Journal Article > ResearchFull Text
Clin Infect Dis. 28 April 2025; DOI:doi: 10.1093/cid/ciaf222
Larsson L, Calderwood CJ, Marambire ET, Held K, Banze D, et al.
Clin Infect Dis. 28 April 2025; DOI:doi: 10.1093/cid/ciaf222
BACKGROUND
Studies have demonstrated an inverse log-linear relationship between body mass index (BMI) and tuberculosis incidence. However, a person’s BMI is dynamic and longitudinal changes may be more informative than cross-sectional assessments. We evaluate the association between cross-sectional and changing BMI and risk of tuberculosis and describe longitudinal trajectories in a high-risk cohort.
METHODS
ERASE-TB was a prospective longitudinal cohort study of household contacts ≥10 years in Southern Africa (Zimbabwe, Tanzania, and Mozambique), with 6-monthly follow-up up to 24 months. Associations between BMI and tuberculosis were investigated based on baseline (including haemoglobin) and changing BMI, using logistic, Poisson, and Cox models. Prevalent tuberculosis was defined as diagnosis during <30 days after recruitment. Growth mixture modelling (GMM) was used to model longitudinal latent trajectories.
RESULTS
Of 2,107 recruited household contacts (621 [29.5%] adolescents and 1,310 [62.2%] female), 520 (24.7%) were underweight. There were 21 and 41 people diagnosed with prevalent and incident tuberculosis, of whom 5/21 (23.8%) and 12/41 (29.3%) were underweight. Being underweight and anaemic (aHR: 3.77, 95% CI: 1.50-9.51) and >10% negative change in BMI during follow-up (aIRR: 2.27 (95% CI: 0.22-22.9) were associated with increased risk of incident tuberculosis. The association between continuous BMI-for-age Z-scores were non-linear, with increased risk of tuberculosis with lower BMI. Four latent groups were defined in the GMM: increasing, decreasing, and low/high stable BMI.
CONCLUSIONS
Declining BMI, regardless of absolute value, is a strong predictor of tuberculosis among household contacts. Longitudinal measurements should be considered in active case finding among tuberculosis-affected households.
Journal Article > LetterFull Text
Eur Respir J. 30 May 2024; Volume 63 (Issue 5); 2400436.; DOI:10.1183/13993003.00436-2024
Mesic A, Decuyper I, Ishaq S, Azizi T, Hadi Ziamal F, et al.
Eur Respir J. 30 May 2024; Volume 63 (Issue 5); 2400436.; DOI:10.1183/13993003.00436-2024
Journal Article > ReviewFull Text
Int Health. 1 May 2024; Volume 16 (Issue 3); 261-278.; DOI:10.1093/inthealth/ihad093
Mesic A, Decroo T, Florence E, Ritmeijer KKD, van Olmen J, et al.
Int Health. 1 May 2024; Volume 16 (Issue 3); 261-278.; DOI:10.1093/inthealth/ihad093
BACKGROUND
We performed a systematic review to generate evidence on the association between cumulative human immunodeficiency virus (HIV) viraemia and health outcomes.
METHODS
Quantitative studies reporting on HIV cumulative viraemia (CV) and its association with health outcomes among people living with HIV (PLHIV) on antiretroviral treatment (ART) were included. We searched MEDLINE via PubMed, Embase, Scopus and Web of Science and conference abstracts from 1 January 2008 to 1 August 2022.
RESULTS
The systematic review included 26 studies. The association between CV and mortality depended on the study population, methods used to calculate CV and its level. Higher CV was not consistently associated with greater risk of acquire immunodeficiency syndrome–defining clinical conditions. However, four studies present a strong relationship between CV and cardiovascular disease. The risk was not confirmed in relation of increased hazards of stroke. Studies that assessed the effect of CV on the risk of cancer reported a positive association between CV and malignancy, although the effect may differ for different types of cancer.
CONCLUSIONS
CV is associated with adverse health outcomes in PLHIV on ART, especially at higher levels. However, its role in clinical and programmatic monitoring and management of PLHIV on ART is yet to be established.
