Learning from drug changes in antiretroviral therapy

aAIDS Research Institute, IrsiCaixa-HIVACAT, Institut d'Investigació en Ciències de la Salut Germans Trias i Pujol, Universitat Autònoma de Barcelona bFundació Lluita contra la SIDA, Badalona, Catalonia, Spain.
AIDS (Impact Factor: 5.55). 03/2013; 27(5):833-834. DOI: 10.1097/QAD.0b013e32835c1213
Source: PubMed


In middle 1990s, the availability of nucleoside analog and non-nucleoside analog inhibitors of the HIV reverse transcriptase (NRTI and NNRTI, respectively) and inhibitors of viral protease (PIs) allowed for the introduction of treatments combining different families of antiretrovirals. This approach was defined as HAART and is currently known as Combined Antiretroviral Therapy (cART). Initial cART combinations included three drugs (two NRTI and a PI or NNRTI) and achieved a durable reduction of HIV replication in HIV-infected patients, resulting in a sharp reduction in AIDS-related deaths and opening a new era in HIV treatment. With HIV replication under pharmacological control, new problems emerged. Resistance to cART resulting in virological failure was rapidly reported, mostly in suboptimally treated individuals [1]. An additional relevant fraction of patients showed short-term drug toxicity or a range of long-term side-effects associated with different drugs or combinations. This fact added complexity to the management of dangerous inflammatory sequels of viral replication [2]. Moreover, the requirement of a lifelong treatment uncovered an additional problem, the adherence to treatment, which was rapidly identified as a source for the appearance of resistances and increased risk of comorbidities. Several attempts to lessen these problems were explored, including proactive treatment switch [3], treatment simplifications [4], structured treatment inter-ruptions (STIs) [5] and development of new drugs. Although the former strategies are still under debate, the use of STI was ruled out by the compelling data of the Strategies for Management of Anti-Retroviral Therapy study [5]. The availability of new drugs (more than 20 antiretrovirals are currently available in developed countries) has broaden drug choice and has improved the patient acceptance and satisfaction to treatment, as well as safety profile of new regimens. However, the definition of the best available starting cART is hampered by the lack of data on the exact impact of long-term durability of different regimens. Under the premise 'never change a winning team', the knowledge of how often a combination regimen is changed can be a good surrogate marker of its success. Moreover, the analysis of the reasons leading to drug change may point up the main limitations of cART regimens, and therefore may help to bring regimens closer to the best achievable setting.

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