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.

"It is still very little; I cannot pass it on": a qualitative study of experiences of diagnosis and treatment of acute HIV infection in Eswatini.

Acute and early HIV infection (AEHI) is rarely diagnosed in sub-Saharan Africa, despite its potential contribution to incidence reduction. This qualitative study in Eswatini explored the experiences of health workers, people diagnosed with AEHI, and their partners towards AEHI diagnosis, to inform its scale-up. In-depth interviews were undertaken with 11 women and four men diagnosed with AEHI. Three patients' partners were interviewed about their understanding of AEHI and six health workers were interviewed about experiences of delivering AEHI services. Data were coded inductively and analysed iteratively following the principles of grounded theory. Experiences with AEHI diagnoses were shaped by (i) understanding the nature and consequences of AEHI, and (ii) social norms that influence disclosure and sexual behaviour. AEHI was a new concept for health workers who struggled to explain it to patients, leading to some confusion over their HIV status and misunderstandings around its high transmissibility and prognosis. Disclosure tended to occur to primary partners, if at all, limiting the ability to provide partner services, and one relationship breakdown was reported. If AEHI diagnosis and care interventions are to realise their full potential, it will be essential to reinforce the accompanying counselling sessions and closely monitor for potential social harms.

Understanding the role of video direct observed therapy for patients on an oral short-course regimen for multi-drug resistant tuberculosis: findings from a qualitative study in Eswatini.

BACKGROUND: Improving treatment success rates among multi drug-resistant tuberculosis (MDR-TB) patients is critical to reducing its incidence and mortality, but adherence poses an important challenge. Video-based direct observed therapy (vDOT) may provide adherence benefits, while addressing the time and cost burden associated with community treatment supporter (CTS)-DOT. This study explored experiences of patients, family members and healthcare workers with different DOT modalities for adherence support in Eswatini. METHODS: Between April 2021 and May 2022, thirteen men and five women with MDR-TB, ten healthcare workers, and nine caregivers were purposively sampled to include a range of characteristics and experiences with DOT modalities. Data were generated through individual in-depth interviews and a smartphone messaging application (WhatsApp). Data coding was undertaken iteratively, and thematic analysis undertaken, supported by Nvivo. RESULTS: Four themes emerged that reflected participants' experiences with different DOT modalities, including stigma, efficiency, perceived risks of TB acquisition, and patient autonomy. vDOT was appreciated by patients for providing them with privacy and shielding them from stigmatisation associated with being seen in TB clinics or with community treatment supporters. vDOT was also seen as more efficient than CTS-DOT. Health workers acknowledged that it saved time, allowing them to attend to more patients, while many patients found vDOT more convenient and less expensive by removing the need to travel for in-person consultations. Health workers also appreciated vDOT because it reduced risks of TB acquisition by minimising exposure through virtual patient monitoring. Although many patients appreciated greater autonomy in managing their illness through vDOT, others preferred human contact or struggled with making video recordings. Most family members appreciated vDOT, although some resented feeling removed from the process of supporting loved ones. CONCLUSIONS: vDOT was generally appreciated by MDR-TB patients, their family members and health workers as it addressed barriers to adherence which could contribute to improved treatment completion rates and reduced workplace exposure. However, patients should be offered an alternative to vDOT such as CTS-DOT if this modality does not suit their circumstances or preferences.

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.

The Impact of Same-Day Antiretroviral Therapy Initiation Under the World Health Organization Treat-All Policy.

Rapid initiation of antiretroviral therapy (ART) is recommended for people living with human immunodeficiency virus (HIV), with the option to start treatment on the day of diagnosis (same-day ART). However, the effect of same-day ART remains unknown in realistic public sector settings. We established a cohort of ≥16-year-old patients who initiated first-line ART under a treat-all policy in Nhlangano (Eswatini) during 2014-2016, either on the day of HIV care enrollment (same-day ART) or 1-14 days thereafter (early ART). Directed acyclic graphs, flexible parametric survival analysis, and targeted maximum likelihood estimation (TMLE) were used to estimate the effect of same-day-ART initiation on a composite unfavorable treatment outcome (loss to follow-up, death, viral failure, treatment switch). Of 1,328 patients, 839 (63.2%) initiated same-day ART. The adjusted hazard ratio of the unfavorable outcome was higher, 1.48 (95% confidence interval: 1.16, 1.89), for same-day ART compared with early ART. TMLE suggested that after 1 year, 28.9% of patients would experience the unfavorable outcome under same-day ART compared with 21.2% under early ART (difference: 7.7%; 1.3%-14.1%). This estimate was driven by loss to follow-up and varied over time, with a higher hazard during the first year after HIV care enrollment and a similar hazard thereafter. We found an increased risk with same-day ART. A limitation was that possible silent transfers that were not captured.