We performed a systematic review to generate evidence on the association between cumulative human immunodeficiency virus (HIV) viraemia and health outcomes.
METHODS
Quantitative studies reporting on HIV cumulative viraemia (CV) and its association with health outcomes among people living with HIV (PLHIV) on antiretroviral treatment (ART) were included. We searched MEDLINE via PubMed, Embase, Scopus and Web of Science and conference abstracts from 1 January 2008 to 1 August 2022.
RESULTS
The systematic review included 26 studies. The association between CV and mortality depended on the study population, methods used to calculate CV and its level. Higher CV was not consistently associated with greater risk of acquire immunodeficiency syndrome–defining clinical conditions. However, four studies present a strong relationship between CV and cardiovascular disease. The risk was not confirmed in relation of increased hazards of stroke. Studies that assessed the effect of CV on the risk of cancer reported a positive association between CV and malignancy, although the effect may differ for different types of cancer.
CONCLUSIONS
CV is associated with adverse health outcomes in PLHIV on ART, especially at higher levels. However, its role in clinical and programmatic monitoring and management of PLHIV on ART is yet to be established.
Journal Article > ResearchFull Text
Int Health. 1 November 2022; Volume 15 (Issue 4); ihac069.; DOI:10.1093/inthealth/ihac069
Mesic A, Homan T, Lenglet AD, Thit P, Mar HT, et al.
Int Health. 1 November 2022; Volume 15 (Issue 4); ihac069.; DOI:10.1093/inthealth/ihac069
BACKGROUND
The burden of advanced HIV disease (AHD) and predictors of outcomes among people living with HIV (PLHIV) re-engaging in care are not well known.
METHODS
We conducted a retrospective cohort study of PLHIV who re-engaged in care after being lost to follow-up (LFU), from 2003 to 2019, in Myanmar. We calculated the incidence rates of attrition after re-engagement and performed Cox regression to identify risk factors for attrition.
RESULTS
Of 44 131 PLHIV who started antiretroviral treatment, 12 338 (28.0%) were LFU at least once: 7608 (61.6%) re-engaged in care, 4672 (61.4%) with AHD at re-engagement. The death and LFU rates were 2.21-fold (95% CI 1.82 to 2.67) and 1.46-fold (95% CI 1.33 to 1.61) higher among patients who re-engaged with AHD (p>0.001). Death in patients who re-engaged with AHD was associated with male sex (adjusted HR [aHR] 2.63; 95% CI 1.31 to 5.26; p=0.006), TB coinfection (aHR 2.26; 95% CI 1.23 to 4.14; p=0.008) and sex work (aHR 7.49, 95% CI 2.29 to 22.52; p<0.001). History of intravenous drug use was identified as a predictor of being LFU.
CONCLUSIONS
Re-engagement in HIV care in Myanmar is frequent and those who re-engage carry a high burden of AHD. As AHD at re-engagement is associated with higher attrition rates, implementation of differentiated interventions that enable earlier linkage to care and prompt identification and management of AHD in this population is necessary.
The burden of advanced HIV disease (AHD) and predictors of outcomes among people living with HIV (PLHIV) re-engaging in care are not well known.
METHODS
We conducted a retrospective cohort study of PLHIV who re-engaged in care after being lost to follow-up (LFU), from 2003 to 2019, in Myanmar. We calculated the incidence rates of attrition after re-engagement and performed Cox regression to identify risk factors for attrition.
RESULTS
Of 44 131 PLHIV who started antiretroviral treatment, 12 338 (28.0%) were LFU at least once: 7608 (61.6%) re-engaged in care, 4672 (61.4%) with AHD at re-engagement. The death and LFU rates were 2.21-fold (95% CI 1.82 to 2.67) and 1.46-fold (95% CI 1.33 to 1.61) higher among patients who re-engaged with AHD (p>0.001). Death in patients who re-engaged with AHD was associated with male sex (adjusted HR [aHR] 2.63; 95% CI 1.31 to 5.26; p=0.006), TB coinfection (aHR 2.26; 95% CI 1.23 to 4.14; p=0.008) and sex work (aHR 7.49, 95% CI 2.29 to 22.52; p<0.001). History of intravenous drug use was identified as a predictor of being LFU.
