmacy and geriatric assessments, and social support from classes were valued ( effectiveness ). Provider adoption was high, and the program was implemented as originally designed. Areas for improvement included challenges of framing aging services to patients. Future efforts will focus on expanding the reach of the program and examining long-term outcomes.

BackgroundAfter a COVID-19 diagnosis, vulnerable populations face considerable logistical and financial challenges to isolate and quarantine. We developed and evaluated a novel, community-based approach ('Test-to-Care' Model) designed to address these barriers for socioeconomically vulnerable Latinx individuals with newly diagnosed COVID-19 and their households.MethodsThis three-week demonstration project was nested within an epidemiologic surveillance study in a primarily Latinx neighborhood in the Mission district of San Francisco, California. The Test-to-Care model was developed with input from community members and public health leaders. Key components included: (1) provision of COVID-19-related education and information about available community resources, (2) home deliveries of material goods to facilitate safe isolation and quarantine (groceries, personal protective equipment and cleaning supplies), and (3) longitudinal clinical and social support. Newly SARS-CoV-2 PCR-positive participants were eligible to participate. Components of the model were delivered by the Test-to-Care team, which was comprised of healthcare providers and community health workers (CHWs) who provided longitudinal clinic- and community-based support for the duration of the isolation period to augment existing services from the Department of Public Health (DPH). We evaluated the Test-to-Care Model using the Reach, Effectiveness, Adoption, Implementation, Maintenance (RE-AIM) Framework and drew upon multiple data sources including: programmatic data, informal interviews with participants and providers/CHWs and structured surveys among providers/CHWs.ResultsOverall, 83 participants in the surveillance study were diagnosed with COVID-19, of whom 95% (79/83) were Latinx and 88% (65/74) had an annual household income ConclusionsThe Test-to-Care Model is a feasible and acceptable intervention for supporting self-isolation and quarantine among newly diagnosed COVID-19 patients and their households by directly addressing key barriers faced by socioeconomically vulnerable populations.

Background: Pharmacologic adherence measures were critical to the interpretation of the tenofovir (TFV)-disoproxil-fumarate/emtricitabine (TDF/FTC) PrEP trials. These measures are being incorporated into PrEP demonstration projects, but currently-available metrics in plasma, cells, hair or urine involve expensive and time-intensive mass-spectrometry (MS)-based methods. No point-of-care method to assess PrEP adherence in real-time has yet been implemented. Antibody-based tests allow for low-cost, easy-to-perform, point-of-care drug detection. In this study, we developed an antibody-based TFV immunoassay and evaluated its test characteristics among individuals taking TDF/FTC. Methods: We synthesized possible immunogens based on TFV's molecular structure, injected rabbits with the conjugated derivatives, and bled them monthly for subsequent ELISA-testing for TFV-specific antibodies. We purified an antibody with specific TFV binding and created dose–response curves for ELISA-quantification. We then quantified TFV in urine from human participants not taking TDF/FTC and from individuals taking daily TDF/FTC 300 mg/200 mg for 7 days with a 7-day washout period using ELISA with this TFV-specific antibody. ELISA results were compared with the gold-standard test for TFV detection/quantification using liquid-chromatography-tandem-MS (LC–MS/MS). Findings: None of the urine samples from 115 participants not taking TDF/FTC showed ELISA- reactivity, indicating 100% specificity (95% CI 97–100%) of the immunoassay. Among participants taking TDF/FTC, 67 of 70 samples positive by LC–MS/MS were positive by the ELISA-immunoassay for an estimated diagnostic sensitivity of 96% (95% CI 88–99%). The precision of the assay was high (coefficient of variation