PrEP reminds me that I am the one to take responsibility of my life: a qualitative study exploring experiences of and attitudes towards pre-exposure prophylaxis use by women in Eswatini.

BACKGROUND: Pre-exposure-prophylaxis (PrEP) has been heralded for its potential to put women in control of preventing HIV infection, but uptake and continuation rates have been disappointing in high-incidence settings in sub-Saharan Africa. We explored structural and social factors that influenced PrEP use among young women and pregnant or breastfeeding women in rural Eswatini. METHODS: We conducted two in-depth interviews with ten women on PrEP, and one-time in-depth interviews with fourteen women who declined or discontinued PrEP. Interviews covered decision-making processes around PrEP initiation and experiences with pill-taking. In-depth interviews were conducted with nine health workers, covering experiences in delivering PrEP services, and two focus group discussions were held with men to elicit their perceptions of PrEP. Interviews and discussions were audio-recorded, translated, transcribed and analysed thematically, using an inductive approach. RESULTS: PrEP initiation and use were experienced by many women as empowering them to take control of their health and well-being, and stay HIV free, facilitating them to realise their aspirations relating to motherhood and educational attainment. However, the social norms that defined relationship dynamics with partners or family members either undermined or promoted this empowerment potential. In particular, young women were rarely supported by family members to take PrEP unless it was perceived to be for protecting an unborn child. Stigmatisation of pill-taking through its associations with HIV and the burden of daily pill-taking also contributed to PrEP discontinuation. CONCLUSIONS: Unlike many prevention tools, PrEP enabled women to achieve a sense of control over their lives. Nevertheless, women's agency to continue and adhere to PrEP was influenced by social and structural factors including gender norms, family expectations of young women, relationship dynamics and stigma related to HIV. Future interventions should address these barriers to promote PrEP use among sexually-active women.

"We have to learn to cooperate with each other": a qualitative study to explore integration of traditional healers into the provision of HIV self-testing and tuberculosis screening in Eswatini.

BACKGROUND: Traditional healing plays an important role in healthcare in Eswatini, and innovative collaborations with traditional healers may enable hard-to-reach men to access HIV and tuberculosis diagnostic services. This study explored attitudes towards integration of traditional healers into the provision of HIV self-testing kits and sputum collection containers. METHODS: A qualitative study was conducted in 2019-2020 in Shiselweni region, Eswatini. Eight male traditional healers were trained on HIV and tuberculosis care including distribution of HIV self-testing kits and sputum collection containers. Attitudes towards the intervention were elicited through in-depth interviews with the eight traditional healers, ten clients, five healthcare workers and seven focus group discussions with community members. Interviews and group discussions were conducted in SiSwati, audio-recorded, translated and transcribed into English. Data were coded inductively and analysed thematically. RESULTS: 81 HIV self-testing kits and 24 sputum collection containers were distributed by the healers to 99 clients, with 14% of participants reporting a reactive HIV self-test result. The distribution of sputum containers did not result in any tuberculosis diagnoses, as samples were refused at health centres. Traditional healers perceived themselves as important healthcare providers, and after training, were willing and able to distribute HIV self-test kits and sputum containers to clients. Many saw themselves as peers who could address barriers to health-seeking among Swazi men that reflected hegemonic masculinities and patriarchal attitudes. Traditional healers were considered to provide services that were private, flexible, efficient and non-judgemental, although some clients and community members expressed concerns over confidentiality breaches. Attitudes among health workers were mixed, with some calling for greater collaboration with traditional healers and others expressing doubts about their potential role in promoting HIV and tuberculosis services. Specifically, many health workers did not accept sputum samples collected outside health facilities. CONCLUSIONS: Offering HIV self-testing kits and sputum containers through traditional healers led to high HIV yields, but no TB diagnoses. The intervention was appreciated by healers' clients, due to the cultural literacy of traditional healers and practical considerations. Scaling-up this approach could bridge testing gaps if traditional healers are supported, but procedures for receiving sputum samples at health facilities need further strengthening.

Evaluating smartphone strategies for reliability, reproducibility, and quality of VIA for cervical cancer screening in the Shiselweni region of Eswatini: A cohort study.

