Attrition during pre-ART and ART time periods among adolescents enrolled in Integrated HIV Care Programme in Myanmar, 2005-2017.

Retaining adolescents (aged 10-19 years), living with HIV (ALHIV) on antiretroviral therapy (ART) is challenging. In Myanmar, 1269 ALHIV were under an Integrated HIV Care (IHC) Programme by June 2017 and their attrition (death and lost to follow-up) rates were not assessed before. We undertook a cohort study using routinely collected data of ALHIV enrolled into HIV care from July 2005 to June 2017 and assessed their attrition rates in June 2018 by time-to-event analysis. Of 1269 enrolled, 197(16%) and of 1054 initiated ART, 224 (21%) had an attrition defining event. The pre-ART and ART attrition rates were 21.8 (95% CI 19.0-25.1) and 6.4 (95% CI 5.6-7.3) per 100 person-years follow-up, respectively. The factors 'at enrolment' that were associated with higher hazards of attrition were: (1) WHO stage 3 or 4; (2) haemoglobin <10 gm/dl; (3) no documented CD4 cell counts, hepatitis B and C test results; and (4) injection drug use. Baseline hazards were high during the initial 1-2 years and after 5-6 years. The pre-ART and ART attrition rates in ALHIV were lower than those in Africa but higher than the children under IHC. This warrants designing and implementing additional care tailored to the needs of ALHIV under IHC.

High prevalence and incidence of tuberculosis in people living with the HIV in Mandalay, Myanmar, 2011-2017.

SETTING: Two human immunodeficiency virus (HIV) clinics providing antiretroviral therapy (ART), Mandalay, Myanmar. OBJECTIVE: To assess prevalent TB at enrolment, incident TB during follow-up and associated risk factors in adult people living with HIV (PLHIV) between 2011 and 2017. DESIGN: Cohort study using secondary data. RESULTS: Of 11 777 PLHIV, 2911 (25%) had prevalent TB at or within 6 weeks of enrolment. Independent risk factors for prevalent TB were being male or single/widowed, daily alcohol consumption, CD4 count 200 cells/µl and anaemia. During 6 years follow-up in 8866 PLHIV with no prevalent TB, the rate of new TB was 2.9 per 100 person-years (95%CI 2.6-3.1). Cumulative TB incidence was 9.6%, with 370 (72%) of 517 new TB cases occurring in the first year. Independent risk factors for incident TB were being male and anaemia. Incident TB was highest in the first year of ART, in PLHIV with CD4 counts 200 cells/µl and those not receiving isoniazid preventive therapy (IPT). Incident TB declined with time on ART and rising CD4 counts. CONCLUSION: Prevalent and incident TB were high in PLHIV in the Mandalay clinics. Consideration should be given to earlier TB diagnosis using more sensitive diagnostic tools, effective ART and scaling up IPT.

IPT in people living with HIV in Myanmar: a five-fold decrease in incidence of TB disease and all-cause mortality.

SETTING: Myanmar, a country with a high human immunodeficiency virus-tuberculosis (HIV-TB) burden, where the tuberculin skin test or interferon-gamma release assays are not routinely available for the diagnosis of latent tuberculous infection. OBJECTIVE: To assess the effect of isoniazid (INH) preventive therapy (IPT) on the risk of TB disease and mortality among people living with HIV (PLHIV). DESIGN: A retrospective cohort study of routinely collected data on PLHIV enrolled into care between 2009 and 2014. RESULTS: Of 7177 patients (median age 36 years, interquartile range 31-42; 53% male) included in the study, 1278 (18%) patients received IPT. Among patients receiving IPT, 855 (67%) completed 6 or 9 months of INH. Patients who completed IPT had a significantly lower risk of incident TB than those who never received IPT (adjusted hazard ratio [aHR] 0.21, 95%CI 0.12-0.34) after controlling for potential confounders. PLHIV who received IPT had a significantly lower risk of death than those who never received IPT (PLHIV who completed IPT, aHR 0.25, 95%CI 0.16-0.37; those who received but did not complete IPT, aHR 0.55, 95%CI 0.37-0.82). CONCLUSION: Among PLHIV in Myanmar, completing a course of IPT significantly reduced the risk of TB disease, and receiving IPT significantly reduced the risk of death.

Challenges and opportunities to prevent tuberculosis in people living with HIV in low-income countries.