CONCLUSIONS
Re-engagement in HIV care in Myanmar is frequent and those who re-engage carry a high burden of AHD. As AHD at re-engagement is associated with higher attrition rates, implementation of differentiated interventions that enable earlier linkage to care and prompt identification and management of AHD in this population is necessary.
Journal Article > ResearchFull Text
PLOS One. 29 July 2022; Volume 17 (Issue 7); e0271910.; DOI:10.1371/journal.pone.0271910
Mesic A, Decroo T, Mar HT, Jacobs BKM, Thandar MP, et al.
PLOS One. 29 July 2022; Volume 17 (Issue 7); e0271910.; DOI:10.1371/journal.pone.0271910
INTRODUCTION
Despite HIV viral load (VL) monitoring being serial, most studies use a cross-sectional design to evaluate the virological status of a cohort. The objective of our study was to use a simplified approach to calculate viraemic-time: the proportion of follow-up time with unsuppressed VL above the limit of detection. We estimated risk factors for higher viraemic-time and whether viraemic-time predicted mortality in a second-line antiretroviral treatment (ART) cohort in Myanmar.
METHODS
We conducted a retrospective cohort analysis of people living with HIV (PLHIV) who received second-line ART for a period >6 months and who had at least two HIV VL test results between 01 January 2014 and 30 April 2018. Fractional logistic regression assessed risk factors for having higher viraemic-time and Cox proportional hazards regression assessed the association between viraemic-time and mortality. Kaplan-Meier curves were plotted to illustrate survival probability for different viraemic-time categories.
RESULTS
Among 1,352 participants, 815 (60.3%) never experienced viraemia, and 172 (12.7%), 214 (15.8%), and 80 (5.9%) participants were viraemic <20%, 20–49%, and 50–79% of their total follow-up time, respectively. Few (71; 5.3%) participants were ≥80% of their total follow-up time viraemic. The odds for having higher viraemic-time were higher among people with a history of injecting drug use (aOR 2.01, 95% CI 1.30–3.10, p = 0.002), sex workers (aOR 2.10, 95% CI 1.11–4.00, p = 0.02) and patients treated with lopinavir/ritonavir (vs. atazanavir; aOR 1.53, 95% CI 1.12–2.10, p = 0.008). Viraemic-time was strongly associated with mortality hazard among those with 50–79% and ≥80% viraemic-time (aHR 2.92, 95% CI 1.21–7.10, p = 0.02 and aHR 2.71, 95% CI 1.22–6.01, p = 0.01). This association was not observed in those with viraemic-time <50%.
CONCLUSIONS
Key populations were at risk for having a higher viraemic-time on second-line ART. Viraemic-time predicts clinical outcomes. Differentiated services should target subgroups at risk for a higher viraemic-time to control both HIV transmission and mortality.
Despite HIV viral load (VL) monitoring being serial, most studies use a cross-sectional design to evaluate the virological status of a cohort. The objective of our study was to use a simplified approach to calculate viraemic-time: the proportion of follow-up time with unsuppressed VL above the limit of detection. We estimated risk factors for higher viraemic-time and whether viraemic-time predicted mortality in a second-line antiretroviral treatment (ART) cohort in Myanmar.
METHODS
We conducted a retrospective cohort analysis of people living with HIV (PLHIV) who received second-line ART for a period >6 months and who had at least two HIV VL test results between 01 January 2014 and 30 April 2018. Fractional logistic regression assessed risk factors for having higher viraemic-time and Cox proportional hazards regression assessed the association between viraemic-time and mortality. Kaplan-Meier curves were plotted to illustrate survival probability for different viraemic-time categories.
