Zidovudine (ZDV) and Lamivudine (3TC) Combination Therapy for HIV Infection - A Review.
Navarrete, Adauto Castelo
Abstract
Navarrete, Adauto Castelo
Abstract
The current state of knowledge regarding the treatment of HIV infection supports the use of antiretroviral agents in such a way as to maximize the likelihood of viral suppression for as long as possible. This goal is more likely to be achieved with the combined use of two nucleoside reverse transcriptase inhibitors (NRTIs) and a potent protease inhibitor (PI). Theoretically, there are 10 different ways of combining 2 NRTIs using the 5 NRTIs currently available on the market. However, some combinations are not recommended, e.g. zidovudine (ZDV) plus stavudine (d4T) or didanosine (ddI) plus zalcitabine (ddC), due to metabolism and toxicity considerations. The ingredients of an ideal combination should be highly potent as isolated drugs, should have different metabolic pathways, different target cells (activated versus resting cells), no overlapping toxicity and resistance profiles, and, of increasing importance, they should be easy to take with infrequent daily dosing in order to optimize patient compliance. The combination of ZDV and lamivudine (3TC) is probably the best documented association of 2 NRTIs. The combination has been through a full development plan and it has displayed many of the required characteristics. The combination of ZDV/ 3TC is thus considered a reliable component of any potent antiviral regimen aiming to maximize viral suppression.
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The current state of knowledge regarding the treatment of HIV infection supports the use of antiretroviral agents in such a way as to maximize the likelihood of viral suppression for as long as possible. This goal is more likely to be achieved with the combined use of two nucleoside reverse transcriptase inhibitors (NRTIs) and a potent protease inhibitor (PI). Theoretically, there are 10 different ways of combining 2 NRTIs using the 5 NRTIs currently available on the market. However, some combinations are not recommended, e.g. zidovudine (ZDV) plus stavudine (d4T) or didanosine (ddI) plus zalcitabine (ddC), due to metabolism and toxicity considerations. The ingredients of an ideal combination should be highly potent as isolated drugs, should have different metabolic pathways, different target cells (activated versus resting cells), no overlapping toxicity and resistance profiles, and, of increasing importance, they should be easy to take with infrequent daily dosing in order to optimize patient compliance. The combination of ZDV and lamivudine (3TC) is probably the best documented association of 2 NRTIs. The combination has been through a full development plan and it has displayed many of the required characteristics. The combination of ZDV/ 3TC is thus considered a reliable component of any potent antiviral regimen aiming to maximize viral suppression.
Key concepts: Didanosine, Lamivudine, Zidovudine, Stavudine, Zalcitabine, Reverse-transcriptase inhibitor, Pharmacology, Nucleoside analogue