Estimating the changing burden of disease attributable to alcohol use in South Africa for 2000, 2006 and 2012.

BACKGROUND: Alcohol use was one of the leading contributors to South Africa (SA)'s disease burden in 2000, accounting for 7% of deaths and disability-adjusted life years (DALYs) in the first South African Comparative Risk Assessment Study (SACRA1). Since then, patterns of alcohol use have changed, as has the epidemiological evidence pertaining to the role of alcohol as a risk factor for infectious diseases, most notably HIV/AIDS and tuberculosis (TB). OBJECTIVES: To estimate the burden of disease attributable to alcohol use by sex and age group in SA in 2000, 2006 and 2012. METHODS: The analysis follows the World Health Organization (WHO)'s comparative risk assessment methodology. Population attributable fractions (PAFs) were calculated from modelled exposure estimated from a systematic assessment and synthesis of 17 nationally representative surveys and relative risks based on the global review by the International Model of Alcohol Harms and Policies. PAFs were applied to the burden of disease estimates from the revised second South African National Burden of Disease Study (SANBD2) to calculate the alcohol-attributable burden for deaths and DALYs for 2000, 2006 and 2012. We quantified the uncertainty by observing the posterior distribution of the estimated prevalence of drinkers and mean use among adult drinkers (≥15 years old) in a Bayesian model. We assumed no uncertainty in the outcome measures. RESULTS: The alcohol-attributable disease burden decreased from 2000 to 2012 after peaking in 2006, owing to shifts in the disease burden, particularly infectious disease and injuries, and changes in drinking patterns. In 2012, alcohol-attributable harm accounted for an estimated 7.1% (95% uncertainty interval (UI) 6.6 - 7.6) of all deaths and 5.6% (95% UI 5.3 - 6.0) of all DALYs. Attributable deaths were split three ways fairly evenly across major disease categories: infectious diseases (36.4%), non-communicable diseases (32.4%) and injuries (31.2%). Top rankings for alcohol-attributable DALYs for specific causes were TB (22.6%), HIV/AIDS (16.0%), road traffic injuries (15.9%), interpersonal violence (12.8%), cardiovascular disease (11.1%), cancer and cirrhosis (both 4%). Alcohol remains an important contributor to the overall disease burden, ranking fifth in terms of deaths and DALYs. CONCLUSION: Although reducing overall alcohol use will decrease the burden of disease at a societal level, alcohol harm reduction strategies in SA should prioritise evidence-based interventions to change drinking patterns. Frequent heavy episodic (i.e. binge) drinking accounts for the unusually large share of injuries and infectious diseases in the alcohol-attributable burden of disease profile. Interventions should focus on the distal causes of heavy drinking by focusing on strategies recommended by the WHO's SAFER initiative.

Bidirectional Screening for Tuberculosis, Diabetes Mellitus and other Comorbid Conditions in a Resource Constrained Setting: A Pilot Study in Lagos, Nigeria.

BACKGROUND: The epidemiological transition in developing countries is increasing the burden of non-communicable diseases such as diabetes. We aimed to determine the outcomes of bidirectional screening for TB and diabetes (DM) in resource constrained communities, Lagos, Nigeria. METHODS: A quasi-experimental study without control was conducted from March 1-31st, 2017 as part of the series of activities to mark the World TB Day. Community screening took place at multiple locations in multiple days. Participants were registered and screened for Tuberculosis (TB), Diabetes Mellitus (DM) and other comorbid conditions (viral hepatitis and HIV) during open medical outreaches carried out across six resource constrained communities in Lagos, Nigeria. Relevant data were collected and analyzed. Yield of TB among DM patients and vice-versa was analyzed. Associations between MTB detection among those with DM (versus those with no DM) and among those who were HIV positive (compared with those HIV negative) were determined at p ≤0.05. RESULTS: Some (24.7%) of the participants were between the ages 25-34 years. Majority were males (65.8%), Christians (55.7%), Married (73.7%), and 37.8% had secondary education. Many (41.0%) of the participants had 3-4 persons per household, and 1-2 persons per room (44.5%). 109(26%) of individuals screened were presumptive and 18(16.5%) of the 109 presumptive were MTB detected. Also, hyperglycemia (Fasting Blood Sugar, FBS >126 mg/dl or random blood sugar, RBS level >200mg/dl) was diagnosed in 31(5%) of the 620 patients screened. Overall, 1(3.2%) of the 32 patients with DM were diagnosed with TB while 1(5.5%) of the 18 patients with MTB detected were diagnosed with DM and no significant difference in TB or DM detection in either of the groups (p=1.000). The overall yield (in all participants) of HIV in this intervention was 1.27%, DM was 5.0% and HBsAg was 2.1%. CONCLUSION: This intervention showed that approximately one out of every twenty newly diagnosed TB patients in resource constrained communities had DM as a comorbid condition. This finding underlines the need to strengthen bidirectional screening for TB-DM in order to achieve additional gains in tuberculosis case findings in resource constrained and high TB burden countries.

