Strengthening accountability for tuberculosis policy implementation in South Africa: perspectives from policymakers, civil society, and communities.

Background: Translating health policy into effective implementation is a core priority for responding effectively to the tuberculosis (TB) crisis. The national TB Recovery Plan was developed in response to the negative impact that the COVID-19 pandemic had on TB care in South Africa. We aimed to explore the implementation of the TB Recovery Plan and develop recommendations for strengthening accountability for policy implementation for this and future TB policies. Methods: We interviewed 24 participants working on or impacted by TB policy implementation in South Africa. This included perspectives from national, provincial, and local health department representatives, civil society, and community representatives. In-depth interviews were conducted in English and isiXhosa and we drew on reflexive thematic methods for analysis. Results: Participants felt that there was potential for COVID-19 innovations and urgency to influence TB policy development and implementation, including the use of data dashboards. Implementation of the TB Recovery Plan predominantly used a top-down approach to implementation (cascading from national policy to local implementers) but experienced bottlenecks at provincial level. Recommendations for closing the TB policy-implementation gap included using phased implementation and enhancing provincial-level accountability. Civil society organisations were concerned about the lack of provincial implementation data which impeded advocacy for improved accountability and inadequate resourcing for implementation. Community health workers were viewed as key to implementation but were not engaged in the policy development process and were often not aware of new TB policies. At local level, there were also opportunities to strengthen community engagement in policy implementation including through community-led monitoring. Participants recommended broader multi-stakeholder engagement that includes community and community health worker representatives in the development and implementation phases of new TB policies. Conclusions: Communities affected by TB, with the support of civil society organisations, could play a bigger role in monitoring policy implementation at local level and need to be capacitated to do this. This bottom-up approach could complement existing top-down strategies and contribute to greater accountability for TB policy implementation. Supplementary Information: The online version contains supplementary material available at 10.1186/s44263-024-00077-y.

Erratum: 'I am afraid the news is not good' - Breaking bad news in the time of COVID: Experiences from a field hospital.

No abstract available.

'I am afraid the news is not good' - Breaking bad news in the time of COVID: Experiences from a field hospital.

BACKGROUND:  The COVID-19 Pandemic had profound effects on healthcare systems around the world. In South Africa, field hospitals, such as the Mitchell's Plain Field Hospital, managed many COVID patients and deaths, largely without family presence. Communicating with families, preparing them for death and breaking bad news was a challenge for all staff. AIM:  This study explores the experiences of healthcare professionals working in a COVID-19 field hospital, specifically around having to break the news of death remotely. SETTING:  A150-bed Mitchells Plain Field Hospital (MPFH) in Cape Town. METHODS:  A qualitative exploratory design was utilised using a semi-structured interview guide. RESULTS:  Four themes were identified: teamwork, breaking the news of death, communication and lessons learnt. The thread linking the themes was the importance of teamwork, the unpredictability of disease progression in breaking bad news and barriers to effective communication. Key lessons learnt included effective management and leadership. Many families had no access to digital technology and linguo-cultural barriers existed. CONCLUSION:  We found that in the Mitchell's Plain Field Hospital, communication challenges were exacerbated by the unpredictability of the illness and the impact of restrictions on families visiting in preparing them for bad news. We identified a need for training using different modalities, the importance of a multidisciplinary team approach and for palliative care guidelines to inform practice.Contribution: Breaking the news of death to the family is never easy for healthcare workers. This article unpacks some of the experiences in dealing with an extraordinary number of deaths by a newly formed team in the COVID era.

Can 'life writing' be therapeutic in response to trauma? An exploratory research project in Medical Humanities in South Africa.

The therapeutic benefit of expressive writing has been well researched in the Global North but there is no literature from the Global South. Potentially healing interventions need to be investigated in different contexts, particularly where there is a need to build social cohesion. South Africa has a violent past and is a highly stressed society. An exploration of self-reports by a diverse group of South Africans on the effects of life writing on their health and well-being was conducted using qualitative methods. Twenty members of a writing collective, the Life Righting Collective (LRC: www.liferighting.co.za), were purposively sampled and interviewed by medical students as part of a Medical Humanities special study module. Five major interconnected themes emerged. The LRC as a specific intervention was central to the benefits described. The findings of this study indicated that life writing is a useful non-medical, cost-efficient method to improve resilience to trauma, as well as improving the psychological well-being of the participants. In addition, participants reported positive experiences regarding personal development, overall wellness and mental health, and that life writing can engender a sense of community. Resource-constrained countries in the Global South, like South Africa, where there have been historical and ongoing multiple traumas, need interventions for healing and wellness that are low cost and can be replicated.