BACKGROUND: Cervical cancer is among the most common preventable cancers with the highest morbidity and mortality. The World Health Organization (WHO) recommends visual inspection of the cervix with acetic acid (VIA) as cervical cancer screening strategy in resource-poor settings. However, there are barriers to the sustainability of VIA programs including declining providers' VIA competence without mentorship and quality assurances and challenges of integration into primary healthcare. This study seeks to evaluate the impact of smartphone-based strategies in improving reliability, reproducibility, and quality of VIA in humanitarian settings. METHODS AND FINDINGS: We implemented smartphone-based VIA that included standard VIA training, adapted refresher, and 6-month mHealth mentorship, sequentially, in the rural Shiselweni region of Eswatini. A remote expert reviewer provided diagnostic and management feedback on patients' cervical images, which were reviewed weekly by nurses. Program's outcomes, VIA image agreement rates, and Kappa statistic were compared before, during, and after training. From September 1, 2016 to December 31, 2018, 4,247 patients underwent screening; 247 were reviewed weekly by a VIA diagnostic expert. Of the 247, 128 (49%) were HIV-positive; mean age was 30.80 years (standard deviation [SD]: 7.74 years). Initial VIA positivity of 16% (436/2,637) after standard training gradually increased to 25.1% (293/1,168), dropped to an average of 9.7% (143/1,469) with a lowest of 7% (20/284) after refresher in 2017 (p = 0.001), increased again to an average of 9.6% (240/2,488) with a highest of 17% (17/100) before the start of mentorship, and dropped to an average of 8.3% (134/1,610) in 2018 with an average of 6.3% (37/591) after the start of mentorship (p = 0.019). Overall, 88% were eligible for and 68% received cryotherapy the same day: 10 cases were clinically suspicious for cancer; however, only 5 of those cases were confirmed using punch biopsy. Agreement rates with the expert reviewer for positive and negative cases were 100% (95% confidence interval [CI]: 79.4% to 100%) and 95.7% (95% CI: 92.2% to 97.9%), respectively, with negative predictive value (NPV) (100%), positive predictive value (PPV) (63.5%), and area under the curve of receiver operating characteristics (AUC ROC) (0.978). Kappa statistic was 0.74 (95% CI; 0.58 to 0.89); 0.64 and 0.79 at 3 and 6 months, respectively. In logistic regression, HIV and age were associated with VIA positivity (adjusted Odds Ratio [aOR]: 3.53, 95% CI: 1.10 to 11.29; p = 0.033 and aOR: 1.06, 95% CI: 1.0004 to 1.13; p = 0.048, respectively). We were unable to incorporate a control arm due to logistical constraints in routine humanitarian settings. CONCLUSIONS: Our findings suggest that smartphone mentorship provided experiential learning to improve nurses' competencies and VIA reliability and reproducibility, reduced false positive, and introduced peer-to-peer education and quality control services. Local collaboration; extending services to remote populations; decreasing unnecessary burden to screened women, providers, and tertiary centers; and capacity building through low-tech high-yield screening are promising strategies for scale-up of VIA programs.

Implementation of community and facility-based HIV self-testing under routine conditions in southern Eswatini.

OBJECTIVES: WHO recommends HIV self-testing (HIVST) as an additional approach to HIV testing services. The study describes the strategies used during phase-in of HIVST under routine conditions in Eswatini (formerly Swaziland). METHODS: Between May 2017 and January 2018, assisted and unassisted oral HIVST was offered at HIV testing services (HTS) sites to people aged ≥ 16 years. Additional support tools were available, including a telephone hotline answered 24/7, HIVST demonstration videos and printed educational information about HIV prevention and care services. Demographic characteristics of HIVST users were described and compared with standard blood-based HTS in the community. HIVST results were monitored with follow-up phone calls and the hotline. RESULTS: During the 9-month period, 1895 people accessed HIVST and 2415 HIVST kits were distributed. More people accessed HIVST kits in the community (n = 1365, 72.0%) than at health facilities (n = 530, 28.0%). The proportion of males and median age among those accessing HIVST and standard HTS in the community were similar (49.3%, 29 years HIVST vs. 48.7%, 27 years standard HTS). In total, 34 (3.9%) reactive results were reported from 938 people with known HIVST results; 32.4% were males, and median age was 30 years (interquartile range 25-36). Twenty-one (62%) patients were known to have received confirmatory blood-based HTS; of these, 20 (95%) had concordant reactive results and 19 (95%) were linked to HIV care at a clinic. CONCLUSION: Integration of HIVST into existing HIV facility- and community-based testing strategies in Eswatini was found to be feasible, and HIVST has been adopted by national testing bodies in Eswatini.

