The missed potential of CD4 and viral load testing to improve clinical outcomes for people living with HIV in lower-resource settings.

In a Policy Forum, Peter Ehrenkranz and colleagues discuss the contribution of CD4 and viral load testing to outcomes for people with HIV in low- and middle-income countries.

Accelerating the Uptake and Timing of Antiretroviral Therapy Initiation in Sub-Saharan Africa: An Operations Research Agenda.

Sydney Rosen and colleagues describe an operations research agenda to accelerating uptake of HIV treatment initiation.

Patient Perspectives of Quality of the Same-Day Antiretroviral Therapy Initiation Process in Gauteng Province, South Africa: Qualitative Dominant Mixed-Methods Analysis of the SLATE II Trial.

BACKGROUND: HIV patients in South Africa continue to report operational barriers to starting antiretroviral therapy (ART). In the Simplified Algorithm for Treatment Eligibility (SLATE) II trial, same-day initiation (SDI) of ART increased the number of patients commencing ART and achieving HIV viral suppression by using a screening tool to distinguish between patients eligible for SDI and those requiring additional care before starting treatment. We conducted a mixed-methods evaluation to explore trial patients' perceptions and experiences of SDI. METHODS: SLATE II was implemented at three urban, public primary health care clinics in Gauteng Province, South Africa. We conducted a short quantitative survey and in-depth interviews among a purposive sample of 89 of the 593 trial participants in the intervention and standard arms, using a mixed inductive-deductive framework approach. RESULTS: Nearly all respondents (95%) were satisfied with their care, despite reporting clinic wait times of ≥ 3 h (72%). Intervention patients found the initiation process to be easy; standard patients found it complicated and were frustrated with being shuffled around the clinic. No intervention arm patients felt that SDI was "too fast" or indicated a preference for a more gradual process. Both groups highlighted the need for good counselling and non-judgmental, respectful staff. Standard patients suggested improving patient-provider relations, strengthening counselling, reducing wait times, and minimising referrals. CONCLUSIONS: While it is difficult to untangle the role of providers from that of the SLATE algorithm in influencing patient experiences, adoption of SLATE II implementation procedures could improve patient experience of treatment initiation. TRIAL REGISTRATION: Clinicaltrials.gov NCT03315013, registered October 19, 2017.

Patterns and Predictors of Incident Return to HIV Care Among Traced, Disengaged Patients in Zambia: Analysis of a Prospective Cohort.

BACKGROUND: Dynamic movement of patients in and out of HIV care is prevalent, but there is limited information on patterns of patient re-engagement or predictors of return to guide HIV programs to better support patient engagement. METHODS: From a probability-based sample of lost to follow-up, adult patients traced by peer educators from 31 Zambian health facilities, we prospectively followed disengaged HIV patients for return clinic visits. We estimated the cumulative incidence of return and the time to return using Kaplan-Meier methods. We used univariate and multivariable Cox proportional hazards regression to conduct a risk factor analysis identifying predictors of incident return across a social ecological framework. RESULTS: Of the 556 disengaged patients, 73.0% [95% confidence interval (CI): 61.0 to 83.8] returned to HIV care. The median follow-up time from disengagement was 32.3 months (interquartile range: 23.6-38.9). The rate of return decreased with time postdisengagement. Independent predictors of incident return included a previous gap in care [adjusted Hazard Ratio (aHR): 1.95, 95% CI: 1.23 to 3.09] and confronting a stigmatizer once in the past year (aHR: 2.14, 95% CI: 1.25 to 3.65). Compared with a rural facility, patients were less likely to return if they sought care from an urban facility (aHR: 0.68, 95% CI: 0.48 to 0.96) or hospital (aHR: 0.52, 95% CI: 0.33 to 0.82). CONCLUSIONS: Interventions are needed to hasten re-engagement in HIV care. Early and differential interventions by time since disengagement may improve intervention effectiveness. Patients in urban and tertiary care settings may need additional support. Improving patient resilience, outreach after a care gap, and community stigma reduction may facilitate return. Future re-engagement research should include causal evaluation of identified factors.

Prevalence of TB symptoms, diagnosis and treatment among people living with HIV (PLHIV) not on ART presenting at outpatient clinics in South Africa and Kenya: baseline results from a clinical trial.