Geographic variation in 5-year mortality following HIV diagnosis: implications for clinical interventions.

Characterizing spatial distribution of HIV outcomes is vital for targeting interventions to areas most at risk. We performed spatial analysis to identify geographic clusters and factors associated with mortality in KwaZulu-Natal, South Africa. We utilized Sizanani trial (NCT01188941) data, which enrolled participants August 2010-January 2013 and obtained vital status at 5.8 (IQR 5.0-6.4) years of follow-up. We mapped geocoded addresses to 2011 Census-defined small area layer (SAL) centroids, used Kulldorff's spatial scan statistic to identify mortality clusters, and compared socio-demographic factors for SALs within and outside mortality clusters. We assigned 1,143 participants living with HIV (260 [23%] of whom died during follow-up) to 677 SALs. One lower mortality cluster (n = 90, RR = 0.23, p = 0.022) was identified near a hospital outside Durban. SALs in the cluster were younger (24y vs 25y, p < 0.001); had fewer bedrooms/household (3 vs 4, p < 0.001); had more females (52% vs 51%, p = 0.013) and residents with no schooling past age 20 (4% vs 3%, p < 0.001) or no education at all (4% vs 3%, p < 0.001); had fewer residents with income >3,200 ZAR/month (5% vs 9%, p < 0.001); and had reduced access to piped water (p < 0.001), refuse disposal (p < 0.001), and toilets (p < 0.001). Targeted interventions may improve outcomes in areas with similar characteristics.

An analysis of the HIV testing cascade of a group of HIV-exposed infants from birth to 18 months in peri-urban Khayelitsha, South Africa.

BACKGROUND: Despite the reduction of HIV mother-to-child transmission, there are concerns regarding transmission rate in the breastfeeding period. We describe the routine uptake of 6 or 10 (6/10) weeks, 9 months and 18 months testing, with and without tracing, in a cohort of infants who received HIV PCR testing at birth (birth PCR) (with and without point of care (POC) testing) in a peri-urban primary health care setting in Khayelitsha, South Africa. METHODS: In this cohort study conducted between November 2014 and February 2018, HIV-positive mothers and their HIV-exposed babies were recruited at birth and all babies were tested with birth PCR. Results of routine 6/10 weeks PCR, 9 months and 18 months testing were followed up by a patient tracer. We compared testing at 6/10 weeks with a subgroup from historical cohort who was not tested with birth PCR. RESULTS: We found that the uptake of 6/10 weeks testing was 77%, compared to 82% with tracing. When including all infants in the cascade and comparing to a historical cohort without birth testing, we found that infants who tested a birth were 22% more likely to have a 6/10 weeks test compared to those not tested at birth. There was no significant difference between the uptake of 6/10 weeks testing after birth PCR POC versus birth PCR testing without POC. Uptake of 9 months and 18 months testing was 39% and 24% respectively. With intense tracing efforts, uptake increased to 45% and 34% respectively. CONCLUSION: Uptake of HIV testing for HIV-exposed uninfected infants in the first 18 months of life shows good completion of the 6/10 weeks PCR but suboptimal uptake of HIV testing at 9 months and 18 months, despite tracing efforts. Birth PCR testing did not negatively affect uptake of the 6/10 weeks HIV test compared to no birth PCR testing.

Changing contextual factors from baseline to 9-months post-HIV diagnosis predict 5-year mortality in Durban, South Africa.

Changes in an individual's contextual factors following HIV diagnosis may influence long-term outcomes. We evaluated how changes to contextual factors between HIV diagnosis and 9-month follow-up predict 5-year mortality among HIV-infected individuals in Durban, South Africa enrolled in the Sizanani Trial (NCT01188941). We used random survival forests to identify 9-month variables and changes from baseline predictive of time to mortality. We incorporated these into a Cox proportional hazards model including age, sex, and starting ART by 9 months a priori, 9-month social support and competing needs, and changes in mental health between baseline and 9 months. Among 1,154 participants with South African ID numbers, 900 (78%) had baseline and 9-month data available of whom 109 (12%) died after 9-month follow-up. Those who reported less social support at 9 months had a 16% higher risk of mortality. Participants who went without basic needs or healthcare at 9 months had a 2.6 times higher hazard of death compared to participants who did not. Low social support and competing needs at 9-month follow-up substantially increase long-term mortality risk. Reassessing contextual factors during follow-up and targeting interventions to increase social support and affordability of care may reduce long-term mortality for HIV-infected individuals in South Africa.