CONTEXTE: La transition épidémiologique dans les pays en développement augmente le fardeau des maladies non transmissibles telles que le diabète. Nous avons cherché à déterminer les résultats du dépistage bidirectionnel de la tuberculose et du diabète (DM) dans les communautés à ressources limitées de Lagos, au Nigeria. MÉTHODES: Une étude quasi-expérimentale sans contrôle a été menée du 1er au 31 mars 2017 dans le cadre de la série d'activités marquant la Journée mondiale de la tuberculose. Le dépistage communautaire a eu lieu à plusieurs endroits en plusieurs jours. Les participants ont été enregistrés et dépistés pour la tuberculose (TB), le diabète sucré (DM) et d'autres conditions de comorbidité (hépatite virale et VIH) lors d'actions de proximité médicales ouvertes menées dans six communautés à ressources limitées de Lagos, au Nigeria. Les données pertinentes ont été collectées et analysées. Le rendement de la TB parmi les patients atteints de DM et vice-versa a été analysé. Les associations entre la détection de la tuberculose chez les personnes atteintes de DM (par rapport à celles qui n'en sont pas atteintes) et chez les personnes séropositives (par rapport aux personnes séronégatives) ont été déterminées à une p≤0.05. RÉSULTATS: Certains (24,7 %) des participants étaient âgés de 25 à 34 ans. La majorité était des hommes (65,8 %), chrétiens (55,7 %), mariés (73,7 %) et 37,8 % avaient une éducation secondaire. Beaucoup (41,0%) des participants avaient 3-4 personnes par foyer, et 1-2 personnes par chambre (44,5%). 109(26%) des individus dépistés étaient présomptifs et 18(16,5%) des 109 présomptifs ont été détectés par MTB. De plus, une hyperglycémie (glycémie à jeun, FBS >126 mg/dl ou glycémie aléatoire, RBS >200mg/dl) a été diagnostiquée chez 31(5%) des 620 patients dépistés. Dans l'ensemble, 1(3,2 %) des 32 patients atteints de DM ont reçu un diagnostic de tuberculose, tandis que 1(5,5 %) des 18 patients chez qui le bacille du charbon a été détecté ont reçu un diagnostic de DM. Il n'y a pas de différence significative dans la détection de la tuberculose ou du DM dans l'un ou l'autre des groupes (p=1,000). Le rendement global (chez tous les participants) du VIH dans cette intervention était de 1,27%, le DM était de 5,0% et l'HBsAg de 2,1%. CONCLUSION: Cette intervention a montré qu'environ un patient tuberculeux sur vingt nouvellement diagnostiqué dans des communautés aux ressources limitées avait un diabète comme comorbidité. Ce résultat souligne la nécessité de renforcer le dépistage bidirectionnel de la tuberculose et du diabète afin d'obtenir des gains supplémentaires dans la découverte de cas de tuberculose dans les pays à ressources limitées et à forte charge de tuberculose. Mots clés: Comorbidités, Diabète sucré, Dépistage bidirectionnel, Tuberculose.

Landscape of TB Infection and Prevention among People Living with HIV.

Tuberculosis (TB) is one of the leading causes of mortality in people living with HIV (PLHIV) and contributes to up to a third of deaths in this population. The World Health Organization guidelines aim to target early detection and treatment of TB among PLHIV, particularly in high-prevalence and low-resource settings. Prevention plays a key role in the fight against TB among PLHIV. This review explores TB screening tools available for PLHIV, including symptom-based screening, chest radiography, tuberculin skin tests, interferon gamma release assays, and serum biomarkers. We then review TB Preventive Treatment (TPT), shown to reduce the progression to active TB and mortality among PLHIV, and available TPT regimens. Last, we highlight policy-practice gaps and barriers to implementation as well as ongoing research needs to lower the burden of TB and HIV coinfection through preventive activities, innovative diagnostic tests, and cost-effectiveness studies.

Outcomes of a model integrating tuberculosis testing into COVID-19 services in South Africa.

The coronavirus disease 2019 (COVID-19) pandemic led to a reordering of healthcare priorities. Health resources were turned to the screening and diagnosis of COVID-19, leading to a reduction in tuberculosis (TB) testing and treatment initiation. An innovative model that integrated TB and COVID-19 services was adopted at primary care facilities in Johannesburg Health District, Gauteng. This short report illustrates results from this model's implementation in two facilities. Patients were screened for COVID-19 at a single point of entry and separated according to screening result. Self-reported human immunodeficiency virus (HIV) status, symptom, and symptom duration were then used to determine TB risk amongst those screening positive for COVID-19. Data from clinical records were extracted. Approximately 9% of patients with a positive symptom screen (n = 76) were sent for a TB test and 84% were sent for a COVID-19 test. Amongst those sent for a TB test, 8% (n = 6) had TB detected, and amongst those sent for a COVID-19 test, 18% (n = 128) were positive. Amongst those with COVID-19-related symptoms, 15% (n = 130) presented with a cough or fever and were known HIV positive and 121 (93%) of these were sent for a COVID-19 test and 31 (24%) were sent for a TB test. Given the HIV prevalence and symptoms in our study, our results show lower-than-expected TB tests conducted.Contribution: Our study documents the outcomes of an innovative way to combine operational workflows for TB and COVID-19. This provides a starting point for countries seeking to integrate TB and COVID-19 screening and testing.

Lessons from Nigeria's Adaptation of Global Health Initiatives during the COVID-19 Pandemic.

Nigeria receives funds from several global health initiatives that are aimed at addressing elevated risks and overall burden of infectious disease outbreaks. These funds include the Global Fund to Fight AIDS, Tuberculosis and Malaria; US President's Emergency Plan for AIDS Relief; US President's Malaria Initiative; and Global Polio Eradication Initiative. These initiatives have contributed to a substantial reduction in illness and death from HIV, tuberculosis, malaria, and polio. However, Nigeria has experienced mixed success with leveraging the capacities built through these donor-funded vertical programs to respond to new health threats. This report describes experiences using resources from vertical disease programs by the Nigeria Centre for Disease Control in response to the 2014-2016 Ebola outbreak in West Africa and the COVID-19 pandemic. Integrating resources from different disease programs with government-led systems and institutions will improve responses to endemic outbreaks and preparedness for future pandemics in Nigeria.