OBJECTIFS: L'OMS recommande l'autotest du VIH (HIVST) comme approche supplémentaire des services de dépistage du VIH. L'étude décrit les stratégies utilisées lors de l'introduction progressive du VIHST dans des conditions de routine à Eswatini (anciennement le Swaziland). MÉTHODES: Entre mai 2017 et janvier 2018, des HIVST orales assistées et non assistées ont été proposés dans les sites des services de dépistage du VIH (HTS) aux personnes âgées de 16 ans et plus. Des outils de soutien supplémentaires étaient disponibles, notamment une permanence téléphonique répondue 24h/24 et 7j/7, des vidéos de démonstration sur le HIVST et des informations éducatives imprimées sur les services de prévention et de soins du VIH. Les caractéristiques démographiques des utilisateurs du VIHST ont été décrites et comparées aux tests sanguins standard des HTS dans la communauté. Les résultats des HIVST ont été contrôlés par des appels téléphoniques de suivi et la hotline. RÉSULTATS: Au cours de la période de 9 mois, 1895 personnes ont eu accès au VIHST et 2415 kits VIHST ont été distribués. Plus de personnes ont eu accès aux kits VIHST dans la communauté (n = 1365, 72,0%) que dans les établissements de santé (n = 530, 28,0%). La proportion d'hommes et l'âge médian parmi ceux qui accèdent au VIHST et au HTS standard dans la communauté étaient similaires (49,3%, 29 ans VIHST vs 48,7%, 27 ans HTS standard). Au total, 34 (3,9%) résultats réactifs ont été signalés chez 938 personnes avec des résultats connus pour le VIHST; 32,4% étaient des hommes et l'âge médian était de 30 ans (intervalle interquartile 25-36). 21 patients (62%) ont reçu un test sanguin de confirmation HTS; parmi ceux-ci, 20 (95%) avaient des résultats réactifs concordants et 19 (95%) ont été reliés aux soins du VIH dans une clinique. CONCLUSION: L'intégration du HIVST dans les structures existantes de dépistage du VIH et les stratégies de dépistage à Eswatini s'est avérée réalisable, et le HIVST a été adopté par les organismes nationaux de dépistage à Eswatini.

"They have been neglected for a long time": a qualitative study on the role and recognition of rural health motivators in the Shiselweni region, Eswatini.

BACKGROUND: Community health workers (CHWs) are increasingly engaged to address human resource shortages and fill primary healthcare gaps. In Eswatini, a cadre of CHWs called Rural Health Motivators (RHM) was introduced in 1976 to respond to key public health challenges. However, the emergence of health needs, particularly HIV/TB, has been met with inadequate programme amendments, and the role of RHMs has become marginalised following the addition of other CHWs supported by non-governmental organisations. This study was implemented to understand the role of RHMs in decentralised HIV/TB activities. In this paper, we explore the findings in relation to the recognition of RHMs and the programme. METHODS: This exploratory qualitative study utilised individual in-depth interviews, group and focus group discussions, participatory methods (utilising a game format) and observations. Participants were purposively selected and comprised RHM programme implementers, community stakeholders and local and non-governmental personnel. Data collection took place between August and September 2019. Interviews were conducted in English or siSwati and transcribed. SiSwati interviews were translated directly into English. All interviews were audio-recorded, manually coded and thematically analysed. Data was validated through methodical triangulation. RESULTS: Suboptimal organisational structure and support, primarily insufficient training and supervision for activities were factors identified through interviews and observation activities. Significant confusion of the RHM role was observed, with community expectations beyond formally endorsed tasks. Community participants expressed dissatisfaction with receiving health information only, preferring physical assistance in the form of goods. Additionally, gender emerged as a significant influencing factor on the acceptability of health messages and the engagement of RHMs with community members. Expectations and structurally limiting factors shape the extent to which RHMs are recognised as integral to the health system, at all social and organisational levels. CONCLUSIONS: Findings highlight the lack of recognition of RHMs and the programme at both community and national levels. This, along with historical neglect, has hindered the capacity of RHMs to successfully contribute to positive health outcomes for rural communities. Renewed attention and support mechanisms for this cadre are needed. Clarification of the RHM role in line with current health challenges and clearer role parameters is essential.

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.

Decreased risk of HIV-associated TB during antiretroviral therapy expansion in rural Eswatini from 2009 to 2016: a cohort and population-based analysis.

