In this study summary, Wafaa El-Sadr, M.D., of the Harlem Hospital Center and Columbia University, discusses the final results of the SMART study, which examined the risks and benefits of CD4-guided treatment interruption compared to continuous therapy. She spoke at a press conference that took place at CROI 2008.

Wafaa El-Sadr: These are the final results of the SMART study, the largest therapeutic HIV trial ever done.¹ As all of you know, there are millions and millions of people with HIV around the world, and now the standard of care is continuous. Once a person starts antiretroviral therapy, they need to continue for life on antiretroviral therapy.

Wafaa El-Sadr, M.D.

The goal of the SMART study, and other studies, was to try and see if interruption of treatment, using a variety of different strategies, might be associated with the benefits of antiretroviral therapy, but avoid some of the complications and the inconvenience of using antiretroviral therapy for life. Exactly two years ago, in February of 2006, we presented the interim results, which demonstrated at that point in time that using interrupted treatment, as used in the SMART study, was associated with worse outcomes, in terms of HIV complications or death. We recommended strongly that continuous therapy is the way to go. All the participants in SMART who were on the interrupted treatment were recommended to start continuous treatment.

Everyone in SMART was followed in a post-study modification period until last July to see what the effect would be in reversal of the excess harm that was seen in the interrupted treatment arm. Final results of SMART show that with resumption of treatment in the interruption group, there was a decrease in the risk of HIV complications or death. However, there was not full reversal of the risk. If you remember, the risk of complications or death was about more than twice in the interruption group at the time of the modification of the study. Today, the findings are that we decreased that to about 50% increase in the risk at this point in time. There's a decrease in the risk, but not full reversal of the risk.

What does this mean? What is the take-home message? I think what it means is that there was lasting effect of treatment interruption -- adverse effects of the treatment interruption. It's very important not to just look at what happens due to treatment interruption. But even when people resume therapy, there are lasting effects, detrimental effects, of treatment interruption, beyond the point of interruption itself, even after people have resumed treatment.

Reporter: In the SMART study, in the group that reinitiated therapy, was the excess risk related to HIV-related opportunistic disease and such? Or was it related to those excessages in the heart and kidney and liver that we're also seeing?

Wafaa El-Sadr: I think with the reinitiation of treatment, there was a decrease in excess risk for all of the above, for the HIV-related complications, for deaths, all cause deaths, as well as for the major cardiovascular, kidney and liver conditions. However, the statistically significant decrease was only shown for the combined endpoint. I think most of the decrease in excess risk was due to a decrease in opportunistic infections. Most of the deaths, however, were due to non-opportunistic infections.

This transcript has been lightly edited for clarity.

Footnote

1. El-Sadr W and the SMART Study Group. Re-initiation of ART in the CD4-guided ART interruption group in the SMART Study lowers risk of opportunistic disease or death. In: Program and abstracts of the 15th Conference on Retroviruses and Opportunistic Infections; February 3-6, 2008; Boston, Mass. Abstract 36.