The most effective HIV drugs. Researchers have identified a specific combination of three drugs that seems to be the best starting point for attacking HIV, the virus that causes Aids.
Delay of additional drug combos
Patients who were started on this particular regimen of zidovudine (ZDV or AZT), lamivudine (3TC) and efavirenz (EFV) delayed having to move on to additional drug combinations, a new study says.
A second report from the same study found that four-drug regimens were better than most three-drug regimens - except for this particular combination of zidovudine/lamivudine/efavirenz - in providing prolonged protection against the virus.
Chess game analogy
Dr Charles Gonzalez, a specialist in infectious diseases and immunology at New York University Medical Center's Aids Clinical Trial Center, compares the design of the study, and the treatment of HIV, to a three-dimensional chess game.
A doctor plays with the virus every day when he has to decide what set of moves he makes, Gonzalez says. If I make this, this and this move, what is the first best move? Then, after I've made that move, which first move allows me to make a second move if there's any problem. This study really does answer that question.
Gonzalez's centre had 20 patients involved in the trial.
Both reports appear in the Dec. 11 issue of the New England Journal of Medicine. The preliminary findings were presented at the 2002 International Aids Conference in Barcelona, Spain, and have already been incorporated into HIV/Aids treatment guidelines from the US Department of Health and Human Services (HHS).
Not a dramatic change in practice
This will probably not change practice terribly much because some of the preliminary data was infused into the (HHS) guidelines that just came out, Gonzalez says. This article essentially says the experts are right, in terms of what to start with.
Combination therapy has been the treatment of choice for HIV/Aids since the 1990s and has essentially transformed a sure killer into a disease that can be managed - at least in the developed world where patients can gain access to the medicines. When one drug combination stops working, as it often does, doctors switch the patient to another.
Many unanswered questions
Still, several questions remained unanswered, including what is the better regimen to start with and what is the better order to give the drugs in.
The clinical goal is to pick a regimen that patients tolerate and that provides a durable response and also keeps options open for the future knowing many patients are ultimately going to fail the first or second regimen, says study leader Dr Gregory Robbins, an infectious disease specialist at Massachusetts General Hospital.
First part of the study
The first part of the study compared four different three-drug regimens in 620 patients at 79 sites in the United States and Italy. The participants, none of whom had been previously treated, were followed for a median of 2,3 years, much longer than previous studies.
Although all drug regimens helped to control HIV infection, when it came to preventing Aids progression and death, the three-drug combination of efavirenz, zidovudine and lamivudine outperformed the other three drug regimens in preventing the initial failure, Robbins says. After 48 weeks on this regimen, about 10 percent of patients' drug therapies had failed, compared with 30 percent to 40 percent in the other three-drug groups.
There was something about the actual combination that appeared to make the regimen more effective, Robbins says. That's an area of active research for us to understand - the potential synergy of this combination.
Individuals receiving this combination also experienced fewer toxic side effects than those receiving the combination of didanosine and stavudine. Experts are now concluding this latter combination should be avoided when possible.
Second part of the study
The second part of the study compared a four-drug regimen with two consecutive three-drug combinations. Three hundred sixty people received one of two four-drug treatments: efavirenz and nelfinavir in combination with either didanosine and stavudine or zidovudine and lamivudine.
Although four-drug combinations were no more effective than sequential three-drug regimens, four-drug regimens delayed drug failure longer, except when compared with the efavirenz-zidovudine-lamivudine combination.
Since four-drug regimens may be more toxic, more expensive, more complicated and may limit future treatment options, the three-drug regimen emerged as the best option for initial therapy in this study.
Is four better than three?
The obvious question that we've all been asking in clinic is whether four is better than three and what this study showed is that they aren't any different than the sequential threes, but it is better for delaying the first failure, Robbins says. As a result, we don't need to use four drugs and expose people to additional toxicity, additional costs and potentially taking away that option in the future.
As a result of this and other studies, the guidelines for treating HIV/Aids are much more specific. The efavirenz-zidovudine-lamivudine combination is one of the three preferred initial regimens outlined by the HHS.