Purpose: The aim of this study is to determine which parameter of Cirrus and RTVue optical coherence tomography (OCT) has the highest ability to discriminate between early, moderate, and advanced glaucoma. Simultaneously, to compare the performance of the two OCT devices in terms of their ability to differentiate the three stages of glaucoma. Further, to analyze the macular parameters of both devices and compare them with the conventional retinal nerve fiber layer (RNFL) parameters. Methods: One hundred and twenty eyes (30 healthy and 90 glaucomatous [30 mild, 30 moderate, and 30 advanced glaucoma]) of 65 participants (15 healthy, 50 glaucomatous [15 mild, 15 moderate, and 20 advanced glaucoma]) underwent Cirrus and RTVue OCT scanning on a single visit. Results: Average RNFL thickness and superior RNFL thickness of both the devices and inferior (ganglion cell complex [GCC] of RTVue device best differentiated normals from all stage glaucomatous eyes (P > 0.05). Cirrus average RNFL thickness and superior RNFL thickness performed better than other parameters (P < 0.05) in differentiating early glaucoma from moderate and advanced. In differentiating advanced from early and moderate glaucoma, RTVue average, superior, and inferior RNFL thickness and inferior GCC parameters had the highest discriminating ability (P < 0.05). Conclusion: Overall, average RNFL thickness had the highest ability to distinguish different stages of the disease. No significant difference was found between RTVue and Cirrus OCT device in different severity levels. No significant difference was observed between RNFL and macular parameters in different stages of glaucoma.

Abstract Background More than half of persons living with HIV (PLWH) in the United States are insufficiently engaged in HIV primary care and not taking antiretroviral therapy (ART), mainly African Americans/Blacks and Hispanics. In the proposed project, a potent and innovative research methodology, the multiphase optimization strategy (MOST), will be employed to develop a highly efficacious, efficient, scalable, and cost-effective intervention to increase engagement along the HIV care continuum. Whereas randomized controlled trials are valuable for evaluating the efficacy of multi-component interventions as a package, they are not designed to evaluate which specific components contribute to efficacy. MOST, a pioneering, engineering-inspired framework, addresses this problem through highly efficient randomized experimentation to assess the performance of individual intervention components and their interactions. We propose to use MOST to engineer an intervention to increase engagement along the HIV care continuum for African American/Black and Hispanic PLWH not well engaged in care and not taking ART. Further, the intervention will be optimized for cost-effectiveness. A similar set of multi-level factors impede both HIV care and ART initiation for African American/Black and Hispanic PLWH, primary among them individual- (e.g., substance use, distrust, fear), social- (e.g., stigma), and structural-level barriers (e.g., difficulties accessing ancillary services). Guided by a multi-level social cognitive theory, and using the motivational interviewing approach, the study will evaluate five distinct culturally based intervention components (i.e., counseling sessions, pre-adherence preparation, support groups, peer mentorship, and patient navigation), each designed to address a specific barrier to HIV care and ART initiation. These components are well-grounded in the empirical literature and were found acceptable, feasible, and promising with respect to efficacy in a preliminary study. Methods/design Study aims are: 1) using a highly efficient fractional factorial experimental design, identify which of five intervention components contribute meaningfully to improvement in HIV viral suppression, and secondary outcomes of ART adherence and engagement in HIV primary care; 2) identify mediators and moderators of intervention component efficacy; and 3) using a mathematical modeling approach, build the most cost-effective and efficient intervention package from the efficacious components. A heterogeneous sample of African American/Black and Hispanic PLWH (with respect to age, substance use, and sexual minority status) will be recruited with a proven hybrid sampling method using targeted sampling in community settings and peer recruitment (N = 512). Discussion This is the first study to apply the MOST framework in the field of HIV prevention and treatment. This innovative study will produce a culturally based HIV care continuum intervention for the nation’s most vulnerable PLWH, optimized for cost-effectiveness, and with exceptional levels of efficacy, efficiency, and scalability. Trial registration ClinicalTrials.gov, NCT02801747 , Registered June 8, 2016.

Therapeutic drug monitoring for drug-resistant tuberculosis (TB) is likely to improve treatment outcomes. While assessments of plasma drug levels can explain pharmacokinetic variability among trial participants, these measures require phlebotomy and a cold chain, and are generally not repeated frequently enough to characterise drug exposure over time. Using a novel multi-analyte assay, we found evidence that higher anti-TB drug concentrations in hair, a non-biohazardous and noninvasively collected biomatrix, predict extensively-drug resistant-TB clinical outcomes in a high-burden setting.