Practices and attitudes towards tuberculosis and latent tuberculosis infection screening in people living with HIV/AIDS among HIV physicians in Japan.

BACKGROUND: Tuberculosis (TB) continues to be the leading cause of death for people living with HIV/AIDS (PLHIV), and HIV is the strongest known risk factor for progression to active TB disease for persons with latent TB infection (LTBI). Screening for active TB and LTBI, and TB preventive therapy (TPT) is recommended, however, clinical practices regarding LTBI screening for HIV positive population have not been uniform, resulting in low rates of LTBI screening and TPT uptake, in both low and high TB-burden countries. We sought to explore the practices and attitudes towards TB and LTBI screening in PLHIV among HIV physicians in Japan. METHODS: We conducted a cross-sectional survey whereby an on-line questionnaire was administered to physicians who are currently, or have the experience of, providing care and treatment for PLHIV in Japan. RESULTS: The questionnaire was sent to a total of 83 physicians, of which 59 responded (response rate; 71.1%). 52.5% (31/59) conducted routine screening and 44.0% (26/59) conducted selectively screening for active TB among HIV/AIDS patients. As for LTBI, 54.2% (32/59) conducted routine screening and 35.6% (21/59) conducted selective screening for LTBI among PLHIV. "T-SPOT only" was the most frequently used method of screening (n = 33), followed by "QFT only" (n = 11). Criteria for LTBI screening included TB burden in the country of birth of the patient, previous contact with a TB patient, and CD4+ cell count. 83.1% (49/59) either "always" or "selectively" offered TPT to PLHIV diagnosed with LTBI, and among the 49 respondents who did provide TPT, 77.6% (38/49) chose 9-months isoniazid as their first choice. None chose regimen including rifampicin. CONCLUSIONS: Our study revealed that practices regarding TB and LTBI screening and treatment for PLHIV among HIV physicians were mixed and not necessarily in accordance with the various published guidelines. Building and disseminating scientific evidence that takes into consideration the local epidemiology of TB and HIV in Japan is urgently needed to assist physicians make decisions.

Uso de Dolutegravir a doble dosis en el paciente coinfectado por TB/VIH / Use of double dose Dolutegravir in coinfected patients by TB/HIV

INTRODUCCIÓN La tuberculosis (TB) sigue siendo la principal causa de muerte de personas infectadas por el VIH en todo el mundo. VIH. La infección aumenta el riesgo de progresión a la enfermedad de TB activa, incluso entre los que están bien controlados con la terapia antirretroviral (TAR) contra el VIH. No obstante, el TAR reduce la morbimortalidad y está indicado para todos los pacientes coinfectados por TB/VIH. Dolutegravir (DTG) es un inhibidor de transferencia de cadena de integrasa de segunda generación recientemente recomendado por la Organización Mundial de la Salud (OMS) como régimen preferido de primera línea para el tratamiento de pacientes infectados por el VIH nuevos y experimentados con TAR (1). Sin embargo, los primeros estudios indican que las interacciones farmacológicas entre DTG y Rifampicina pueden resultar en una disminución concentraciones de DTG, lo que plantea preocupaciones sobre la seguridad y el desarrollo potencial de resistencia del VIH en el contexto de niveles subterapéuticos de DTG. OBJETIVO: El objetivo de esta revisión es identificar y sistematizar la evidencia disponible sobre la eficacia y seguridad de la doble dosis de dolutegravir (100 mg) en comparación con la dosis habitual (50 mg) en pacientes con infección por VIH y tuberculosis que se encuentran recibiendo el esquema estándar de tratamiento para tuberculosis. METODOLOGÍA: Se realizó una revisión rápida basada en la comparación con el esquema estándar. Para ello, se elaboró una búsqueda sistemática en las bases de datos MEDLINE/PubMed, LILACS (BVS), la Biblioteca Cochrane, además de una búsqueda manual. Luego de eliminar duplicados, fueron seleccionaron los artículos que cumplieran con la pregunta de investigación. RESULTADOS: La búsqueda sistemática identificó 139 registros, de ellos 120 fueron tamizados por títulos y resúmenes, solo dos artículos pasaron a lectura de texto completo. Finalmente, no se incluyó ningún estudio con evidencia tanto para el desenlace de eficacia y seguridad. CONCLUSIONES: No se identificaron ensayos clínicos para evaluar la eficacia y seguridad de la dosis de 100mg de dolutegravir vs la dosis de 50 mg en pacientes coinfección por TB/VIH. Actualmente, se encuentra em desarrollo el ensayo clínico fase 2 RADIANT-TB que compara la doble dosis dolutegravir (100 mg) vs la dosis habitual de 50 mg en pacientes con coinfección por TB/VIH (ID: NCT03851588).

