Pregnancy-associated atypical hemolytic uremic syndrome. Case report.

Pregnancy-associated atypical hemolytic uremic syndrome (P-aHUS) is a rare disease. There are only few reports in the literature, and most are in the puerperium period. It is a thrombotic microangiopathy (TMA) characterized for microangiopathic hemolytic anemia, thrombocytopenia, and renal dysfunction. We report the case of a pregnant patient at 26.3 gestation weeks, who developed clinical features of TMA, neurological alterations, and septic shock; then after fetus and placental delivery, no clinical improvement was observed; a diagnostic protocol was performed due to suspicion of P-aHUS, showing improvement after the plasma exchange sessions and eculizumab. We present here a brief review of the case since it is an entity that needs to be suspected during pregnancy when TMA features and requires an immediate diagnosis to provide timely treatment.

Transitional community adherence support for people leaving incarceration in South Africa: a pragmatic, open-label, randomised controlled trial.

BACKGROUND: People released from correctional facilities face multifactorial barriers to continuing HIV treatment. We hypothesised that barriers faced in the first 6 months of community re-entry would be decreased by a multilevel group-based and peer-led intervention, the Transitional Community Adherence Club (TCAC). METHODS: We did a pragmatic, open-label, individually randomised controlled trial in five correctional facilities in Gauteng, South Africa. Participants aged 18 years and older and receiving antiretroviral therapy (ART) in correctional facilities were enrolled before release and randomly assigned (1:2) to either passive referral (usual care) or TCACs. TCACs followed a 12-session curriculum over 6 months and were facilitated by trained peer and social workers. Participants were followed up by telephone and in person to assess the primary outcome: post-release enrolment in HIV treatment services at 6 months from the date of release. We did an intention-to-treat analysis to determine the effectiveness of TCACs compared with usual care. The trial was registered with the South African National Clinical Trials Register (DOH-27-0419-605) and ClinicalTrials.gov (NCT03340428). This study is completed and is listed as such on ClinicalTrials.gov. FINDINGS: From March 1, to Dec 13, 2019, we screened 222 individuals and enrolled 176 participants who were randomly assigned 1:2 to the usual care group (n=59) or TCACs (n=117). 175 participants were included in the final analysis. In the usual care group, 21 (36%) of 59 participants had enrolled in HIV treatment services at 6 months, compared with 71 (61%) of 116 in the TCAC group (risk ratio 1·7, 95% CI 1·2-2·5; p=0·0010). No adverse events were reported. INTERPRETATION: We found strong evidence that a differentiated service delivery model with curriculum and peer support designed specifically to address the needs of people with HIV returning from incarceration improved the primary outcome of enrolment in HIV treatment services. Our approach is a reasonable model to build further HIV treatment continuity interventions for individuals in the criminal justice system in South Africa and elsewhere. FUNDING: National Institute of Mental Health.

Reducing HIV-associated post-hospital mortality through home-based care in South Africa: a randomized controlled trial.

BACKGROUND: Twenty-three percent of people with HIV (PWH) die within 6-months of hospital discharge. We tested the hypothesis whether a series of structured home visits could reduce mortality. METHODS: We designed a disease neutral home visit package with up to 6 home visits starting 1-week post-hospitalization and every 2 weeks thereafter. The home visit team used a structured assessment algorithm to evaluate and triage social and medical needs of the participant and provide nutritional support. We compared all-cause mortality 6-months following discharge for the intervention compared to usual care in a pilot randomized trial conducted in South Africa. To inform potential scale-up we also included and separately analyzed a group of people without HIV (PWOH). RESULTS: We enrolled 125 people with HIV and randomized them 1:1 to the home visit intervention or usual care. Fourteen were late exclusions because of death prior to discharge or delayed discharge leaving 111 for analysis. The median age was 39 years, 31% were men; and 70% had advanced HIV disease. At six months among PWH 4 (7.3%) in the home visit arm and 10 (17.9%) in the usual care arm (p = 0.09) had died. Among the 70 PWOH enrolled overall 6-month mortality was 10.1%. Of those in the home visit arm, 91% received at least one home visit. CONCLUSIONS: We demonstrated feasibility of delivering post-hospital home visits and demonstrated preliminary efficacy among PWH with a substantial, but not statistically significant, effect size (59% reduction in mortality). COVID-19 related challenges resulted in under-enrollment.

Brief Report: Changing Characteristics Among In-Hospital HIV Deaths: An 11-Year Retrospective Review of a Regional Hospital in South Africa.

