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UNLABELLED: IntroductionInnovative interventions are needed to improve HIV outcomes among adolescents and young adults (AYAs) living with HIV. Engaging AYAs in intervention development could increase effectiveness and youth acceptance, yet research is limited. We applied human-centred design (HCD) to refine adherence-support interventions pretrial and assessed HCD workshop acceptability. METHODS: We applied an iterative, four-phased HCD process in Kenya that included: (1) systematic review of extant knowledge, (2) prioritisation of design challenges, (3) a co-creation workshop and (4) translation tables to pair insights with trial intervention adaptations. The co-creation workshop was co-led by youth facilitators employing participatory activities to inform intervention adaptations. Iterative data analysis included rapid thematic analysis of visualised workshop outputs and notes using affinity mapping and dialogue to identify key themes. We conducted a survey to assess workshop acceptability among participants. RESULTS: Twenty-two participants engaged in the 4-day workshop. Co-creation activities yielded recommendations for improving planned interventions (eg, message frequency and content; strategies to engage hard-to-reach participants), critical principles to employ across interventions (eg, personalisation, AYA empowerment) and identification of unanticipated AYA HIV treatment priorities (eg, drug holidays, transition from adolescent to adult services). We revised intervention content, peer navigator training materials and study inclusion criteria in response to findings. The youth-led HCD workshop was highly acceptable to participants. CONCLUSIONS: Research employing HCD among youth can improve interventions preimplementation through empathy, youth-led inquiry and real-time problem solving. Peer navigation may be most influential in improving retention when engagement with young people is based on mutual trust, respect, privacy and extends beyond HIV-specific support. Identifying opportunities for personalisation and adaptation within intervention delivery is important for AYAs. Patient engagement interventions that target young people should prioritise improved transition between youth and adult services, youth HIV status disclosure, AYA empowerment and healthcare worker responsiveness in interactions and episodic adherence interruptions.

Personalized intervention strategies, in particular those that modify treatment based on a participants own response, are a core component of precision medicine approaches. Sequential multiple assignment randomized trials (SMARTs) are growing in popularity and are specifically designed to facilitate the evaluation of sequential adaptive strategies, in particular those embedded within the SMART. Advances in efficient estimation approaches that are able to incorporate machine learning while retaining valid inference can allow for more precise estimates of the effectiveness of these embedded regimes. However, to the best of our knowledge, such approaches have not yet been applied as the primary analysis in SMART trials. In this paper, we present a robust and efficient approach using targeted maximum likelihood estimation (TMLE) for estimating and contrasting expected outcomes under the dynamic regimes embedded in a SMART, together with generating simultaneous confidence intervals for the resulting estimates. We contrast this method with two alternatives (G-computation and inverse probability weighting estimators). The precision gains and robust inference achievable through the use of TMLE to evaluate the effects of embedded regimes are illustrated using both outcome-blind simulations and a real-data analysis from the Adaptive Strategies for Preventing and Treating Lapses of Retention in Human Immunodeficiency Virus (HIV) Care (ADAPT-R) trial (NCT02338739), a SMART with a primary aim of identifying strategies to improve retention in HIV care among people living with HIV in sub-Saharan Africa.

Author(s): Elvin H. Geng 1,*, Ana Mocumbi 2, Wilbroad Mutale 3, Victor Davila-Roman 1, Michael Reid 4,5 Pinto and colleagues find that growth of the community-based primary care led to [...]

BACKGROUND: Adolescents and young adults living with HIV (AYAH) aged 14-24 years in Africa experience substantially higher rates of virological failure and HIV-related mortality than adults. We propose to utilize developmentally appropriate interventions with high potential for effectiveness, tailored by AYAH pre-implementation, in a sequential multiple assignment randomized trial (SMART) aimed at improving viral suppression for AYAH in Kenya. METHODS: Using a SMART design, we will randomize 880 AYAH in Kisumu, Kenya to either youth-centered education and counseling (standard of care) or electronic peer navigation in which a peer provides support, information, and counseling via phone and automated monthly text messages. Those with a lapse in engagement (defined as either a missed clinic visit by ≥14 days or HIV viral load ≥1000 copies/ml) will be randomized a second time to one of three higher-intensity re-engagement interventions: This study will evaluate which interventions and which dynamic sequence of interventions improve sustained viral suppression and HIV care engagement in AYAH at 24 months post-enrollment and assess the cost-effectiveness of successful strategies. DISCUSSION: The study utilizes promising interventions tailored to AYAH while optimizing resources by intensifying services only for those AYAH who need more support. Findings from this innovative study will offer evidence for public health programming to end the HIV epidemic as a public health threat for AYAH in Africa. TRIAL REGISTRATION: Clinicaltrials.govNCT04432571, registered June 16, 2020.

BACKGROUND: Optimizing retention in human immunodeficiency virus (HIV) treatment may require sequential behavioral interventions based on patients response. METHODS: In a sequential multiple assignment randomized trial in Kenya, we randomly assigned adults initiating HIV treatment to standard of care (SOC), Short Message Service (SMS) messages, or conditional cash transfers (CCT). Those with retention lapse (missed a clinic visit by ≥14 days) were randomly assigned again to standard-of-care outreach (SOC-Outreach), SMS+CCT, or peer navigation. Those randomly assigned to SMS or CCT who did not lapse after 1 year were randomly assigned again to either stop or continue the initial intervention. Primary outcomes were retention in care without an initial lapse, return to the clinic among those who lapsed, and time in care; secondary outcomes included adjudicated viral suppression. Average treatment effect (ATE) was calculated using targeted maximum likelihood estimation with adjustment for baseline characteristics at randomization and certain time-varying characteristics at rerandomization. RESULTS: Among 1809 participants, 79.7% of those randomly assigned to CCT (n=523/656), 71.7% to SMS (n=393/548), and 70.7% to SOC (n=428/605) were retained in care in the first year (ATE: 9.9%; 95% confidence interval [CI]: 5.4%, 14.4% and ATE: 4.2%; 95% CI: -0.7%, 9.2% for CCT and SMS compared with SOC, respectively). Among 312 participants with an initial lapse who were randomly assigned again, 69.1% who were randomly assigned to a navigator (n=76/110) returned, 69.5% randomly assigned to CCT+SMS (n=73/105) returned, and 55.7% randomly assigned to SOC-Outreach (n=54/97) returned (ATE: 14.1%; 95% CI: 0.6%, 27.6% and ATE: 11.4%; 95% CI: -2.2%, 24.9% for navigator and CCT+SMS compared with SOC-Outreach, respectively). Among participants without lapse on SMS, continuing SMS did not affect retention (n=122/180; 67.8% retained) versus stopping (n=151/209; 72.2% retained; ATE: -4.4%; 95% CI: -16.6%, 7.9%). Among participants without lapse on CCT, those continuing CCT had higher retention (n=192/230; 83.5% retained) than those stopping (n=173/287; 60.3% retained; ATE: 28.6%; 95% CI: 19.9%, 37.3%). Among 15 sequenced strategies, initial CCT, escalated to navigator if lapse occurred and continued if no lapse occurred, increased time in care (ATE: 7.2%, 95% CI: 3.7%, 10.7%) and viral suppression (ATE: 8.2%, 95% CI: 2.2%, 14.2%), the most compared with SOC throughout. Initial SMS escalated to navigator if lapse occurred, and otherwise continued, showed similar effect sizes compared with SOC throughout. CONCLUSIONS: Active interventions to prevent retention lapses followed by navigation for those who lapse and maintenance of initial intervention for those without lapse resulted in best overall retention and viral suppression among the strategies studied. Among those who remained in care, discontinuation of CCT, but not SMS, compromised retention and suppression. (Funded by National Institutes of Health grants R01 MH104123, K24 AI134413, and R01 AI074345; ClinicalTrials.gov number, NCT02338739.).

