HIV / AIDS Update July 27 from the 3rd International AIDS Society Conference
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 27, 2005
- Simplifying Therapy
- Single Drug Treatment Caution
- Other Important Studies with Lopinavir / Ritonavir
- New Regimens and Side Effect Profiles
- New Drug - Reverset
Welcome from the third and last day of the 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment in Rio de Janeiro Brazil. Many of the most important presentations related to the treatment of HIV infection occurred today. Many of these studies challenged current treatment strategies and described new drugs that may provide options for the future.
There were several studies testing new ways to use old drugs either in combination or alone. Two studies tested whether we can simplify therapy from a traditional combination of agents to a single drug. There were an updated report on the "OK Study" which took patients on combination therapy and either left them on this treatment or switched them to lopinavir/ritonavir (Kaletra) alone. Although the field moved away from single drug treatment many years ago, lopinavir/ritonavir is a unique option because it is very potent and rarely allows for drug resistance to develop. In fact, a small study reported last year showed that some people experienced complete viral suppression when taking this medication as single drug therapy. In the current study the majority of subjects did maintain viral suppression when continued on lopinavir/ritonavir alone although there were three individuals out of approximately 20 that did experience viral rebound. While this strategy holds some promise, it is a very small study and probably requires further research before it should be considered for routine care.
In a related study, subjects on antiretroviral therapy with undetectable viral loads were switched to lone therapy with once daily atazanavir (Reyataz) with ritonavir. This was also a very preliminary report but showed early promise for this strategy. Nevertheless, more experience and clinical research is needed before this should be seriously considered in the clinic.
An important reminder of the concerns of once per day lopinavir/ritonavir treatment came from a report of a patient who developed resistance to lopinavir/ritonavir. Such a report would not be noteworthy for most drugs but in this case it is only the fourth report of someone without previous protease inhibitor treatment prior to starting lopinavir/ritonavir developing resistance to this drug. In three of the four reports the person was taking this drug alone, and in the fourth it was said that the person missed many doses. Consequently, single drug treatment with lopinavir/ritonavir should be done with great caution until more research is performed. In fact, other studies are underway to further test this treatment strategy.
There were two other important studies related to more traditional use of lopinavir/ritonavir. One was follow-up of subjects enrolled in a pivotal study that established that lopinavir/ritonavir can be given as a once daily protease inhibitor. The drug was originally approved as three capsules twice per day until this study demonstrated that those who had never been on antiretroviral therapy did as well with six capsules once daily as they did with the standard twice daily dose. A major limitation to this study was that the six capsules once per day were associated with substantial more gastrointestinal side effect, particularly diarrhea than twice-daily dosing. Another presentation reported data using a new tablet form of lopinavir/ritonavir. In this case the equivalent dose given with capsules would be taken as only two tablets twice per day or four once per day. The study showed that the levels of drug in the blood were equivalent using the tablets as with the capsules. It is hoped that in addition to being less pills it will also cause less gastrointestinal symptoms, such as diarrhea. The latter remains to be seen in future clinical trials.
Follow-up data was also reported from an important study that compared a state-of-the-art well established drug regimen to another that has more recently become available. The standard option was zidovudine (AZT, Retrovir™) with lamivudine (3TC, Epivir) as the fixed dose combination of Combivir with efavirenz (Sustiva). This regimen is simple to take as one pill in the morning and two at night and is generally well tolerated. Another combination that has more recently been used uses tenofovir DF (Viread) with emtricitabine (FTC, Emtriva), which can now be used as fixed dose combination Truvada and efavirenz. This follow-up data was consistent with previous reports demonstrating that both regimens were very effective at suppressing viral load in blood; however, the tenofovir DF/FTC treated subjects had less side-effects, particularly less nausea and anemia. Although one of the concerns using this new regimen is the potential for more severe resistance developing than what is seen with the other treatment, this did not prove to be the case, as least thus far. Consequently, it is reasonable to consider either regimen, recognizing that side effect profiles may differ.
Data on an important new drug was presented at one of the closing sessions of the meeting. This medication is known as Reverset and is a nucleoside reverse transcriptase inhibitor that was previously shown to be active in the test tube against viruses that were resistant to many other related drugs. There have also been small studies with short term follow-up showing that viral load declined in those with drug resistant virus treated with Reverset. The current study extended the previous observations showing that this drug is effective in reducing viral load in those with highly resistant virus. Further studies of this drug will certainly be reported at future meetings and there is great hope that this will prove to be an important options for many treatment experienced patients in the future.
Go to our HIV / AIDS center for more information.
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