Aspects of Tuberculosis and HIV Coinfection in Patients at Ethiopian Health Centers

Sammanfattning: HIV and tuberculosis (TB) remain the two most common infectious causes of death worldwide. During the recent decade antiretroviral treatment (ART) has become available for millions of people living with HIV (PLHIV) globally; yet more than half of PLHIV have not yet initiated ART. In order to achieve universal access, further decentralization of care is needed. This is a major challenge to health systems, since access to expertise and adapted diagnostic methods to diagnose and monitor patients on treatment in these areas are lacking. Most notably, two issues face clinicians treating PLHIV in high TB endemic areas; is this HIV-patient also infected with TB? and when should ART be started in patients with both HIV and TB? In two papers we developed clinical scoring algorithms to help answer these questions in areas with restricted access to laboratory facilities. In paper I, a clinical screening algorithm could increase the number of patients with low risk of TB, thereby limiting those in need of further investigations for TB as compared to only using the existing WHO-TB symptom screening algorithm. In paper II, a similar scoring algorithm was developed to assess the level of immunosuppression in patients with HIV and TB coinfection. For more than one third of these patients, severe immunosuppression could be excluded. According to current recommendations, this subset would therefore not be in need of immediate ART initiation during TB treatment providing time to prepare patients for life-long ART. In a second part of the thesis, we evaluated the impact of TB on the immune system, both on peripheral CD4 cells and neopterin as a marker of immune activation. In paper III, we found that 25% of HIV negative patients with TB had low CD4 cell count (below 500 cells/mm3). These levels increased until end of TB treatment but not to levels found in healthy controls, suggesting a sustained impact of TB on CD4 cell homeostasis. CD4 cell levels were associated with signs of severe TB (positive sputum smear microscopy, low mid upper arm circumference and bedridden status). In paper IV, neopterin levels were increased in TB patients (23.2 nmol/l) compared to controls (3.8nmol/l), particularly in HIV/TB coinfected patients (54nmol/l). Neopterin correlated to low CD4 cell count, and high neopterin levels were associated with increasing CD4 cell levels during treatment for TB. Yet, neopterin was not suitable as surrogate markers for CD4 cell count. In conclusion, this thesis shows that clinical evaluation of patients should be an integral part in the building of health care for HIV and TB in low-income settings, and that clinically based instruments may be helpful for triage and clinical decisions. Furthermore, we found that TB has an impact on both CD4 cell levels and immune activation. This further emphasizes the need to detect and treat TB in PLHIV.