OBJECTIVES: This paper assesses patient- and population-level trends in TB notifications during rapid expansion of antiretroviral therapy in Eswatini which has an extremely high incidence of both TB and HIV. METHODS: Patient- and population-level predictors and rates of HIV-associated TB were examined in the Shiselweni region in Eswatini from 2009 to 2016. Annual population-level denominators obtained from projected census data and prevalence estimates obtained from population-based surveys were combined with individual-level TB treatment data. Patient- and population-level predictors of HIV-associated TB were assessed with multivariate logistic and multivariate negative binomial regression models. RESULTS: Of 11 328 TB cases, 71.4% were HIV co-infected and 51.8% were women. TB notifications decreased fivefold between 2009 and 2016, from 1341 to 269 cases per 100 000 person-years. The decline was sixfold in PLHIV vs. threefold in the HIV-negative population. Main patient-level predictors of HIV-associated TB were recurrent TB treatment (adjusted odds ratio [aOR] 1.40, 95% confidence interval [CI]: 1.19-1.65), negative (aOR 1.31, 1.15-1.49) and missing (aOR 1.30, 1.11-1.53) bacteriological status and diagnosis at secondary healthcare level (aOR 1.18, 1.06-1.33). Compared with 2009, the probability of TB decreased for all years from 2011 (aOR 0.69, 0.58-0.83) to 2016 (aOR 0.54, 0.43-0.69). The most pronounced population-level predictor of TB was HIV-positive status (adjusted incidence risk ratio 19.47, 14.89-25.46). CONCLUSIONS: This high HIV-TB prevalence setting experienced a rapid decline in TB notifications, most pronounced in PLHIV. Achievements in HIV-TB programming were likely contributing factors.

OBJECTIFS: Ce document évalue les tendances des notifications de la tuberculose (TB) à l'échelle des patients et de la population lors de l'expansion rapide du traitement antirétroviral à Eswatini, où l'incidence de la TB et du VIH est extrêmement élevée. MÉTHODES: Les prédicteurs et les taux de TB associée au VIH à l'échelle des patients et de la population ont été examinés dans la région de Shiselweni à Eswatini de 2009 à 2016. Les dénominateurs annuels à l'échelle de la population obtenus à partir des données de recensement projetées et des estimations de la prévalence obtenues à partir d'enquêtes de population ont été combinés avec des données de traitement de la TB à l'échelle individuel. Les prédicteurs de la TB associée au VIH à l'échelle du patient et de la population ont été évalués à l'aide de modèles de régression logistique multivariée et binomiale négative multivariée. RÉSULTATS: Sur 11.328 cas de TB, 71,4% étaient coinfectés par le VIH et 51,8% étaient des femmes. Les notifications de TB ont été réduites de 5,0 fois entre 2009 et 2016, passant de 1.341 à 269 cas par 100.000 personnes-années. Le déclin était de 6,0 fois chez les PVVIH contre 3,0 fois dans la population négative pour le VIH. Les principaux prédicteurs de la TB associée au VIH à l'échelle des patients étaient les traitements antituberculeux récurrents (rapport de cotes ajusté [aOR] 1,40; intervalle de confiance à 95% [IC]: 1,19 à 1,65), un statut bactériologique négatif (aOR: 1,31; 1,15 à 1,49) et manquant (aOR: 1,30; 1,11 à 1,53) et le diagnostic au niveau des soins de santé secondaires (AOR 1,18; 1,06 à 1,33). Par rapport à 2009, la probabilité de contracter la TB a diminué pour toutes les années, de 2011 (aOR: 0,69; 0,58 à 0,83) à 2016 (aOR: 0,5; 0,43 à 0,69). Le prédicteur le plus prononcé de la TB à l'échelle de la population était le statut VIH-positif (rapport de risque d'incidence ajusté: 19,47; 14,89 à 25,46). CONCLUSIONS: Ce contexte de prévalence élevée de la TB-VIH a connu un déclin rapide du nombre de notifications de TB, plus prononcé chez les PVVIH. Les réalisations dans la programmation VIH-TB étaient probablement des facteurs contributifs.

Successful expansion of community-based drug-resistant TB care in rural Eswatini - a retrospective cohort study.