BACKGROUND: Elevated HIV-associated mortality persists, despite a notable decline with the expansion of antiretroviral therapy (ART). In South Africa, the relative majority of deaths occur in health facilities, providing an opportunity to track decedent characteristics. SETTING: We analyzed data from 14,870 adult patients who died between 2008 and 2018 at Klerksdorp/Tshepong Hospital Complex in South Africa. METHODS: Recorded data included demographics, causes of death, HIV status, ART, and tuberculosis (TB) history. We present summary statistics and results from linear, log-binomial, and multinomial regressions to quantify changes over time. RESULTS: Over the study period, the median age of decedents with HIV in the hospital increased from 39.3 to 43.4 years, and there was a switch to male predominance (46%-54%). Those who died at a younger age (<40 years) remained more likely to be HIV-positive than the older age group, despite the overall proportion of HIV-positivity decreasing over time. The proportion of decedents with HIV ever started on ART increased from 21% to 67%. The proportion of HIV patients dying from TB and AIDS-defining illnesses decreased from 31% to 22%. CONCLUSIONS: We noted a shift in deaths over time to more men and older individuals, whereas the burden of HIV was heaviest on the younger age groups. Advanced HIV disease remained an important cause of mortality. We also observed an increase in less-traditional opportunistic illnesses among those with HIV, including malignancy, cardiovascular disease, and kidney disease. The high proportion of patients on ART who died prematurely requires further research and interventions.

Modeling the impact of universal tuberculosis molecular testing and timing of tuberculosis preventive treatment during antiretroviral therapy initiation in South Africa.

OBJECTIVES: Targeted universal tuberculosis (TB) testing can improve TB detection among people with HIV. This approach is being scaled up in South Africa through Xpert MTB/RIF Ultra testing for individuals starting antiretroviral therapy and annually thereafter. Clarity is needed on how Universal Xpert testing may affect TB preventive treatment (TPT) provision, and on whether TPT should be delayed until TB is ruled out. DESIGN: State-transition microsimulation. METHODS: We simulated a cohort of South African patients being screened for TB while entering HIV care. We compared clinical and cost outcomes between four TB screening algorithms: symptom-based, C-reactive protein-based, and Universal Xpert testing with either simultaneous or delayed TPT initiation. RESULTS: Prompt TB treatment initiation among simulated patients with TB increased from 26% (24-28%) under symptom screening to 53% (50-56%) with Universal Xpert testing. Universal Xpert testing led to increased TPT uptake when TPT initiation was simultaneous, but to approximately 50% lower TPT uptake if TPT was delayed. Universal Xpert with simultaneous TPT prevented incident TB compared to either symptom screening (median 17 cases averted per 5000 patients) or Universal Xpert with delayed TPT (median 23 averted). Universal Xpert with Simultaneous TPT cost approximately $39 per incremental TPT course compared to Universal Xpert with delayed TPT. CONCLUSIONS: Universal Xpert testing can promote timely treatment for newly diagnosed people with HIV who have active TB. Pairing universal testing with immediate TPT will improve the promptness, uptake, and preventive effects of TPT. Simultaneous improvements to TB care cascades are needed to maximize impact.

Opioid use and HIV treatment services experiences among male criminal justice-involved persons in South Africa: a qualitative study.

BACKGROUND: Opioid use disorder (OUD) is overrepresented among people with criminal justice involvement; HIV is a common comorbidity in this population. This study aimed to examine how formerly incarcerated men living with HIV and OUD in South Africa experienced HIV and OUD services in correctional facilities and the community. METHODS: Three focus group discussions were conducted with 16 formerly incarcerated men living with HIV and OUD in Gauteng, South Africa. Discussions explored available healthcare services in correctional facilities and the community and procedural and practice differences in health care between the two types of settings. Data were analyzed thematically, using a comparative lens to explore the relationships between themes. RESULTS: Participants described an absence of medical services for OUD in correctional facilities and the harms caused by opioid withdrawal without medical support during incarceration. They reported that there were limited OUD services in the community and that what was available was not connected with public HIV clinics. Participants perceived correctional and community HIV care systems as readily accessible but suggested that a formal system did not exist to ensure care continuity post-release. CONCLUSIONS: OUD was perceived to be medically unaddressed in correctional facilities and marginally attended to in the community. In contrast, HIV treatment was widely available within the two settings. The current model of OUD care in South Africa leaves many of the needs of re-entrants unmet. Integrating harm reduction into all primary care medical services may address some of these needs. Successful HIV care models provide examples of approaches that can be applied to developing and expanding OUD services in South Africa.

Strengthening HIV and HIV co-morbidity care in low- and middle-income countries: insights from behavioural economics to improve healthcare worker behaviour.