PURPOSE OF REVIEW: Despite the growing availability of effective HIV prevention and treatment interventions, there are large gaps in their uptake and sustained use across settings. It is crucial to elicit and apply patients and stakeholders preferences to maximize the impact of existing and future interventions. This review summarizes quantitative preference elicitation methods (PEM) and how they can be applied to improve the delivery and uptake of HIV prevention and treatment interventions. RECENT FINDINGS: PEM are increasingly applied in HIV implementation research; however, discrete choice experiments (DCEs) have predominated. Beyond DCEs, there are other underutilized PEM that may improve the reach and effectiveness of HIV prevention and treatment interventions among individuals by prioritizing their barriers to engagement and determining which attributes of interventions and delivery strategies are most valued. PEM can also enhance the adoption and sustained implementation of strategies to deliver HIV prevention and treatment interventions by assessing which attributes are the most acceptable and appropriate to key stakeholders. SUMMARY: Greater attention to and incorporation of patients and stakeholders preferences for HIV prevention and treatment interventions and their delivery has the potential to increase the number of persons accessing and retained in HIV prevention and treatment services.

: Introduction: Person‐centred care (PCC) has been recognized as a critical element in delivering quality and responsive health services. The patient−provider relationship, conceptualized at the core of PCC in multiple models, remains largely unexamined in HIV care. We conducted a systematic review to better understand the types of PCC interventions implemented to improve patient−provider interactions and how these interventions have improved HIV care continuum outcomes and person‐reported outcomes (PROs) among people living with HIV in low‐ and middle‐income countries. Methods: We searched databases, conference proceedings and conducted manual targeted searches to identify randomized trials and observational studies published up to January 2023. The PCC search terms were guided by the Integrative Model of Patient‐Centeredness by Scholl. We included person‐centred interventions aiming to enhance the patient−provider interactions. We included HIV care continuum outcomes and PROs. Results: We included 28 unique studies: 18 (64.3%) were quantitative, eight (28.6.%) were mixed methods and two (7.1%) were qualitative. Within PCC patient−provider interventions, we inductively identified five categories of PCC interventions: (1) providing friendly and welcoming services; (2) patient empowerment and improved communication skills (e.g. supporting patient‐led skills such as health literacy and approaches when communicating with a provider); (3) improved individualized counselling and patient‐centred communication (e.g. supporting provider skills such as training on motivational interviewing); (4) audit and feedback; and (5) provider sensitisation to patient experiences and identities. Among the included studies with a comparison arm and effect size reported, 62.5% reported a significant positive effect of the intervention on at least one HIV care continuum outcome, and 100% reported a positive effect of the intervention on at least one of the included PROs. Discussion: Among published HIV PCC interventions, there is heterogeneity in the components of PCC addressed, the actors involved and the expected outcomes. While results are also heterogeneous across clinical and PROs, there is more evidence for significant improvement in PROs. Further research is necessary to better understand the clinical implications of PCC, with fewer studies measuring linkage or long‐term retention or viral suppression. Conclusions: Improved understanding of PCC domains, mechanisms and consistency of measurement will advance PCC research and implementation., INTRODUCTION Person‐centred care (PCC) offers principles that promise to improve HIV prevention and care, potentially even in resource‐constrained and public health settings that typically emphasize standardization and scale. The initial [...]

BackgroundDespite longstanding guidelines endorsing isoniazid preventive therapy (IPT) for people with HIV, uptake is low across sub-Saharan Africa. Mid-level health managers oversee IPT programmes nationally; interventions aimed at this group have not been tested. We aimed to establish whether providing structured leadership and management training and facilitating subregional collaboration and routine data feedback to mid-level managers could increase IPT initiation among people with HIV compared with standard practice.MethodsWe conducted a cluster randomised trial in Uganda among district-level health managers. We randomly assigned clusters of between four and seven managers in a 1:1 ratio to intervention or control groups. Our intervention convened managers into mini-collaboratives facilitated by Ugandan experts in tuberculosis and HIV, and provided business leadership and management training, SMS platform access, and data feedback. The control was standard practice. Participants were not masked to trial group, but study statisticians were masked until trial completion. The primary outcome was IPT initiation rates among adults with HIV in facilities overseen by participants over a period of 2 years (2019-21). We conducted prespecified analyses that excluded the third quarter of 2019 (Q3-2019) to understand intervention effects independent of a national 100-day IPT push tied to a financial contingency during Q3-2019. This trial is registered with ClinicalTrials.gov (NCT03315962), and is ongoing.FindingsBetween Nov 15, 2017, and March 14, 2018, managers from 82 of 82 eligible districts (61% of Uganda's 135 districts) were enrolled and randomised: 43 districts to intervention, 39 to control. Intervention delivery took place between Dec 6, 2017, and Feb 2, 2022. Over 2 years, IPT initiation rates were 0·74 versus 0·65 starts per person-year in intervention versus control groups (incidence rate ratio [IRR] 1·14, 95% CI 0·88-1·46; p=0·16). Excluding Q3-2019, IPT initiation was higher in the intervention group versus the control group: 0·32 versus 0·25 starts per person-year (IRR 1·27, 95% CI 1·00-1·61; p=0·026).InterpretationFollowing an intervention targeting managers in more than 60% of Uganda's districts, IPT initiation rates were not significantly higher in intervention than control groups. After accounting for large increases in IPT from a 100-day push in both groups, the intervention led to significantly increased IPT rates, sustained after the push and during the COVID-19 pandemic. Our findings suggest that interventions centred on mid-level health managers can improve IPT implementation on a large, subnational scale, and merit further exploration to address key public health challenges for which strong evidence exists but implementation remains suboptimal.FundingNational Institute of Allergy and Infectious Diseases.