Identifying and predicting longitudinal trajectories of care for people newly diagnosed with HIV in South Africa.

BACKGROUND: Predicting long-term care trajectories at the time of HIV diagnosis may allow targeted interventions. Our objective was to uncover distinct CD4-based trajectories and determine baseline demographic, clinical, and contextual factors associated with trajectory membership. METHODS: We used data from the Sizanani trial (NCT01188941), in which adults were enrolled prior to HIV testing in Durban, South Africa from August 2010-January 2013. We ascertained CD4 counts from the National Health Laboratory Service over 5y follow-up. We used group-based statistical modeling to identify groups with similar CD4 count trajectories and Bayesian information criteria to determine distinct CD4 trajectories. We evaluated baseline factors that predict membership in specific trajectories using multinomial logistic regression. We examined calendar year of participant enrollment, age, gender, cohabitation, TB positivity, self-identified barriers to care, and ART initiation within 3 months of diagnosis. RESULTS: 688 participants had longitudinal data available. Group-based trajectory modeling identified four distinct trajectories: one with consistently low CD4 counts (21%), one with low CD4 counts that increased over time (22%), one with moderate CD4 counts that remained stable (41%), and one with high CD4 counts that increased over time (16%). Those with higher CD4 counts at diagnosis were younger, less likely to have TB, and less likely to identify barriers to care. Those in the least favorable trajectory (consistently low CD4 count) were least likely to start ART within 3 months. CONCLUSIONS: One-fifth of people newly-diagnosed with HIV presented with low CD4 counts that failed to rise over time. Less than 40% were in a trajectory characterized by increasing CD4 counts. Patients in more favorable trajectories were younger, less likely to have TB, and less likely to report barriers to healthcare. Better understanding barriers to early care engagement and ART initiation will be necessary to improve long-term clinical outcomes.

Virologic response to efavirenz-based first-line antiretroviral therapy in children with previous exposure to antiretrovirals to prevent mother-to-child transmission.

Efavirenz-based first-line regimens have been widely used for children ≥3 years of age starting antiretroviral therapy, despite possible resistance with prior exposure to non-nucleoside reverse transcriptase inhibitors for prevention of mother-to-child transmission (PMTCT). We used logistic regression to examine the association between PMTCT exposure and viral failure (VF) defined as two consecutive viral loads (VL)>1000 copies/ml between 6-18 months on ART. Children with previous nevirapine exposure for PMTCT were not at higher risk of VF compared to unexposed children (adjusted Odds Ratio (aOR): 0.79; 95% CI:0.56, 1.11).

Cervical cancer risk in women living with HIV across four continents: A multicohort study.

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/µl decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities.

Assessing rates and contextual predictors of 5-year mortality among HIV-infected and HIV-uninfected individuals following HIV testing in Durban, South Africa.

BACKGROUND: Little is known about contextual factors that predict long-term mortality following HIV testing in resource-limited settings. We evaluated the impact of contextual factors on 5-year mortality among HIV-infected and HIV-uninfected individuals in Durban, South Africa. METHODS: We used data from the Sizanani trial (NCT01188941) in which adults (≥18y) were enrolled prior to HIV testing at 4 outpatient sites. We ascertained vital status via the South African National Population Register. We used random survival forests to identify the most influential predictors of time to death and incorporated these into a Cox model that included age, gender, HIV status, CD4 count, healthcare usage, health facility type, mental health, and self-identified barriers to care (i.e., service delivery, financial, logistical, structural and perceived health). RESULTS: Among 4816 participants, 39% were HIV-infected. Median age was 31y and 49% were female. 380 of 2508 with survival information (15%) died during median follow-up of 5.8y. For both HIV-infected and HIV-uninfected participants, each additional barrier domain increased the HR of dying by 11% (HR 1.11, 95% CI 1.05-1.18). Every 10-point increase in mental health score decreased the HR by 7% (HR 0.93, 95% CI 0.89-0.97). The hazard ratio (HR) for death of HIV-infected versus HIV-uninfected varied by age: HR of 6.59 (95% CI: 4.79-9.06) at age 20 dropping to a HR of 1.13 (95% CI: 0.86-1.48) at age 60. CONCLUSIONS: Independent of serostatus, more self-identified barrier domains and poorer mental health increased mortality risk. Additionally, the impact of HIV on mortality was most pronounced in younger persons. These factors may be used to identify high-risk individuals requiring intensive follow up, regardless of serostatus. TRIAL REGISTRATION: Clinical Trials.gov Identifier NCT01188941. Registered 26 August 2010.

