| So far, certainly in Africa our knowledge about adverse effects of HAART remains limited. This project is complementary to project E (To determine the incidence of and risk factors for selected adverse effects of HAART treatment in HIV-1 infected persons without a clinical suspicion of TB co-infection) which will be conducted in Rwanda, this project F will be enrolling patients with active HIV-TB coinfection who are to commence HAART therapy in an outpatient clinic setting in Kampala, Uganda. The aims will be twofold: 1) to study in an identical fashion the same selected adverse effects outlined in project E (anaemia, peripheral neuropathy, lactic acidemia/acidosis, and changes in body fat distribution (lipodystrophy)) and 2) to study the incidence of, risk factors for, and clinical outcome of TB immune reactivation inflammatory syndrome (IRIS). The diagnosis of TB IRIS is difficult and at the moment we lack simple laboratory or other tests to diagnose this condition. An observational cohort will be established at the IDI clinic in Uganda of patients with HIV-1 treated for newly diagnosed TB who subsequently start HAART to study TB IRIS and other selected adverse effects of HAART. Two hundred consecutive patients providing informed consent will be enrolled in the study and followed for at least 3 years. Patients will have follow-up visits to see both a study doctor and study nurse at weeks 2, 4, 8, 12 and then every 3 months in the first year after starting HAART, and every 6 months in subsequent years. At each assessment visit, the following will be undertaken: a study nurse will administer a symptom check-list and patients will be examined by a study doctor to detect intercurrent illness, TB IRIS, HIV disease progression or selected adverse effects of HAART. Body weight and body mass index will be recorded. Patients will also be followed biologically (including CD4+ lymphocyte count and VL testing). Other investigations will include: chest X ray, bacilloscopy, mycobacterial cultures and mycobacterial resistance testing, and abdominal ultrasound. Serum, cells and mycobacterial cultures will be stored. TB treatment and ART will be given according to the Ugandan national guidelines. In case a patient develops TB IRIS, the TB treatment and the ART will be continued but prednisolone 40 mg per day during the first 2 weeks followed by 20 mg per day during the third week and 10 mg during the fourth week after diagnosing IRIS will be added. This strategy could be changed if new relevant scientific information becomes available on how to best manage TB IRIS. All patients will receive co-trimoxazole prophylaxis. The total duration of this project will be 5 years. Improvement of our knowledge concerning the incidence of TB IRIS in a population with a high prevalence of HIV-TB co-infection will be important to appropriately estimate sample sizes for clinical trials to prevent or treat TB IRIS. In addition, improved knowledge about the incidence of TB-IRIS may also be relevant to rethinking strategies on when to best start HAART for HIV-infection. Finally, this project will be able to assess whether the incidence of some selected adverse effects of HAART such as anaemia, neutropenia and peripheral neuropathy are markedly different in TB co-infected patients as compared to patients without concomitant TB. This project will strengthen the study site in its capacity to carry out cohort studies and to analyse data of such studies. A short course training in GCP and ART management will be offered to the study team. Researchers will be trained in protocol development, cohort analysis and biostatistics. Many of the skills to be acquired from this research, including the systematic data collection and follow-up of patients, are needed to be able to conduct clinical trials. This cohort study will also provide an opportunity for the research staff to improve their skills required to submit research results to scientific conferences and journals. |
