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Conference
"Clinical Pharmacology in the HIV patient: Considerations for Switching Therapy" Dr. Elizabeth Phillips (biography) English - 2008-07-21 - 50 minutes
(39 slides)
Summary : Treatment for HIV has greatly evolved over the past few decades. With the use of combinations of agents has come the possibility of achieving response rates in treatment-experienced patients equal to that of treatment-naive patients. So under what circumstances should a change of therapy be considered? Dr. Phillips discusses the problem that is HIV-associated lipodystrophy syndrome, which consists of changes in fat distribution, but also of metabolic complications such as insulin resistance that make it more than a cosmetic issue.
The mechanism through which nucleotide reverse transcriptase inhibitors (NRTIs) cause lipodystrophy involves toxicity to the mitochondria, which results in loss of adipocyte mtDNA and consequent decrease in function. This is associated with a chronic inflammatory state. The severity of this change varies with the choice of treatment, being worse with d4T than with AZT, and with duration of treatment.
An important issue to consider is that the changes brought about through NRTIs are not completely reversible. It is therefore important to detect the changes early and prevent them by changing to newer regimens, which seems to have more benefit than any other intervention. Data has also been collected on the onset of diabetes with AZT/3TC, with insulin resistance prior to any apparent body fat changes, suggesting a different mechanism of action.
When changing HIV medication, however, there are several points to consider. There is data supporting the use of screening for HLA-B*5701 to prevent hypersensitivity reactions to Abacavir. As for Tenofovir, it is advised to measure the glomerular filtration rate to detect renal disease, especially in patients with risk factors such as low CD4+ and anemia. Different agents also vary in their penetration into the central nervous system, with better penetration leading to a decrease in viral load in this compartment and consequently less HIV-associated dementia and progressive multifocal leukoencephalopathy.
Learning objectives : After viewing this presentation the participant will be able to discuss:
-The pathogenesis and prevention of HIV-associated lipodystrophy syndrome.
-Other considerations for switching therapy.
Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, Jägel-Guedes E, Rugina S, Kozyrev O, Cid JF, Hay P, Nolan D, Hughes S, Hughes A, Ryan S, Fitch N, Thorborn D, Benbow A; PREDICT-1 Study Team.HLA-B*5701 Screening for Hypersensitivity to Abacavir N Engl J Med. 2008 Feb 7;358(6):568-79
Strategies for Management of Antiretroviral Therapy (SMART) Study Group, El-Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, Cohn D, Cooper D, Darbyshire J, Emery S, Fätkenheuer G, Gazzard B, Grund B, Hoy J, Klingman K, Losso M, Markowitz N, Neuhaus J, Phillips A, Rappoport C.CD4+ count-guided interruption of antiretroviral treatment N Engl J Med. 2006 Nov 30;355(22):2283-96
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