RESULTS
Among 1,352 participants, 815 (60.3%) never experienced viraemia, and 172 (12.7%), 214 (15.8%), and 80 (5.9%) participants were viraemic <20%, 20–49%, and 50–79% of their total follow-up time, respectively. Few (71; 5.3%) participants were ≥80% of their total follow-up time viraemic. The odds for having higher viraemic-time were higher among people with a history of injecting drug use (aOR 2.01, 95% CI 1.30–3.10, p = 0.002), sex workers (aOR 2.10, 95% CI 1.11–4.00, p = 0.02) and patients treated with lopinavir/ritonavir (vs. atazanavir; aOR 1.53, 95% CI 1.12–2.10, p = 0.008). Viraemic-time was strongly associated with mortality hazard among those with 50–79% and ≥80% viraemic-time (aHR 2.92, 95% CI 1.21–7.10, p = 0.02 and aHR 2.71, 95% CI 1.22–6.01, p = 0.01). This association was not observed in those with viraemic-time <50%.
CONCLUSIONS
Key populations were at risk for having a higher viraemic-time on second-line ART. Viraemic-time predicts clinical outcomes. Differentiated services should target subgroups at risk for a higher viraemic-time to control both HIV transmission and mortality.
Journal Article > EditorialFull Text
BMJ. 10 January 2022; Volume 376; o46.; DOI:10.1136/bmj.o46
Mesic A
BMJ. 10 January 2022; Volume 376; o46.; DOI:10.1136/bmj.o46
Journal Article > CommentaryFull Text
Int J Tuberc Lung Dis. 1 October 2020; Volume 24 (Issue 10); 1081-1086.; DOI:10.5588/ijtld.20.0141
Seung KJ, Khan UT, Varaine FFV, Ahmed SM, Bastard M, et al.
Int J Tuberc Lung Dis. 1 October 2020; Volume 24 (Issue 10); 1081-1086.; DOI:10.5588/ijtld.20.0141
In 2015, the initiative Expand New Drug Markets for TB (endTB) began, with the objective of reducing barriers to access to the new and repurposed TB drugs. Here we describe the major implementation challenges encountered in 17 endTB countries. We provide insights on how national TB programmes and other stakeholders can scale-up the programmatic use of new and repurposed TB drugs, while building scientific evidence about their safety and efficacy. For any new drug or diagnostic, multiple market barriers can slow the pace of scale-up. During 2015–2019, endTB was successful in increasing the number of patients receiving new and repurposed TB drugs in 17 countries. The endTB experience has many lessons, which are relevant to country level introduction of new TB drugs, as well as non-TB drugs and diagnostics. For example: the importation of TB drugs is possible even in the absence of registration; emphasis on good clinical monitoring is more important than pharmacovigilance reporting; national guidelines and expert committees can both facilitate and hinder innovative practice; clinicians use new and repurposed TB drugs when they are available; data collection to generate scientific evidence requires financial and human resources; pilot projects can drive national scale-up.
Journal Article > ResearchFull Text
J Int AIDS Soc. 21 July 2017; Volume 20 (Issue S4); 21644.; DOI: 10.7448/IAS.20.5.21644
Mesic A, Fontaine J, Aye T, Greig J, Thwe TT, et al.
