Prevention of mother-to-child transmission of hepatitis B virus in antenatal care and maternity services, Mozambique.

OBJECTIVE: To pilot an intervention on the prevention of mother-to-child transmission (PMTCT) of hepatitis B virus (HBV) in an antenatal care and maternity unit in Maputo, Mozambique, during 2017-2019. METHODS: We included HBV in the existing screening programme (for human immunodeficiency virus (HIV) and syphilis) for pregnant women at their first consultation, and followed mother-child dyads until 9 months after delivery. We referred women who tested positive for hepatitis B surface antigen (HBsAg) for further tests, including hepatitis B e antigen (HBeAg) and HBV viral load. According to the results, we proposed tenofovir for their own health or for PMTCT. We administered birth-dose HBV vaccine and assessed infant HBV status at 9 months. FINDINGS: Of 6775 screened women, 270 (4.0%) were HBsAg positive; in those for whom data were available, 24/265 (9.1%) were HBeAg positive and 14/267 (5.2%) had a viral load of > 200 000 IU/mL. Ninety-eight (36.3%) HBsAg-positive women were HIV coinfected, 97 of whom were receiving antiretroviral treatment with tenofovir. Among HIV-negative women, four had an indication for tenofovir treatment and four for tenofovir PMTCT. Of 217 exposed liveborn babies, 181 (83.4%) received birth-dose HBV vaccine, 160 (88.4%) of these < 24 hours after birth. At the 9-month follow-up, only one out of the 134 tested infants was HBV positive. CONCLUSION: Our nurse-led intervention highlights the feasibility of integrating PMTCT of HBV into existing antenatal care departments, essential for the implementation of the triple elimination initiative. Universal birth-dose vaccination is key to achieving HBV elimination.

Outcomes of AIDS-associated Kaposi sarcoma in Mozambique after treatment with pegylated liposomal doxorubicin.

BACKGROUND: Kaposi's sarcoma (KS) is a common HIV-associated malignancy frequently associated with poor outcomes. It is the most frequently diagnosed cancer in major cities of Mozambique. Antiretroviral therapy is the cornerstone of KS treatment, but many patients require cytotoxic chemotherapy. The traditional regimen in Mozambique includes conventional doxorubicin, bleomycin and vincristine, which is poorly tolerated. In 2016, pegylated liposomal doxorubicin was introduced at a specialized outpatient center in Maputo, Mozambique. METHODS: We performed a prospective, single-arm, open-label observational study to demonstrate the feasibility, safety, and outcomes of treatment with pegylated liposomal doxorubicin (PLD) in patients with AIDS-associated Kaposi sarcoma (KS) in a low-resource setting. Chemotherapy-naïve adults with AIDS-associated KS (T1 or T0 not responding to 6 months of antiretroviral therapy) were eligible if they were willing to follow up for 2 years. Patients with Karnofsky scores < 50 or contraindications to PLD were excluded. One hundred eighty-three patients were screened and 116 participants were enrolled. Patients received PLD on three-week cycles until meeting clinical stopping criteria. Follow-up visits monitored HIV status, KS disease, side effects of chemotherapy, mental health (PHQ-9) and quality of life (SF-12). Primary outcome measures included vital status and disease status at 6, 12, and 24 months after enrollment. RESULTS: At 24 months, 23 participants (20%) had died and 15 (13%) were lost to follow-up. Baseline CD4 < 100 was associated with death (HR 2.7, 95%CI [1.2-6.2], p = 0.016), as was T1S1 disease compared to T1S0 disease (HR 2.7, 95%CI [1.1-6.4], p = 0.023). Ninety-two participants achieved complete or partial remission at any point (overall response rate 80%), including 15 (13%) who achieved complete remission. PLD was well-tolerated, and the most common AEs were neutropenia and anemia. Quality of life improved rapidly after beginning PLD. DISCUSSION: PLD was safe, well-tolerated and effective as first-line treatment of KS in Mozambique. High mortality was likely due to advanced immunosuppression at presentation, underscoring the importance of earlier screening and referral for KS.

