July 9, 2001
Winter in this part of Argentina is not very wintry. In fact, we have had some really warm weather in the 80s. The meeting is pleasant, the town is interesting and the wine and the beef are spectacular!
This is a study designed to address the most burning issue in HIV drug development today: Is once-daily dosing possible for most regimens? This will reduce pill burden and adherence to treatment and make life generally better for anyone taking antiretrovirals. The easier it is to take the medication, the more likely most people will take it. The benefits of once-daily dosing don't really have to be explained to most people.
The study design is a unique one looking at the same combination of drugs, Abacavir, 3TC and AZT, in three arms. The first arm is the standard one of all three drugs given twice per day. The second arm is 3TC given once daily and the others given twice daily. The third arm is abacavir given once daily and the other two twice daily. This is a factorial design.
The other unique thing about this study, other than that it was performed in Thailand, was its demographics. Of the 151 patients enrolled, 100% were Asian (Thai), 70% were female, which is very high for an HIV study, and 99% contracted HIV through heterosexual sex.
The results were not surprising. The virologic drops were basically the same in all three groups (about 2 logs), the CD4 increases were about 150 cells and about 90% of the patients got to <400 copies of HIV at 24 weeks. That means that once-daily 3TC and once-daily abacavir are equal in efficacy to twice-daily administration.
In terms of side effects, there was 10% anemia in the standard twice-daily regimen, 4% in the 3TC daily arm and 0% in the abacavir arm. It was not clear if this was statistically significant, but might be for patients experiencing anemia. The only down side noted on this study was the occurrence of the M184V mutation in HIV which confers resistance to 3TC in 67% of the patients in the 3TC arm 57% in the abacavir arm and only 50% in the standard twice-daily arm. This might mean that patients taking 3TC once daily may be more susceptible to viral resistance. On the other hand, this is not necessarily a bad mutation, because it increases susceptibility to AZT. Hypersensitivity to abacavir was seen in 8% of the patients in the twice-daily arm and 8% in the abacavir once-daily arm, so giving it once daily posed no increased risk.
Overall this is a good result, indicating that both 3TC and abacavir can be used once daily. AZT will probably not be a once-daily drug. If 3TC and ABC were combined in one drug they could be administered once daily with one of the new once-daily drugs and make for a combination of two, three or four pills administered once daily for good control of HIV. This would make a great deal of difference to patients who would like easier-to-take regimens. All of us in the field are looking for ways to make life easier for our patients and this is a step in the right direction.