Optimizing treatment outcomes in HIV-infected individuals

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Copyright: Carey, Dianne Lauraine
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Abstract
Combination antiretroviral therapy has dramatically reduced the incidence of HIV-related opportunistic diseases and increased life expectancy. However, antiretroviral therapy is associated with a range of toxicities that can complicate disease management and compromise treatment benefits. Once commenced, antiretroviral therapy is lifelong. Sustained high adherence is essential to maintain clinical benefits, hence prevention of drug-related adverse effects and clinical management of established toxicities are important in ensuring long-term adherence and clinical benefit. Altered lipid metabolism is a common complication of HIV infection and its treatment and a well-established marker of cardiovascular risk. Among antiretroviral agents both inter- and intra-drug class differences in lipid profiles have been described and are essential considerations in drug selection to order to minimize toxicity and reduce future risk. Similarities between the metabolic toxicities of antiretroviral therapy and metabolic syndrome (visceral obesity, dyslipidaemia, hyperglycaemia and hypertension) are of concern given its association with cardiometabolic risk. Few studies have investigated progression to metabolic syndrome in adults commencing antiretroviral therapy. Better understandings of links between metabolic syndrome and subsequent morbidities might allow for more effective clinical management. Morphological changes can be disfiguring and socially stigmatizing leading to reduced antiretroviral adherence. Management of established fat loss is challenging as restoration is modest and slow at best. This is particularly so for facial lipoatrophy. Diagnosis of facial lipoatrophy presence and its severity are problematic. Facial ultrasound, a non-validated measure, is a poor measure of facial lipoatrophy and does not correlate with objective measures of lipoatrophy severity. Few randomized studies have objectively assessed the efficacy of soft tissue filling agents for facial lipoatrophy and long-term safety data are lacking, hence elucidating optimal treatments for this distressing condition is difficult. Apart from the modest benefits of thymidine nucleoside reverse transcriptase inhibitor cessation, there are no effective therapies for lipoatrophy. Hence a biological marker(s) that could predict peripheral fat loss following antiretroviral therapy initiation would enable treatment modification prior to clinically evident lipoatrophy. Endeavours to prevent or better manage treatment-related adverse effects and toxicities are important initiatives to support the long-term, effective use of antiretroviral therapy in HIV-infected individuals.
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Author(s)
Carey, Dianne Lauraine
Supervisor(s)
Emery, Sean
Cooper, David
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Publication Year
2011
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Thesis
Degree Type
PhD Doctorate
UNSW Faculty
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