Novel "differentiated service delivery" models for HIV treatment that reduce clinic visit frequency, minimize waiting time, and deliver treatment in the community promise retention improvement for HIV treatment in Sub-Saharan Africa. Quantitative assessments of differentiated service delivery (DSD) feature most preferred by patient populations do not widely exist but could inform selection and prioritization of different DSD models. We used a discrete choice experiment (DCE) to elicit patient preferences of HIV treatment services and how they differ across DSD models. We surveyed 18+year-olds, enrolled in HIV care for ≥6 months between February-March, 2019 at four facilities in Kisumu County, Kenya. DCE offered patients a series of comparisons between three treatment models, each varying across seven attributes: ART refill location, quantity of dispensed ART at each refill, medication pick-up hours, type of adherence support, clinical visit frequency, staff attitude, and professional cadre of person providing ART refills. We used hierarchical Bayesian model to estimate attribute importance and relative desirability of care characteristics, latent class analysis (LCA) for groups of preferences and mixed logit model for willingness to trade analysis. Of 242 patients, 128 (53.8%) were females and 150 (62.8%) lived in rural areas. Patients placed greatest importance on ART refill location [19.5% (95% CI 18.4, 10.6) and adherence support [19.5% (95% CI 18.17, 20.3)], followed by staff attitude [16.1% (95% CI 15.1, 17.2)]. In the mixed logit, patients preferred nice attitude of staff (coefficient = 1.60), refill ART health center (Coeff = 1.58) and individual adherence support (Coeff = 1.54), 3 or 6 months for ART refill (Coeff = 0.95 and 0.80, respectively) and pharmacists (instead of lay health workers) providing ART refill (Coeff = 0.64). No differences were observed by gender or urbanicity. LCA revealed two distinct groups (59.5% vs. 40.5%). Participants preferred 3 to 6-month refill interval or clinic visit spacing, which DSD offers stable patients. While DSD has encouraged community ART group options, our results suggest strong preferences for ART refills from health-centers or pharmacists over lay-caregivers or community members. These preferences held across gender&urban/rural subpopulations.

Growing literature has shown heterogenous effects of conditional cash incentives (CCIs) on HIV care retention. The field lacks insights into reasons why incentives impact various patients in different ways-differences that may be due to variations in psychological and social mechanisms of effect. A deeper understanding of patients' perceptions and experiences of CCIs for retention may help to clarify these mechanisms. We conducted a qualitative study embedded in the ADAPT-R trial (NCT#02338739), a sequential multiple assignment randomized trial (SMART) that evaluated economic incentives to support retention in HIV care among persons living with HIV (PLHIV) initiating antiretroviral therapy in Kenya. Participants who attended their scheduled clinic visits received an incentive of approximately $4 each visit. Interviews were conducted between July 2016 and June 2017 with 39 participants to explore attitudes and experiences with economic incentives conditional on care engagement. Analyses revealed that incentives helped PLHIV prioritize care-seeking by alleviating transport barriers and food insecurity: "I decided to forgo [work] and attend clinic […] the voucher relieved me". Patients who borrowed money for care-seeking reported feeling relieved from the burden of indebtedness to others: "I borrow with confidence that I will pay after my appointment." Incentives fostered their autonomy, and enabled them to support others: "I used the money to buy some clothes and Pampers for the children." Participants who were intrinsically motivated to engage in care ("my life depends on the drugs, not the incentive"), and those who mistrusted researchers, reported being less prompted by the incentive itself. For patients not already prioritizing care-seeking, incentives facilitated care engagement through alleviating transport costs, indebtedness and food insecurity, and also supported social role fulfillment. Conditional cash incentives may be an important cue to action to improve progression through the HIV treatment cascade, and contribute to better care retention.

BackgroundOptimizing services to facilitate engagement and retention in care of people living with HIV (PLWH) on antiretroviral therapies (ARTs) is critical to decrease HIV-related morbidity and mortality and HIV transmission. We systematically reviewed the literature for the effectiveness of implementation strategies to reestablish and subsequently retain clinical contact, improve viral load suppression, and reduce mortality among patients who had been lost to follow-up (LTFU) from HIV services.Methods and findingsWe searched 7 databases (PubMed, Cochrane, ERIC, PsycINFO, EMBASE, Web of Science, and the WHO regional databases) and 3 conference abstract archives (CROI, IAC, and IAS) to find randomized trials and observational studies published through 13 April 2020. Eligible studies included those involving children and adults who were diagnosed with HIV, had initiated ART, and were subsequently lost to care and that reported at least one review outcome (return to care, retention, viral suppression, or mortality). Data were extracted by 2 reviewers, with discrepancies resolved by a third. We characterized reengagement strategies according to how, where, and by whom tracing was conducted. We explored effects, first, among all categorized as LTFU from the HIV program (reengagement program effect) and second among those found to be alive and out of care (reengagement contact outcome). We used random-effect models for meta-analysis and conducted subgroup analyses to explore heterogeneity. Searches yielded 4,244 titles, resulting in 37 included studies (6 randomized trials and 31 observational studies). In low- and middle-income countries (LMICs) (N = 16), tracing most frequently involved identification of LTFU from the electronic medical record (EMR) and paper records followed by a combination of telephone calls and field tracing (including home visits), by a team of outreach workers within 3 months of becoming LTFU (N = 7), with few incorporating additional strategies to support reengagement beyond contact (N = 2). In high-income countries (HICs) (N = 21 studies), LTFU were similarly identified through EMR systems, at times matched with other public health records (N = 4), followed by telephone calls and letters sent by mail or email and conducted by outreach specialist teams. Home visits were less common (N = 7) than in LMICs, and additional reengagement support was similarly infrequent (N = 5). Overall, reengagement programs were able to return 39% (95% CI: 31% to 47%) of all patients who were characterized as LTFU (n = 29). Reengagement contact resulted in 58% (95% CI: 51% to 65%) return among those found to be alive and out of care (N = 17). In 9 studies that had a control condition, the return was higher among those in the reengagement intervention group than the standard of care group (RR: 1.20 (95% CI: 1.08 to 1.32, P < 0.001). There were insufficient data to generate pooled estimates of retention, viral suppression, or mortality after the return.ConclusionsWhile the types of interventions are markedly heterogeneity, reengagement interventions increase return to care. HIV programs should consider investing in systems to better characterize LTFU to identify those who are alive and out of care, and further research on the optimum time to initiate reengagement efforts after missed visits and how to best support sustained reengagement could improve efficiency and effectiveness.

BackgroundUnderstanding patient-reported reasons for lapses of retention in human immunodeficiency virus (HIV) treatment can drive improvements in the care cascade. A systematic assessment of outcomes among a random sample of patients lost to follow-up (LTFU) from 32 clinics in Zambia to understand the reasons for silent transfers and disengagement from care was undertaken.MethodsWe traced a simple random sample of LTFU patients (>90 days from last scheduled visit) as determined from clinic-based electronic medical records from a probability sample of facilities. Among patients found in person, we solicited reasons for either stopping or switching care and predictors for re-engagement. We coded reasons into structural, psychosocial, and clinic-based barriers.ResultsAmong 1751 LTFU patients traced and found alive, 31% of patients starting antiretroviral therapy (ART) between 1 July 2013 and 31 July 2015 silently transferred or were disengaged (40% male; median age, 35 years; median CD4 level, 239 cells/μL); median time on ART at LTFU was 480 days (interquartile range, 110-1295). Among the 544 patients not in care, median prevalences for patient-reported structural, psychosocial, and clinic-level barriers were 27.3%, 13.9%, and 13.4%, respectively, and were highly variable across facilities. Structural reasons, including, "relocated to a new place" were mostly cited among 289 patients who silently transferred (35.5%). We found that men were less likely to re-engage in care than women (odds ratio, .39; 95% confidence interval, .22-.67; P = .001).ConclusionsEfforts to improve retention of patients on ART may need to be tailored at the facility level to address patient-reported barriers.