OBJECTIVE: We used screening data and routine clinic records for intervention arm patients in the Simplified Algorithm for Treatment Eligibility (SLATE) trials to describe the prevalence of tuberculosis (TB) symptoms, diagnosis and treatment among people living with HIV (PLHIV), not on antiretroviral therapy (ART) and presenting at outpatient clinics in South Africa and Kenya. We compared the performance of the WHO four-symptom TB screening tool with a baseline Xpert test. SETTING: Outpatient HIV clinics in South Africa and Kenya. PARTICIPANTS: Eligible patients were non-pregnant, PLHIV, >18 years of age, not on ART, willing to provide written informed consent. A total of 594 patients in South Africa and 240 in Kenya were eligible. RESULTS: Prevalence of any TB symptom was 38% in Kenya, 35% (SLATE I) and 47% (SLATE II) in South Africa. During SLATE I, 70% of patients in Kenya and 57% in South Africa with ≥1 TB symptom were tested for TB. In SLATE II, 79% of patients with ≥1 TB symptom were tested. Of those, 19% tested positive for TB in Kenya, 15% (SLATE I) and 5% (SLATE II) tested positive in South Africa. Of the 28 patients who tested positive in both trials, 20 initiated TB treatment. The lowest median CD4 counts were among those with active TB (Kenya 124 cells/mm3; South Africa 193 cells/mm3). When comparing the WHO four-symptom screening tool to the Xpert test (SLATE II), we found that increasing the number of symptoms required for a positive screen from one to three or four decreased sensitivity but increased the positive predictive value to >30%. CONCLUSIONS: 80% of patients assessed for ART initiation presented with ≥1 TB symptoms. Reconsideration of the 'any symptom' rule may be appropriate, with ART initiation among patients with fewer/milder symptoms commencing while TB test results are pending. TRIAL REGISTRATION NUMBER: NCT02891135 and NCT03315013.

Human-Centered Design Lessons for Implementation Science: Improving the Implementation of a Patient-Centered Care Intervention.

BACKGROUND: Evidence-based HIV interventions often fail to reach anticipated impact due to insufficient utilization in real-world health systems. Human-centered design (HCD) represents a novel approach in tailoring innovations to fit end-users, narrowing the gap between efficacious interventions and impact at scale. METHODS: We combined a narrative literature review of HCD in HIV programs with our experience using HCD to redesign an intervention promoting patient-centered care (PCC) practices among health care workers (HCW) in Zambia. We summarize the use and results of HCD in the global HIV response and share case study insights to advance conceptualization of HCD applications. RESULTS: The literature review identified 13 articles (representing 7 studies) on the use of HCD in HIV. All studies featured HCD hallmarks including empathy development, user-driven inquiry, ideation, and iterative refinement. HCD was applied to mHealth design, a management intervention and pre-exposure prophylaxis delivery. Our HCD application addressed a behavioral service delivery target: changing HCW patient-centered beliefs, attitudes, and practices. Through in-depth developer-user interaction, our HCD approach revealed specific HCW support for and resistance to PCC, suggesting intervention revisions to improve feasibility and acceptability and PCC considerations that could inform implementation in transferable settings. CONCLUSIONS: As both a research and implementation tool, HCD has potential to improve effective implementation of the HIV response, particularly for product development; new intervention introduction; and complex system interventions. Further research on HCD application strengths and limitations is needed. Those promoting PCC may improve implementation success by seeking out resonance and anticipating the challenges our HCD process identified.

A pragmatic approach to monitor and evaluate implementation and impact of differentiated ART delivery for global and national stakeholders.

