Sustained high fatality during TB therapy amid rapid decline in TB mortality at population level: A retrospective cohort and ecological analysis from Shiselweni, Eswatini.

OBJECTIVES: Despite declining TB notifications in Southern Africa, TB-related deaths remain high. We describe patient- and population-level trends in TB-related deaths in Eswatini over a period of 11 years. METHODS: Patient-level (retrospective cohort, from 2009 to 2019) and population-level (ecological analysis, 2009-2017) predictors and rates of TB-related deaths were analysed in HIV-negative and HIV-coinfected first-line TB treatment cases and the population of the Shiselweni region. Patient-level TB treatment data, and population and HIV prevalence estimates were combined to obtain stratified annual mortality rates. Multivariable Poisson regressions models were fitted to identify patient-level and population-level predictors of deaths. RESULTS: Of 11,883 TB treatment cases, 1302 (11.0%) patients died during treatment: 210/2798 (7.5%) HIV-negative patients, 984/8443 (11.7%) people living with HIV (PLHIV), and 108/642 (16.8%) patients with unknown HIV-status. The treatment case fatality ratio remained above 10% in most years. At patient-level, fatality risk was higher in PLHIV (aRR 1.74, 1.51-2.02), and for older age and extra-pulmonary TB irrespective of HIV-status. For PLHIV, fatality risk was higher for TB retreatment cases (aRR 1.38, 1.18-1.61) and patients without antiretroviral therapy (aRR 1.70, 1.47-1.97). It decreases with increasing higher CD4 strata and the programmatic availability of TB-LAM testing (aRR 0.65, 0.35-0.90). At population-level, mortality rates decreased 6.4-fold (-147/100,000 population) between 2009 (174/100,000) and 2017 (27/100,000), coinciding with a decline in TB treatment cases (2785 in 2009 to 497 in 2017). Although the absolute decline in mortality rates was most pronounced in PLHIV (-826/100,000 vs. HIV-negative: -23/100,000), the relative population-level mortality risk remained higher in PLHIV (aRR 4.68, 3.25-6.72) compared to the HIV-negative population. CONCLUSIONS: TB-related mortality rapidly decreased at population-level and most pronounced in PLHIV. However, case fatality among TB treatment cases remained high. Further strategies to reduce active TB disease and introduce improved TB therapies are warranted.

The introduction of video-enabled directly observed therapy (video-DOT) for patients with drug-resistant TB disease in Eswatini amid the COVID-19 pandemic - a retrospective cohort study.

BACKGROUND: Video-enabled directly observed therapy (video-DOT) has been proposed as an additional option for treatment provision besides in-person DOT for patients with drug-resistant TB (DRTB) disease. However, evidence and implementation experience mainly originate from well-resourced contexts. This study describes the operationalization of video-DOT in a low-resourced setting in Eswatini facing a high burden of HIV and TB amid the emergence of the COVID-19 pandemic. METHODS: This is a retrospectively established cohort of patients receiving DRTB treatment during the implementation of video-DOT in Shiselweni from May 2020 to March 2022. We described intervention uptake (vs. in-person DOT) and assessed unfavorable DRTB treatment outcome (death, loss to care) using Kaplan-Meier statistics and multivariable Cox-regression models. Video-related statistics were described with frequencies and medians. We calculated the fraction of expected doses observed (FEDO) under video-DOT and assessed associations with missed video uploads using multivariable Poisson regression analysis. RESULTS: Of 71 DRTB patients eligible for video-DOT, the median age was 39 (IQR 30-54) years, 31.0% (n = 22) were women, 67.1% (n = 47/70) were HIV-positive, and 42.3% (n = 30) were already receiving DRTB treatment when video-DOT became available. About half of the patients (n = 37; 52.1%) chose video-DOT, mostly during the time when COVID-19 appeared in Eswatini. Video-DOT initiations were lower in new DRTB patients (aHR 0.24, 95% CI 0.12-0.48) and those aged ≥ 60 years (aHR 0.27, 95% CI 0.08-0.89). Overall, 20,634 videos were uploaded with a median number of 553 (IQR 309-748) videos per patient and a median FEDO of 92% (IQR 84-97%). Patients aged ≥ 60 years were less likely to miss video uploads (aIRR 0.07, 95% CI 0.01-0.51). The cumulative Kaplan-Meier estimate of an unfavorable treatment outcome among all patients was 0.08 (95% CI 0.03-0.19), with no differences detected by DOT approach and other baseline factors in multivariable analysis. CONCLUSIONS: Implementing video-DOT for monitoring of DRTB care provision amid the intersection of the HIV and COVID-19 pandemics seemed feasible. Digital health technologies provide additional options for patients to choose their preferred way to support treatment taking, thus possibly increasing patient-centered health care while sustaining favorable treatment outcomes.