'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.

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.

"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.

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.

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.

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.

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.

Treatment Outcomes of Patients Switching From an Injectable Drug to Bedaquiline During Short Standardized Treatment for Multidrug-resistant Tuberculosis in Mozambique.

Bedaquiline was recommended by the World Health Organization as the preferred option in treatment of multidrug-resistant tuberculosis (MDR-TB) with long regimens. However, no recommendation was given for the short MDR-TB regimen. Data from our small cohort of patients who switched from injectable drug to bedaquiline suggest that a bedaquiline-based short regimen is effective and safe.

"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.

"Is it making any difference?" A qualitative study examining the treatment-taking experiences of asymptomatic people living with HIV in the context of Treat-all in Eswatini.

INTRODUCTION: Treat-all is being implemented in several African settings, in accordance with 2015 World Health Organisation guidelines. The factors known to undermine adherence to antiretroviral therapy (ART) may change in the context of Treat-all, where people living with HIV (PLHIV) increasingly initiate ART at earlier, asymptomatic stages of disease, soon after diagnosis. This paper aimed to examine the asymptomatic PLHIV's experiences engaging with early ART initiation under the Treat-all policy, including how they navigate treatment-taking over the longer term. METHODS: A longitudinal qualitative study was conducted within a Médecins Sans Frontières/Ministry of Health Treat-all pilot in Shiselweni, southern Eswatini. The Treat-all pilot began in October 2014, adopted into national policy in October 2016. Participants were recruited purposively to include newly diagnosed, clinically asymptomatic PLHIV with a range of treatment-taking experiences, and healthcare workers (HCW) with various roles. This analysis drew upon a sub-sample of 17 PLHIV who had been on ART for at least 12 months, with mean 20 months on ART at first interview, and who undertook three interviews each. Additionally, 20 HCWs were interviewed once. Interviews were conducted from August 2016 to September 2017. Data were analysed thematically using coding, drawing upon principles of grounded theory, and aided by Nvivo 11. RESULTS: It was important for PLHIV to perceive the need for treatment, and to have evidence of its effectiveness to motivate their treatment-taking, thereby supporting engagement with care. For some, coming to terms with a HIV diagnosis or re-interpreting past illnesses as signs of HIV could point to the need for ART to prevent health deterioration and prolong life. However, others doubted the accuracy of an HIV diagnosis and the need for treatment in the absence of symptoms or signs of ill health, with some experimenting with treatment-taking as a means of seeking evidence of their need for treatment and its effect. Viral load monitoring appeared important in offering a view of the effect of treatment on the level of the virus, thereby motivating continued treatment-taking. CONCLUSIONS: These findings highlight the importance of PLHIV perceiving need for treatment and having evidence of the difference that ART is making to them for motivating treatment-taking. Patient support should be adapted to address these concerns, and viral load monitoring made routinely available within Treat-all care, with communication of suppressed results emphasized to patients.

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-associated Kaposi's sarcoma in Maputo, Mozambique: outcomes in a specialized treatment center, 2010-2015.

BACKGROUND: Kaposi's sarcoma (KS) is a common HIV-associated malignancy associated with disability, pain and poor outcomes. The cornerstone of its treatment is antiretroviral therapy, but advanced disease necessitates the addition of chemotherapy. In high-income settings, this often consists of liposomal anthracyclines, but in Mozambique, the first line includes conventional doxorubicin, bleomycin and vincristine, which is poorly-tolerated. Médecins Sans Frontières supports the Ministry of Health (MOH) in a specialized HIV and KS treatment center at the Centro de Referencia de Alto Maé in Maputo. METHODS: We performed a retrospective analysis of data collected on patients enrolled at the CRAM between 2010 and 2015, extracting routinely-collected clinical information from patient care databases. KS treatment followed national guidelines, and KS staging followed AIDS Clinical Trials Group and MOH criteria. Baseline description of the cohort and patient outcomes was performed. Risk factors for negative outcomes (death or loss to follow-up) were explored using Cox regression. RESULTS: Between 2010 and 2015, 1573 patients were enrolled, and 1210 began chemotherapy. A majority were young adult males. At enrollment, CD4 was < 200 cells/µl in 45% of patients. Among patients receiving chemotherapy, 78% received combination doxorubicin-bleomycin-vincristine. Among patients receiving chemotherapy, 43% were lost to follow-up and 8% were known to have died. In multivariate regression, the only risk factors identified with poor outcomes were CD4 < 100 cells/µl at enrollment (Risk ratio 1.5, 95%CI 1.1-2.1, p = 0.02 and having S1 disease (RR 1.7, 95%CI 1.2-2.3, p = 0.001). DISCUSSION: We describe a large cohort of patients receiving care for HIV-associated KS in a specialized clinic in an urban setting. Outcomes were nonetheless unsatisfactory. Efforts should be made to decrease late referrals and entry into care and to increase access to more effective and better-tolerated treatments like liposomal doxorubicin.