BackgroundIn the USA, Black and Hispanic or Latinx individuals continue to be disproportionately affected by HIV. Applying a distributional cost-effectiveness framework, we estimated the cost-effectiveness and epidemiological impact of two combination implementation approaches to identify the approach that best meets the dual objectives of improving population health and reducing racial or ethnic health disparities.MethodsWe adapted a dynamic, compartmental HIV transmission model to characterise HIV micro-epidemics in six US cities: Atlanta, Baltimore, Los Angeles, Miami, New York, and Seattle. We considered combinations of 16 evidence-based interventions to diagnose, treat, and prevent HIV transmission according to previously documented levels of scale-up. We then identified optimal combination strategies for each city, with the distribution of each intervention implemented according to existing service levels (proportional services approach) and the racial or ethnic distribution of new diagnoses (between Black, Hispanic or Latinx, and White or other ethnicity individuals; equity approach). We estimated total costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios of strategies implemented from 2020 to 2030 (health-care perspective; 20-year time horizon; 3% annual discount rate). We estimated three measures of health inequality (between-group variance, index of disparity, Theil index), incidence rate ratios, and rate differences for the selected strategies under each approach.FindingsIn all cities, optimal combination strategies under the equity approach generated more QALYs than those with proportional services, ranging from a 3·1% increase (95% credible interval [CrI] 1·4-5·3) in New York to more than double (101·9% [75·4-134·6]) in Atlanta. Compared with proportional services, the equity approach delivered lower costs over 20 years in all cities except Los Angeles; cost reductions ranged from $22·9 million (95% CrI 5·3-55·7 million) in Seattle to $579·8 million (255·4-940·5 million) in Atlanta. The equity approach also reduced incidence disparities and health inequality measures in all cities except Los Angeles.InterpretationEquity-focused HIV combination implementation strategies that reduce disparities for Black and Hispanic or Latinx individuals can significantly improve population health, reduce costs, and drive progress towards Ending the HIV Epidemic goals in the USA.FundingNational Institute on Drug Abuse.

Subgroup analyses of randomized controlled trials guide resource allocation and implementation of new interventions by identifying groups of individuals who are likely to benefit most from the intervention. Unfortunately, trial populations are rarely representative of the target populations of public health or clinical interest. Unless the relevant differences between trial and target populations are accounted for, subgroup results from trials might not reflect which groups in the target population will benefit most from the intervention. Transportability provides a rigorous framework for applying results derived in potentially highly selected study populations to external target populations. The method requires that researchers measure and adjust for all variables that 1) modify the effect of interest and 2) differ between the target and trial populations. To date, applications of transportability have focused on the external validity of overall study results and understanding within-trial heterogeneity; however, this approach has not yet been used for subgroup analyses of trials. Through an example from the Iniciativa Profilaxis Pre-Exposición (iPrEx) study (multiple countries, 2007-2010) of preexposure prophylaxis for human immunodeficiency virus, we illustrate how transporting subgroup analyses can produce target-specific subgroup effect estimates and numbers needed to treat. This approach could lead to more tailored and accurate guidance for resource allocation and cost-effectiveness analyses.

BackgroundIdentifying individuals at high risk of missing HIV care provider visits could support proactive intervention. Previous prediction models for missed visits have not incorporated data beyond the individual level.MethodsWe developed prediction models for missed visits among people with HIV (PWH) with ≥1 follow-up visit in the Center for AIDS Research Network of Integrated Clinical Systems from 2010 to 2016. Individual-level (medical record data and patient-reported outcomes), community-level (American Community Survey), HIV care site-level (standardized clinic leadership survey), and structural-level (HIV criminalization laws, Medicaid expansion, and state AIDS Drug Assistance Program budget) predictors were included. Models were developed using random forests with 10-fold cross-validation; candidate models with the highest area under the curve (AUC) were identified.ResultsData from 382 432 visits among 20 807 PWH followed for a median of 3.8 years were included; the median age was 44 years, 81% were male, 37% were Black, 15% reported injection drug use, and 57% reported male-to-male sexual contact. The highest AUC was 0.76, and the strongest predictors were at the individual level (prior visit adherence, age, CD4+ count) and community level (proportion living in poverty, unemployed, and of Black race). A simplified model, including readily accessible variables available in a web-based calculator, had a slightly lower AUC of .700.ConclusionsPrediction models validated using multilevel data had a similar AUC to previous models developed using only individual-level data. The strongest predictors were individual-level variables, particularly prior visit adherence, though community-level variables were also predictive. Absent additional data, PWH with previous missed visits should be prioritized by interventions to improve visit adherence.

We examined HIV viral load non-suppression ([Formula: see text] 200 copies/mL) subsequent to person-periods (3-18 months) bookended by two self-reports of alcohol use on a standardized patient reported outcome assessment among adults in routine HIV care. We examined the relative risk (RR) of non-suppression associated with increases and decreases in alcohol use (relative to stable use), stratified by use at the start of the person-period. Increases in drinking from abstinence were associated with higher risk of viral non-suppression (low-risk without binge: RR 1.16, 95% CI 1.03, 1.32; low-risk with binge: RR 1.35, 95% CI 1.11, 1.63; high-risk: RR 1.89, 95% CI 1.16, 3.08). Decreases in drinking from high-risk drinking were weakly, and not statistically significantly associated with lower risk of viral non-suppression. Other changes in alcohol use were not associated with viral load non-suppression. Most changes in alcohol consumption among people using alcohol at baseline were not strongly associated with viral non-suppression.

ObjectivesEvaluate differences in weight change by regimen among people living with HIV (PLWH) initiating antiretroviral therapy (ART) in the current era.MethodsBetween 2012 and 2019, 3232 ART-naïve PLWH initiated ≥3-drug ART regimens in 8 Centers for AIDS Research Network of Integrated Clinical Systems sites. We estimated weight change by regimen for 11 regimens in the immediate (first 6 months) and extended (all follow-up on initial regimen) periods using linear mixed models adjusted for time on regimen, interaction between time and regimen, age, sex, race/ethnicity, hepatitis B/C coinfection, nadir CD4, smoking, diabetes, antipsychotic medication, and site. We included more recently approved regimens [eg, with tenofovir alafenamide fumarate (TAF)] only in the immediate period analyses to ensure comparable follow-up time.ResultsMean follow-up was 1.9 years on initial ART regimen. In comparison to efavirenz/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC), initiating bictegravir/TAF/FTC {3.9 kg [95% confidence interval (CI): 2.2 to 5.5]} and dolutegravir/TAF/FTC [4.4 kg (95% CI: 2.1 to 6.6)] were associated with the greatest weight gain in the immediate period, followed by darunavir/TDF/FTC [3.7 kg (95% CI: 2.1 to 5.2)] and dolutegravir/TDF/FTC [2.6 kg (95% CI: 1.3 to 3.9)]. In the extended period, compared with efavirenz/TDF/FTC, initiating darunavir/TDF/FTC was associated with a 1.0 kg (95% CI: 0.5 to 1.5) per 6-months greater weight gain, whereas dolutegravir/abacavir/FTC was associated with a 0.6-kg (95% CI: 0.3 to 0.9) and dolutegravir/TDF/FTC was associated with a 0.6-kg (95% CI: 0.1 to 1.1) per 6-months greater gain. Weight gain on dolutegravir/abacavir/FTC and darunavir/TDF/FTC was significantly greater than that for several integrase inhibitor-based regimens.ConclusionsThere is heterogeneity between regimens in weight gain following ART initiation among previously ART-naïve PLWH; we observed greater gain among PLWH taking newer integrase strand transfer inhibitors (DTG, BIC) and DRV-based regimens.