Programmatic outcomes and impact of rapid public sector antiretroviral therapy expansion in adults prior to introduction of the WHO treat-all approach in rural Eswatini.

OBJECTIVES: To assess long-term antiretroviral therapy (ART) outcomes during rapid HIV programme expansion in the public sector of Eswatini (formerly Swaziland). METHODS: This is a retrospectively established cohort of HIV-positive adults (≥16 years) who started first-line ART in 25 health facilities in Shiselweni (Eswatini) between 01/2006 and 12/2014. Temporal trends in ART attrition, treatment expansion and ART coverage were described over 9 years. We used flexible parametric survival models to assess the relationship between time to ART attrition and covariates. RESULTS: Of 24 772 ART initiations, 6% (n = 1488) occurred in 2006, vs. 13% (n = 3192) in 2014. Between these years, median CD4 cell count at ART initiation increased (113-265 cells/mm3 ). The active treatment cohort expanded 8.4-fold, ART coverage increased 8.0-fold (7.1% in 2006 vs. 56.8% in 2014) and 12-month crude ART retention improved from 71% to 86%. Compared with the pre-decentralisation period (2006-2007), attrition decreased by 5% (adjusted hazard ratio [aHR] 0.95, 95% confidence interval 0.88-1.02) during HIV-TB service decentralisation (2008-2010), by 17% (aHR 0.83, 0.75-0.92) during service consolidation (2011-2012), and by 20% (aHR 0.80, 0.71-0.90) during further treatment expansion (2013-2014). The risk of attrition was higher for young age, male sex, pathological baseline haemoglobin and biochemistry results, more toxic drug regimens, WHO III/IV staging and low CD4 cell count; access to a telephone was protective. CONCLUSIONS: Programmatic outcomes improved during large expansion of the treatment cohort and increased ART coverage. Changes in ART programming may have contributed to better outcomes.

OBJECTIFS: Evaluer les résultats du traitement antirétroviral (ART) à long terme durant l'expansion rapide du programme de lutte contre le VIH dans le secteur public d'Eswatini (anciennement Swaziland). MÉTHODES: Il s'agit d'une cohorte établie de manière rétrospective d'adultes VIH positifs (≥ 16 ans) qui ont commencé un ART de première ligne dans 25 établissements de santé à Shiselweni (Eswatini) entre janvier 2006 et décembre 2014. Les tendances temporelles de l'attrition dans l'ART, de l'extension de la couverture ART ont été décrites sur 9 ans. Nous avons utilisé des modèles de survie paramétriques flexibles pour évaluer la relation entre le temps écoulé avant l'attrition dans l'ART et les covariables. RÉSULTATS: Sur 24.772 initiations à l'ART, 6% (n = 1.488) ont eu lieu en 2006 contre 13% (n = 3.192) en 2014. Entre ces années, le nombre médian de cellules CD4 au début du traitement ART a augmenté (113 à 265 cellules/mm3 ). La cohorte de traitement actif a été multipliée par 8,4, la couverture ART par 8,0 (7,1% en 2006 contre 56,8% en 2014) et la rétention brute sous ART est passée de 71% à 86%. Par rapport à la période antérieure à la décentralisation (2006-2007), l'attrition a diminué de 5% (rapport de risque ajusté [aHR]: 0,95, intervalle de confiance à 95%: 0,88 à 1,02) au cours de la décentralisation des services VIH-TB (2008-2010), de 17% (HR: 0,83; 0,75-0,92) lors de la consolidation du service (2011-2012) et de 20% (HR: 0,80; 0,71-0,90) lors de la poursuite de l'extension du traitement (2013-2014). Le risque d'attrition était plus élevé pour le jeune âge, le sexe masculin, les résultats pathologiques de l'hémoglobine initiale et biochimiques, des schémas thérapeutiques plus toxiques, un stade III/IV de l'OMS et une faible numération des cellules CD4; l'accès au téléphone était protecteur. CONCLUSIONS: Les résultats programmatiques se sont améliorés au cours de l'expansion importante de la cohorte de traitement et de l'augmentation de la couverture ART. Les changements apportés au programme ART peuvent avoir contribué à de meilleurs résultats.