Using national laboratory data to assess cumulative frequency of linkage after transfer to community-based HIV clinics in South Africa.

INTRODUCTION: Changes to the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) funding have led to closures of non-governmental HIV clinics with patient transfers to government-funded clinics. We sought to determine the success of transfers in South Africa using a national data source. METHODS: All adults (≥18 years) on antiretroviral therapy (ART) who visited a single PEPFAR-funded hospital-based HIV clinic in Durban, South Africa from March to June 2012 were transferred to community-based clinics. Previously, we matched patient records from the hospital-based HIV clinic with National Health Laboratory Services (NHLS) Corporate Data Warehouse (CDW) data to estimate the proportion of patients with a CD4 count or viral load (VL) in the CDW during the year before transfer. As a proxy for retention in care, in this study we evaluated whether patients had a CD4 count or VL at another facility within approximately three years of transfer. Patients referred to a private doctor at transfer were excluded from the analysis. We assessed predictors (age, sex, CD4 count, VL status, ART duration and location of future care) of not having post-transfer laboratory data using Cox proportional hazards models. RESULTS: Of the 3893 patients referred to a government facility at transfer, 41% were male and median age was 39 years (IQR 34 to 46). There was a post-transfer CD4 count or VL from another facility for 23% of these individuals within six months, 44% within one year, 57% within two years and 61% within approximately three years. Male sex (aHR 1.20, 95% CI 1.10 to 1.31) and shorter duration on ART (<3 months, aHR 3.80, 95% CI 2.77 to 5.21; three months to one year, aHR 1.32, 95% CI 1.15 to 1.51, each compared with >1 year) were associated with not having a post-transfer record. CONCLUSIONS: Using data from the NHLS CDW, 61% of patients had evidence of a post-transfer laboratory record at another facility within approximately three years after closure of a large South African HIV clinic. Males and those with shorter time on ART prior to transfer were at highest risk for lacking follow-up laboratory data. As patients transfer care, national data sources can be used to evaluate long-term patient care trajectories.

What Should We Do When HIV-positive Children Fail First-line Combination Antiretroviral Therapy? A Comparison of 4 ART Management Strategies.

BACKGROUND: Managing virologic failure (VF) in HIV-infected children is especially difficult in resource-limited settings, given limited availability of alternative drugs, concerns around adherence, and the development of HIV resistance mutations. We aimed to evaluate 4 management strategies for children following their first episode of VF by comparing their immunologic and virologic outcomes. METHODS: We included children (< 16 years of age) with VF from 8 International Epidemiologic Database to Evaluate AIDS Southern Africa cohorts, initiating combination antiretroviral therapy (cART) between 2004 and 2010, who followed one of the 4 management strategies: continuing on their failing regimen; switching to a second-line regimen; switching to a holding regimen (either lamivudine monotherapy or other non-cART regimen); discontinuing all ART. We compared the effect of management strategy on the 52-week change in CD4% and log10VL from VF, using inverse probability weighting of marginal structural linear models. RESULTS: Nine hundred eighty-two patients were followed over 54,168 weeks. Relative to remaining on a failing regimen, switching to second-line showed improved immunologic and virologic responses 52 weeks after VF with gains in CD4% of 1.5% (95% confidence interval [CI], 0.2-2.8) and declines in log10VL of -1.4 copies/mL (95% CI, -2.0, -0.8), while switching to holding regimens or discontinuing treatment had worse immunologic (-5.4% (95% CI, -12.1, 1.3) and -5.6% (95% CI, -15.4, 4.1) and virologic outcomes (0.2 (95% CI, -3.6, 4.1) and 0.8 (95% CI, -0.6, 2.1), respectively. CONCLUSIONS: The results provide useful guidance for managing children with VF. Consideration should be given to switching children failing first-line cART to second-line, given the improved virologic and immune responses when compared with other strategies.

Assessing the completeness and accuracy of South African National Laboratory CD4 and viral load data: a cross-sectional study.