INTRODUCTION: Despite advances in HIV and HIV co-morbidity service delivery, substantial challenges remain in translating evidence-based interventions into routine practice to bring optimal care and prevention to all populations. While barriers to successful implementation are often multifactorial, healthcare worker behaviour is critical for on-the-ground and in-clinic service delivery. Implementation science offers a systematic approach to understanding service delivery, including approaches to overcoming delivery gaps. Behavioural economics is a field that seeks to understand when and how behaviour deviates from traditional models of decision-making, deviations which are described as biases. Clinical policies and implementation strategies that incorporate an understanding of behavioural economics can add to implementation science approaches and play an important role in bridging the gap between healthcare worker knowledge and service delivery. DISCUSSION: In HIV care in low- and middle-income countries (LMICs), potential behavioural economic strategies that may be utilized alone or in conjunction with more traditional approaches include using choice architecture to exploit status quo bias and reduce the effects of cognitive load, overcoming the impact of anchoring and availability bias through tailored clinical training and clinical mentoring, reducing the effects of present bias by changing the cost-benefit calculus of interventions with few short-term benefits and leveraging social norms through peer comparison. As with any implementation strategy, understanding the local context and catalysts of behaviour is crucial for success. CONCLUSIONS: As the focus of HIV care shifts beyond the goal of initiating patients on antiretroviral therapy to a more general retention in high-quality care to support longevity and quality of life, there is an increasing need for innovation to achieve improved care delivery and management. Clinical policies and implementation strategies that incorporate elements of behavioural economic theory, alongside local testing and adaptation, may increase the delivery of evidence-based interventions and improve health outcomes for people living with HIV in LMIC settings.

Contextualizing and optimizing novel strategies to improve the latent TB continuum of care: Insights from people living with HIV and health care providers in Brazil.

Tuberculosis (TB) causes 1 in 3 deaths among people living with HIV (PLHIV). Diagnosing and treating latent tuberculosis infection (LTBI) is critical to reducing TB incidence and mortality. Blood-based screening tests (e.g., QuantiFERON-TB Gold Plus (QFT+)) and shorter-course TB preventive therapy (TPT) regimens such as 3HP (3 months weekly isoniazid-rifapentine) hold significant promise to improve TB outcomes. We qualitatively explored barriers and solutions to optimizing QFT+ and 3HP among PLHIV in three cities in Brazil. We conducted 110 in-depth interviews with PLHIV, health care providers (HCP) and key informants (KI). Content analysis was conducted including the use of case summaries and comparison of themes across populations and contexts. LTBI screening and treatment practices were dependent on HCP's perceptions of whether they were critical to improving TB outcomes. Many HCP lacked a strong understanding of LTBI and perceived the current TPT regimen as complicated. HCP reported that LTBI screening and treatment were constrained by clinic staffing challenges. While PLHIV generally expressed willingness to consider any test or treatment that doctors recommended, they indicated HCP rarely discussed LTBI and TPT. TB testing and treatment requests were constrained by structural factors including financial and food insecurity, difficulties leaving work for appointments, stigma and family responsibilities. QFT+ and 3HP were viewed by all participants as tools that could significantly improve the LTBI cascade by avoiding complexities of TB skin tests and longer LTBI treatment courses. QFT+ and 3HP were perceived to have challenges, including the potential to increase workload on over-burdened health systems if not implemented alongside improved supply chains, staffing, and training, and follow-up initiatives. Multi-level interventions that increase understanding of the importance of LTBI and TPT among HCP, improve patient-provider communication, and streamline clinic-level operations related to QFT+ and 3HP are needed to optimize their impact among PLHIV and reduce TB mortality.

Fatal Case of Heartland Virus Disease Acquired in the Mid-Atlantic Region, United States.

Heartland virus (HRTV) disease is an emerging tickborne illness in the midwestern and southern United States. We describe a reported fatal case of HRTV infection in the Maryland and Virginia region, states not widely recognized to have human HRTV disease cases. The range of HRTV could be expanding in the United States.

Clonally expanded HIV-1 proviruses with 5'-leader defects can give rise to nonsuppressible residual viremia.

