Tuberculosis in HIV-infected Patients Managed in Health Centres in Ethiopia - Identification of a Screening Algorithm for Active Tuberculosis and Determination of Outcome of Combined Antituberculosis and Antiretroviral Treatment

Background: Tuberculosis (TB) remains as the leading opportunistic infection and cause of death among HIV-infected subjects in resource-limited settings (1). HIV infection is the strongest risk factor known for developing active TB, and as a consequence, the HIV epidemic in Sub-Saharan Africa has fuelled the incidence of TB (2). The interactions between HIV and TB are great challenges for health care, both with regard to diagnosis and treatment. In HIV-infected persons TB often has atypical manifestations, making correct and timely diagnosis difficult (3, 4). Recognition of TB before starting antiretroviral therapy (ART) is critical since a missed diagnosis of TB is associated with high early mortality after ART initiation (1, 5). Screening for TB is recommended for HIV-positive subjects, but a method with both satisfactory specificity and sensitivity that can be used in primary health care settings in Africa has not yet been identified. New diagnostic techniques for TB have recently been developed, such as the GenXpert PCR (6), but the optimal use of these alternative methods needs to be investigated.

In settings where both TB and HIV infection are common, a high proportion of patients are in need both of anti-tuberculosis treatment (ATT) and ART. Combined ART and ATT is associated with risks of drug interactions, overlapping side effects, immune reconstitution disease and poor adherence, but at least in patients with severe immunodeficiency, these risks are outweighed by decreased mortality (7-9). Studies performed in developed countries have shown that rates of virological suppression during ART in patients receiving concomitant ATT are comparable to those in persons not taking ATT (10, 11), but this topic has not been extensively investigated at primary health care level in Africa.

The number of HIV-infected subjects receiving ART in Sub-Saharan Africa has increased dramatically during the last years. Still, it is estimated that less than half of all patients in need of ART currently receive such treatment (12). In order to improve access, it will become necessary to further decentralize ART and to integrate this treatment into the primary health care system. Since many patients starting ART have unrecognized active TB at this time point, it is important to find a practical and reliable screening algorithm for TB among such individuals. Furthermore, the outcome of combined ATT and ART delivered in health centres must be assessed, especially with regard to HIV RNA suppression and selection of ART resistance.

This project aims to develop an algorithm with the potential to identify indicators of prevalent and incident TB among patients initiating ART by correlating baseline clinical signs and symptoms with results of culture- and PCR-based investigations for TB. Such clinical characteristics will be compared both to TB present before starting ART, as well as to TB presenting during the first year after ART initiation. Results from this comparison will be used to construct an algorithm for TB screening in Ethiopian patients eligible for ART. In addition, clinical, immunological and virological outcomes of ART in patients with concomitant ATT will be compared to those in patients only receiving ART. Specific aims are to study rates of virological suppression during ART, the development of antiretroviral drug resistance, and treatment adherence.

Work plan: HIV-infected adult patients eligible to start ART will be recruited from HIV clinics in several health centres providing integrated for HIV and TB in the Oromia region. 812 patients have been prospectively included into the cohort, and are under continued follow-up.