The Body Covers: The 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention
IAS 2007 Study Summaries: An Interview With Daniel J. Skiest, M.D.
July 25, 2007
My name is Daniel Skiest. I'm from Baystate Medical Center in Springfield, Massachusetts. The study is a sub-study of ACTG 5170, which was a study of [HIV] treatment interruption. Patients generally had high CD4 counts, never had a low CD4 count and wanted to stop therapy.
What do you mean by high?
Their CD4 counts had to be over 350 cells/mm3 and could never have been below 350 cells/mm3 prior to initiation of their initial antiretroviral therapy. They voluntarily interrupted the therapy, and then we followed them for up to two years. The primary study, which has already been published, showed that patients generally did very well. They had a very low rate of events in terms of CDC [U.S. Centers for Disease Control and Prevention] category B or C events, which are minor or major opportunistic infections. They tolerated [treatment interruption] very well.
We found out that their CD4 nadir and their viral load before therapy were predictive of their outcomes in terms of advanced CD4 count drop. In this particular study, we looked at their quality of life when they stopped therapy. We had 167 patients. We assessed their quality of life with several instruments. We looked at an overall "Likert scale," rating their quality of life from 0 to 100 [A Likert scale measures to what extent a person agrees or disagrees with a question. It is one of the most common scales used in research using surveys.] We did something called "the Symptoms Distress Form," which had 20 symptoms. We summarized those symptoms, and rated bothersome symptoms -- three or four on a scale of one to four were considered bothersome. We did something called a multidimensional health status, which was 20 questions. All of these have been validated in other studies.
Most of the patients had a very high CD4 count when they entered the study. The median CD4 count was 833 cells/mm3. The patients were generally doing very well. Most were undetectable. The median viral load was less than 50 copies/mL when they started. The median nadir CD4 count was 436 cells/mm3, so the patients were generally doing very well. They had been on therapy for about 4.5 years. About a third were on a nucleoside [nucleoside reverse transcriptase inhibitor] regimen, an NNRTI [non-nucleoside reverse transcriptase inhibitor] and a protease [inhibitor]-based regimen. The bottom line is that the mean quality of life scores over time did not really change over the 96 weeks, over two years.
Then we looked at all symptoms and bothersome symptoms at different time points. Some of the symptoms, some of the bothersome symptoms, got worse at week 24 and then sort of leveled out. Overall, symptoms didn't change much.
Can you characterize "bothersome?"
Bothersome symptoms [were those] the patients rated as three or four on a scale of zero to four.
And particularly, what were they?
Symptoms that they had included feeling nervous, feeling sad, feeling nauseous, and having difficulty falling asleep.
That sounds like it's psychological rather than medical.
Some of it may have been. That may have been an issue, being on therapy or not being on therapy. It's hard to say how much is medical and how much is psychological. Basically, the quality of life remained high. In any parameter, it didn't get worse when they stopped therapy. The patients generally liked being off therapy. The overall number of symptoms actually improved while they were off therapy.
Did you have any coinfected patients, with hepatitis C or B?
We did have some with hepatitis C or B. We didn't look at them separately, though.
You don't know if they did better or worse?
Correct; I can't answer that question.
This study is sort of an alternative to the SMART study.1 Meaning, everyone got so scared about treatment interruptions, but this study seems to suggest that treatment interruptions are still possible. Did you have any cardiovascular events or deaths?
We did have five deaths. We had no controls. Three of those deaths may have been cardiovascular. When we looked at them -- with all the data that we had -- three of them may have been cardiovascular. Again, there was no control. Many of the patients were smokers. Two of the patients had already had prior cardiovascular disease before entering the study. They had a history of heart attack. One of the patients had previously undergone a bypass surgery. We have to keep this in mind: These patients have HIV, but they also have comorbidities. [The deaths] could've happened anyway. We don't know whether it was related to [stopping treatment].
I notice from your data that this was an older group. The median age was 42.
Forty-two. As with most HIV studies, you see the median age is getting older and older. It used to be in the 30s, now it's in the 40s. The patients are older and they're getting more comorbidities. Overall, the difference from the SMART study though is: The SMART study had a CD4 of 250 cells/mm3 for restarting [therapy]. All of the patients in this study were over 350 cells/mm3. Other trials, which used higher CD4 thresholds, showed that outcomes may be OK.
Staccato, right. Staccato was the one I was mainly thinking about. In general, we certainly don't want patients to stop [HIV] therapy. In carefully selected patients -- those who are having problems with their therapy, can't afford therapy, or are getting treatment fatigue and are at risk for stopping on their own -- [a treatment interruption] may be OK if it's carefully supervised. If you pick the correct patient; that is, a patient who you know is going to do well, because they have a high CD4 nadir, and well controlled [viral load], etc.
Click here to view the study abstract from Dr. Skiest's presentation.
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