BackgroundAntiretroviral therapy (ART) halts HIV-1 replication, decreasing viremia to below the detection limit of clinical assays. However, some individuals experience persistent nonsuppressible viremia (NSV) originating from CD4+ T cell clones carrying infectious proviruses. Defective proviruses represent over 90% of all proviruses persisting during ART and can express viral genes, but whether they can cause NSV and complicate ART management is unknown.MethodsWe undertook an in-depth characterization of proviruses causing NSV in 4 study participants with optimal adherence and no drug resistance. We investigated the impact of the observed defects on 5'-leader RNA properties, virus infectivity, and gene expression. Integration-site specific assays were used to track these proviruses over time and among cell subsets.ResultsClones carrying proviruses with 5'-leader defects can cause persistent NSV up to approximately 103 copies/mL. These proviruses had small, often identical deletions or point mutations involving the major splicing donor (MSD) site and showed partially reduced RNA dimerization and nucleocapsid binding. Nevertheless, they were inducible and produced noninfectious virions containing viral RNA, but lacking envelope.ConclusionThese findings show that proviruses with 5'-leader defects in CD4+ T cell clones can give rise to NSV, affecting clinical care. Sequencing of the 5'-leader can help in understanding failure to completely suppress viremia.FundingOffice of the NIH Director and National Institute of Dental and Craniofacial Research, NIH; Howard Hughes Medical Institute; Johns Hopkins University Center for AIDS Research; National Institute for Allergy and Infectious Diseases (NIAID), NIH, to the PAVE, BEAT-HIV, and DARE Martin Delaney collaboratories.

Costs of implementing universal test and treat in three correctional facilities in South Africa and Zambia.

INTRODUCTION: Universal test and treat (UTT) is a population-based strategy that aims to ensure widespread HIV testing and rapid antiretroviral therapy (ART) for all who have tested positive regardless of CD4 count to decrease HIV incidence and improve health outcomes. Little is known about the specific resources required to implement UTT in correctional facilities for incarcerated people. The primary aim of this study was to describe the resources used to implement UTT and to provide detailed costing to inform UTT scale-up in similar settings. METHODS: The costing study was a cross-sectional descriptive study conducted in three correctional complexes, Johannesburg Correctional Facility in Johannesburg (>4000 inmates) South Africa, and Brandvlei (~3000 inmates), South Africa and Lusaka Central (~1400 inmates), Zambia. Costing was determined through a survey conducted between September and December 2017 that identified materials and labour used for three separate components of UTT: HIV testing services (HTS), ART initiation, and ART maintenance. Our study participants were staff working in the correctional facilities involved in any activity related to UTT implementation. Unit costs were reported as cost per client served while total costs were reported for all clients seen over a 12-month period. RESULTS: The cost of HIV testing services (HTS) per client was $ 92.12 at Brandvlei, $ 73.82 at Johannesburg, and $ 65.15 at Lusaka. The largest cost driver for HIV testing at Brandvlei were staff costs at 55.6% of the total cost, while at Johannesburg (56.5%) and Lusaka (86.6%) supplies were the largest contributor. The cost per client initiated on ART was $917 for Brandvlei, $421.8 for Johannesburg, and $252.1 for Lusaka. The activity cost drivers were adherence counselling at Brandvlei (59%), and at Johannesburg and Lusaka it was the actual ART initiation at 75.6% and 75.8%, respectively. The annual unit cost for ART maintenance was $2,640.6 for Brandvlei, $710 for Johannesburg, and $385.5 for Lusaka. The activity cost drivers for all three facilities were side effect monitoring, and initiation of isoniazid preventive treatment (IPT), cotrimoxazole, and fluconazole, with this comprising 44.7% of the total cost at Brandvlei, 88.9% at Johannesburg, and 50.5% at Lusaka. CONCLUSION: Given the needs of this population, the opportunity to reach inmates at high risk for HIV, and overall national and global 95-95-95 goals, the UTT policies for incarcerated individuals are of vital importance. Our findings provide comparator costing data and highlight key drivers of UTT cost by facility.

Digitally supported HIV self-testing increases facility-based HIV testing capacity in Ekurhuleni, South Africa.

Background: HIV testing is the first step for linkage to HIV prevention or treatment services. Facility-based HIV testing is the most utilised method, but faces challenges such as limited work space and human resources. Digitally supported HIV self-testing (HIVST) provided in clinics shifts testing to the client, potentially empowering the client, and addresses such constraints. Objectives: The study primary objective was to determine the feasibility of integrating digitally supported HIVST into the clinic. Secondary objectives were to describe HIV testing volume, populations reached, and antiretroviral treatment (ART) initiation. Method: We conducted an analysis of prospectively collected data during implementation of digitally supported HIVST in two healthcare facilities based in South Africa from June 2019 to September 2019. We described implementation and client characteristics using HIVST and compared testing before and during implementation. Results: During the 4-month implementation period there were 35 248 client visits. A total of 6997 (19.9%) of these visits involved HIV testing. Of those testing, 2278 (32.5%) used HIVST. Of the 2267 analysed, 264 (11.6%) were positive: 182 (12%) women and 82 (11%) men. Of those, 230 (95.4%) were confirmed HIV positive and 150 (65%) initiated ART within 14 days. During a four-month pre-implementation period, 14.5% of the clients tested for HIV. Compared to the pre-implementation period, we observed a 25% increase in HIV testing. Conclusion: Digitally supported HIVST increased the number of clients completing HIV testing in the health facility, without a need to significantly increase staff or space. Facility-based digitally assisted HIVST has the potential to increase HIV testing in high HIV prevalence clinic populations.