Due to marked reductions in morbidity and mortality, antiretroviral (ARV) adherence monitoring is of high interest. Researchers and clinicians often resort to the most feasible and cost-effective adherence methods possible, which may result in biased or inaccurate estimates and require the physical presence of a participant at a research or clinic site. The objective of our study was to evaluate the feasibility and acceptability of three objective, innovative, and remote methods to estimate ARV adherence which may be conducted with less time and financial resources in a wide range of clinic and research settings. These three methods included: (a) text-messaged photographs of pharmacy refill dates to measure refill-based adherence, (b) text-messaged photographs of ARV medications to estimate pill-count-based adherence, and (c) home-collected hair samples for the measurement of ARV concentration to determine pharmacologic-based adherence. We conducted a pilot study from March through October 2017 to examine the feasibility and acceptability of these three adherence measures and the remotely conducted study procedures in 93 adults living with HIV nationwide. From our diverse national sample of participants, 95.7% were retained until the end of the study, 89.9% sent all text messages, and 84.3% sent all hair samples. Approximately 74.2% of participants reported excellent overall experience with the study, 60.2% were very or extremely satisfied with participating in a hair collection study, and 76.3% noted extremely high likelihood of participating in a similar study including text messaging pictures of medications or refill dates. We noted high levels of feasibility and acceptability with the remote study methodology, collection of photographed and text messaged pharmacy refill dates and pill counts, and home-collected hair samples. Here we describe the feasibility and acceptability metrics, results from the exit qualitative interviews with the participants, and lessons learned. These adherence measures represent innovative approaches to expand monitoring tools for HIV treatment and prevention adherence in future research.

Women and girls comprise nearly half of HIV-infected individuals globally and 20% of new infections in the United States, indicating an urgent need to optimise HIV prevention options in this population. HIV pre-exposure prophylaxis (PrEP) – where antiretrovirals are administered to HIV-non-infected individuals at risk of HIV acquisition – is a promising, female-controlled HIV prevention strategy but has so far been underutilised in women. Clinical trial data demonstrate efficacy of daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for reduction of HIV acquisition among women when used consistently. Limited HIV risk perception and suboptimal PrEP awareness among women and healthcare personnel are among the challenges with PrEP delivery for women. Future research into the development of new drugs and delivery systems, and integrating PrEP delivery with reproductive healthcare services, provide opportunities to optimise this prevention strategy for women.

Objectives: Excellent adherence to combination antiretroviral therapy can suppress HIV replication and produce life expectancies nearing those of individuals without HIV infection. This qualitative study sought to identify the barriers and facilitators to good antiretroviral medication adherence in Thai patients living with HIV. Methods: Semi-structured interviews were conducted with a convenience sample (n=21) of patients attending routine clinic visits at Srinagarind Hospital in Khon Kaen, or HIV-NAT, the Thai Red Cross AIDS Research Centre in Bangkok. Results: Median informant age was 43 years (range 27–60 years) and 43% were female. We identified key facilitators and barriers to adherence among HIV-infected Thai patients along three major themes (patient-related, health system-related and medication-related). Stigma was a primary concern for most informants, operating throughout Thai society to induce feelings of shame for Thai people living with HIV. Determination to stay healthy and incorporate taking cART into their daily routine were key components of good adherence. Supportive and trusting relationships, particularly with the clinic team, empowered patients to maintain good medication adherence. Conclusions: Changing public perceptions about HIV, and training of HIV clinic staff on the importance of trusting and supportive provider–patient relationships in promoting good health outcomes, will help Thailand achieve its aim of having zero new HIV infections, zero discrimination and zero AIDS-related deaths by 2030.

ObjectivePeople living with HIV (PLWH) are living longer and developing comorbidities and aging-related syndromes. New care models are needed to address the combined burden and complexity of HIV and its comorbidities in this group. The goal of this study is to describe qualitative data from patients and providers that informed the development of a comprehensive care model for older PLWH.MethodsPatient and provider perspectives on the clinical care and service needs of patients living and aging with HIV were explored via surveys and focus groups at a safety net HIV clinic in San Francisco. We surveyed 77 patients and 26 providers and conducted separate focus groups of older patients living with HIV (n = 31) and staff (n = 20). Transcripts were analyzed using thematic analysis. Themes for a care program were additionally explored using findings from the literature on HIV and aging.FindingsThemes from surveys and focus groups emphasized (a) the need for knowledge expertise in HIV and aging, (b) focus on medical conditions and determinants of health of particular import (e.g. marginal housing) among older PLWH, (c) co-locating specialty services (e.g. cardiology, geriatrics) with primary care, and (d) addressing social isolation. Findings informed the design of a comprehensive, multidisciplinary care model for PLWH called the Golden Compass program composed of four "points": Heart and Mind (North), Bones and Strength (East), Network and Navigation (South), and Dental, Hearing, and Vision (West).ConclusionBased on patient and clinic staff perspectives from surveys and focus groups, we designed a multidisciplinary program of integrated primary and specialty care, as well as housing and social support, to address the needs of older PLWH within a safety-net infrastructure. Golden Compass launched in 2017 for PLWH older than 50 years. Future research to evaluate the effectiveness of this care program in improving patient outcomes and satisfaction is ongoing.