Adherence, tolerability, and outcome after 36 months of isoniazid-preventive therapy in 2 rural clinics of Swaziland: A prospective observational feasibility study.

Although efficacy of 36 months isoniazid preventive therapy (IPT) among HIV-positive individuals has been proven in trial settings, outcome, tolerance, and adherence have rarely been evaluated in real-life settings.This is a prospective observational cohort study conducted in 2 primary care rural clinics in Swaziland.After negative tuberculosis symptom screening, patients either with the positive tuberculin skin test (TST) or after tuberculosis treatment were initiated on IPT for 144 weeks. In addition to routine clinic visits, adherence was assessed every semester.Of 288 eligible patients, 2 patients never started IPT (1 refusal, 1 contraindication), and 253 (87.8%), 234 (81.3%), and 228 (79.2%) were still on IPT after 48, 96, and 144 weeks, respectively (chiP = .01). Of 41 patients who interrupted IPT before 144 weeks, 21 defaulted (of which 17 also defaulted HIV care); 16 stopped because of adverse drug reactions; 2 were discontinued by clinicians' mistake and 1 because of TB symptoms. Five patients (1.7%) died of causes not related to IPT, 5 (1.7%) developed TB of which 2 were isoniazid-resistant, and 9 (3.1%) were transferred to another clinic. As an indicator of adherence, isoniazid could be detected in the urine during 86.3% (302/350) and 73.6% (248/337) of patient visits in the 2 clinics, respectively (chiP < .001).The routine implementation of IPT 36 months was feasible and good patient outcomes were achieved, with low TB incidence, good tolerance, and sustained adherence.

"Life is so easy on ART, once you accept it": Acceptance, denial and linkage to HIV care in Shiselweni, Swaziland.

BACKGROUND: Timely uptake of antiretroviral therapy, adherence and retention in care for people living with HIV (PLHIV) can improve health outcomes and reduce transmission. Médecins Sans Frontières and the Swaziland Ministry of Health provide community-based HIV testing services (HTS) in Shiselweni, Swaziland, with high HTS coverage but sub-optimal linkage to HIV care. This qualitative study examined factors influencing linkage to HIV care for PLHIV diagnosed by community-based HTS. METHODS: Participants were sampled purposively, exploring linkage experiences among both genders and different age groups. Interviews were conducted with 28 PLHIV (linked and not linked) and 11 health practitioners. Data were thematically analysed to identify emergent patterns and categories using NVivo 10. Principles of grounded theory were applied, including constant comparison of findings, raising codes to a conceptual level, and inductively generating theory from participant accounts. RESULTS: The process of HIV status acceptance or denial influenced the accounts of patients' health seeking and linkage to care. This process was non-linear and varied temporally, with some experiencing non-acceptance for an extended period of time. Non-acceptance was linked to perceptions of HIV risk, with those not identifying as at risk less likely to expect and therefore be prepared for a positive result. Status disclosure was seen to support linkage, reportedly occurring after the acceptance of HIV status. HIV status acceptance motivated health seeking and tended to be accompanied by a perceived need for, and positive value placed on, HIV health care. CONCLUSIONS: The manner in which PLHIV process a positive result can influence their engagement with HIV treatment and care. Thus, there is a need for individually tailored approaches to HTS, including the potential for counselling over multiple sessions if required, supporting status acceptance, and disclosure. This is particularly relevant considering 90-90-90 targets and the need to better support PLHIV to engage with HIV treatment and care following diagnosis.