I Jornadas de Actualización en Enfermería, VIH, ITS y Sexualidades: Desafíos y Herramientas para Fortalecer Nuestras Prácticas desde una Perspectiva de Géneros y Derechos Humanos

Jornada – taller de modalidad virtual sincrónica realizada el 16 de noviembre de 2022, coordinada por la Dirección de Prevención de VIH, ITS y Hepatitis Virales del Ministerio de Salud de la Provincia de Buenos Aires. La capacitación tuvo como destinatarios a enfermeros y enfermeras del sistema de salud pública provincial y surge en el marco de la nueva Ley de Respuesta Integral al VIH, Hepatitis Virales, ITS y Tuberculosis (Ley 27.675), sancionada por el Congreso Nacional en el año 2022; ante la urgencia de repensar las prácticas y los discursos de los profesionales de la salud en las instituciones. También se destaca la importancia de establecer un diálogo entre sistema de salud y la universidad, con el fin de producir nuevos saberes. Dividida en dos partes, la jornada inicia con la exposición de Christian Torno (Trabajador Social - UNLP) miembro de la Dirección de Prevención de VIH, ITS y Hepatitis Virales. En este segmento se abordan, en primer lugar: Objetivos del encuentro, a saber: 1) Contribuir a la actualización de saberes vinculados a la atención de personas que viven con VIH y Sífilis desde una perspectiva de Derechos Humanos. 2) Abordar aspectos biomédicos, transmisión, prevención, diagnóstico, clínica y tratamiento del VIH y las ITS. 3) Diseñar estrategias basadas en conocimiento científico que contribuyan a producir cambios sustantivos en el abordaje del VIH, las ITS y las sexualidades desde las perspectivas de cuidado. Más adelante se tratan las Perspectivas de abordaje: 1) Enfoque de Derechos Humanos en salud. 2) Enfoque de géneros, centrados en los cuidados y el ejercicio libre de las sexualidades. Por último, se analizan cuestiones como las características del Modelo médico hegemónico, la Ley 27.675 de Respuesta Integral al VIH, Hepatitis Virales, ITS y Tuberculosis, la Estrategia de Atención Primaria de la Salud, la Prevención integral y combinada, la Asistencia interdisciplinaria, la Reducción de riesgos y daños del estigma, discriminación y criminalización. Confidencialidad: empatía, diversidades, participación. Derecho a la intimidad. En la segunda parte, Josefina Mauro (Médica infectóloga) miembro de la Dirección de Prevención de VIH, ITS y Hepatitis Virales, expone cuestiones generales de las “Infecciones de trasmisión sexual”, a saber: Conceptos de VIH y Sífilis. Sobre ambos puntos la clase aborda: ¿Qué son las ITS? Síntomas ¿Qué es el VIH? Historia Natural del VIH. Etapas del virus. Transmisión: ¿Cómo se transmite, cómo no se transmite, cómo se diagnostica, cómo se trata? Acceso al tratamiento retroviral. Objetivos del tratamiento retroviral. Indetectable=intrasmisible. Prevención: Profilaxis Post Exposición (PEP) para VIH. Situaciones de exposición ¿Cómo asisto en mi trabajo a una persona con VIH? ¿Qué es la sífilis? Historia Natural de la Sífilis ¿Cómo se trasmite? ¿Cómo se diagnostica? Tipos de prueba y algoritmos. Tratamiento: Penicilina. Alergia a la Penicilina. Riesgo alergia al Diclofenax. Prevención: vía sexual, vía perinatal.

Intensified tuberculosis treatment to reduce the mortality of HIV-infected and uninfected patients with tuberculosis meningitis (INTENSE-TBM): study protocol for a phase III randomized controlled trial.

BACKGROUND: Tuberculous meningitis (TBM) is the most lethal and disabling form of tuberculosis (TB), particularly in sub-Saharan Africa. Current anti-TB treatment is poorly effective since TBM mortality reaches 40% in HIV-negative patients and up to 70% in HIV-co-infected patients. To reduce TBM-induced morbidity and mortality, the INTENSE-TBM trial evaluates two interventions in both HIV-infected and uninfected patients: an anti-TB treatment intensification using oral high-dose rifampicin (35 mg/kg daily) and linezolid (1200 mg daily and then 600 mg daily) during the first 8 weeks of the anti-TB treatment and the use of adjunctive aspirin (200 mg daily). METHODS: This is a randomized controlled, phase III, multicenter, 2 × 2 factorial plan superiority trial. The trial has four arms, combining the two experimental treatments (intensified TBM regimen and aspirin) with the two reference treatments (WHO standard TB treatment and placebo), and is open-label for anti-TB treatment and double-blind placebo-controlled for aspirin treatment. This trial is conducted in adults or adolescents of age ≥15 years with TBM defined as "definite," "probable," or "possible" using Tuberculosis Meningitis International Research Consortium criteria, in four African countries: Ivory Coast, Madagascar, Uganda, and South Africa. The primary outcome is all-cause death between inclusion and week 40. DISCUSSION: The INTENSE-TBM trial represents a key opportunity to enhance TBM treatment with widely available existing drugs notably in high-incidence settings of both TB and HIV. The trial design is pragmatic and the results will permit early and effective applications in TBM patient care, in both HIV and TB high-incidence countries. TRIAL REGISTRATION: ClinicalTrials.gov NCT04145258. Registered on October 30, 2019.

Clinical characteristics of nontuberculous mycobacterial disease in people living with HIV/AIDS in South Korea: A multi-center, retrospective study.