Challenges and successes in the implementation of option B+ to prevent mother-to-child transmission of HIV in southern Swaziland.

BACKGROUND: Universal antiretroviral therapy (ART) for all pregnant/ breastfeeding women living with Human Immunodeficiency Virus (HIV), known as Prevention of mother-to child transmission of HIV (PMTCT) Option B+ (PMTCTB+), is being scaled up in most countries in Sub-Saharan Africa. In the transition to PMTCTB+, many countries face challenges with proper implementation of the HIV care cascade. We aimed to describe the feasibility of a PMTCTB+ approach in the public health sector in Swaziland. METHODS: Lifelong ART was offered to a cohort of HIV+ pregnant women aged ≥16 years at the first antenatal care (ANC1) visit in 9 public sector facilities, between 01/2013 and 06/2014. The study enrolment period was divided into 3 phases (early: 01-06/2013, mid: 07-12/2013 and late: 01-06/2014) to account for temporal trends. Kaplan-Meier estimates and Cox proportional-hazards regression models were applied for ART initiation and attrition analyses. RESULTS: Of 665 HIV+ pregnant women, 496 (74.6%) initiated ART. ART initiation increased in later study enrolment phases (mid: aHR: 1.41; later: aHR: 2.36), and decreased at CD4 ≥ 500 (aHR: 0.69). 52.9% were retained in care at 24 months. Attrition was associated with ANC1 in the third trimester (aHR: 2.37), attending a secondary care facility (aHR: 1.98) and ART initiation during later enrolment phases (mid aHR: 1.48; late aHR: 1.67). Of 373 women eligible, 67.3% received a first VL. 223/251 (88.8%) were virologically suppressed (< 1000 copies/mL). Of 670 infants, 53.6% received an EID test, 320/359 had a test result recorded and of whom 7 (2.2%) were HIV+. CONCLUSIONS: PMTCTB+ was found to be feasible in this setting, with high rates of maternal viral suppression and low transmission to the infant. High treatment attrition, poor follow-up of mother-baby pairs and under-utilisation of VL and EID testing are important programmatic challenges.

HIV programmatic outcomes following implementation of the 'Treat-All' policy in a public sector setting in Eswatini: a prospective cohort study.