We now know that just selecting or substituting drugs as part of a regimen might change their potency, Robbins says. We don't understand that interaction. We need to explore that. - (health24.com)
Delay of additional drug combos
Patients who were started on this particular regimen of zidovudine (ZDV or AZT), lamivudine (3TC) and efavirenz (EFV) delayed having to move on to additional drug combinations, a new study says.
A second report from the same study found that four-drug regimens were better than most three-drug regimens - except for this particular combination of zidovudine/lamivudine/efavirenz - in providing prolonged protection against the virus.
Chess game analogy
Dr Charles Gonzalez, a specialist in infectious diseases and immunology at New York University Medical Center's Aids Clinical Trial Center, compares the design of the study, and the treatment of HIV, to a three-dimensional chess game.
A doctor plays with the virus every day when he has to decide what set of moves he makes, Gonzalez says. If I make this, this and this move, what is the first best move? Then, after I've made that move, which first move allows me to make a second move if there's any problem. This study really does answer that question.
Gonzalez's centre had 20 patients involved in the trial.
Both reports appear in the Dec. 11 issue of the New England Journal of Medicine. The preliminary findings were presented at the 2002 International Aids Conference in Barcelona, Spain, and have already been incorporated into HIV/Aids treatment guidelines from the US Department of Health and Human Services (HHS).
Not a dramatic change in practice
This will probably not change practice terribly much because some of the preliminary data was infused into the (HHS) guidelines that just came out, Gonzalez says. This article essentially says the experts are right, in terms of what to start with.
Combination therapy has been the treatment of choice for HIV/Aids since the 1990s and has essentially transformed a sure killer into a disease that can be managed - at least in the developed world where patients can gain access to the medicines. When one drug combination stops working, as it often does, doctors switch the patient to another.
Many unanswered questions
Still, several questions remained unanswered, including what is the better regimen to start with and what is the better order to give the drugs in.
The clinical goal is to pick a regimen that patients tolerate and that provides a durable response and also keeps options open for the future knowing many patients are ultimately going to fail the first or second regimen, says study leader Dr Gregory Robbins, an infectious disease specialist at Massachusetts General Hospital.
First part of the study
The first part of the study compared four different three-drug regimens in 620 patients at 79 sites in the United States and Italy. The participants, none of whom had been previously treated, were followed for a median of 2,3 years, much longer than previous studies.
Although all drug regimens helped to control HIV infection, when it came to preventing Aids progression and death, the three-drug combination of efavirenz, zidovudine and lamivudine outperformed the other three drug regimens in preventing the initial failure, Robbins says. After 48 weeks on this regimen, about 10 percent of patients' drug therapies had failed, compared with 30 percent to 40 percent in the other three-drug groups.
There was something about the actual combination that appeared to make the regimen more effective, Robbins says. That's an area of active research for us to understand - the potential synergy of this combination.
Individuals receiving this combination also experienced fewer toxic side effects than those receiving the combination of didanosine and stavudine. Experts are now concluding this latter combination should be avoided when possible.
Second part of the study
The second part of the study compared a four-drug regimen with two consecutive three-drug combinations. Three hundred sixty people received one of two four-drug treatments: efavirenz and nelfinavir in combination with either didanosine and stavudine or zidovudine and lamivudine.
Although four-drug combinations were no more effective than sequential three-drug regimens, four-drug regimens delayed drug failure longer, except when compared with the efavirenz-zidovudine-lamivudine combination.
Since four-drug regimens may be more toxic, more expensive, more complicated and may limit future treatment options, the three-drug regimen emerged as the best option for initial therapy in this study.
Is four better than three?
The obvious question that we've all been asking in clinic is whether four is better than three and what this study showed is that they aren't any different than the sequential threes, but it is better for delaying the first failure, Robbins says. As a result, we don't need to use four drugs and expose people to additional toxicity, additional costs and potentially taking away that option in the future.
As a result of this and other studies, the guidelines for treating HIV/Aids are much more specific. The efavirenz-zidovudine-lamivudine combination is one of the three preferred initial regimens outlined by the HHS.
We now know that just selecting or substituting drugs as part of a regimen might change their potency, Robbins says. We don't understand that interaction. We need to explore that. - (health24.com)
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