J Int AIDS Soc. 21 July 2017; Volume 20 (Issue S4); 21644.; DOI: 10.7448/IAS.20.5.21644
Introduction: National AIDS Programme in Myanmar has made significant progress in scaling up antiretroviral treatment (ART) services and recognizes the importance of differentiated care for people living with HIV. Indeed, long centred around the hospital and reliant on physicians, the country’s HIV response is undergoing a process of successful decentralization with HIV care increasingly being integrated into other health services as part of a systematic effort to expand access to HIV treatment. This study describes implementation of differentiated care in Médecins Sans Frontières (MSF)-supported programmes and reports its outcomes. Methods: A descriptive cohort analysis of adult patients on antiretroviral treatment was performed. We assessed stability of patients as of 31 December 2014 and introduced an intervention of reduced frequency of physicians’ consultations for stable patients, and fast tract ART refills. We measured a number of saved physician’s visits as the result of this intervention. Main outcomes, remained under care, death, lost to follow up, treatment failure, were assessed on 31 December 2015 and reported as rates for different stable groups. Results: On 31 December 2014, our programme counted 16, 272 adult patients enrolled in HIV care, of whom 80.34% were stable. The model allowed for an increase in the average number of patients one medical team could care for – from 745 patients in 2011 to 1, 627 in 2014 – and, thus, a reduction in the number of teams needed. An assessment of stable patients enrolled on ART one year after the implementation of the new model revealed excellent outcomes, aggregated for stable patients as 98.7% remaining in care, 0.4% dead, 0.8% lost to follow-up, 0.8% clinical treatment failure and 5.8% with immunological treatment failure. Conclusions: Implementation of a differentiated model reduced the number of visits between stable clients and physicians, reduced the medical resources required for treatment and enabled integrated treatment of the main co-morbidities. We hope that these findings will encourage other stakeholders to implement innovative models of HIV care in Myanmar, further expediting the scale up of ART services, the decentralization of treatment and the integration of care for the main HIV co-morbidities in this context.
Journal Article > ResearchFull Text
J Int AIDS Soc. 21 July 2017; Volume 20 (Issue Suppl 4); 21654.; DOI:10.7448/IAS.20.5.21654
Ssonko C, Gonzalez L, Mesic A, da Fonseca M, Achar J, et al.
J Int AIDS Soc. 21 July 2017; Volume 20 (Issue Suppl 4); 21654.; DOI:10.7448/IAS.20.5.21654
INTRODUCTION
Countries in the West and Central African regions struggle to offer quality HIV care at scale, despite HIV prevalence being relatively low. In these challenging operating environments, basic health care needs are multiple, systems are highly fragile and conflict disrupts health care. Médecins Sans Frontières (MSF) has been working to integrate HIV care in basic health services in such settings since 2000. We review the implementation of differentiated HIV care and treatment approaches in MSF-supported programmes in South Sudan (RoSS), Central African Republic (CAR) and Democratic Republic of Congo (DRC).
METHODS
A descriptive analysis from CAR, DRC and RoSS programmes reviewing methodology and strategies of HIV care integration between 2010 and 2015 was performed. We describe HIV care models integrated within the provision of general health care and highlight best practices and challenges.
RESULTS
Services included provision of general health care, with out-patient care (range between countries 43,343 and 287,163 consultations/year in 2015) and in-patient care (range 1076–16,595 in 2015). By the end of 2015 antiretroviral therapy (ART) initiations reached 12–255 patients/year. A total of 1101 and 1053 patients were on ART in CAR and DRC, respectively. In RoSS 186 patients were on ART when conflict recommenced late in 2013. While ART initiation and monitoring were mostly clinically driven in the early phase of the programmes, DRC implemented CD4 monitoring and progressively HIV viral load (VL) monitoring during study period. Attacks to health care facilities in CAR and RoSS disrupted service provision temporarily. Programmatic challenges include: competing health priorities influencing HIV care and need to integrate within general health services. Differentiated care approaches that support continuity of care in these programmes include simplification of medical protocols, multi-month ART prescriptions, and community strategies such as ART delivery groups, contingency plans and peer support activities.
CONCLUSIONS
The principles of differentiated HIV care for high-quality ART delivery can successfully be applied in challenging operating environments. However, success heavily depends on specific adaptations to each setting.
Countries in the West and Central African regions struggle to offer quality HIV care at scale, despite HIV prevalence being relatively low. In these challenging operating environments, basic health care needs are multiple, systems are highly fragile and conflict disrupts health care. Médecins Sans Frontières (MSF) has been working to integrate HIV care in basic health services in such settings since 2000. We review the implementation of differentiated HIV care and treatment approaches in MSF-supported programmes in South Sudan (RoSS), Central African Republic (CAR) and Democratic Republic of Congo (DRC).
METHODS
A descriptive analysis from CAR, DRC and RoSS programmes reviewing methodology and strategies of HIV care integration between 2010 and 2015 was performed. We describe HIV care models integrated within the provision of general health care and highlight best practices and challenges.