IntroductionTo improve retention on HIV treatment in Africa, public health programs are promoting a family of innovations to service delivery-referred to as "differentiated service delivery" (DSD) models-which seek to better meet the needs of both systems and patients by reducing unnecessary encounters, expanding access, and incorporating peers and patients in patient care. Data on the relative desirability of different models to target populations, which is currently sparse, can help guide prioritization of specific models during scale-up.MethodsWe conducted a discrete choice experiment to assess patient preferences for various characteristics of treatment services. Clinically stable people living with HIV were recruited from an HIV clinic in Kisumu, Kenya. We selected seven attributes of DSD models drawn from literature review and previous qualitative work. We created a balanced and orthogonal design to identify main term effects. A total of ten choice tasks were solicited per respondent. We calculated relative utility (RU) for each attribute level, a numerical representation of the strength of patient preference. Data were analyzed using a Hierarchical Bayesian model via Sawtooth Software.ResultsOne hundred and four respondents (37.5% men, 41.1 years mean age) preferred receiving care at a health facility, compared with home-delivery or a community meeting point (RU = 69.3, -16.2, and -53.1, respectively; p << 0.05); receiving those services from clinicians and pharmacists-as opposed to lay health workers or peers (RU = 21.5, 5.9, -24.5; p < 0.05); and preferred an individual support system over a group support system (RU = 15.0 and 4.2; p < 0.05). Likewise, patients strongly preferred longer intervals between both clinical reviews (RU = 40.1 and -50.7 for 6- and 1-month spacing, respectively; p < 0.05) and between ART collections (RU = 33.6 and -49.5 for 6- and1-month spacing, respectively; p < 0.05).ConclusionAlthough health systems find community- and peer-based DSD models attractive, clinically stable patients expressed a preference for facility-based care as long as clinical visits were extended to biannual. These data suggest that multi-month scripting and fast-track models best align with patient preferences, an insight which can help prioritize use of different DSD models in the region.

BackgroundDelays in the diagnosis of tuberculosis (TB) contribute to a substantial proportion of TB-related mortality, especially among people living with HIV (PLHIV). We sought to characterize the diagnostic journey for HIV-positive and HIV-negative patients with a new TB diagnosis in Zambia, to understand drivers of delay, and characterize their preferences for service characteristics to inform improvements in TB services.MethodsWe assessed consecutive adults with newly microbiologically-confirmed TB at two public health treatment facilities in Lusaka, Zambia. We administered a survey to document critical intervals in the TB care pathway (time to initial care-seeking, diagnosis and treatment initiation), identify bottlenecks and their reasons. We quantified patient preferences for a range of characteristics of health services using a discrete choice experiment (DCE) that assessed 7 attributes (distance, wait times, hours of operation, confidentiality, sex of provider, testing incentive, TB test speed and notification method).ResultsAmong 401 patients enrolled (median age of 34 years, 68.7% male, 46.6% HIV-positive), 60.9% and 39.1% were from a first-level and tertiary hospital, respectively. The median time from symptom onset to receipt of TB treatment was 5.0 weeks (IQR: 3.6-8.0) and was longer among HIV-positive patients seeking care at a tertiary hospital than HIV-negative patients (6.4 vs. 4.9 weeks, p = 0.002). The time from symptom onset to initial presentation for evaluation accounted for the majority of time until treatment initiation (median 3.0 weeks, IQR: 1.0-5.0)-an important minority of 11.0% of patients delayed care-seeking ≥8 weeks. The DCE found that patients strongly preferred same-day TB test results (relative importance, 37.2%), facilities close to home (18.0%), and facilities with short wait times (16.9%). Patients were willing to travel to a facility up to 7.6 kilometers further away in order to access same-day TB test results. Preferences for improving current TB services did not differ according to HIV status.ConclusionsProlonged intervals from TB symptom onset to treatment initiation were common, especially among PLHIV, and were driven by delayed health-seeking. Addressing known barriers to timely diagnosis and incorporating patients' preferences into TB services, including same-day TB test results, may facilitate earlier TB care engagement in high burden settings.

BackgroundExisting social relationships are a potential source of "social capital" that can enhance support for sustained retention in HIV care. A previous pilot study of a social network-based 'microclinic' intervention, including group health education and facilitated HIV status disclosure, reduced disengagement from HIV care. We conducted a pragmatic randomized trial to evaluate microclinic effectiveness.MethodsIn nine rural health facilities in western Kenya, we randomized HIV-positive adults with a recent missed clinic visit to either participation in a microclinic or usual care (NCT02474992). We collected visit data at all clinics where participants accessed care and evaluated intervention effect on disengagement from care (≥90-day absence from care after a missed visit) and the proportion of time patients were adherent to clinic visits ('time-in-care'). We also evaluated changes in social support, HIV status disclosure, and HIV-associated stigma.ResultsOf 350 eligible patients, 304 (87%) enrolled, with 154 randomized to intervention and 150 to control. Over one year of follow-up, disengagement from care was similar in intervention and control (18% vs 17%, hazard ratio 1.03, 95% CI 0.61-1.75), as was time-in-care (risk difference -2.8%, 95% CI -10.0% to +4.5%). The intervention improved social support for attending clinic appointments (+0.4 units on 5-point scale, 95% CI 0.08-0.63), HIV status disclosure to close social supports (+0.3 persons, 95% CI 0.2-0.5), and reduced stigma (-0.3 units on 5-point scale, 95% CI -0.40 to -0.17).ConclusionsThe data from our pragmatic randomized trial in rural western Kenya are compatible with the null hypothesis of no difference in HIV care engagement between those who participated in a microclinic intervention and those who did not, despite improvements in proposed intervention mechanisms of action. However, some benefit or harm cannot be ruled out because the confidence intervals were wide. Results differ from a prior quasi-experimental pilot study, highlighting important implementation considerations when evaluating complex social interventions for HIV care.Trial registrationClinical trial number: NCT02474992.

BackgroundRetention in care (RIC) leads to reduced HIV transmission and mortality. Few studies have investigated clinic services and RIC among people living with HIV (PLWH) in the United States. We conducted a multisite retrospective cohort study to identify clinic services associated with RIC from 2010-2016 in the United States.MethodsPLWH with ≥1 HIV primary care visit from 2010-2016 at 7 sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) were included. Clinic-level factors evaluated via site survey included patients per provider/trainee, navigation, RIC posters/brochures, laboratory test timing, flexible scheduling, appointment reminder methods, and stigma support services. RIC was defined as ≥2 encounters per year, ≥90 days apart, observed until death, administrative censoring (31 December 2016), or loss to follow-up (censoring at first 12-month interval without a visit with no future visits). Poisson regression with robust error variance, clustered by site adjusting for calendar year, age, sex, race/ethnicity, and HIV transmission risk factor, estimated risk ratios (RRs) and 95% confidence intervals (CIs) for RIC.ResultsAmong 21 046 PLWH contributing 103 348 person-years, 67% of person-years were retained. Availability of text appointment reminders (RR, 1.13; 95% CI, 1.03-1.24) and stigma support services (RR, 1.11; 95% CI, 1.04-1.19) were associated with better RIC. Disparities persisted for age, sex, and race.ConclusionsAvailability of text appointment reminders and stigma support services was associated with higher rates of RIC, indicating that these may be feasible and effective approaches for improving RIC.