People living with the human immunodeficiency virus (HIV) (PLHIV) are at high risk for tuberculosis (TB), and TB is a major cause of death in PLHIV. Preventing TB in PLHIV is therefore a key priority. Early initiation of antiretroviral therapy (ART) in asymptomatic PLHIV has a potent TB preventive effect, with even more benefits in those with advanced immunodeficiency. Applying the most recent World Health Organization recommendations that all PLHIV initiate ART regardless of clinical stage or CD4 cell count could provide a considerable TB preventive benefit at the population level in high HIV prevalence settings. Preventive therapy can treat tuberculous infection and prevent new infections during the course of treatment. It is now established that isoniazid preventive therapy (IPT) combined with ART among PLHIV significantly reduces the risk of TB and mortality compared with ART alone, and therefore has huge potential benefits for millions of sufferers. However, despite the evidence, this intervention is not implemented in most low-income countries with high burdens of HIV-associated TB. HIV and TB programme commitment, integration of services, appropriate screening procedures for excluding active TB, reliable drug supplies, patient-centred support to ensure adherence and well-organised follow-up and monitoring that includes drug safety are needed for successful implementation of IPT, and these features would also be needed for future shorter preventive regimens. A holistic approach to TB prevention in PLHIV should also include other important preventive measures, such as the detection and treatment of active TB, particularly among contacts of PLHIV, and control measures for tuberculous infection in health facilities, the homes of index patients and congregate settings.

FRAX® based intervention thresholds for management of osteoporosis in Singaporean women.

Potential FRAX®-based major osteoporotic fracture (MOF) and hip fracture (HF) intervention thresholds (ITs) for postmenopausal Singaporean women were explored. Age-dependent ethnic-specific and weighted mean ITs progressively increased with increasing age. Fixed ITs were derived via discriminatory value analysis. MOF and HF ITs with highest the Youden index were chosen as optimal. INTRODUCTION: We aimed to explore FRAX®-based intervention thresholds (ITs) to potentially guide osteoporosis treatment in Singapore, a multi-ethnic nation. METHOD: One thousand and one Singaporean postmenopausal community-dwelling women belonging to Chinese, Malay and Indian ethnicities underwent clinical risk factor (CRF) and BMD assessment. FRAX® major osteoporotic fracture (MOF) and hip fracture (HF) probabilities were calculated using ethnic-specific models. We employed the translational logic adopted by NOGG (UK), whereby osteoporosis treatment is recommended to any postmenopausal woman whose fracture probability based on other CRFs is similar to or exceeds that of an age-matched woman with a fracture. Using the same logic, ethnic-specific and mean weighted age-dependent ITs were computed. Employing these age-dependent ITs as a reference, the performance of fixed (age-independent) ITs were examined using ROC curves and discriminatory analysis, with the highest Youden index (YI) (sensitivity + specificity - 1) used to identify the optimal MOF and HF ITs. RESULTS: The mean age was 58.9 (6.9) years. Seven hundred and eighty-nine (79%) women were Chinese, 136 (13.5%) Indian and 76 (7.5%) Malay. Age-dependent MOF ITs ranged from 3.1 to 33%, 2.5 to 17% and 2.5 to 16% whilst HF ITs ranged from 0.7 to 17%, 0.4 to 6% and 0.4 to 6.3% in Chinese, Malay and Indian women, respectively, between the ages of 50 and 90 years. The weighted age-dependent MOF and HF ITs ranged from 2.9% and 0.6%, respectively, at the age of 50, to 28% and 14% at 90 years of age. Fixed MOF/HF ITs of 5.5%/1%, 2.5%/1% and 2.5%/0.25% were identified as the most optimal by the highest YI in Chinese, Malay and Indian women, respectively. Fixed MOFP and HF ITs of 4% and 1%, respectively, were found to be most optimal on the weighted means analysis. CONCLUSION: The ITs for osteoporosis treatment in Singapore show marked variations across ethnicities. Weighted mean thresholds may overcome the dilemma of intervening at different thresholds for different ethnicities. Choosing fixed ITs may have to involve trade-offs between sensitivity and specificity. FRAX®-based age-dependent or the fixed intervention thresholds suggested as an alternative to be considered for use in Singapore though further studies on the societal and health economic impacts of choosing these thresholds in Singapore are needed.

Timing of antiretroviral therapy and TB treatment outcomes in patients with TB-HIV in Myanmar.