OBJECTIVE: To assess the accuracy of the South African National Health Laboratory Services (NHLS) corporate data warehouse (CDW) using a novel data cross-matching method. METHODS: Adults (≥18 years) on antiretroviral therapy (ART) who visited a hospital-based HIV clinic in Durban from March to June 2012 were included. We matched patient identifiers, CD4 and viral load (VL) records from the HIV clinic's electronic record with the NHLS CDW according to a set of matching criteria for patient identifiers, test values and test dates. We calculated the matching rates for patient identifiers, CD4 and VL records, and an overall matching rate. RESULTS: NHLS returned records for 3498 (89.6%) of the 3906 individuals requested. Using our computer algorithm, we confidently matched 3278 patients (83.9% of the total request). Considering less than confident matches as well, and then manually reviewing questionable matches using only patient identifiers, only nine (0.3% of records returned by NHLS) of the suggested matches were judged incorrect. CONCLUSIONS: We developed a data cross-matching method to evaluate national laboratory data and were able to match almost 9 of 10 patients with data we expected to find in the NHLS CDW. We found few questionable matches, suggesting that manual review of records returned was not essential. As the number of patients initiating ART in South Africa grows, maintaining a comprehensive and accurate national data repository is of critical importance, since it may serve as a valuable tool to evaluate the effectiveness of the country's HIV care system. This study helps validate the use of NHLS CDW data in future research on South Africa's HIV care system and may inform analyses in similar settings with national laboratory systems.

Brief Report: Assessing the Association Between Changing NRTIs When Initiating Second-Line ART and Treatment Outcomes.

BACKGROUND: After first-line antiretroviral therapy failure, the importance of change in nucleoside reverse transcriptase inhibitor (NRTI) in second line is uncertain due to the high potency of protease inhibitors used in second line. SETTING: We used clinical data from 6290 adult patients in South Africa and Zambia from the International Epidemiologic Databases to Evaluate AIDS (IeDEA) Southern Africa cohort. METHODS: We included patients who initiated on standard first-line antiretroviral therapy and had evidence of first-line failure. We used propensity score-adjusted Cox proportional-hazards models to evaluate the impact of change in NRTI on second-line failure compared with remaining on the same NRTI in second line. In South Africa, where viral load monitoring was available, treatment failure was defined as 2 consecutive viral loads >1000 copies/mL. In Zambia, it was defined as 2 consecutive CD4 counts <100 cells/mm. RESULTS: Among patients in South Africa initiated on zidovudine (AZT), the adjusted hazard ratio for second-line virologic failure was 0.25 (95% confidence interval: 0.11 to 0.57) for those switching to tenofovir (TDF) vs. remaining on AZT. Among patients in South Africa initiated on TDF, switching to AZT in second line was associated with reduced second-line failure (adjusted hazard ratio = 0.35 [95% confidence interval: 0.13 to 0.96]). In Zambia, where viral load monitoring was not available, results were less conclusive. CONCLUSIONS: Changing NRTI in second line was associated with better clinical outcomes in South Africa. Additional clinical trial research regarding second-line NRTI choices for patients initiated on TDF or with contraindications to specific NRTIs is needed.

Clinic-Based Urinary Lipoarabinomannan as a Biomarker of Clinical Disease Severity and Mortality Among Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Infected Adults in South Africa.

BACKGROUND: Urinary lipoarabinomannan (LAM) has limited sensitivity for diagnosing active human immunodeficiency virus (HIV)-associated tuberculosis (TB) disease, but LAM screening at HIV diagnosis might identify adults with more severe clinical disease or greater risk of mortality. METHODS: We enrolled antiretroviral therapy-naive HIV-infected adults from 4 clinics in Durban. Nurses performed urine LAM testing using a rapid assay (Determine TB LAM) graded from low (1+) to high (≥3+) intensity. Urine LAM results were not used to guide anti-TB therapy. We assessed TB-related symptoms and obtained sputum for mycobacterial smear and culture. Participants were observed for 12 months, and we used multivariable Cox proportional hazard models to determine hazard ratios for all-cause mortality. RESULTS: Among 726 HIV-infected adults with median CD4 of 205 cells/mm3 (interquartile range, 79-350 cells/mm3), 93 (13%) were LAM positive and 89 (12%) participants died during the follow-up period. In multivariable analyses, urine LAM-positive participants had a mortality hazard ratio (MHR) of 3.58 (95% confidence interval [CI], 2.20-5.81) for all-cause mortality. Among participants with mycobacterial-confirmed TB, urine LAM-positivity had a 2.91 (95% CI, 1.26-6.73) MHR for all participants and a 4.55 (95% CI, 1.71-12.1) MHR for participants with CD4 ≤100 cell/mm3. Participants with LAM-positive TB had significantly more clinical signs and symptoms of disease, compared with participants with LAM-negative TB disease. CONCLUSIONS: Among HIV-infected adults, urinary LAM-positive patients had more clinical disease severity and a 3-fold increase in 12-month mortality compared with those who were LAM negative.