BackgroundRetention in human immunodeficiency virus (HIV) care is dynamic, with patients frequently transitioning in and out of care. Analytical approaches (eg, survival analyses) commonly used to assess HIV care cascade outcomes fail to capture such transitions and therefore incompletely represent care outcomes over time.MethodsWe analyzed antiretroviral therapy (ART)-eligible adults newly linking to care at 64 clinics in Zambia between 1 April 2014 and 31 July 2015. We used electronic medical record data and supplemented these with updated care outcomes ascertained by tracing a multistage random sample of patients lost to follow-up (LTFU, >90 days late for last appointment). We performed multistate analyses, incorporating weights from sampling, to estimate the prevalence of 9 care states over time since linkage with respect to ART initiation, retention in care, transfers, and mortality.ResultsIn sum, 23 227 patients (58% female; median age 34 years [interquartile range 28-41]) were ART-eligible at enrollment. At 1 year, 75.2% had initiated ART and were in care: 61.8% were continuously retained, 6.1% had reengaged after LTFU, and 7.3% had transferred. Also, 10.1% were LTFU within 7 days of enrollment, and 15.2% were LTFU at 1 year (6.7% prior to ART). One year after LTFU, 51.6% of those LTFU prior to ART remained out of care compared to 30.2% of those LTFU after initiating ART. Overall, 6.9% of patients had died by 1 year with 3.0% dying prior to ART.ConclusionMultistate analyses provide more complete assessments of longitudinal HIV cascade outcomes and reveal treatment gaps at distinct timepoints in care that will still need to be addressed even with universal treatment.

BackgroundRates of early syphilis in US women are steadily increasing, but predictors of infection in this group are not clearly defined.MethodsThis retrospective analysis focused on women enrolled in the US CFAR Network of Integrated Clinical Systems cohort between January 2005 and December 2016 with syphilis testing performed. The primary outcome of incident syphilis infection was defined serologically as a newly positive test with positive confirmatory testing after a negative test or a 2-dilution increase in rapid plasma regain titer. Infection rates were calculated for each woman-year in care with testing. Predictors of syphilis were sought among sociodemographics, clinical information, and self-reported behaviors. Multivariable logistic regression models were created; a subgroup analysis assessed predictors in women of reproductive age.ResultsThe annual rate of incident syphilis among 4416 women engaged in human immunodeficiency virus (HIV) care and tested during the 12-year study period was 760/100 000 person-years. Independent predictors of infection were injection drug use as a risk factor for HIV acquisition (aOR, 2.2; 95% CI, 1.3-3.9), hepatitis C infection (aOR, 1.9; 95% CI, 1.1-3.4), black race (aOR, 2.2; 95% CI, 1.3-3.7 compared with white race), and more recent entry to care (since 2005 compared with 1994-2004). Predictors were similar in women aged 18-49.ConclusionsSyphilis infection is common among US women in HIV care. Syphilis screening and prevention efforts should focus on women reporting drug use and with hepatitis C coinfection. Future studies should identify specific behaviors that mediate syphilis acquisition risk in women who use drugs.

BACKGROUND:Homelessness and unstable housing (HUH) negatively impact care outcomes for people living with HIV (PLWH). To inform design of a clinic program for PLWH experiencing HUH, we quantified patient preferences and trade-offs across multiple HIV-service domains using a discrete choice experiment (DCE). METHODS:We sequentially sampled PLWH experiencing HUH presenting at an urban HIV clinic with missed primary care visit and viremia in the last year to conduct a DCE. Participants chose between two hypothetical clinics varying across five service attributes: care team "get to know me as a person" versus not; receiving $10, $15 or $20 gift cards for clinic visits; drop-in versus scheduled visits; direct phone communication to care team versus front-desk staff; staying 2 versus 20 blocks from the clinic. We estimated attribute relative utility (i.e., preference) using mixed-effects logistic regression and calculated the monetary trade-off of preferred options. RESULTS:Among 65 individuals interviewed, 61% were >40 years-old; 45% white; 77% male; 25% heterosexual; 56% lived outdoors/emergency housing, and 44% in temporary housing. Strongest preferences were for patient-centered care team (β = 3.80; 95%CI 2.57-5.02) and drop-in clinic appointments (β = 1.33; 95%CI 0.85-1.80), with a willingness to trade $32.79 (95%CI 14.75-50.81) and $11.45 (95%CI 2.95-19.95) in gift cards/visit, respectively. CONCLUSION:In this DCE, PLWH-HUH were willing to trade significant financial gain to have a personal relationship with and drop-in access to their care team rather than clinic proximity and gift cards. These findings informed Ward 86's "POP-UP" program for PLWH-HUH and can inform "Ending the HIV Epidemic" efforts.

ObjectiveHistorically, a high burden of resistance to antiretroviral therapy (ART) in heavily treatment-experienced (HTE) persons with HIV (PWH) resulted in limited treatment options (LTOs). We evaluated the prevalence, risk factors, and virologic control of HTE PWH with LTO throughout the modern ART era.DesignWe examined all ART-experienced PWH in care between 2000 and 2017 in the Centers for AIDS Research Network of Integrated Clinical Systems cohort.MethodsWe computed the annual prevalence of HTE PWH with LTO defined as having two or less available classes with two or less active drugs per class based on genotypic data and cumulative antiretroviral resistance. We used multivariable Cox proportional hazards models to examine risk of LTO by 3-year study entry periods adjusting for demographic and clinical characteristics.ResultsAmong 27 133 ART-experienced PWH, 916 were classified as having LTO. The prevalence of PWH with LTO was 5.2-7.5% in 2000-2006, decreased to 1.8% in 2007, and remained less than 1% after 2012. Persons entering the study in 2009-2011 had an 80% lower risk of LTO compared with those entering in 2006-2008 (adjusted hazard ratio 0.20; 95% confidence interval: 0.09-0.42). We found a significant increase in undetectable HIV viral loads among PWH ever classified as having LTO from less than 30% in 2001 to more than 80% in 2011, comparable with persons who never had LTO.ConclusionResults of this large multicenter study show a dramatic decline in the prevalence of PWH with LTO to less than 1% with the availability of more potent drugs and a marked increase in virologic suppression in the current ART era.

Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR) = 1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR = 0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR = 2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research.

Purpose of reviewSingular interventions targeting vulnerable populations of people living with HIV (PLWH) are necessary for reducing new infections and optimizing individual-level outcomes, but extant literature for PLWH who experience homelessness and unstable housing (HUH) has not been compiled. To inform implementation of clinic-based programs that improve care outcomes in this population, we present a synthetic review of key studies examining clinic-based interventions, specifically case management, patient navigation, financial incentives, and the use of mobile technology.Recent findingsResults from unimodal interventions are mixed or descriptive, are limited by inability to address related multi-modal barriers to care, and do not address major challenges to implementation. Multi-component interventions are needed, but gaps in our knowledge base may limit widespread uptake of such interventions before further data are compiled. Future research evaluating interventions for PLWH experiencing HUH should include implementation outcomes in order to facilitate adaptation across diverse clinical settings.