INTRODUCTION: The World Health Organization's (WHO) recommendation of "Treat All" has accelerated the call for differentiated antiretroviral therapy (ART) delivery, a method of care that efficiently uses limited resources to increase access to HIV treatment. WHO has further recommended that stable individuals on ART receive refills every 3 to 6 months and attend clinical visits every 3 to 6 months. However, there is not yet consensus on how to ensure that the quality of services is maintained as countries strive to meet these standards. This commentary responds to this gap by defining a pragmatic approach to the monitoring and evaluation (M&E) of the scale up of differentiated ART delivery for global and national stakeholders. DISCUSSION: Programme managers need to demonstrate that the scale up of differentiated ART delivery is achieving the desired effectiveness and efficiency outcomes to justify continued support by national and global stakeholders. To achieve this goal, the two existing global WHO HIV treatment indicators of ART retention and viral suppression should be augmented with two broad aggregate measures. The addition of indicators measuring the frequency of (1) clinical and (2) refill visits by PLHIV per year will allow evaluation of the pace of scale up while monitoring its overall effect on the quality and efficiency of services. The combination of these four routinely collected aggregate indicators will also facilitate the comparison of outcomes among facilities, regions or countries implementing different models of ART delivery. Enhanced monitoring or additional assessments will be required to answer other critical questions on the process of implementation, acceptability, effectiveness and efficiency. CONCLUSIONS: These proposed outcomes are useful markers for the effectiveness and efficiency of the health system's attempts to deliver quality treatment to those who need it-and still reserve as much of the available resource pool as possible for other key elements of the HIV response.

Simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE): protocol for a randomised evaluation.

INTRODUCTION: African countries are rapidly adopting guidelines to offer antiretroviral therapy (ART) to all HIV-infected individuals, regardless of CD4 count. For this policy of 'treat all' to succeed, millions of new patients must be initiated on ART as efficiently as possible. Studies have documented high losses of treatment-eligible patients from care before they receive their first dose of antiretrovirals (ARVs), due in part to a cumbersome, resource-intensive process for treatment initiation, requiring multiple clinic visits over a several-week period. METHODS AND ANALYSIS: The Simplified Algorithm for Treatment Eligibility (SLATE) study is an individually randomised evaluation of a simplified clinical algorithm for clinicians to reliably determine a patient's eligibility for immediate ART initiation without waiting for laboratory results or additional clinic visits. SLATE will enrol and randomise (1:1) 960 adult, HIV-positive patients who present for HIV testing or care and are not yet on ART in South Africa and Kenya. Patients randomised to the standard arm will receive routine, standard of care ART initiation from clinic staff. Patients randomised to the intervention arm will be administered a symptom report, medical history, brief physical exam and readiness assessment. Patients who have positive (satisfactory) results for all four components of SLATE will be dispensed ARVs immediately, at the same clinic visit. Patients who have any negative results will be referred for further clinical investigation, counselling, tests or other services prior to being dispensed ARVs. After the initial visit, follow-up will be by passive medical record review. The primary outcomes will be ART initiation ≤28 days and retention in care 8 months after study enrolment. ETHICS AND DISSEMINATION: Ethics approval has been provided by the Boston University Institutional Review Board, the University of the Witwatersrand Human Research Ethics Committee (Medical) and the KEMRI Scientific and Ethics Review Unit. Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents. TRIAL REGISTRATION: NCT02891135.

Changing Antiretroviral Eligibility Criteria: Impact on the Number and Proportion of Adults Requiring Treatment in Swaziland.

OBJECTIVE: Early initiation of antiretroviral treatment (ART) at CD4 cell count ≥ 500 cells per microliter reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment. DESIGN: A randomly selected subset of a nationally representative sample of HIV-infected adults in Swaziland in 2012. METHODS: Eight to 12 months after a national survey to determine adult HIV prevalence, 1067 of 5802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4 cell enumeration, VL measurements, and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (≥ 1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission. RESULTS: Of the 927 (87% of 1067) participants enrolled, 466 (50%) reported no ART use. Among them, 424 (91%) had VL ≥ 1000 copies per milliliter; of these, 148 (35%) were eligible for ART at the then existing CD4 count threshold of <350 cells per microliter; an additional 107 (25%) were eligible with expanded CD4 criterion of <500 cells per microliter; and 169 (40%) remained ART ineligible. Thus, 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART ineligible under a CD4 criterion of <500 cells per microliter. CONCLUSIONS: A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART.

Factors associated with delayed entry into primary HIV medical care after HIV diagnosis.

