lec7 - Lecture 7: Antiretroviral Drugs At the beginning of...

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Lecture 7: Antiretroviral Drugs At the beginning of his second term in office, George W. Bush declared that one of the priorities of his administration was to find a cure for AIDS. Among scientists, however, this goal doesn’t really exist. In fact it could be said that the search for a cure effectively ended in 1983 when Luc Montagnier announced that AIDS is caused by a retrovirus. To cure a person, that is to rid the body of the virus, would require either removing all extracellular particles and killing all infected cells (which might kill the patient), or finding a way to excise the provirus from the DNA of all infected cells. This is very likely to be impossible. Therefore, if we are going to end this pandemic, our efforts must focus on prevention (vaccines or behavior change through education and leadership), and meanwhile we need to find ways to suppress the symptoms of HIV infections to extend life and reduce suffering for the infected. In the period from 1987 to 2005, 20 drugs and 5 combinations were approved and came to market in the US. (These are drugs aimed at HIV itself. There are many more aimed at opportunistic infections.) Drugs currently in use for the treatment of HIV infection fall into four main categories: nucleoside (and nucleotide) analog reverse transcriptase inhibitors (NRTIs, or “nukes”), non-nucleoside analog reverse transcriptase inhibitors (nNRTIs or “non-nukes”), protease inhibitors (PIs), and fusion inhibitors . The 20 drugs represent 7 nucleoside analogs, 1 nucleotide analog, 3 non-nucleoside RT inhibitors, 8 protease inhibitors and 1 fusion inhibitor. No individual drug as yet exists that can by itself eliminate the infection or even provide indefinite remission, because HIV is able to accumulate mutations rapidly, and thus resistance to individual drugs rapidly evolves within the virus population of any given patient. Indeed if you are infected with HIV today, you stand a 30 to 50% chance of being infected with a strain that has already acquired resistance to some anti-retroviral drugs through random mutation and selection following exposure to drugs in previous hosts. One recent study of HIV+ people who had not yet received any anti-retroviral therapy found that 50% harbored a strain of HIV resistant to at least one antiretroviral, and 14% had been infected with a strain resistant to two or more. In Britain it is reported that 13% of all new HIV infections are with viruses resistant to drugs in all 3 of the major categories (see below). Even worse, a report at the International AIDS Conference in Switzerland held in 2003 indicated that one strain of HIV has been found that is resistant to all known antiretrovirals, including the very recently developed fusion inhibitors. Last year a man in New York was found to be infected with an HIV strain that not only was resistant to 19 of the 20 drugs, but also caused progression from initial infection to AIDS in a few months rather than years. The same virus subsequently showed up in a person in San Diego. An industry is
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lec7 - Lecture 7: Antiretroviral Drugs At the beginning of...

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