Barriers to Care and 1-Year Mortality Among Newly Diagnosed HIV-Infected People in Durban, South Africa.

BACKGROUND: Prompt entry into HIV care is often hindered by personal and structural barriers. Our objective was to evaluate the impact of self-perceived barriers to health care on 1-year mortality among newly diagnosed HIV-infected individuals in Durban, South Africa. METHODS: Before HIV testing at 4 outpatient sites, adults (≥18 years) were surveyed regarding perceived barriers to care including (1) service delivery, (2) financial, (3) personal health perception, (4) logistical, and (5) structural. We assessed deaths via phone calls and the South African National Population Register. We used multivariable Cox proportional hazards models to determine the association between number of perceived barriers and death within 1 year. RESULTS: One thousand eight hundred ninety-nine HIV-infected participants enrolled. Median age was 33 years (interquartile range: 27-41 years), 49% were females, and median CD4 count was 192/µL (interquartile range: 72-346/µL). One thousand fifty-seven participants (56%) reported no, 370 (20%) reported 1-3, and 460 (24%) reported >3 barriers to care. By 1 year, 250 [13%, 95% confidence interval (CI): 12% to 15%] participants died. Adjusting for age, sex, education, baseline CD4 count, distance to clinic, and tuberculosis status, participants with 1-3 barriers (adjusted hazard ratio: 1.49, 95% CI: 1.06 to 2.08) and >3 barriers (adjusted hazard ratio: 1.81, 95% CI: 1.35 to 2.43) had higher 1-year mortality risk compared with those without barriers. CONCLUSIONS: HIV-infected individuals in South Africa who reported perceived barriers to medical care at diagnosis were more likely to die within 1 year. Targeted structural interventions, such as extended clinic hours, travel vouchers, and streamlined clinic operations, may improve linkage to care and antiretroviral therapy initiation for these people.

Optimal timing of antiretroviral treatment initiation in HIV-positive children and adolescents: a multiregional analysis from Southern Africa, West Africa and Europe.

Background: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents. Methods: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula. Results: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm 3 (394; 1037) (children aged ≥ 1 and < 5 years), 373 (172; 630) (≥ 5 and < 10 years) and 238 (88; 425) (≥ 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm 3 (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and height-for-age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (≥ 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (≥ 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes. Conclusions: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.

Rapid urine lipoarabinomannan assay as a clinic-based screening test for active tuberculosis at HIV diagnosis.

BACKGROUND: World Health Organization (WHO) recommends tuberculosis (TB) screening at HIV diagnosis. We evaluated the inclusion of rapid urine lipoarabinomannan (LAM) testing in TB screening algorithms. METHODS: We enrolled ART-naïve adults who screened HIV-infected in KwaZulu-Natal, assessed TB-related symptoms (cough, fever, night sweats, weight loss), and obtained sputum specimens for mycobacterial culture. Trained nurses performed clinic-based urine LAM testing using a rapid assay. We used diagnostic accuracy, negative predictive value (NPV), and negative likelihood ratio, stratified by CD4 count, to evaluate screening for culture-positive TB. RESULTS: Among 675 HIV-infected adults with median CD4 of 213/mm3 (interquartile range 85-360/mm3), 123 (18%) had culture-confirmed pulmonary TB. The WHO-recommended algorithm of any TB-related symptom had a sensitivity of 77% [95% confidence interval (CI) 69-84%] and NPV of 89% (95% CI 84-92%) for identifying active pulmonary TB. Including the LAM assay improved sensitivity (83%; 95% CI 75-89%) and NPV (91%; 95% CI 86-94%), while decreasing the negative likelihood ratio (0.45 versus 0.57). Among participants with CD4 < 100/mm3, including urine LAM testing improved the negative predictive value of symptom based screening from 83% to 87%. All screening algorithms with urine LAM performed better among participants with CD4 < 100/mm3, compared to those with CD4 ≥ 100/mm3. CONCLUSION: Clinic-based urine LAM screening increased the sensitivity of symptom-based screening by 6% among ART-naïve HIV-infected adults in a TB-endemic setting, thereby providing marginal benefit.