OBJECTIVES: Provision of drug-resistant tuberculosis (DR-TB) treatment is scarce in resource-limited settings. We assessed the feasibility of ambulatory DR-TB care for treatment expansion in rural Eswatini. METHODS: Retrospective patient-level data were used to evaluate ambulatory DR-TB treatment provision in rural Shiselweni (Eswatini), from 2008 to 2016. DR-TB care was either clinic-based led by nurses or community-based at the patient's home with involvement of community treatment supporters for provision of treatment to patients with difficulties in accessing facilities. We describe programmatic outcomes and used multivariate flexible parametric survival models to assess time to adverse outcomes. Both care models were costed in supplementary analyses. RESULTS: Of 698 patients initiated on DR-TB treatment, 57% were women and 84% were HIV-positive. Treatment initiations increased from 27 in 2008 to 127 in 2011 and decreased thereafter to 51 in 2016. Proportionally, community-based care increased from 19% in 2009 to 77% in 2016. Treatment success was higher for community-based care (79%) than clinic-based care (68%, P = 0.002). After adjustment for covariate factors among adults (n = 552), the risk of adverse outcomes (death, loss to follow-up, treatment failure) in community-based care was reduced by 41% (adjusted hazard ratio 0.59, 95% CI: 0.39-0.91). Findings were supported by sensitivity analyses. The care provider's per-patient costs for community-based (USD13 345) and clinic-based (USD12 990) care were similar. CONCLUSIONS: Ambulatory treatment outcomes were good, and community-based care achieved better treatment outcomes than clinic-based care at comparable costs. Contextualised DR-TB care programmes are feasible and can support treatment expansion in rural settings.

OBJECTIFS: La fourniture de traitement de la tuberculose résistante aux médicaments (TB-R) est rare dans les pays à ressources limitées. Nous avons évalué la faisabilité des soins ambulatoires de la TB-R pour l'extension du traitement en zone rurale d'Eswatini. MÉTHODES: Des données rétrospectives au niveau du patient ont été utilisées pour évaluer la fourniture d'un traitement ambulatoire de la TB-R dans la zone rurale de Shiselweni (Eswatini), de 2008 à 2016. Les soins pour la TB-R étaient dispensés soit en clinique sous la direction d'infirmiers ou en milieu communautaire au domicile du patient avec l'implication des aidants au traitement pour la fourniture d'un traitement aux patients ayant des difficultés à accéder aux établissements. Nous décrivons ici les résultats programmatiques et avons utilisé des modèles de survie paramétriques flexibles multivariés pour évaluer le délai d'apparition de résultats défavorables. Les deux modèles de soins ont été chiffrés dans des analyses supplémentaires. RÉSULTATS: Sur 698 patients initiés sous traitement de la TB-R, 57% étaient des femmes et 84% étaient VIH positifs. Les initiations aux traitements sont passées de 27 en 2008 à 127 en 2011 et ont ensuite diminué à 51 en 2016. Proportionnellement, les soins communautaires ont augmenté de 19% en 2009 à 77% en 2016. Le taux de réussite du traitement était supérieur pour les soins communautaires (79%) que pour ceux dispensés en clinique (68%, P = 0,002). Après ajustement pour les facteurs de covariable chez les adultes (n = 552), le risque de résultats indésirables (décès, perte au suivi, échec du traitement) dans les soins communautaires a été réduit de 41% (rapport de risque ajusté de 0,59, IC95%: 0,39-0,91). Les résultats ont été étayés par des analyses de sensibilité. Les coûts par patient sur base du prestataire de soins pour les soins communautaires (13.345 USD) et en clinique (12.990 USD) étaient similaires. CONCLUSIONS: Les résultats des traitements ambulatoires ont été bons et les soins dispensés dans la communauté ont obtenu de meilleurs résultats que ceux dispensés en clinique à des coûts comparables. Des programmes de prise en charge contextualisés de la TB-R sont réalisables et peuvent soutenir l'expansion du traitement en milieu rural.

"I don't want them to know": how stigma creates dilemmas for engagement with Treat-all HIV care for people living with HIV in Eswatini.

"Treat-all" programmes aim to improve clinical outcomes and to reduce HIV transmission through regular HIV testing and immediate offer of antiretroviral therapy (ART) for those diagnosed HIV-positive, irrespective of immunological status and symptoms of disease. Global narratives on the benefits of Treat-all anticipate reduced HIV-related stigma and increased "normalisation" of HIV with Treat-all implementation, whereby HIV is remoulded as a manageable, chronic condition where stigmatising symptoms can be concealed. Drawing on Goffman's stigma work, we aimed to investigate how stigma may influence the engagement of clinically asymptomatic people living with HIV (PLHIV) with Treat-all HIV care in Shiselweni, Eswatini (formerly Swaziland). This longitudinal research comprised 106 interviews conducted from August 2016 to September 2017, including repeated interviews with 30 PLHIV, and one-off interviews with 20 healthcare workers. Data were analysed thematically using NVivo 11, drawing upon principles of grounded theory to generate findings inductively from participants' accounts. Stigma was pervasive within the narratives of PLHIV, framing their engagement with treatment and care. Many asymptomatic PLHIV were motivated to initiate ART in order to maintain a "discreditable" status, by preventing the development of visible and exposing symptoms. However, engagement with treatment and care services could itself be exposing. PLHIV described the ways in which these "invisibilising" benefits and exposing risks of ART were continually assessed and navigated over time. Where the risk of exposure was deemed too great, this could lead to intermittent treatment-taking, and disengagement from care. Addressing HIV related stigma is crucial to the success of Treat-all, and should thus be a core component of HIV responses.

