Antiretroviral Treatment at Ethiopian Health Centers

Abstract: In 2017,for the first time, more than half of all people living with HIV (PLHIV) had access to antiretroviral treatment (ART). This expansion of ART has in part been achieved through decentralization of HIV care in resource-limited settings. There, many PLHIV now receive care at ART clinics integrated within the primary health care system. At these clinics, non-physician clinicians are responsible for all aspects of care. Concomitant tuberculosis (TB) is common among PLHIV in many high-burden countries. Therefore, clinicians at these clinics must be able to diagnose and treat concomitant TB in parallell with ART in order to achieve satisfactory outcome of care. Failing ART results in high mortality and risk of drug resistance development that can be detrimental both for the individual and for the community at large. The first three papers in this thesis explores aspects of ART outcome among patients receiving care at Ethiopian public health centers. In particular, the impact of concomitant TB on ART outcome is investigated. For this purpose, 812 ART-naïve adults eligible to start ART (CD4 count <350 cells/mm3 or WHO stage 4) were prospectively recruited and followed for up to four years after ART initiation. At study inclusion, all participants were investigated for concomitant TB by active case-finding. We found that concomitant TB, present in nearly 1/5 study participants, did not negatively impact short-term virological suppression (paper I), risk of short-term mortality (paper II), or long-term virological, clinical, or immunological outcome of ART (paper III). However, we did find men to have an increased risk of poor virological outcome of ART both in short- and long-term, and that they had an increased risk of becoming lost to follow-up. Additionally, subjects with malnutrition had an elevated risk of mortality both soon after study enrollment, and during the long-term follow-up. Furthermore, these individuals had high risk of poor long-term virological outcome of ART. In the fourth paper, a clinical algorithm for targeted viral load testing was constructed. Through the use of three simple criteria (current CD4 count, mid-upper arm circumference, and adherence to ART) subjects with high risk of virological failure 12 months after ART initiation could be identified. If the performance is validated, this algorithm could be used to guide virological monitoring of ART more efficiently in areas where viral load resources are limited. In conclusion, we found that most PLHIV – regardless of concomitant TB – have good outcome of ART at Ethiopian public health centers during up to four years of follow-up. These findings demonstrate the feasibility of health center-based ART in settings where concomitant TB is common. In addition, we identified factors associated with poor outcome of care. If these individuals are identified in time, outcome of care might be improved and drug resistance development prevented. Finally, we constructed an algorithm for targeted viral load testing.