INTRODUCTION: The Treat-All policy - antiretroviral therapy (ART) initiation irrespective of CD4 cell criteria - increases access to treatment. Many ART programmes, however, reported increasing attrition and viral failure during treatment expansion, questioning the programmatic feasibility of Treat-All in resource-limited settings. We aimed to describe and compare programmatic outcomes between Treat-All and standard of care (SOC) in the public sectors of Eswatini. METHODS: This is a prospective cohort study of ≥16-year-old HIV-positive patients initiated on first-line ART under Treat-All and SOC in 18 health facilities of the Shiselweni region, from October 2014 to March 2016. SOC followed the CD4 350 and 500 cells/mm3 treatment eligibility thresholds. Kaplan-Meier estimates were used to describe crude programmatic outcomes. Multivariate flexible parametric survival models were built to assess associations of time from ART initiation with the composite unfavourable outcome of all-cause attrition and viral failure. RESULTS: Of the 3170 patients, 1888 (59.6%) initiated ART under Treat-All at a median CD4 cell count of 329 (IQR 168 to 488) cells/mm3 compared with 292 (IQR 161 to 430) (p < 0.001) under SOC. Although crude programme retention at 36 months tended to be lower under Treat-All (71%) than SOC (75%) (p = 0.002), it was similar in covariate-adjusted analysis (adjusted hazard ratio [aHR] 1.06, 95% CI 0.91 to 1.23). The hazard of viral suppression was higher for Treat-All (aHR 1.12, 95% CI 1.01 to 1.23), while the hazard of viral failure was comparable (Treat-All: aHR 0.89, 95% CI 0.53 to 1.49). Among patients with advanced HIV disease (n = 1080), those under Treat-All (aHR 1.13, 95% CI 0.88 to 1.44) had a similar risk of an composite unfavourable outcome to SOC. Factors increasing the risk of the composite unfavourable outcome under both interventions were aged 16 to 24 years, being unmarried, anaemia, ART initiation on the same day as HIV care enrolment and CD4 ≤ 100 cells/mm3 . Under Treat-All only, the risk of the unfavourable outcome was higher for pregnant women, WHO III/IV clinical stage and elevated creatinine. CONCLUSIONS: Compared to SOC, Treat-All resulted in comparable retention, improved viral suppression and comparable composite outcomes of retention without viral failure.

Feasibility of antiretroviral therapy initiation under the treat-all policy under routine conditions: a prospective cohort study from Eswatini.

INTRODUCTION: The World Health Organization recommends the Treat-All policy of immediate antiretroviral therapy (ART) initiation, but questions persist about its feasibility in resource-poor settings. We assessed the feasibility of Treat-All compared with standard of care (SOC) under routine conditions. METHODS: This prospective cohort study from southern Eswatini followed adults from HIV care enrolment to ART initiation. Between October 2014 and March 2016, Treat-All was offered in one health zone and SOC according to the CD4 350 and 500 cells/mm3 treatment eligibility thresholds in the neighbouring health zone, each of which comprised one secondary and eight primary care facilities. We used Kaplan-Meier estimates, multivariate flexible parametric survival models and standardized survival curves to compare ART initiation between the two interventions. RESULTS: Of the 1726 (57.3%) patients enrolled under Treat-All and 1287 (42.7%) under SOC, cumulative three-month ART initiation was higher under Treat-All (91%) than SOC (74%; p < 0.001) with a median time to ART of 1 (IQR 0 to 14) and 10 (IQR 2 to 117) days respectively. Under Treat-All, ART initiation was higher in pregnant women (vs. non-pregnant women: adjusted hazard ratio (aHR) 1.96, 95% confidence interval (CI) 1.70 to 2.26), those with secondary education (vs. no formal education: aHR 1.48, 95% CI 1.12 to 1.95), and patients with an HIV-positive diagnosis before care enrolment (aHR 1.22, 95% CI 1.10 to 1.36). ART initiation was lower in patients attending secondary care facilities (aHR 0.64, 95% CI 0.58 to 0.72) and for CD4 351 to 500 when compared with CD4 201 to 350 cells/mm3 (aHR 0.84, 95% CI 0.72 to 1.00). ART initiation varied over time for TB cases, with lower hazard during the first two weeks after HIV care enrolment and higher hazards thereafter. Of patients with advanced HIV disease (n = 1085; 36.0%), crude 3-month ART initiation was similar in both interventions (91% to 92%) although Treat-All initiated patients more quickly during the first month after HIV care enrolment. CONCLUSIONS: ART initiation was high under Treat-All and without evidence of de-prioritization of patients with advanced HIV disease. Additional studies are needed to understand the long-term impact of Treat-All on patient outcomes.