SETTING: Integrated HIV Care programme, Mandalay, Myanmar. OBJECTIVES: To determine time to starting antiretroviral treatment (ART) in relation to anti-tuberculosis treatment (ATT) and its association with TB treatment outcomes in patients co-infected with tuberculosis (TB) and the human immunodeficiency virus (HIV) enrolled from 2011 to 2014. DESIGN: Retrospective cohort study. RESULTS: Of 1708 TB-HIV patients, 1565 (92%) started ATT first and 143 (8%) started ART first. Treatment outcomes were missing for 226 patients and were thus not included. In those starting ATT first, the median time to starting ART was 8.6 weeks. ART was initiated after 8 weeks in 830 (53%) patients. Unsuccessful outcome was found in 7%, with anaemia being an independent predictor. In patients starting ART first, the median time to starting ATT was 21.6 weeks. ATT was initiated within 3 months in 56 (39%) patients. Unsuccessful outcome was found in 12%, and in 20% of those starting ATT within 3 months. Patients with CD4 count <100/mm(3) had a four times higher risk of an unsuccessful outcome. CONCLUSIONS: Timing of ART in relation to ATT was not an independent risk factor for unsuccessful outcome. Extensive screening for TB with rapid and sensitive diagnostic tests in HIV-infected persons and close monitoring of anaemia and immunosuppression are recommended to further improve TB treatment outcomes among patients with TB-HIV.

Contexte : Programme intégré de prise en charge du virus de l'immunodéficience humaine (VIH), Mandalay, Myanmar.Objectifs : Chez les patients atteints de tuberculose (TB) et VIH enrôlés entre 2011 et 2014, déterminer la date du début du traitement antirétroviral (TAR) en relation avec le traitement antituberculeux (ATT) et son association avec le résultat d'ATT.Schéma : Etude rétrospective de cohorte.Résultats : Sur 1708 patients TB-VIH, 1565 (92%) ont débuté l'ATT en premier et 143 (8%) ont commencé le TAR en premier. Le résultat du traitement a été manquant pour 226 patients qui n'ont pas été inclus. Chez les patients ayant débuté l'ATT en premier, le délai médian de mise en route du TAR a été de 8,6 semaines. L'initiation du TAR a été retardée d'un délai médian de 8 semaines chez 830 (53%) patients. Parmi ces patients, 7% ont eu un résultat médiocre, avec une anémie qui a constitué un facteur de risque indépendant. Chez les patients ayant débuté le TAR en premier, le délai médian de mise en route de l'ATT a été de 21,6 semaines. L'ATT a été initié au cours des 3 mois chez 56 (39%) patients. Le traitement a échoué chez 12% des patients et chez 20% de ceux qui ont débuté l'ATT dans les 3 mois. Les patients ayant des CD4 <100/mm3 ont eu un risque quatre fois plus élevé d'échec.Conclusions: La chronologie du TAR en rapport avec l'ATT n'a pas été un facteur de risque indépendant d'échec du traitement. Un dépistage extensif de la TB avec des tests de diagnostic rapides et sensibles chez les personnes infectées par le VIH et un suivi étroit de l'anémie et de l'immunosuppression sont recommandés afin d'améliorer encore le résultat du traitement de TB parmi les patients TB-VIH.

Marco de referencia: El programa integrado de atención de la infección por el virus de la inmunodeficiencia humana (VIH) en Mandalay, en Birmania.Objetivos: Determinar el lapso entre el comienzo del tratamiento antirretrovírico (ART) y el inicio del tratamiento antituberculoso (ATT) en los pacientes coinfectados registrados del 2011 al 2014 y su asociación con el desenlace del ATT.Método: Fue este un estudio retrospectivo de cohortes.Resultados: De los 1708 pacientes coinfectados por el VIH y la tuberculosis (TB), 1565 iniciaron primero el ATT (92%) y 143 comenzaron en primer lugar el ART (8%). Se excluyeron 226 casos que carecían de registro del desenlace terapéutico. En los pacientes que iniciaron en primer lugar el ATT, la mediana del lapso hasta el comienzo del ART fue 8,6 semanas; este tratamiento se inició después de 8 semanas en 830 pacientes (53%). Se observó un desenlace terapéutico desfavorable en 7% de estos pacientes; la principal variable independiente asociada fue la presencia de anemia. Cuando el ART se inició en primer lugar, la mediana hasta el comienzo del ATT fue 21,6 semanas; este tratamiento se inició durante los 3 primeros meses en 56 pacientes (39%). Se observó un desenlace terapéutico desfavorable en 12% de estos pacientes y en 20% de los pacientes que iniciaron el ART en los primeros 3 meses. El riesgo de un desenlace desfavorable fue cuatro veces más alto en los pacientes con un recuento de linfocitos CD4 <100 células/mm3.Conclusión: La coordinación cronológica del ART y el ATT no representó un factor independiente de riesgo de obtener un desenlace desfavorable. Se recomienda la detección sistemática de la TB en los pacientes infectados por el VIH mediante pruebas diagnósticas rápidas y sensibles y una supervisión cuidadosa de la anemia y la inmunodepresión, con el objeto de obtener aun mejores desenlaces del ATT en los pacientes aquejados de coinfección TB-VIH.