THE CAUSES OF UNFAVORABLE OUTCOMES AMONG PATIENTS TAKING HAART. Part II

A retrospective comparative analysis of antiretroviral drugs identity was carried out in the groups of patients who died and in the general group of patients treated with HAART in 2010-2013. Assessed were the rates and durations of using specific HAART regimens and their combinations from the onset of therapy to its discontinuation because of non-adherence or death and the associations of ARD with the immediate causes of death. Results: In the group of patients who died compared with all patients treated with HAART, Lamivudin and Efavirenz were prescribed 1,5-2,0 times more often and the fusion inhibitor Enfuvitride was prescribed 4 times more often (р<0,0001). The medians of durations of taking different ARD suggest that the need to change drugs occurred up to 4-5 times over a short period, and the prescription of specific drugs was associated with the severity of HIV infection. No significant relationships were found between ARD and the immediate causes of death. At the same time, a multivariate analysis of 22 ARD showed that the rates of intake of five of them were associated with certain immediate causes of death. The regimens comprising Abacavir and Lopinavir/Ritonavir were associated with cardiovascular causes of death, whereas EFV, Stavudin and 3TC were associated with tuberculosis. HAART failure in some patients was associated with the development of HIV resistance to ARD, which promoted HIV disease. Among 47 patients examined, mutations causing the genotypic HIV resistance to ARD were found in 62% of cases, including resistance to NRTI in 36%, to NNTRI in 51%, to protease inhibitors in 2%, and to both NRTI and NNRTI in 44,8%. The discontinuation of HAART increased the rate of deaths because of AIDS by 12,4% and because of tuberculosis by 50%. Liver pathology as the cause of death was found 3 times more often among patients who did not interrupt HAART. Cardiovascular diseases caused death significantly less often among patients who discontinued HIV treatment. However, myocardial infarction, acute disturbances of cerebral circulation, and sudden heart arrest were found more often among patients who did not interrupt HAART, whereas different cardiomyopathies (toxic, alcoholic, mixed-type etc.) were found in most patients who discontinued HAART. Conclusions: Each of factors analyzed contributed independently to the risk of lethal outcome, irrespective of HAART received by patients. The degree of immunosuppression at the onset of HAART, the discontinuation of therapy, and the acquired HIV resistance to drugs were of key importance for progression of HIV infection. The presence of social risk factors at work before the onset of HAART was another predictor of therapeutic failure in most patients. The finding that cardiovascular and liver diseases are the immediate causes of lethal outcomes associated with HAART warrants further studies to define the categories of patients at the risk of such complications and to develop approaches to HAART correction and therapy optimization by supplementing it with other groups of drugs.

ВИЧ-инфекция, ВААРТ, HIV infection, HAART

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