Field suitability and diagnostic accuracy of the Biocentric® open real-time PCR platform for plasma-based HIV viral load quantification in Swaziland.

BACKGROUND: Viral load (VL) testing is being scaled up in resource-limited settings. However, not all commercially available VL testing methods have been evaluated under field conditions. This study is one of a few to evaluate the Biocentric platform for VL quantification in routine practice in Sub-Saharan Africa. METHODS: Venous blood specimens were obtained from patients eligible for VL testing at two health facilities in Swaziland from October 2016 to March 2017. Samples were centrifuged at two laboratories (LAB-1, LAB-2) to obtain paired plasma specimens for VL quantification with the national reference method and on the Biocentric platform. Agreement (correlation, Bland-Altman) and accuracy (sensitivity, specificity) indicators were calculated at the VL thresholds of 416 (2.62 log10) and 1000 (3.0 log10) copies/mL. Leftover samples from patients with discordant VL results were re-quantified and accuracy indicators recalculated. Logistic regression was used to compare laboratory performance. RESULTS: A total of 364 paired plasma samples (LAB-1: n = 198; LAB-2: n = 166) were successfully tested using both methods. The correlation was high (R = 0.82, p < 0.01), and the Bland-Altman analysis showed a minimal mean difference (- 0.03 log10 copies/mL; 95% CI: -1.15 to 1.08). At the clinical threshold level of 3.0 log10 copies/mL, the sensitivity was 88.6% (95% CI: 78.7 to 94.9) and the specificity was 98.3% (95% CI: 96.1 to 99.4). Sensitivity was higher in LAB-1 (100%; 95% CI: 71.5 to 100) than in LAB-2 (86.4%; 95% CI: 75.0 to 94.0). Most upward (n = 8, 2.2%) and downward (n = 11, 3.0%) misclassifications occurred at the 2.62 log threshold, with LAB-2 having a 16 (95% CI: 2.26 to 113.27; p = 0.006) times higher odds of downward misclassification. After retesting of discordant leftover samples (n = 17), overall sensitivity increased to 93.5% (95% CI: 85.5 to 97.9) and 97.1% (95% CI: 90.1 to 99.7) at the 2.62 and 3.0 thresholds, and specificity increased to 98.6% (95% CI: 96.5 to 99.6) and 99.0% (95% CI: 97.0 to 99.8) respectively. CONCLUSIONS: The test characteristics of the Biocentric platform were overall comparable to the national reference method for VL quantification. One laboratory tended to misclassify VL results downwards, likely owing to unmet training needs and lack of previous hands-on practice.

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.

Feasibility and effectiveness of two community-based HIV testing models in rural Swaziland.

OBJECTIVES: To evaluate the feasibility (population reached, costs) and effectiveness (positivity rates, linkage to care) of two strategies of community-based HIV testing and counselling (HTC) in rural Swaziland. METHODS: Strategies used were mobile HTC (MHTC) and home-based HTC (HBHTC). Information on age, sex, previous testing and HIV results was obtained from routine HTC records. A consecutive series of individuals testing HIV-positive were followed up for 6 months from the test date to assess linkage to care. RESULTS: A total of 9 060 people were tested: 2 034 through MHTC and 7 026 through HBHTC. A higher proportion of children and adolescents (<20 years) were tested through HBHTC than MHTC (57% vs. 17%; P < 0.001). MHTC reached a higher proportion of adult men than HBHTC (42% vs. 39%; P = 0.015). Of 398 HIV-positive individuals, only 135 (34%) were enrolled in HIV care within 6 months. Of 42 individuals eligible for antiretroviral therapy, 22 (52%) started treatment within 6 months. Linkage to care was lowest among people who had tested previously and those aged 20-40 years. HBHTC was 50% cheaper (US$11 per person tested; $797 per individual enrolled in HIV care) than MHTC ($24 and $1698, respectively). CONCLUSION: In this high HIV prevalence setting, a community-based testing programme achieved high uptake of testing and appears to be an effective and affordable way to encourage large numbers of people to learn their HIV status (particularly underserved populations such as men and young people). However, for community HTC to impact mortality and incidence, strategies need to be implemented to ensure people testing HIV-positive in the community are linked to HIV care.

