Isoniazid preventive therapy for the prevention of tuberculosis in HIV infected people in Ethiopia

Background: Mycobacterium tuberculosis (TB) is the most common cause of bacterial infection in humans and is globally a leading cause of morbidity and mortality, especially in developing countries. Human Immunodeficiency Virus (HIV) infection is the strongest risk factor for TB and over 4 million people are co-infected with both organisms, the majority of whom reside in Africa. Such co-infection worsens the prognosis of HIV infection by increasing HIV replication and may result in rapid progression of HIV and subsequent immunosuppression, and a higher risk of acquiring other, potentially lethal, opportunistic infections. However, the reason for low uptake of TB preventive strategies including isoniazid preventive therapy (IPT) is not well known. Evidence about the potential emergence of drug resistant TB after IPT use is inconclusive; and the benefit of IPT on HIV disease progression is not well studied either. Methods: Lists of epidemiological methodologies are used to assess IPT implementation in Ethiopia. The methodologies are a mix of review, meta-analysis, prospective and retrospective cohort study designs, and descriptive analysis. Objective: This thesis aims to assess the effect of IPT on the risks of TB, all-cause mortality, and HIV disease progression, in real-life settings with increasing ART adoption. In addition, this thesis aimed at systematically synthesizing evidence from clinical trials, assessing the potential predictors of HIV patients’ adherence to IPT, describing factors related to MDR TB, and assessing the effects of IPT on HIV disease progression. Result and discussion: The studies in this thesis demonstrated that IPT reduces the risk of TB in HIV infected people even though this effect could not be shown in prevention of all-cause mortality or HIV disease progression. TB/HIV incidence and prevalence has substantially reduced in the last three decades, but this disease continues to affect the poorest in both developed and developing countries, disproportionally in Sub-Saharan African countries. The WHO has set a new global plan, the so-called “Sustainable Development Goals (SDG)”, which, among other goals, aims at TB and HIV elimination by year 2030. So as to achieve this target, IPT should be implemented on a large scale in addition to other TB-HIV prevention packages. Potential predictors of adherence to IPT such as HIV related stigma, opportunistic infections, and concomitant therapies should be addressed. In addition, IPT likely is more effective if it is initiated at the earlier stages of HIV disease. It needs a proper strategy to engage health care providers in timely prescription of IPT for HIV infected people. Training programs on the benefits and risks of IPT and subsequent monitoring of health care providers might improve early prescription of IPT. The risk of MDR TB after IPT and adverse drug reactions seems limited, but further quantification is needed. For this purpose, close coupling of implementation with research programs could provide the much needed information. In sum, IPT implementation should be strengthened globally especially in countries with and elevated burden of HIV infection.