Coverage of CROI 2008 (Conference on Retroviruses and Opportunistic Infections)

February 4–6, 2008, Boston, MA

SMART study reports on re-starting ART

February 4, 2008

In what might be the final large presentation from the landmark SMART study, researchers reported that people who re-started HIV treatment on the recommendation of the study experienced significant immune recovery and improved survival. Today’s CROI presentation showed that participants in the intermittent treatment group of SMART who chose to re-start treatment gained most, but not all, of the benefits experienced by people in the continuous group. This marks another important chapter in the strange odyssey of SMART.
                 
SMART was the largest randomized, prospective trial ever done in HIV. It compared two treatment strategies: CD4 guided intermittent treatment (drug conservation or DC group) vs. continuous treatment (viral suppression or VS group). As widely reported, enrolling in SMART was stopped early, and the study was altered when an early look at the data showed much higher rates or opportunistic and non-opportunistic diseases and death for people in the DC group. After enrollment was stopped, all the participants were informed of the results. Anyone in the DC group who had stopped taking HIV drugs was recommended to start HIV drugs.

The study presented today at CROI looked at this group. The combined risk of opportunistic diseases and death dropped by about half (from 3.4 to 1.9 per 100 person years). This risk remained somewhat higher than in the VS group, at 1.4 per 100 person years. Similar reductions were seen in rates of cardiovascular disease, where the incidence went from 1.8 to 1.1 in the DC group, still above the 0.9 in the VS group.

People who chose to re-start HIV drugs in the DC group also showed higher CD4 counts, but they remained below the levels at the start of the study. This confirms results from other treatment interruption studies showing that immune recovery is slower after interrupting treatment compared to starting treatment.

The designers of the SMART study had hypothesized that by reducing the amount of time that a person was exposed to HIV drugs, they would likely have lower rates of heart disease and other problems thought to be linked to the drugs. The results showed just the opposite and made many question the wisdom of treatment interruptions. It also highlighted the growing understanding of the damage that untreated HIV does to the body.