With the introduction of combination antiretroviral therapy (cART), the prevalence of human immunodeficiency virus (HIV)-associated nontuberculous mycobacteria (NTM) disease has declined. However, NTM diseases still occur in people living with HIV/acquired immunodeficiency syndrome (AIDS) (PLWHA). We analysed the clinical and microbiological features of NTM diseases in PLWHA in South Korea. PLWHA who were diagnosed with NTM diseases between January 2000 and March 2021 were retrospectively enrolled from five different hospitals in South Korea. Data on baseline demographics, HIV status, CD4+ T cell counts, viral load, past and current cART regimens, isolated NTM species, results of antimicrobial susceptibility tests, treatment regimens, and outcomes were collected by reviewing medical records. A total of 34 cases of NTM in PLWHA were included. Pulmonary and extrapulmonary NTM diseases accounted for 58.8% (n = 20) and 41.2% (n = 14), respectively. The lymph node was the most common site of extrapulmonary NTM disease (64.3%). The age at the time of NTM disease diagnosis was younger in the extrapulmonary NTM group than in the pulmonary NTM group (37.0 vs. 49.0 years). Mean CD4+ T cell counts at the time of NTM disease diagnosis was 186.6 cells/µL (range: 1-1394). Nine patients (26.5%) had fully suppressed viral loads at the time of NTM disease diagnosis. Mycobacterium avium complex (MAC) was the most common species found, followed by M. intracellulare and M. kansasii. MAC isolates were all susceptible to clarithromycin, but the rates of non-susceptibility to moxifloxacin, linezolid, ethambutol, and rifampin were 75%, 37.5%, 12.5%, and 12.5%, respectively. The average duration of treatment was 17 months and the mortality rate was 8.8%. NTM diseases may occur in PLWHA, even with completely suppressed viral loads. The identified clinical features of NTM diseases are essential for its clinical management in South Korea.

Using joint models to study the association between CD4 count and the risk of death in TB/HIV data.

BACKGROUND: The association structure linking the longitudinal and survival sub-models is of fundamental importance in the joint modeling framework and the choice of this structure should be made based on the clinical background of the study. However, this information may not always be accessible and rationale for selecting this association structure has received relatively little attention in the literature. To this end, we aim to explore four alternative functional forms of the association structure between the CD4 count and the risk of death and provide rationale for selecting the optimal association structure for our data. We also aim to compare the results obtained from the joint model to those obtained from the time-varying Cox model. METHODS: We used data from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) AIDS Treatment programme, the Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) study, an open-label, three armed randomised, controlled trial between June 2005 and July 2010 (N=642). In our analysis, we combined the early and late integrated arms and compared results to the sequential arm. We utilized the Deviance Information Criterion (DIC) to select the final model with the best structure, with smaller values indicating better model adjustments to the data. RESULTS: Patient characteristics were similar across the study arms. Combined integrated therapy arms had a reduction of 55% in mortality (HR:0.45, 95% CI:0.28-0.72) compared to the sequential therapy arm. The joint model with a cumulative effects functional form was chosen as the best association structure. In particular, our joint model found that the area under the longitudinal profile of CD4 count was strongly associated with a 21% reduction in mortality (HR:0.79, 95% CI:0.72-0.86). Where as results from the time-varying Cox model showed a 19% reduction in mortality (HR:0.81, 95% CI:0.77-0.84). CONCLUSIONS: In this paper we have shown that the "current value" association structure is not always the best structure that expresses the correct relationship between the outcomes in all settings, which is why it is crucial to explore alternative clinically meaningful association structures that links the longitudinal and survival processes.

Prevalence, associated factors and rifampicin resistance pattern of pulmonary tuberculosis among HIV-positive patients attending antiretroviral treatment clinic at East Gojjam Zone, Ethiopia: An institution-based cross-sectional study.

Background: Drug-resistant tuberculosis (TB) threatens global TB care and prevention, and it remains a major public health concern in many countries particularly in sub-Saharan countries. Pulmonary TB is the most common serious opportunistic infection on HIV-positive patients and it is the leading cause of death among HIV-positive patients in developing countries. Ethiopia is one of the high TB burden countries with high morbidity and mortality. Objective: To determine the prevalence, associated factors and rifampicin resistance of pulmonary TB among HIV-positive attending antiretroviral treatment clinic at East Gojjam. Methods: Hospital-based cross-sectional study was conducted at Debre Markos Referral Hospital, from February to June 2019. A total of 112 HIV-positive TB suspected patients were included using convenient sampling techniques and a bacteriological confirmation test for tuberculosis was performed using Gene-Xpert MTB/RIF assay from a spot sputum sample. Viral load was determined by using a quantitative real-time polymerase chain reaction (RT-PCR) from the blood sample. Socio-demographic and clinical data were collected by face-to-face interview using a semi-structured questionnaire. The data were analyzed by using Statistical Package for Social Sciences (SPSS) software (version 24). Result: Out of the 112 study participants, the prevalence of Pulmonary TB was 11.6 %. Among TB positives 23.1 % were rifampicin resistant. Rifampicin resistance was 100 % among female patients. Having family members treated for pulmonary TB (P = 0.003, [AOR = 4.5; 95 % CI = 3.59-58.8]), cigarette smoking (P = 0.039, [AOR = 2.18; 95 %CI = 1.17-40.5]), being on WHO HIV disease clinical stage II (P = 0.024, [AOR = 1.81; 95 %CI = 1.50-30.99]), and having viral load (1000-9999) RNA copies/ml (P = 0.031, [AOR = 1.54; 95 %CI = 1.32-31.41]) were found to be significantly associated with pulmonary TB. Conclusion: The prevalence of pulmonary TB and rifampicin resistance was high among HIV patients. Having family members treated for Pulmonary TB, history of cigarette smoking, WHO HIV clinical stage, and high viral load were associated risk factors for TB. Therefore, strengthening awareness creation on TB transmission, drug resistance, and treatment adherence are essential. Moreover, early screening and treatment are vital for preventing the transmission and occurrence of drug-resistant TB among study populations.