Kidney function in tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis users: a systematic review and meta-analysis of published literature and a multi-country meta-analysis of individual participant data.

BACKGROUND: Previous WHO guidance on tenofovir disoproxil fumarate-based oral pre-exposure prophylaxis (PrEP) suggests measuring creatinine levels at PrEP initiation and regularly afterwards, which might represent barriers to PrEP implementation and uptake. We aimed to systematically review published literature on kidney toxicity among tenofovir disoproxil fumarate-based oral PrEP users and conducted an individual participant data meta-analysis (IPDMA) on kidney function among PrEP users in a global implementation project dataset. METHODS: In this systematic review and meta-analysis we searched PubMed up to June 30, 2021, for randomised controlled trials (RCTs) or cohort studies that reported on graded kidney-related adverse events among oral PrEP users (tenofovir disoproxil fumarate-based PrEP alone or in combination with emtricitabine or lamivudine). We extracted summary data and conducted meta-analyses with random-effects models to estimate relative risks of grade 1 and higher and grade 2 and higher kidney-related adverse events, measured by elevated serum creatinine or decline in estimated creatinine clearance or estimated glomerular filtration rate. The IPDMA included (largely unpublished) individual participant data from 17 PrEP implementation projects and two RCTs. Estimated baseline creatinine clearance and creatinine clearance change after initiation were described by age, gender, and comorbidities. We used random-effects regressions to estimate the risk in decline of creatinine clearance to less than 60 mL/min. FINDINGS: We identified 62 unique records and included 17 articles reporting on 11 RCTs with 13 523 participants in meta-analyses. PrEP use was associated with increased risk of grade 1 and higher kidney adverse events (pooled odds ratio [OR] 1·49, 95% CI 1·22-1·81; I2=25%) and grade 2 and higher events (OR 1·75, 0·68-4·49; I2=0%), although the grade 2 and higher association was not statistically significant and events were rare (13 out of 6764 in the intervention group vs six out of 6782 in the control group). The IPDMA included 18 676 individuals from 15 countries (1453 [7·8%] from RCTs) and 79 (0·42%) had a baseline estimated creatinine clearance of less than 60 mL/min (increasing proportions with increasing age). Longitudinal analyses included 14 368 PrEP users and 349 (2·43%) individuals had a decline to less than 60 mL/min creatinine clearance, with higher risks associated with increasing age and baseline creatinine clearance of 60·00-89·99 mL/min (adjusted hazard ratio [aHR] 8·49, 95% CI 6·44-11·20) and less than 60 mL/min (aHR 20·83, 12·83-33·82). INTERPRETATION: RCTs suggest that risks of kidney-related adverse events among tenofovir disoproxil fumarate-based oral PrEP users are increased but generally mild and small. Our global PrEP user analysis found varying risks by age and baseline creatinine clearance. Kidney function screening and monitoring might focus on older individuals, those with baseline creatinine clearance of less than 90 mL/min, and those with kidney-related comorbidities. Less frequent or optional screening among younger individuals without kidney-related comorbidities may reduce barriers to PrEP implementation and use. FUNDING: Unitaid, Bill & Melinda Gates Foundation, WHO.

'She is like my mother': Community-based care of drug-resistant tuberculosis in rural Eswatini.

Patients with drug-resistant tuberculosis (DR-TB) have received community-based care in Eswatini since 2009. Trained and compensated community treatment supporters (CTSs) provide directly observed therapy (DOT), injectables and psychological support. We examined the acceptability of this model of care among DR-TB patients, including the perspective of family members of DR-TB patients and their CTSs in relation to the patient's experience of care and quality of life. This qualitative research was conducted in rural Eswatini in February 2018. DR-TB patients, CTSs and family members participated in in-depth interviews, paired interviews, focus group discussions and PhotoVoice. Data were thematically analysed and coded, and themes were extracted. Methodological triangulation enhanced the interpretation. All patients and CTSs and most family members considered community-based DR-TB care to be supportive. Positive aspects were emotional support, trust and dedicated individual care, including enabling practical, financial and social factors. Concerns were related to social and economic problems within the family and fears about infection risks for the family and the CTSs. Community-based DR-TB care was acceptable to patients, family members and CTSs. To reduce family members' fears of TB infection, information and sensitisation within the family and constant follow-up appear crucial.