Hepatitis C virus (HCV) infection is common among people living with human immunodeficiency virus (PLWH). Extrahepatic manifestations of HCV, including myocardial infarction (MI), are a topic of active research. MI is classified into types, predominantly atheroembolic type 1 MI (T1MI) and supply-demand mismatch type 2 MI (T2MI). We examined the association between HCV and MI among patients in the Centers for AIDS Research (CFAR) Network of Integrated Clinical Systems, a US multicenter clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Third Universal Definition of Myocardial Infarction. We estimated the association between chronic HCV (RNA+) and time to MI while adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics, and history of injecting drug use. Among 23,407 PLWH aged ≥18 years, there were 336 T1MIs and 330 T2MIs during a median of 4.7 years of follow-up between 1998 and 2016. HCV was associated with a 46% greater risk of T2MI (adjusted hazard ratio (aHR) = 1.46, 95% confidence interval (CI): 1.09, 1.97) but not T1MI (aHR = 0.87, 95% CI: 0.58, 1.29). In an exploratory cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR = 2.01, 95% CI: 1.25, 3.24). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research.

Despite its potential to improve metabolic health outcomes, longitudinal physical activity (PA) patterns and their association with cardiometabolic disease among people living with HIV (PLWH) have not been well characterized. We investigated this relationship among PLWH in the Centers for AIDS Research Network of Integrated Clinical Systems with at least one PA self-report between 2008 and 2015. The 4-item Lipid Research Clinics PA instrument was used to categorize habitual PA levels as: Very Low, Low, Moderate, or High. We analyzed demographic differences in PA patterns. Multivariable generalized estimating equation regression models were fit to assess longitudinal associations of PA with blood pressure, lipid, and glucose levels. Logistic regression modeling was used to assess the odds of being diagnosed with obesity, cardiovascular disease (CVD), cerebrovascular disease, hypertension, diabetes, or multimorbidity. A total of 40,462 unique PA assessments were provided by 11,719 participants. Only 13% of PLWH reported High PA, while 68% reported Very Low/Low PA at baseline and did not increase PA levels during the study period. Compared to those reporting High PA, participants with Very Low PA had almost 2-fold increased risk for CVD. Very Low PA was also associated with several risk factors associated with CVD, most notably elevated triglycerides (odds ratio 25.4), obesity (odds ratio 1.9), hypertension (odds ratio 1.4), and diabetes (odds ratio 2.3; all p

BackgroundCurrent models of HIV service delivery, with frequent facility visits, have led to facility congestion, patient and healthcare provider dissatisfaction, and suboptimal quality of services and retention in care. The Zambian urban adherence club (AC) is a health service innovation designed to improve on-time drug pickup and retention in HIV care through off-hours facility access and pharmacist-led group drug distribution. Similar models of differentiated service delivery (DSD) have shown promise in South Africa, but observational analyses of these models are prone to bias and confounding. We sought to evaluate the effectiveness and implementation of ACs in Zambia using a more rigorous study design.Methods and findingsUsing a matched-pair cluster randomized study design (ClinicalTrials.gov: NCT02776254), 10 clinics were randomized to intervention (5 clinics) or control (5 clinics). At each clinic, between May 19 and October 27, 2016, a systematic random sample was assessed for eligibility (HIV+, age ≥ 14 years, on ART >6 months, not acutely ill, CD4 count not 7 days late). Intervention effect was estimated using unadjusted Kaplan-Meier survival curves and a Cox proportional hazards model to derive an adjusted hazard ratio (aHR). Medication possession ratio (MPR) and implementation outcomes (adoption, acceptability, appropriateness, feasibility, and fidelity) were additionally evaluated as secondary outcomes. Baseline characteristics were similar between 571 intervention and 489 control participants with respect to median age (42 versus 41 years), sex (62% versus 66% female), median time since ART initiation (4.8 versus 5.0 years), median CD4 count at study enrollment (506 versus 533 cells/mm3), and baseline retention (53% versus 55% with at least 1 late drug pickup in previous 12 months). The rate of late drug pickup was lower in intervention participants compared to control participants (aHR 0.26, 95% CI 0.15-0.45, p < 0.001). Median MPR was 100% in intervention participants compared to 96% in control participants (p < 0.001). Although 18% (683/3,734) of AC group meeting visits were missed, on-time drug pickup (within 7 days) still occurred in 51% (350/683) of these missed visits through alternate means (use of buddy pickup or early return to the facility). Qualitative evaluation suggests that the intervention was acceptable to both patients and providers. While patients embraced the convenience and patient-centeredness of the model, preference for traditional adherence counseling and need for greater human resources influenced intervention appropriateness and feasibility from the provider perspective. The main limitations of this study were the small number of clusters, lack of viral load data, and relatively short follow-up period.ConclusionsACs were found to be an effective model of service delivery for reducing late ART drug pickup among HIV-infected adults in Zambia. Drug pickup outside of group meetings was relatively common and underscores the need for DSD models to be flexible and patient-centered if they are to be effective.Trial registrationClinicalTrials.gov NCT02776254.

BackgroundMen in sub-Saharan Africa have lower engagement and retention in HIV services compared to women, which may result in differential survival. However, the true magnitude of difference in HIV-related mortality between men and women receiving antiretroviral therapy (ART) is incompletely characterized.Methods and findingsWe evaluated HIV-positive adults ≥18 years old newly initiating ART in 4 Zambian provinces (Eastern, Lusaka, Southern, and Western). In addition to mortality data obtained from routine electronic medical records, we intensively traced a random sample of patients lost to follow-up (LTFU) and incorporated tracing outcomes through inverse probability weights. Sex-specific mortality rates and rate differences were determined using Poisson regression. Parametric g-computation was used to estimate adjusted mortality rates by sex and age. The study included 49,129 adults newly initiated on ART between August 2013 and July 2015; overall, the median age among patients was 35 years, the median baseline CD4 count was 262 cells/μl, and 37.2% were men. Men comprised a smaller proportion of individuals starting ART (37.2% versus 62.8%), tended to be older (median age 37 versus 33 years), and tended to have lower CD4 counts (median 220 versus 289 cells/μl) at the time of ART initiation compared to women. The overall rate of mortality among men was 10.3 (95% CI 8.2-12.4) deaths/100 person-years (PYs), compared to 5.5 (95% CI 4.3-6.8) deaths/100 PYs among women (difference +4.7 [95% CI 2.3-7.2] deaths/100 PYs; p < 0.001). Compared to women in the same age groups, men's mortality rates were particularly elevated among those

BackgroundImplementation science focuses on evaluating strategies for delivering evidence-based interventions to improve HIV prevention and treatment. The effectiveness of these implementation strategies is often context-dependent and reconciling the desire to produce generalizable knowledge in the face of these contextual interventions is a central challenge for implementation science researchers.MethodsWe provide an overview of the causal transportability theory and conceptualize context under this framework. We review how causal graphs can be used to illustrate the assumptions necessary to apply the results of a study to a new context, and we illustrate this approach using an example of a community adherence group intervention that aims to improve retention in HIV care. Finally, we discuss several key insights highlighted by the transportability theory that are relevant to implementation science researchers.ResultsBy adopting causal transportability to consider how context may affect the success of an implementation strategy, researchers can formally diagnose when the results of a study are likely to generalize to a given setting. Moreover, selection diagrams can highlight what additional measurements would be needed in a target population to estimate the effect of an implementation strategy in that target population without having to repeat the initial study.ConclusionsTransportability translates intuition about context-dependent interventions and external validity into actionable and testable insight.

