PhD defence Anita Mesic

Supervisors

• Prof. Dr. Lut Lynen (ITM)

• Dr. Tom Decroo (ITM)

• Prof. Dr. Josefien van Olmen (University of Antwerp)

• Dr. Koert Ritmeijer (Médecins sans Frontières, the Netherlands)

Abstract

The public health approach to the HIV epidemic stands behind successful global scale up of access to HIV care and reduced morbidity and mortality among people living with HIV (PLHIV) over the last two decades. However, with increasing size and lifespan of the HIV cohorts, programs are facing challenging tasks to maintain virological suppression among PLHIV on antiretroviral treatment (ART) and their retention in care over time. Achievement of the virological suppression is key to the success of ART in an individual and for public health. Viral load (VL) monitoring is considered as the main tool to assess if the desired response is achieved. Most frequently, programs report virological outcomes as proportion of PLHIV on ART who achieved virological suppression at a given point of time. This cross-sectional approach does not reflect that, while on treatment, PLHIV might transition between suppressed and unsuppressed VL, causing over- or underestimation of the viremic state of the cohort. Furthermore, with the increasing longevity of HIV cohorts, retention in HIV-care follows a more cyclical pattern: PLHIV disengage from care for a short or long period, followed by re-engagement. HIV care for these populations can be challenging due to pre-existing ART exposure and HIV drug resistance, and frequent re-engagement with advanced HIV disease. Studies examining retention in HIV care often capture a cross-sectional status. There is limited evidence on the effect of cyclical patterns  of retention on health outcomes. The research presented in this thesis studied virological outcomes, disengagement/re-engagement in care and advanced HIV disease and evaluated their relationship with unfavorable outcomes, based on the Médecins Sans Frontières (MSF) HIV program in Myanmar. The studies were conducted between 2001 and 2019. To achieve set objectives, four studies were conducted. Three studies used an observational, retrospective cohort design and one study was a systematic review of existing literature. The observational studies of this thesis were set up in the MSF HIV programs in Yangon Region, Kachin and Shan States in Myanmar. PLHIV receiving ART in the MSF HIV program in Myanmar were enrolled in the observational studies.

The thesis shows that the implementation of the VL cascade continues to be a major challenge. With the VL cascade, we refer to all the steps needed to achieve viral suppression: do a VL test, if not suppressed ensure better pill intake or a stronger regimen is used, so that viral suppression is again achieved. Instead of reporting general country-level VL coverage, the VL cascade analysis should be routinely performed as stratified by regions and populations, including all the steps of the cascade. This will support the national programs to develop strategies which maximize the potential effect of VL monitoring on outcomes among all population groups. Based on the findings presented in this thesis, cross-sectional VL should remain the main indicator for clinical decision-making and programmatic monitoring. Cumulative viremia (CV) indicators, which show how many people with HIV had a detectable VL over a certain period, can estimate total burden of viremia over time and as such could better reflect quality of HIV care or act as predictor of health outcomes and local HIV epidemic control. However, methods to estimate CV indicators need to be improved, standardized and adapted for use in programmatic and clinical settings.

Our findings confirm that disengagement from care and reengagement were frequent and were associated with a high burden of advanced HIV disease, virological failure and subsequent disengagement. Therefore, we highlight the need for improved monitoring of retention and monitoring of access to a package of care for advanced HIV disease in each program. Three population groups were identified as being at risk for unfavorable health outcomes in our studies, namely PLHIV with advanced HIV disease, those re-engaging with HIV care or key population (people who inject drugs and sex workers). Differentiated service delivery, thus adapted to the needs of subgroups, is necessary. Additional research questions were identified, addressing knowledge gaps, that the studies included in this thesis were not able to address.