Assessment of contextual factors shaping delivery and uptake of isoniazid preventive therapy among people living with HIV in Dar es salaam, Tanzania.

BACKGROUND: Tuberculosis has remained a leading cause of death among people living with HIV (PLHIV) globally. Isoniazid preventive therapy (IPT) is the recommended strategy by the World Health Organization to prevent TB disease and related deaths among PLHIV. However, delivery and uptake of IPT has remained suboptimal particularly in countries where HIV and TB are endemic such as Tanzania. This study sought to assess contextual factors that shape delivery and uptake of IPT in Dar es Salaam region, Tanzania. METHODOLOGY: We employed a qualitative case study design comprising of in-depth interviews with people living with HIV (n = 17), as well as key informant interviews with clinicians (n = 7) and health administrators (n = 7). We used thematic data analysis approach and reporting of the results was guided by the Consolidated Framework for Implementation Research (CFIR). RESULTS: Characteristics of IPT such as aligning the therapy to individual patient schedules and its relatively low cost facilitated its delivery and uptake. On the contrary, perceived adverse side effects negatively affected the delivery and uptake of IPT. Characteristics of individuals delivering the therapy including their knowledge, good attitudes, and commitment to meeting set targets facilitated the delivery and uptake of IPT. The process of IPT delivery comprised collective planning and collaboration among various facilities which facilitated its delivery and uptake. Organisational characteristics including communication among units and supportive leadership facilitated the delivery and uptake of IPT. External system factors including HIV stigma, negative cultural and religious values, limited funding as well as shortage of skilled healthcare workers presented as barriers to the delivery and uptake of IPT. CONCLUSION: The factors influencing the delivery and uptake of IPT among people living with HIV are multifaceted and exist at different levels of the health system. Therefore, it is imperative that IPT program implementers and policy makers adopt multilevel approaches that address the identified barriers and leverage the facilitators in delivery and uptake of IPT at both community and health system levels.

Transitioning Long-Acting Products to a Generic Marketplace: What's Missing?

Development of and increased access to generic oral medications to treat high-burden diseases including human immunodeficiency virus (HIV), tuberculosis, viral hepatitis, and malaria have had a major impact on reducing global morbidity and mortality. However, access and adherence to these life-saving treatments remains limited for some of the most vulnerable and underserved populations, for whom stigma, control, and discretion are critical to decisions around care. Current efforts to develop long-acting formulations to treat and prevent these conditions could overcome many of these barriers. However, generic manufacturing of these innovative products will be required to ensure affordable access to the communities and patients in greatest need. Strategic investments in new infrastructure will be required even before markets and manufacturing costs are clear, to ensure that access to these new products is not delayed, particularly for patients in low- and middle-income countries. Unlike conventional oral medications, long-acting products require greater investment for formulation, packaging, and delivery. The requirement for long-term bioequivalence studies will introduce additional delays in regulatory approval of generic long-acting products, and expedited approval pathways must be developed. Lessons learned from the development of long-acting hormonal contraceptives and long-acting antiretroviral products may provide a way forward.

Factors Associated with Mortality with Tuberculosis Diagnosis in Indigenous Populations in Peru 2015-2019.

OBJECTIVE: To identify factors associated with mortality in indigenous populations diagnosed with tuberculosis in Peru, 2015-2019. METHODS: We conducted a nested case-control study in a retrospective cohort using the registry of indigenous peoples of the National Health Strategy for TB Prevention and Control of the Ministry of Health of Peru. A descriptive analysis was performed, and then bivariate and multivariate logistic regression was used to evaluate associations between the variables and the outcome (alive-deceased). The results are shown as OR with their respective 95% confidence intervals. RESULTS: The mortality rate of the total indigenous population of Peru was 1.75 deaths per 100,000 indigenous people diagnosed with TB. The community of Kukama Kukamiria-Yagua reported 505 (28.48%) individuals, followed by the Shipibo-Konibo community with 385. The final logistic model showed that indigenous males (OR = 1.93; 95% CI: 1.001-3.7) with a history of HIV prior to TB (OR = 16.7; 95% CI: 4.7-58.7), and indigenous people in old age (OR = 2.95; 95% CI: 1.5-5.7) were factors associated with a greater chance of dying from TB. CONCLUSIONS: It is important to reorient health services among indigenous populations, especially those related to improving a timely diagnosis and early treatment of TB/HIV co-infection, to ensure comprehensive care for this population considering that they are vulnerable groups.

INSTIs for the management of HIV-associated TB (INSIGHT study): a phase 2b study to evaluate the efficacy, safety and pharmacokinetics of a combination of bictegravir, emtricitabine and tenofovir alafenamide fumarate for the treatment of HIV-1 infection in patients with drug-susceptible tuberculosis on a rifampicin-based treatment regimen: a phase 2b open-label randomised controlled trial.

