Salvage Therapies – New drugs offer hope to patients with multiple-drug resistance HIV virus. By Nelson Vergel
I have been HIV positive since 1983 and tested in 1986. Like many long- term survivors who started nucleoside monotherapy (AZT, D4T, DDI) in the late ’80s/early ’90s, I have developed multi-drug resistance. Over 40 of my friends have died either of opportunistic infections or drug resistance. Many of my friends who are living now have under 50 CD4 and are trying to survive. Most of us have added every new drug as it got approved to failing regimens (what we call sequential or virtual monotherapy), which rendered them useless in a few weeks or months. Most of us are taking drugs that we have resistance to in hopes that they keep viral replication capacity (viral fitness) down. Many of the people who show up to my lectures are also going through this problem, yet all we hear in the media and conferences is how well people with HIV in the developed world are doing!
After 25 years of the AIDS epidemic, 17 new drugs belonging to four drug classes are available in the U.S. As a result, mortality and morbidity have decreased significantly in the HIV-infected patient population. Unfortunately, an increasing number of patients living with HIV are developing resistance to all available nucleosides, non-nucleosides, protease inhibitors, and the latest fusion inhibitor (Fuzeon), making it impossible for them to construct viable drug combinations for effective control of HIV replication. Of an estimated 400,000 people under treatment for HIV in the United States, 14-20% of these may have multi-drug resistance (MDR). This means that as many as 80,000 patients are running out of life-saving options, increasing the risks of opportunistic infections and death. Additionally, an estimated 40,000 new HIV infections occur in the U.S. annually. Up to 14% of these, or 5,600 patients per year, have acquired resistance to three drug classes.
Fortunately, there are eight new agents offering hope to patients with MDR virus. These include one fusion inhibitor (Fuzeon), one protease inhibitor (Tipranavir-Aptivus) that got approved last year, and several drugs in Phase III trials (one protease inhibitor called TMC 114, one non nucleoside called TMC 125, an integrase inhibitor called MRK-518, two entry inhibitors called Maraviroc and Vicriviroc, and a CD4 antagonist called TNX-355 that will be given only every two weeks). Within a year, all or most of these products will be available to patients in need via expanded access programs. The key for many is to buy time and stay healthy until this new wave comes through!
Clinical guidelines dictate that at least two to three active medicines (that your virus does not have resistance to) be present in a drug combination for patients with multiple drug resistance (MDR). Unfortunately, these new drugs have been only available in a sequential monotherapy manner (adding one “active” drug to a failing combo) through clinical research. Most studies do not allow the use of other investigational agents in combination, making it impossible in many cases for MDR patients to avoid sequential monotherapy. This approach encourages further development of drug resistance in patients participating in such research protocols and will not help us survive.
Luckily, we will be able to combine several new medications in the next year, so I encourage everyone to talk to their doctor and also keep abreast of the latest information. For those who have low T cells and have declining health, doctors can access some of these new drugs through emergency access.
For more information, e-mail Nelson Vergel at firstname.lastname@example.org and visit his web site www.salvagetherapies.org.