CLINICAL TRIAL REGISTRATION:Clinical Trials.gov NCT00131677.

We measured hair and plasma concentrations of isoniazid among sixteen children with tuberculosis who underwent personal or video-assisted directly observed therapy and thus had 100% adherence. This study therefore defined typical isoniazid exposure parameters after two months of treatment among fully-adherent patients in both hair and plasma (plasma area under the concentration-time curve, AUC, estimated using pharmacokinetic data collected 0, 2, 4, and 6 hours after drug administration). We found that INH levels in hair among highly-adherent individuals did not correlate well with plasma AUC or trough concentrations, suggesting that each measure may provide incremental and complementary information regarding drug exposure in the context of TB treatment.

BACKGROUND:Tuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges. Drug concentrations in hair assess long-term exposure and have demonstrated pharmacodynamic relevance in HIV. METHODS:A large hair sample from a patient with active TB was obtained for assay development. Methods to pulverize hair and extract isoniazid were optimized and then the drug detected by liquid chromatography/ tandem mass spectrometry (LC/MS-MS). The method was validated for specificity, accuracy, precision, recovery, linearity and stability to establish the assay's suitability for therapeutic drug monitoring (TDM). Hair samples from patients on directly-observe isoniazid-based latent or active TB therapy from the San Francisco Department of Public Health TB clinic were then tested. RESULTS:Our LC/MS-MS-based assay detected isoniazid in quantities as low as 0.02ng/mg using 10-25 strands hair. Concentrations in spiked samples demonstrated linearity from 0.05-50ng/mg. Assay precision and accuracy for spiked quality-control samples were high, with an overall recovery rate of 79.5%. In 18 patients with latent or active TB on treatment, isoniazid was detected across a wide linear dynamic range. CONCLUSIONS:An LC-MS/MS-based assay to quantify isoniazid levels in hair with performance characteristics suitable for TDM was developed and validated. Hair concentrations of isoniazid assess long-term exposure and may be useful for monitoring adherence to latent or active TB treatment in the setting of HIV.

Effective antiretroviral (ARV) therapy depends on adequate drug exposure, yet methods to assess ARV exposure are limited. Concentrations of ARV in hair are the product of steady-state pharmacokinetics factors and longitudinal adherence. We investigated nevirapine (NVP) concentrations in hair as a predictor of treatment response in women receiving ARVs. In participants of the Women's Interagency HIV Study, who reported NVP use for >1 month from 2003-2008, NVP concentrations in hair were measured via liquid-chromatography-tandem mass-spectrometry. The outcome was virologic suppression (plasma HIV RNA below assay threshold) at the time of hair sampling and the primary predictor was nevirapine concentration categorized into quartiles. We controlled for age, race/ethnicity, pre-treatment HIV RNA, CD4 cell count, and self-reported adherence over the 6-month visit interval (categorized ≤ 74%, 75%-94% or ≥ 95%). We also assessed the relation of NVP concentration with changes in hepatic transaminase levels via multivariate random intercept logistic regression and linear regression analyses. 271 women contributed 1089 person-visits to the analysis (median 3 of semi-annual visits). Viral suppression was least frequent in concentration quartile 1 (86/178 (48.3%)) and increased in higher quartiles (to 158/204 (77.5%) for quartile 4). The odds of viral suppression in the highest concentration quartile were 9.17 times (95% CI 3.2-26, P < 0.0001) those in the lowest. African-American race was associated with lower rates of virologic suppression independent of NVP hair concentration. NVP concentration was not significantly associated with patterns of serum transaminases. Concentration of NVP in hair was a strong independent predictor of virologic suppression in women taking NVP, stronger than self-reported adherence, but did not appear to be strongly predictive of hepatotoxicity.