INTRODUCTION: Cotreatment of HIV and tuberculosis (TB) reduces morbidity and mortality in coinfected patients. Availability of antiretroviral treatment (ART) drug options, including within drug classes, is important, particularly in high HIV/TB burden low and middle-income countries. METHODS AND ANALYSIS: This is a phase 2b, open-label, non-comparative randomised controlled trial to assess the antiretroviral activity of a fixed-drug, single tablet, combination of bictegravir (BIC) 50 mg/emtricitabine (FTC) 200 mg/tenofovir alafenamide (TAF) 25 mg (Biktarvy). The primary objective is to determine the efficacy, safety and pharmacokinetics of two times per day, coformulated BIC 50 mg/FTC 200 mg/TAF 25 mg in HIV-positive ART-naïve patients with TB who are receiving a rifampicin-based treatment regimen and to characterise viral suppression rates at week 24 through to week 48 in the BIC/FTC/TAF arm. We will enrol 120 patients randomised in a 2:1 ratio to the intervention or control arm of the study. A non-comparative contemporaneous control arm in which participants receive a dolutegravir-based regimen (standard of care) will also be enrolled. ETHICS AND DISSEMINATION: The University of KwaZulu-Natal Biomedical Research Ethics Committee (BREC) and the South African Health Products Regulatory Authority (SAHPRA) have granted regulatory approval (trial reference numbers: BREC/00001300/2020 and SAHPRA 20200810). Trial results will be disseminated through conference presentations, peer-reviewed publications and the clinical trial registry. TRIAL REGISTRATION NUMBER: Clinicaltrials.gov; Trial registration number: NCT04734652; South African National Clinical Trials Register (SANCTR DOH-27-012021-6789).

Evaluation of two short standardised regimens for the treatment of rifampicin-resistant tuberculosis (STREAM stage 2): an open-label, multicentre, randomised, non-inferiority trial.

BACKGROUND: The STREAM stage 1 trial showed that a 9-month regimen for the treatment of rifampicin-resistant tuberculosis was non-inferior to the 20-month 2011 WHO-recommended regimen. In STREAM stage 2, we aimed to compare two bedaquiline-containing regimens with the 9-month STREAM stage 1 regimen. METHODS: We did a randomised, phase 3, non-inferiority trial in 13 hospital clinics in seven countries, in individuals aged 15 years or older with rifampicin-resistant tuberculosis without fluoroquinolone or aminoglycoside resistance. Participants were randomly assigned 1:2:2:2 to the 2011 WHO regimen (terminated early), a 9-month control regimen, a 9-month oral regimen with bedaquiline (primary comparison), or a 6-month regimen with bedaquiline and 8 weeks of second-line injectable. Randomisations were stratified by site, HIV status, and CD4 count. Participants and clinicians were aware of treatment-group assignments, but laboratory staff were masked. The primary outcome was favourable status (negative cultures for Mycobacterium tuberculosis without a preceding unfavourable outcome) at 76 weeks; any death, bacteriological failure or recurrence, and major treatment change were considered unfavourable outcomes. All comparisons used groups of participants randomly assigned concurrently. For non-inferiority to be shown, the upper boundary of the 95% CI should be less than 10% in both modified intention-to-treat (mITT) and per-protocol analyses, with prespecified tests for superiority done if non-inferiority was shown. This trial is registered with ISRCTN, ISRCTN18148631. FINDINGS: Between March 28, 2016, and Jan 28, 2020, 1436 participants were screened and 588 were randomly assigned. Of 517 participants in the mITT population, 133 (71%) of 187 on the control regimen and 162 (83%) of 196 on the oral regimen had a favourable outcome: a difference of 11·0% (95% CI 2·9-19·0), adjusted for HIV status and randomisation protocol (p<0·0001 for non-inferiority). By 76 weeks, 108 (53%) of 202 participants on the control regimen and 106 (50%) of 211 allocated to the oral regimen had an adverse event of grade 3 or 4; five (2%) participants on the control regimen and seven (3%) on the oral regimen had died. Hearing loss (Brock grade 3 or 4) was more frequent in participants on the control regimen than in those on the oral regimen (18 [9%] vs four [2%], p=0·0015). Of 134 participants in the mITT population who were allocated to the 6-month regimen, 122 (91%) had a favourable outcome compared with 87 (69%) of 127 participants randomly assigned concurrently to the control regimen (adjusted difference 22·2%, 95% CI 13·1-31·2); six (4%) of 143 participants on the 6-month regimen had grade 3 or 4 hearing loss. INTERPRETATION: Both bedaquiline-containing regimens, a 9-month oral regimen and a 6-month regimen with 8 weeks of second-line injectable, had superior efficacy compared with a 9-month injectable-containing regimen, with fewer cases of hearing loss. FUNDING: USAID and Janssen Research & Development.

Fórum internacional sobre políticas de saúde para a eliminação do HTLV: Promoção de políticas de saúde para o HTLV em todo o mundo. Relatório da reunião, 10 de novembro de 2021