RESULTS
Services included provision of general health care, with out-patient care (range between countries 43,343 and 287,163 consultations/year in 2015) and in-patient care (range 1076–16,595 in 2015). By the end of 2015 antiretroviral therapy (ART) initiations reached 12–255 patients/year. A total of 1101 and 1053 patients were on ART in CAR and DRC, respectively. In RoSS 186 patients were on ART when conflict recommenced late in 2013. While ART initiation and monitoring were mostly clinically driven in the early phase of the programmes, DRC implemented CD4 monitoring and progressively HIV viral load (VL) monitoring during study period. Attacks to health care facilities in CAR and RoSS disrupted service provision temporarily. Programmatic challenges include: competing health priorities influencing HIV care and need to integrate within general health services. Differentiated care approaches that support continuity of care in these programmes include simplification of medical protocols, multi-month ART prescriptions, and community strategies such as ART delivery groups, contingency plans and peer support activities.
CONCLUSIONS
The principles of differentiated HIV care for high-quality ART delivery can successfully be applied in challenging operating environments. However, success heavily depends on specific adaptations to each setting.
Journal Article > ResearchFull Text
Trop Med Int Health. 3 January 2022; Volume 27 (Issue 2); 207-215.; DOI:10.1111/tmi.13716
Mesic A, Ishaq S, Khan WH, Mureed A, Mar HT, et al.
Trop Med Int Health. 3 January 2022; Volume 27 (Issue 2); 207-215.; DOI:10.1111/tmi.13716
OBJECTIVES
To describe the effect of adaptations to a person-centred care with short oral regimens on retention in care for rifampicin-resistant TB (RR-TB) in Kandahar province, Afghanistan.
METHODS
The study included people with RR-TB registered in the programme between 01 October 2016 and 18 April 2021. From 19 November 2019, the programme implemented a trial investigating the safety and effectiveness of short oral RR-TB regimens. During the trial, person-centred care was adapted. We included the data from people living with RR-TB treated in the period before and after the care model was adapted and applied Kaplan-Meier statistics to compare rates of retention in care.
RESULTS
Of 236 patients registered in the RR-TB programme, 146 (61.9%) were registered before and 90 (38.1%) after the model of care was adapted. Before adaptations enhancing person-centred care, pre-treatment attrition was 23.3% (n = 34/146), whilst under the adapted care model it was 5.6% (n = 5/90). Attrition on treatment was 22.3% (n = 25/112) before adaptations, whilst during the study period none of the participants were lost-to-follow-up on treatment and 3.3% died (n = 3/90).
CONCLUSIONS
As person-centred care delivery and treatment regimens were adapted to better fit-specific contextual challenges and the needs of the target population, retention in care improved amongst people with RR-TB in Kandahar, Afghanistan.
To describe the effect of adaptations to a person-centred care with short oral regimens on retention in care for rifampicin-resistant TB (RR-TB) in Kandahar province, Afghanistan.
METHODS
The study included people with RR-TB registered in the programme between 01 October 2016 and 18 April 2021. From 19 November 2019, the programme implemented a trial investigating the safety and effectiveness of short oral RR-TB regimens. During the trial, person-centred care was adapted. We included the data from people living with RR-TB treated in the period before and after the care model was adapted and applied Kaplan-Meier statistics to compare rates of retention in care.
RESULTS
Of 236 patients registered in the RR-TB programme, 146 (61.9%) were registered before and 90 (38.1%) after the model of care was adapted. Before adaptations enhancing person-centred care, pre-treatment attrition was 23.3% (n = 34/146), whilst under the adapted care model it was 5.6% (n = 5/90). Attrition on treatment was 22.3% (n = 25/112) before adaptations, whilst during the study period none of the participants were lost-to-follow-up on treatment and 3.3% died (n = 3/90).
CONCLUSIONS
As person-centred care delivery and treatment regimens were adapted to better fit-specific contextual challenges and the needs of the target population, retention in care improved amongst people with RR-TB in Kandahar, Afghanistan.