Tuberculosis (TB) Aftermath: study protocol for a hybrid type I effectiveness-implementation non-inferiority randomized trial in India comparing two active case finding (ACF) strategies among individuals treated for TB and their household contacts.

BACKGROUND: Approximately 7% of all reported tuberculosis (TB) cases each year are recurrent, occurring among people who have had TB in the recent or distant past. TB recurrence is particularly common in India, which has the largest TB burden worldwide. Although patients recently treated for TB are at high risk of developing TB again, evidence around effective active case finding (ACF) strategies in this population is scarce. We will conduct a hybrid type I effectiveness-implementation non-inferiority randomized trial to compare the effectiveness, cost-effectiveness, and feasibility of two ACF strategies among individuals who have completed TB treatment and their household contacts (HHCs). METHODS: We will enroll 1076 adults (≥ 18 years) who have completed TB treatment at a public TB unit (TU) in Pune, India, along with their HHCs (averaging two per patient, n = 2152). Participants will undergo symptom-based ACF by existing healthcare workers (HCWs) at 6-month intervals and will be randomized to either home-based ACF (HACF) or telephonic ACF (TACF). Symptomatic participants will undergo microbiologic testing through the program. Asymptomatic HHCs will be referred for TB preventive treatment (TPT) per national guidelines. The primary outcome is rate per 100 person-years of people diagnosed with new or recurrent TB by study arm, within 12 months following treatment completion. The secondary outcome is proportion of HHCs < 6 years, by study arm, initiated on TPT after ruling out TB disease. Study staff will collect socio-demographic and clinical data to identify risk factors for TB recurrence and will measure post-TB lung impairment. In both arms, an 18-month "mop-up" visit will be conducted to ascertain outcomes. We will use the RE-AIM framework to characterize implementation processes and explore acceptability through in-depth interviews with index patients, HHCs and HCWs (n = 100). Cost-effectiveness will be assessed by calculating the incremental cost per TB case detected within 12 months and projected for disability-adjusted life years averted based on modeled estimates of morbidity, mortality, and time with infectious TB. DISCUSSION: This novel trial will guide India's scale-up of post-treatment ACF and provide an evidence base for designing strategies to detect recurrent and new TB in other high burden settings. TRIAL REGISTRATION: NCT04333485 , registered April 3, 2020. CTRI/2020/05/025059 [Clinical Trials Registry of India], registered May 6 2020.

"That makes me feel human": a qualitative evaluation of the acceptability of an HIV differentiated care intervention for formerly incarcerated people re-entering community settings in South Africa.

BACKGROUND: Correctional settings in South Africa have disproportionately high rates of HIV infection; a large number of inmates living with HIV return to the community each year. The transition community adherence club (TCAC) intervention was a differentiated care delivery approach with structural and peer components designed to increase antiretroviral therapy (ART) adherence and HIV care engagement following release from incarceration. The objective of this study was to assess the acceptability of the TCAC intervention among HIV-infected community re-entrants to inform program revisions and future intervention designs. METHODS: This was a qualitative study set within a randomized controlled trial (RCT) of the TCAC intervention in South Africa. We conducted semi-structured, in-depth interviews with 16 re-entrants living with HIV and assigned to the intervention arm. All interviews were audio-recorded, transcribed, translated, and de-identified. Transcripts were coded and analyzed using content analysis, and acceptability was assessed using the Theoretical Framework of Acceptability (TFA). RESULTS: Overall, study participants reported that the TCAC intervention was acceptable. Development of supportive relationships between participants, non-judgmental attitudes from peer-facilitators, and perceived effectiveness of the intervention to support ART adherence and HIV care were noted as the most valued components. An altruistic desire to help other participants facing similar post-incarceration and HIV-related challenges was a key motivator for TCAC attendance. A lack of access to reliable transportation to intervention sites and clinic-based medication collection were described as burdens to program participation. Illicit drug use by other group members and negative social influences were also identified as potential barriers to optimal program engagement. CONCLUSION: The TCAC was a well-accepted model of differentiated care delivery among re-entrants living with HIV in South Africa. To further enhance intervention acceptability for future scale-ups, program revisions should address logistical barriers related to reaching TCAC sites and implementing ART distribution at TCAC group sessions.

