Temporarily stopping antiretroviral (ARV) therapy may turn out to be safe and advantageous in some circumstances, according to two studies presented at the Ninth International Congress on Drug Therapy in HIV Infection held in Glasgow and reported by AIDSmap.

Results from the Strategic Management of Antiretroviral Therapy (SMART) study have largely put the kibosh on the idea of HIV treatment breaks. The largest treatment interruption study conducted to date, SMART compared people who remained on continuous ARV therapy with people who either delayed or stopped treatment until their CD4 counts fell below 250 cells. In January 2006, the 5,500-patient study was stopped early because of more side effects, health complications and deaths among people who delayed or stopped treatment.

Data from the smaller LOTTI study, reported in Glasgow by Franco Maggiolo, MD, from the Ospital Riuniti in Bergamo, Italy, paint a more optimistic picture. In this clinical trial, where 329 HIV-positive people stopped and restarted treatment at higher CD4 counts than in SMART—700 cells and 350 cells, respectively—the rate of deaths and complications was similar among those who interrupted therapy and those who remained on continuous treatment.

The primary outcomes measured in the study were deaths, progression to AIDS or hospitalization for any reason. After an average of four years in the study, Dr. Maggiolo reported, 12 percent of those who took treatment breaks and 11 percent of those who remained on therapy reached one of these outcomes. People in the drug holiday group were able to remain off treatment 65 percent of the time, and people whose lowest-ever CD4 count was 500 were able to remain off treatment 85 percent of the time.

In direct contrast with SMART, there were actually 10 times as many cardiovascular and metabolic complications in the continuous therapy group in LOTTI than in the treatment break group. Maggiolo pointed to several possible explanations for the contradictory results. First, only 5 percent of patients in the LOTTI study ever had CD4 counts below 350 compared with 35 percent in SMART. Second, because SMART was stopped early, it may not have had enough time for cardiovascular and metabolic events to occur in the continuous treatment group.

A second treatment interruption study, presented by Cal Cohen, MD, from Harvard Medical School in Boston, tried a completely different approach. Called the FOTO study, for “Five On, Two Off,” this trial compared 42 people who stopped taking their meds for two days every weekend with people who remained on continuous therapy. All the patients took Sustiva (efavirenz) plus Truvada (tenofovir plus emtricitabine).

After 24 weeks, 83 percent of those who took treatment breaks had viral loads under 50 compared with 80 percent of those who remained on continuous treatment. Excluding study drop-outs—most left due to the intensive monitoring involved—100 percent of those who took treatment breaks had viral loads under 50, compared with 85 percent in the continuous treatment arm.

While there are still more data to be analyzed from LOTTI and FOTO, the authors of both studies suggest that treatment breaks may still have a future in HIV treatment, despite the results of SMART. This could be good news for people with HIV, who in the FOTO study overwhelmingly liked the option of taking a drug holiday every weekend.