Assessment of Immunosuppression in HIV-infected Patients With Tuberculosis With Access to Antiretroviral Therapy in Primary Health Care Centres in Ethiopia - Clinical and Immunological Markers and Associations With Treatment Outcome

Tuberculosis (TB) remains as the leading opportunistic infection and cause of death among HIV-infected subjects in resource-limited settings (1). The management of TB-HIV co-infection constitutes a great challenge for health care systems. Often, HIV infection is first detected when patients are diagnosed with active TB, and many such patients have advanced immunosuppression (2, 3). However, TB can also occur in individuals with relatively well preserved CD4 cell counts, especially in areas with high TB endemicity (4). In settings where both TB and HIV infection are common, a high proportion of patients are in need both of anti-TB treatment (ATT) and antiretroviral therapy (ART) at diagnosis. Combined ART and ATT is associated with risks of drug-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 (5-7).

Although the optimal timing for when to start ART in patients receiving ATT is not completely understood, CD4 cell count thresholds are currently often used to guide clinicians on when to start ART in co-infected patients (8). Briefly, initiation of ART during ATT is indicated for patients with CD4 counts lower than 350 cells/mm3, whereas it is usually recommended to defer ART for patients without other clinical signs of immunodeficiency and CD4 cell counts higher than 350 cells/mm3. In a recently published WHO document, initiation of ART is proposed for all patients with active TB, but timing of ART remains uncertain, as well as the need for ART in subjects with CD4 cell counts exceeding 350 cells/mm3 (9). Studies aiming at defining optimal time points for ART initiation in patients receiving ATT are ongoing, and might lead to revised recommendations with regard to co-administration of these therapies.

The number of HIV-infected subjects initiating ART has increased impressively over recent years, especially in Subsaharan Africa. Still, it is estimated that less than half of all patients in need of ART currently receive such treatment (10). In order to improve access, it is necessary to decentralize treatment and integrate ART into the primary health care system. In such settings, CD4 cell count analysis is rarely available, and patients are usually managed by health care workers with limited knowledge and experience of HIV-TB co-infection. Finding simple alternative tools to identify immunosuppressed patients in these circumstances could therefore lead to significant improvements in care.

The investigators hypothesize that a structured scoring system based on clinical symptoms and signs could be used to assess the degree of immunosuppression in HIV-infected patients with TB, and thus help to categorize patients to determine when ART should be initiated in settings with limited access to laboratory resources. The principal aim of the project is to investigate how clinical scoring correlates with CD4 cell levels and specific CD4 cell cut-off points that are used to identify patients who fulfil criteria for starting ART during ATT (specifically for thresholds of 200, 350 and 500 cells/mm3), and to compare these results with scoring in TB patients without HIV co-infection. The study will also evaluate whether scoring results can predict short term mortality and treatment outcome. In addition, the investigators aim to investigate a panel of alternative immunological surrogate markers that could be used to measure HIV-related immunosuppression in patients co-infected with TB.

Work plan Methods: Patients diagnosed with active tuberculosis in health care facilities in the Oromia region, Ethiopia are eligible for inclusion. The study has been performed in the district hospital of Bishofto and in 4 health centres providing integrated care for TB and HIV (Adama, Welenchity, Mojo and Dukam health centres). Approximately 1 112 patients have been included. In these regions, approximately 40% of patients newly diagnosed with TB are HIV seropositive.