Risk Factors for Hospitalization or Death Among Adults With Advanced HIV at Enrollment for Care in South Africa: A Secondary Analysis of the TB Fast Track Trial.

Background: Individuals with advanced HIV experience high mortality, especially before and during the first months of antiretroviral therapy (ART). We aimed to identify factors, measurable in routine, primary health clinic-based services, associated with the greatest risk of poor outcome. Methods: We included all individuals enrolled in the standard-of-care arm of a cluster-randomized trial (TB Fast Track); adults attending participating health clinics with CD4 ≤150 cells/µL and no recent ART were eligible. Associations between baseline exposures and a composite outcome (hospitalization/death) over 6 months were estimated using multivariable Cox regression. Results: Among 1515 individuals (12 clinics), 56% were female, the median age was 36 years, and the median CD4 count was 70 cells/µL. Within 6 months, 89% started ART. The overall rate of hospitalization/death was 32.5 per 100 person-years (218 outcomes/671 person-years). Lower baseline CD4 count (adjusted hazard ratio [aHR], 2.27 for <50 vs 100-150 cells/µL; 95% CI, 1.57-3.27), lower body mass index (aHR, 2.13 for BMI <17 vs ≥25 kg/m2; 95% CI, 1.31-3.45), presence of tuberculosis-related symptoms (aHR, 1.87 for 3-4 symptoms vs none; 95% CI, 1.20-2.93), detectable urine lipoarabinomannan (aHR, 1.97 for 1+ positivity vs negative; 95% CI, 1.37-2.83), and anemia (aHR, 4.42 for severe anemia [hemoglobin <8 g/dL] vs none; 95% CI, CI 2.38-8.21) were strong independent risk factors for hospitalization/death. Conclusions: Simple measures that can be routinely assessed in primary health care in resource-limited settings identify individuals with advanced HIV at high risk of poor outcomes; these may guide targeted interventions to improve outcomes.

Changing HCW attitudes: a case study of normalizing HIV service delivery in emergency departments.

BACKGROUND: Delays in the implementation of evidence-based practices are significant and ubiquitous, compromising health outcomes. Resistance to change is a key factor in hindering adoption and integration of new evidence-based interventions. This study seeks to understand the impact of exposure to HIV testing within a research context on provider attitudes towards HIV counselling and testing (HCT) in emergency departments (ED). METHODS: This is a pre-and-post study design measuring the effect of a new ED-based HCT intervention, conducted by lay counsellors, on provider attitudes in Eastern Cape, South Africa. A validated, anonymized, 7-item survey was self-completed by routine care providers (physicians, nurses, and case managers). Questions were scored on a 5-point Likert scale with 5 consistently reflecting a positive attitude. Mean scores were calculated for each question and compared using a two-sample t-test to assess change in sample means for attitudes among providers surveyed before and after the intervention. RESULTS: A total of 132 surveys were completed across three EDs. Majority of respondents were female (70.5%), 20-29 years old (37.9%), of African race (81.1%), nurses (39.4%), and practicing medicine for 0-4 years (37.9%). Pre-intervention, providers displayed a positive attitude towards 'the benefit of offering ED-based HCT to patients' (4.33), 'the ED offering HCT' (3.53), 'all ED patients receiving HCT' (3.42), 'concern about patient reaction to HCT' (3.26), and 'comfort with disclosing HCT results' (3.21); and a mildly negative attitude towards 'only high-risk ED patients receiving HCT' (2.68), and 'the burden of offering HCT in a clinical environment' (2.80). Post-intervention, provider attitudes improved significantly towards 'all ED patients receiving HCT' (3.86, p < 0.05), 'only high-risk ED patients receiving HCT' (2.30, p < 0.05), 'the burden of offering HCT in a clinical environment' (3.21, p < 0.05), and 'comfort with disclosing HCT results' (3.81, p < 0.05). CONCLUSIONS: Controlled exposure to new practices with a structured implementation period can shift attitudes beginning a process of practice normalization. In our study, we observed improvements in provider attitudes regarding the benefits of HCT and the burden of offering HCT to all patients in the ED. Research activities may have a role in mitigating resistance to change and supporting intervention adoption.

Facilitators and barriers to implementing provider-initiated HIV counselling and testing at the clinic-level in Ekurhuleni District, South Africa.