A infecção pelo vírus linfotrópico de células T humanas (HTLV) afeta principalmente grupos populacionais vulneráveis: pessoas vivendo em situação de pobreza em áreas com índices de desenvolvimento humano muito baixos, profissionais do sexo, homens que fazem sexo com homens, pessoas que injetam drogas e grupos populacionais epidemiologicamente fechados e semifechados, incluindo populações tradicionais e indígenas. Esse vírus e suas consequências foram negligenciados por décadas, apesar da alta morbidade e mortalidade atribuíveis à infecção pelo HTLV. As políticas públicas de saúde para o HTLV-1/2 são consideradas escassas na região das Américas e geralmente se limitam à triagem de doadores de sangue. A expansão da testagem para HTLV-1/2 deve ser priorizado, e o aconselhamento das pessoas que vivem com HTLV é uma oportunidade para evitar a transmissão. A testagem de gestantes, seguido de interrupção ou limitação da amamentação, deve ser uma prioridade, e testes direcionados para aqueles grupos de populações com alto risco de infecção deve ser considerados. A falta de conscientização sobre a HTLV é um grande desafio, e o engajamento da OPAS/OMS é crucial para superar esse obstáculo. A inclusão do HTLV em programas existentes, como IST e saúde materna, e programas focados na eliminação de doenças infecciosas e infecções negligenciadas, foi identificada como uma oportunidade para facilitar a implementação de políticas de saúde relativas ao HTLV-1/2 na Região. O investimento em pesquisa é necessário para fechar lacunas no conhecimento e desenvolver políticas e ferramentas econômicas que apoiem o avanço de respostas bem-sucedidas em saúde pública, como testes de ponto de cuidado de baixo custo para o diagnóstico HTLV-1/2. A infecção por HTLV também tem impacto negativo nos desfechos de coinfecções comuns na Região, incluindo tuberculose, strongyloidiasis, ISTs e micose. Aspectos genéticos, ambientais e socioculturais podem influenciar os desfechos de agrupamento ou doenças do HTLV-1 na Região. A agregação familiar também é importante e deve ser considerada ao avaliar o impacto das infecções pelo HTLV-1 e projetar políticas de combate a esse vírus. HTLV-2 é o tipo de vírus predominante entre populações indígenas nas américas. Políticas bem-sucedidas para controlar essa infecção devem contar com uma abordagem combinada para superar barreiras linguísticas, culturais e geográficas. Este relatório destaca algumas das principais intervenções disponíveis para a prevenção e controle da infecção pelo vírus linfotrópico de células T humanas (HTLV) e suas consequências e resume experiências nacionais e institucionais, discussões, sucessos e desafios associados à implementação de políticas públicas de saúde para a eliminação da infecção pelo HTLV. Esses temas foram apresentados no webinar "HTLV World Day 2021: Fórum Internacional de Política de Saúde para a eliminação do HTLV – Avanço das políticas de saúde HTLV em todo o mundo".

Evidence for Implementation: Management of TB in HIV and Pregnancy.

PURPOSE OF REVIEW: Pregnant people living with HIV (PLWH) are at especially high risk for progression from latent tuberculosis infection (LTBI) to active tuberculosis (TB) disease. Among pregnant PLWH, concurrent TB increases the risk of complications such as preeclampsia, intrauterine fetal-growth restriction, low birth weight, preterm-delivery, perinatal transmission of HIV, and admission to the neonatal intensive care unit. The grave impact of superimposed TB disease on maternal morbidity and mortality among PLWH necessitates clear guidelines for concomitant therapy and an understanding of the pharmacokinetics (PK) and potential drug-drug interactions (DDIs) between antitubercular (anti-TB) agents and antiretroviral therapy (ART) in pregnancy. RECENT FINDINGS: This review discusses the currently available evidence on the use of anti-TB agents in pregnant PLWH on ART. Pharmacokinetic and safety studies of anti-TB agents during pregnancy and postpartum are limited, and available data on second-line and newer anti-TB agents used in pregnancy suggest that several research gaps exist. DDIs between ART and anti-TB agents can decrease plasma concentration of ART, with the potential for perinatal transmission of HIV. Current recommendations for the treatment of LTBI, drug-susceptible TB, and multidrug-resistant TB (MDR-TB) are derived from observational studies and case reports in pregnant PLWH. While the use of isoniazid, rifamycins, and ethambutol in pregnancy and their DDIs with various ARTs are well-characterized, there is limited data on the use of pyrazinamide and several new and second-line antitubercular drugs in pregnant PLWH. Further research into treatment outcomes, PK, and safety data for anti-TB agent use during pregnancy and postpartum is urgently needed.

[Primary isoniazid preventive therapy : A strategy still relevant in the era of test and treat ; literature review]. / Chimioprophylaxie antituberculeuse primaire à l'isoniazide : une stratégie d'actualité à l'ère du tester et traiter ; revue de la littérature.

BACKGROUND: Tuberculosis remains a public health threat responsible as recently as 2018 for more than one million deaths. Chemoprophylaxis with isoniazid is one of the strategies implemented to control the disease. Although it is not yet widely prescribed, its utilization raises additional questions in the "test and treat" era of for anti-retroviral therapy. The objective of this study is to review the different randomized controlled trials of antitubercular Isoniazid Preventive Therapy (IPT). We have distinguished (a) "efficacy trials" (ET) comparing IPT to a placebo or the absence of chemoprophylaxis and (b) "IPT regimen trials" (RT) comparing IPT to one or several other regimens. METHODS: Literature search (keywords from published articles found in the Medline and Scopus data bases: "tuberculosis", "prophylaxis", "HIV", "randomized controlled trial") and standardized reading of selected articles reporting results from randomized trials of IPT in HIV-infected people. RESULTS: Eighteen selected trials (11 ET and 7 RT), including 19,725 participants. The regimens studied were 3H, 6H, 9H, 12H, 12H, 36H/2RZ, 3RH, 3RZ, 3RHZ, and 3HP [H: Isoniazid, R: Rifampicin, Z: Pyrazinamide, P: Rifapentine]. LOCATIONS: Ten in Africa, three in Haiti, one in India, one in the USA, one in the Americas and two multi-continental trials. In ET with or without antiretrovirals (ART), IPT significantly reduces the risk of tuberculosis, by 32 to 71%. In ET prior to ART, IPT does not appear to reduce mortality. In ET in patients receiving ART, on the other hand, IPT reduces mortality. As regards RT, there seems to be no reason to prefer other regimens to IPT. Tolerance is good. Importantly, IPT may reduce (rather than worsen) the risk of multidrug-resistant bacilli selection by decreasing the number of TB episodes and, consequently, the number of curative tuberculosis treatments. CONCLUSION: Far from becoming obsolete due to ARV treatment, IPT has remained a timely and relevant intervention.