Marchenko O. Predicting the course of HIV infection in patients taking antiretroviral therapy according to clinical and immunological characteristics

The dissertation is devoted to the optimization of diagnostic tactics based on studying the dynamics of clinical and immunological characteristics and identifying predictors of HIV infection progression in patients receiving antiretroviral therapy. Prospective and retrospective cohort studies and case-control studies were conducted to solve the tasks set in the work. The data of outpatient cards were analyzed and an in-depth comprehensive examination of 181 HIV-infected patients was performed. The population control group consisted of 175 practically healthy individuals of the Poltava region. Comprehensive clinical and laboratory examination of patients and analysis of medical records was conducted in the ME «Regional Center for HIV/AIDS Prevention and Control of Poltava Regional Council». The clinical and immunological characteristics of the course of HIV infection were clarified and the analysis of opportunistic infections was accomplished before the appointment and on ART. The prevalence of carriage of a 299Gly allele of the TLR4 gene and 11Leu allele of the TLR7 gene among HIV-infected patients was studied. The features of the course of HIV infection and the incidence of opportunistic infections before and on ART were assessed considering the levels of CD4 lymphocytes and the carriage of 299Gly allele of the TLR4 gene and 11Leu allele of the TLR7 gene. Scientific data on clinical and genetic factors of HIV progression prior ART prescription – parenteral route of HIV transmission, HIV testing for clinical indications, the initial level of CD4 lymphocytes <350 cells / μl, hemoglobin level below 100 g/l – was updated. Predictors of AIDS-indicative OI in HIV-infected patients receiving ART have been substantiated for the first time: male gender, lack of immunological response to ART, hemoglobin level below 100 g/l, low adherence to ART, and carrier of the 299Gly allele of the TLR4 gene. Predictors of TB development/reactivation in HIV-infected patients on ART were identified for the first time: male gender, lack of immunological response to ART, initial HIV viral load > 1.0x105 copies/ml, low adherence to ART, and carrier of the 299Gly allele of the TLR4 gene. It is proposed to research the carrier of the 299Gly allele of the TLR4 gene to assess the increased risk of HIV infection and its progression on ART. Recommendations for dispensary surveillance of HIV-infected patients on ART, who are carriers of the 299Gly allele of the TLR4 gene and have a higher risk of HIV progression and the development of disseminated forms of TB were designed. They include examination, screening for TB and other OI before antiretroviral therapy, assessment of adherence to ART, laboratory and/or instrumental examinations as needed with a 2 months maximum interval. The main risk factors for the progression of HIV infection to clinical stage 4 in patients before ART were identified. Clinical and genetic predictors have been identified and a prognostic model for the development of AIDS-indicative opportunistic infections in HIV-infected patients on ART was created. Clinical and genetic predictors were identified and a prognostic model for the development of tuberculosis in HIV-infected patients on ART was created.