The aim of the study was to assess the median time between HIV diagnosis and entry into primary HIV medical care in a large urban area and to assess the potential individual, diagnosing facility, and community level factors influencing entry into care. One thousand two hundred and sixty-six individuals diagnosed with HIV in Philadelphia between 1 July 2005 and 30 June 2006 were followed until entry into care through 15 June 2007. Time to entry into care was calculated as a survival time variable and was defined as the time in months between the date of HIV diagnosis and the date more than 3 weeks after diagnosis when a CD4 cell count or percentage and/or HIV viral load were obtained. The median time to entry into care for all individuals was 8 months, with a range of 1-26 months. Factors associated with delayed entry into care included age more than 40 years [hazard ratio (HR) = 0.85; 95% confidence interval (CI) = 0.75-0.97] and diagnosis as an inpatient in the hospital (HR = 0.37; 95% CI = 0.37-0.57). Factors associated with earlier entry into care included Hispanic ethnicity (HR = 1.39; 95% CI = 1.05-1.84), male sex with men as HIV transmission risk factor (HR = 1.27; 95% CI = 1.03-1.56), and residence in a census tract with a high poverty rate (HR = 1.68; 95% CI = 1.22-2.30). Individuals newly diagnosed with HIV in Philadelphia demonstrated marked delays in accessing care highlighting the tremendous need for interventions to improve overall linkage. These interventions should especially be targeted at those aged more than 40 years and those diagnosed in the hospital.

Written informed-consent statutes and HIV testing.

BACKGROUND: Almost 1 million Americans are infected with HIV, yet it is estimated that as many as 250,000 of them do not know their serostatus. This study examined whether people residing in states with statutes requiring written informed consent prior to HIV testing were less likely to report a recent HIV test. METHODS: The study is based on survey data from the 2004 Behavioral Risk Factor Surveillance System. Logistic regression was used to assess the association between residence in a state with a pre-test written informed-consent requirement and individual self-report of recent HIV testing. The regression analyses controlled for potential state- and individual-level confounders. RESULTS: Almost 17% of respondents reported that they had been tested for HIV in the prior 12 months. Ten states had statutes requiring written informed consent prior to routine HIV testing; nine of those were analyzed in this study. After adjusting for other state- and individual-level factors, people who resided in these nine states were less likely to report a recent history of HIV testing (OR=0.85; 95% CI=0.80, 0.90). The average marginal effect was -0.02 (p<0.001, 95% CI=-0.03, -0.01); thus, written informed-consent statutes are associated with a 12% reduction in HIV testing from the baseline testing level of 17%. The association between a consent requirement and lack of testing was greatest among respondents who denied HIV risk factors, were non-Hispanic whites, or who had higher levels of education. CONCLUSIONS: This study's findings suggest that the removal of written informed-consent requirements might promote the non-risk-based routine-testing approach that the Centers for Disease Control and Prevention (CDC) advocates in its new testing guidelines.

Availability of rapid human immunodeficiency virus testing in academic emergency departments.

OBJECTIVES: The Centers for Disease Control and Prevention (CDC) recommends routine human immunodeficiency virus (HIV) screening of emergency department (ED) patients aged 13 to 64 years. The study objectives were to determine the accessibility of rapid HIV testing in academic EDs, to identify factors that influence an ED's adoption of testing, and to describe current HIV testing practices. METHODS: Online surveys were sent to EDs affiliated with emergency medicine (EM) residency programs (n = 128), excluding federal hospitals and facilities in U.S. territories. Eighty percent (n = 102) responded. Most e-mail recipients (n = 121) were Emergency Medicine Network (EMNet) investigators; remaining contacts were obtained from residency-related Web sites. RESULTS: Most academic EDs (n = 58; 57%; 95% confidence interval (CI) = 47% to 66%) offer rapid HIV testing. Among this group, 26 (45%) allow providers to order tests without restrictions. Of the other 32 EDs, 100% have policies allowing for rapid HIV testing following occupational exposures, but less than 10% have guidelines for testing in other clinical situations. Forty-seven percent expect to routinely offer HIV testing in the next 2 to 3 years. Only 59% of the EDs that offered rapid tests in any situation could link an HIV-positive patient to subspecialty care. The facility characteristic most important to availability of rapid HIV testing was the presence of on-site HIV counselors. CONCLUSIONS: Most academic EDs now offer rapid HIV testing (57%), but few use it in situations other than occupational exposure. Less than half of academic EDs expect to implement CDC guidelines regarding routine screening within the next few years. The authors identified facility characteristics (e.g., counseling, ability to refer) that may influence adoption of rapid HIV testing.