BACKGROUND: HIV testing is the entry point into the HIV care continuum and critical for HIV epidemic control. Facility-based HIV testing services (HTS) reach individuals who are already seeking clinical care and engaging with the medical care system. For this reason, individuals diagnosed with HIV during facility-based HIV testing are more likely to continue into HIV care. To increase the number of PLHIV who are diagnosed and initiated on ART, in 2015, the South African Department of Health instituted Provider-Initiated Counselling and Testing (PICT) policy-encouraging healthcare providers to recommend HIV testing, but this strategy remains under-utilized. We aimed to identify key constraints to the normalization of PICT implementation in 10 Ekurhuleni District healthcare facilities in South Africa. METHODS: In-depth interviews were conducted with 40 healthcare workers (28 clinicians and 12 lay counsellors). Health care workers were purposefully selected to participate in the interviews, stratified by health facility and work category. Interviews were audio-recorded, transcribed, and translated for analysis. Thematic analysis was guided by the normalization process theory (NPT). NPT theory explains how practices are routinely embedded within organizational contexts. We used NVivo 10 software for qualitative data management. RESULTS: Both clinicians and lay counsellors exhibited a clear understanding of the PICT policy- acknowledging its purpose and value. The identified barrier to normalization of PICT among clinicians was offering HIV testing based on suspicion of HIV despite understanding that PICT involves offering testing to all clients. Additionally, clinicians perceived PICT as incongruent with their clinical roles and perceived it to be lay counsellors' responsibility. The main facilitator was the participation of all healthcare workers, specifically the presence of lay counsellors, although they also faced barriers such as a lack of workspace and under-appreciation. CONCLUSIONS: Use of NPT helped identify barriers that prevent the normalization of PITC and its integration into routine patient care. These barriers can be modified by low-cost interventions that promote congruence of PICT to the roles of clinicians and integrate the role of lay counsellors within the patient flow in the facility.

In-facility HIV peer-based rehabilitation programs' role in linkage to care among persons transitioning from correctional to community-based HIV care in South Africa.

PURPOSE: This analysis aims to examine the role of pre-release, HIV-related, peer-based rehabilitation program attendance on post-release linkage to community-based HIV care in South Africa. DESIGN/METHODOLOGY/APPROACH: During a post-release linkage-to-care prospective study, participants from six correctional facilities who had an HIV-positive diagnosis and were taking anti-retroviral medications at release (N = 351) self-reported rehabilitation program participation. Linkage-to-care status 90 days post-release was verified by medical chart review. FINDINGS: In a binomial regression model, HIV-related, peer-based rehabilitation program attendance was insignificant (relative risk [RR] 1.1, 95% confidence interval [CI] [0.8, 1.4], p-value = 0.7), but short-/long-term incarceration site (RR 1.5, 95% CI [1.0, 2.1], p-value = 0.04) and relationship status pre-incarceration (RR 1.9, 95% CI [1.0, 3.6], p-value = 0.05) were significantly associated with linkage to HIV care post-release. ORIGINALITY/VALUE: Rehabilitation and peer-based HIV programs have had demonstrated benefit in other settings. Assessment of current programs may identify opportunities for improvement.

Digital Chest X-Ray with Computer-aided Detection for Tuberculosis Screening within Correctional Facilities.

Rationale: Realizing the Global Plan to End Tuberculosis (TB) will require reaching at least 90% of people in key populations, such as inmates, through optimizing case-finding approaches. Objectives: To evaluate the value of adding digital chest X-ray (d-CXR) with computer-aided detection (CAD) to symptom-based screening on TB yield among inmates. Methods: Consecutive adult inmates from four correctional facilities in South Africa were screened for TB using symptoms and d-CXR. Any person with at least one symptom or CAD score of ⩾50 provided two sputa for liquid culture and GeneXpert MTB/RIF Ultra (Xpert Ultra) testing. In a sample of 800 symptom-negative inmates with CAD score <50, Xpert Ultra testing was also conducted. TB yield was defined as the proportion of new patients with bacteriologically confirmed TB who were identified. Results: We enrolled 3,576 participants: 99.6% male, median age of 34 years (interquartile range, 28-41), and 584 (16.3%) with positive test results for human immunodeficiency virus. Of those screened, 867 (24.2%) participants required investigation (394 [11.2%] symptomatic, 685 [19.1%] with abnormal CAD results, and 867 [24.2%] with either). Sputum was taken in 747 (86.2%) participants, with 28 (7.8 per 1,000 population) new TB cases diagnosed. On the basis of hypothesized screening modalities, yield would have been 3.6 per 1,000 population on the basis of symptoms alone and 7.0 per 1,000 population on the basis of d-CXR alone. Among an additional 800 inmates tested who initially screened symptom negative and had a CAD score <50, five TB cases were diagnosed. There was no difference in TB yield when comparing Xpert Ultra against culture (5.6 vs. 4.8 per 1,000 population; P = 0.21). Conclusions: The addition of d-CXR identified two times more patients with undiagnosed TB than did investigation of symptoms alone. Complementary use of d-CXR may potentially overcome the subjectivity inherent in symptom screening alone for identifying TB in this population.