Differential Diagnosis of Skin Ulcers in a Mycobacterium ulcerans Endemic Area: Data from a Prospective Study in Cameroon.

BACKGROUND: Clinical diagnosis of Buruli ulcer (BU) due to Mycobacterium ulcerans can be challenging. We aimed to specify the differential diagnosis of skin lesions in a BU endemic area. METHOD: We conducted a prospective diagnostic study in Akonolinga, Cameroon. Patients presenting with a skin ulcer suspect of BU were included. M. ulcerans was detected using swabs for Ziehl-Neelsen staining, PCR and culture. Skin punch biopsies were taken and reviewed by two histopathologists. Photographs of the lesions were taken and independently reviewed by two dermatologists. Final diagnosis was based on consensus, combining the results of laboratory tests and expert opinion. RESULTS/ DISCUSSION: Between October 2011 and December 2013, 327 patients with ulcerative lesions were included. Median age was 37 years (0 to 87), 65% were males, and 19% HIV-positive. BU was considered the final diagnosis for 27% of the lesions, 85% of which had at least one positive laboratory test. Differential diagnoses were vascular lesions (22%), bacterial infections (21%), post-traumatic (8%), fistulated osteomyelitis (6%), neoplasia (5%), inflammatory lesions (3%), hemopathies and other systemic diseases (2%) and others (2%). The proportion of BU was similar between HIV-positive and HIV-negative patients (27.0% vs. 26.5%; p = 0.940). Half of children below 15 years of age were diagnosed with BU, compared to 26.8% and 13.9% among individuals 15 to 44 years of age and above, respectively (chi2 p<0.001). Children had more superficial bacterial infections (24.3%) and osteomyelitis (11.4%). CONCLUSION: We described differential diagnosis of skin lesions in a BU endemic area, stratifying results by age and HIV-status.

The "Buruli Score": Development of a Multivariable Prediction Model for Diagnosis of Mycobacterium ulcerans Infection in Individuals with Ulcerative Skin Lesions, Akonolinga, Cameroon.

BACKGROUND: Access to laboratory diagnosis can be a challenge for individuals suspected of Buruli Ulcer (BU). Our objective was to develop a clinical score to assist clinicians working in resource-limited settings for BU diagnosis. METHODODOLOGY/PRINCIPAL FINDINGS: Between 2011 and 2013, individuals presenting at Akonolinga District Hospital, Cameroon, were enrolled consecutively. Clinical data were collected prospectively. Based on a latent class model using laboratory test results (ZN, PCR, culture), patients were categorized into high, or low BU likelihood. Variables associated with a high BU likelihood in a multivariate logistic model were included in the Buruli score. Score cut-offs were chosen based on calculated predictive values. Of 325 patients with an ulcerative lesion, 51 (15.7%) had a high BU likelihood. The variables identified for the Buruli score were: characteristic smell (+3 points), yellow color (+2), female gender (+2), undermining (+1), green color (+1), lesion hyposensitivity (+1), pain at rest (-1), size >5cm (-1), locoregional adenopathy (-2), age above 20 up to 40 years (-3), or above 40 (-5). This score had AUC of 0.86 (95%CI 0.82-0.89), indicating good discrimination between infected and non-infected individuals. The cut-off to reasonably exclude BU was set at scores <0 (NPV 96.5%; 95%CI 93.0-98.6). The treatment threshold was set at a cut-off ≥4 (PPV 69.0%; 95%CI 49.2-84.7). Patients with intermediate BU probability needed to be tested by PCR. CONCLUSIONS/SIGNIFICANCE: We developed a decisional algorithm based on a clinical score assessing BU probability. The Buruli score still requires further validation before it can be recommended for wide use.