BackgroundPersons with human immunodeficiency virus (HIV) have higher risks for myocardial infarction (MI) than the general population. This is driven in part by higher type 2 MI (T2MI, due to coronary supply-demand mismatch) rates among persons with HIV (PWH). In the general population, T2MI has higher mortality than type 1 MI (T1MI, spontaneous and generally due to plaque rupture and thrombosis). PWH have a greater burden of comorbidities and may therefore have an even greater excess risk for complication and death in the setting of T2MI. However, mortality patterns after T1MI and T2MI in HIV are unknown.MethodsWe analyzed mortality after MI among PWH enrolled in the multicenter, US-based Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort (N = 28,186). Incident MIs occurring between January 1, 1996, and December 31, 2014, were centrally adjudicated and classified as T1MI or T2MI. We first compared mortality following T1MI vs. T2MI among PWH. Cox survival analyses and Bayesian model averaging were then used to evaluate pre-MI covariates associated with mortality following T1MI and T2MI.ResultsAmong the 596 out of 28,186 PWH who experienced MI (2.1%; 293 T1MI and 303 T2MI), mortality rates were significantly greater after T2MI (22.2/100 person-years; 1-, 3-, and 5-year mortality 39%, 52%, and 62%) than T1MI (8.2/100 person-years; 1-, 3-, and 5-year mortality 15%, 22%, and 30%). Significant mortality predictors after T1MI were higher HIV viral load, renal dysfunction, and older age. Significant predictors of mortality after T2MI were low body-mass index (BMI) and detectable HIV viral load.ConclusionsMortality is high following MI for PWH and substantially greater after T2MI than T1MI. Predictors of death after MI differed by type of MI, reinforcing the different clinical scenarios associated with each MI type and the importance of considering MI types separately.

Various ongoing trials seek to evaluate long-acting pre-exposure prophylaxis (PrEP) agents by showing that they are non-inferior to daily oral tenofovir disoproxil fumarate and emtricitabine. Trials comparing oral PrEP to new methods examine effectiveness in a setting where only one or the other is provided; however, a new product will probably be delivered in a context where oral PrEP is also available. The effectiveness of a new PrEP product is best measured by its potential effect in a context that also includes oral tenofovir disoproxil fumarate and emtricitabine as an option. We offer an alternative standard for long-acting products-a measure of the effectiveness of the new product in addition to oral tenofovir disoproxil fumarate and emtricitabine as compared with oral PrEP alone. We term this measure mosaic effectiveness. We illustrate scenarios where a novel product can fail to show non-inferiority but show substantial mosaic effectiveness, thus implying the public health value of the novel product even if it is less effective than oral PrEP. Regulatory standards should consider mosaic effectiveness, not just comparative effectiveness. We assert that measurements that combine rigor with public health relevance can accelerate progress against the HIV epidemic.

BackgroundThe relationship of internalized HIV stigma to key care cascade metrics in the United States is not well established using large-scale, geographically diverse data.SettingCenter for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort study.MethodsBeginning in February 2016, we administered a yearly, validated 4-item internalized HIV stigma scale (response scale 1 = strongly disagree to 5 = strongly agree, Cronbach's alpha 0.91) at 7 CNICS sites and obtained cohort data through November 2017. We compared mean stigma levels by sociodemographic characteristics and used multivariable logistic regression, controlling for the same sociodemographic covariates, to evaluate the association between mean stigma and (1) concurrent viremia; (2) missed visits; and (3) poor visit constancy. We used inverse probability weighting (IPW) to account for differences between patients who did and did not undergo stigma assessment.ResultsOf 13,183 CNICS patients, 6448 (49%) underwent stigma assessment. Mean stigma was 1.99 (SD 1.07), and 28.6% agreed/strongly agreed with at least 1 stigma question. Patients younger than 50 years, racial/ethnic minorities, cis-women, and heterosexuals had higher mean stigma. Mean stigma score was associated with concurrent viremia [adjusted odds ratio (AOR) 1.13, 95% confidence interval (CI): 1.02 to 1.25, P 0.02], missed visits (AOR 1.10, 95% CI: 1.02 to 1.19, P 0.01), and poor visit constancy, although the effect on visit constancy was attenuated in the IPW model (AOR 1.05, 95% CI: 0.98 to 1.13, P 0.17).ConclusionsHigher internalized HIV stigma had a modest but statistically significant association with concurrent viremia and poor retention in care. Further inquiry with prospective analyses is warranted.

: Introduction: Poor client−provider communication is a critical barrier to long‐term retention in care among people living with HIV. However, standardized assessments of this key metric are limited in Africa. We used the Roter Interaction Analysis System (RIAS) to quantitatively characterize patterns of person‐centred communication (PCC) behaviours in Zambia. Methods: We enrolled pairs of people living with HIV making routine HIV follow‐up visit and their providers at 24 Ministry of Health‐facilities supported by the Centre for Infectious Disease Research in Zambia in Lusaka province between August 2019 and November 2021. Client−provider encounters were audio‐recorded and coded using RIAS by trained research staff. We performed latent class analysis to identify interactions with distinctive patterns of provider PCC behaviours (i.e. rapport building, person‐centred counselling, PCC micropractices [e.g. brief empathy statements], assessing barriers to care, shared decision‐making and leveraging discretionary power) and compared their distribution across client, provider, interaction and facility characteristics. Results: We enrolled 478 people living with HIV and 139 providers (14% nurses, 73.6% clinical officers, 12.3% were medical officers). We identified four distinct profiles: (1) “Medically Oriented Interaction, Minimal PCC Behaviours” (47.6% of interactions) was characterized by medical discussion, minimal psychosocial/non‐medical talk and low use of PCC behaviours; (2) “Balanced Medical/Non‐medical Interaction, Low PCC Behaviours” (21.0%) was characterized by medical and non‐medical discussion but limited use of other PCC behaviours; (3) “Medically Oriented Interaction, Good PCC Behaviours” (23.9%) was characterized by medically oriented discussion, more information‐giving and increased use of PCC behaviours; and (4) “Highly person‐centred Interaction” (7.5%) was characterized by both balanced medical/non‐medical focus and the highest use of PCC behaviours. Nurse interactions were more likely to be characterized by more PCC behaviours (i.e. Class 3 or 4) (44.8%), followed by medical officers (33.9%) and clinical officers (27.3%) (p = 0.031). Longer interactions were also more likely to integrate more PCC behaviours (p < 0.001). Conclusions: PCC behaviours are relatively uncommon in HIV care in Zambia, and often limited to brief rapport‐building statements and PCC micropractices. Strengthening PCC, such as shared decision‐making and leveraging discretionary power to better accommodate client needs and preferences, may be an important strategy for improving the quality in HIV treatment programmes., INTRODUCTION The encounter with healthcare providers is a pivotal moment in the client experience, but negative experiences with providers have remained one of the critical drivers of loss to follow‐up [...]