Tuberculosis screening among ambulatory people living with HIV: a systematic review and individual participant data meta-analysis.

BACKGROUND: The WHO-recommended tuberculosis screening and diagnostic algorithm in ambulatory people living with HIV is a four-symptom screen (known as the WHO-recommended four symptom screen [W4SS]) followed by a WHO-recommended molecular rapid diagnostic test (eg Xpert MTB/RIF [hereafter referred to as Xpert]) if W4SS is positive. To inform updated WHO guidelines, we aimed to assess the diagnostic accuracy of alternative screening tests and strategies for tuberculosis in this population. METHODS: In this systematic review and individual participant data meta-analysis, we updated a search of PubMed (MEDLINE), Embase, the Cochrane Library, and conference abstracts for publications from Jan 1, 2011, to March 12, 2018, done in a previous systematic review to include the period up to Aug 2, 2019. We screened the reference lists of identified pieces and contacted experts in the field. We included prospective cross-sectional, observational studies and randomised trials among adult and adolescent (age ≥10 years) ambulatory people living with HIV, irrespective of signs and symptoms of tuberculosis. We extracted study-level data using a standardised data extraction form, and we requested individual participant data from study authors. We aimed to compare the W4SS with alternative screening tests and strategies and the WHO-recommended algorithm (ie, W4SS followed by Xpert) with Xpert for all in terms of diagnostic accuracy (sensitivity and specificity), overall and in key subgroups (eg, by antiretroviral therapy [ART] status). The reference standard was culture. This study is registered with PROSPERO, CRD42020155895. FINDINGS: We identified 25 studies, and obtained data from 22 studies (including 15 666 participants; 4347 [27·7%] of 15 663 participants with data were on ART). W4SS sensitivity was 82% (95% CI 72-89) and specificity was 42% (29-57). C-reactive protein (≥10 mg/L) had similar sensitivity to (77% [61-88]), but higher specificity (74% [61-83]; n=3571) than, W4SS. Cough (lasting ≥2 weeks), haemoglobin (<10 g/dL), body-mass index (<18·5 kg/m2), and lymphadenopathy had high specificities (80-90%) but low sensitivities (29-43%). The WHO-recommended algorithm had a sensitivity of 58% (50-66) and a specificity of 99% (98-100); Xpert for all had a sensitivity of 68% (57-76) and a specificity of 99% (98-99). In the one study that assessed both, the sensitivity of sputum Xpert Ultra was higher than sputum Xpert (73% [62-81] vs 57% [47-67]) and specificities were similar (98% [96-98] vs 99% [98-100]). Among outpatients on ART (4309 [99·1%] of 4347 people on ART), W4SS sensitivity was 53% (35-71) and specificity was 71% (51-85). In this population, a parallel strategy (two tests done at the same time) of W4SS with any chest x-ray abnormality had higher sensitivity (89% [70-97]) and lower specificity (33% [17-54]; n=2670) than W4SS alone; at a tuberculosis prevalence of 5%, this strategy would require 379 more rapid diagnostic tests per 1000 people living with HIV than W4SS but detect 18 more tuberculosis cases. Among outpatients not on ART (11 160 [71·8%] of 15 541 outpatients), W4SS sensitivity was 85% (76-91) and specificity was 37% (25-51). C-reactive protein (≥10 mg/L) alone had a similar sensitivity to (83% [79-86]), but higher specificity (67% [60-73]; n=3187) than, W4SS and a sequential strategy (both test positive) of W4SS then C-reactive protein (≥5 mg/L) had a similar sensitivity to (84% [75-90]), but higher specificity than (64% [57-71]; n=3187), W4SS alone; at 10% tuberculosis prevalence, these strategies would require 272 and 244 fewer rapid diagnostic tests per 1000 people living with HIV than W4SS but miss two and one more tuberculosis cases, respectively. INTERPRETATION: C-reactive protein reduces the need for further rapid diagnostic tests without compromising sensitivity and has been included in the updated WHO tuberculosis screening guidelines. However, C-reactive protein data were scarce for outpatients on ART, necessitating future research regarding the utility of C-reactive protein in this group. Chest x-ray can be useful in outpatients on ART when combined with W4SS. The WHO-recommended algorithm has suboptimal sensitivity; Xpert for all offers slight sensitivity gains and would have major resource implications. FUNDING: World Health Organization.