Dr. Eric Daar presents highlights and daily summaries from the 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment in Rio de Janeiro, Brazil. (held July 24-27 2005)
HIV / AIDS Conference - Tuesday July 26, 2005
Welcome from day 2 of the 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment in Rio de Janeiro Brazil. Hundreds of presentations were made on day 2 of this meeting with many being informative about the disease itself, select side-effects and treatment.
The morning plenary sessions elegantly described important new science related to the immune system and genetic factors that influence HIV disease. Sarah Rowland-Jones from Cambridge provided an overview of how the immune system attempts to fight HIV infection. Perhaps most revealing was discussion as to how much we still need to learn about the body's response to HIV before we are likely to be able to develop and effective vaccine to prevent infection.
Genetic Studies and AIDS
Professor Telenti from Switzerland reviewing genetic factors that influence the behavior of HIV in a given individual, as well as how such factors might be used to predict who is at risk for select drug toxicity. Genetic studies have been a growing area of interest in all aspects of medicine including in the field of HIV. Studies have attempted to identify what is different in the genes of those who experience disease progression slower or quicker than others. After all, one of the most intriguing aspects of this infection is that disease progression occurs at such different rates with some developing AIDS within a few years of infection while others remain asymptomatic with essentially normal immune system for more than a decade. In fact, several genes have been identified that may account for these differences. The same has been shown for select side effects from medications, such as predictors of developing severe allergic reactions to select drugs such as abacavir (Ziagen). Although at this time we do not have technology to change peoples genes these types of studies may provide a means by which we can better assess ones risk of disease progression, or who is at risk for developing important side effects from select medications. Currently such genetic testing is mostly limited to research settings until more is learned.
CCR5 Blockers and HIV Suppression
Studies of how unique genetic characteristics influence disease progression has led to some clinical advances. It was the discovery that there is a secondary receptor on the surface of CD4 cells (the targets for HIV infection) and that some remain healthy with delayed progression if they have a specific genetic alteration in this gene that led to the development of new class of drugs to combat HIV infection. At this meeting there was data presented on two new drugs being developed to block one of these co-receptors, referred to as CCR5. In fact, CCR5 blockers are being simultaneously developed by three different companies. The data presented on the drug called maraviroc and SCH 417,690, both demonstrating excellent HIV suppression in blood with short term therapy and to be very well tolerated. Larger studies are underway with these drugs, as well as one being developed by a third company, to define the utility of these promising agents in those who are starting antiretroviral therapy for the first time and who are drug experienced with limited options. These are very promising agents for the future and offer people living with HIV great hope in their individual battles against HIV infection.
Limitations of Current Therapy
While these studies show great promise for the future, other studies demonstrated limitations of current therapy, including one showing how didanosine (Videx and tenofovir DF (Viread), both agents that are very effective as part of combination therapy should not be used together as part of a first line regimen. In this case, the study showed what these drugs combined with efavirenz (Sustiva) had led to an unacceptable failure rate. This does not necessarily mean that those doing well on this combination should necessarily stop, just that it should be avoided when possible as up front therapy. Further studies reviewed available literature on a potential toxicity associated with tenofovir DF, namely kidney problems. There were several studies that looked at this carefully and while many did show some mild decreases in kidney function in those on this drug, the change was for the most part quite modest and remains of unknown clinical significance.
Use of Multiple Active Drugs
There were several important presentations related to the management of those highly-treatment experienced with antiretroviral therapy and who have developed resistance to many drugs. One study showed data from those treated with the recently approved protease inhibitor tipranavir (Aptivus) with very high rates of viral suppression. This was particularly true when it was used with another active agent, enfuvirtide (T-20, Fuzeon). The importance of using multiple active drugs in a new regimen had been shown before and demonstrates that the new protease inhibitor is an important option for those with drug resistance. For many with drug resistance starting a new regimen they will use enfuvirtide as a second active agent. Enfuvirtide works at a unique step in the virus's replication cycle and is administered with a small needle under the skin twice per day. While the drug is very effective its use is limited by the need for injection and the resultant local skin redness and pain that are occasionally associated with its use.
Another important presentation described the experience in those who had achieved undetectable levels of virus on an enfuvirtide-contain regimen that then either continued the same therapy or were followed after stopping the enfuvirtide part of the regimen. This was a very small study but did show a few more individuals experiencing viral rebound after stopping treatment than those who did not. Consequently, if undetectable levels of virus are achieved on such a regimen stopping the enfuvirtide should be done with caution.
There was another presentation at this meeting demonstrating that enfuvirtide can be used with a new needleless system that provides equivalent amounts of drug with less skin reaction. While preliminary, this might offer important new options for patients in the future.
Go to our HIV / AIDS center for more information.
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