Most of the STI studies so far have been small and exploratory in nature, primarily seeking to determine the safety of such a strategy. Results are emerging from one larger European STI study, which is looking at the safety as well as the effectiveness of this kind of approach to treatment.
A slight variation on previous studies, called SIT (Structured Intermittent Therapy), seeks to determine whether carefully planned bursts of intermittent therapy might sustain viral control while reducing the cost of treatment. Early results of two such studies have been reported by the National Institutes of Health (NIH). The first study enrolled eight people who started on cycles of seven days on anti-HIV therapy [d4T+3TC+ indinavir (Crixivan) + low dose ritonavir (Norvir)] and seven days off therapy. The seven-day cycle was selected because previous studies have shown thatamong people receiving optimal anti-HIV therapyit generally takes at least seven days before viral loads climb back up to detectable levels over 500 copies HIV RNA after therapy is discontinued. "Failure" in this study is defined as having a viral load above 500 copies HIV RNA on two consecutive tests or more than a 25% drop in CD4+ cell counts on two consecutive measurements.
After 14 weeks, seven out of the eight participants continued to maintain viral loads below 500 copies; the one person who did not had forgotten to take his medications with him on vacation. While these results are very preliminary, they are encouraging and warrant further exploration.
The second SIT study only enrolled three people on a cycle of two days on therapy (same regimen as above) and five days off. All participants had maintained viral loads below 500 copies for at least six months before starting the new treatment cycles. Results from this study have not been as encouraging with only one person maintaining viral loads below 500 copies HIV RNA after 14 weeks. The other two participants both had detectable viral loads at some point during the off therapy period. However, once anti-HIV therapy was restarted both had viral loads return to undetectable levels. Based on the disappointing results, this study will not be continued.
Further preliminary results have been presented from the Swiss Spanish Intermittent Treatment Trial (SSITT). We previously reported on this ongoing study in PI Perspective 30. The study includes 122 people with viral loads below 50 copies HIV RNA and CD4+ cell counts above 300. It is evaluating cycles of eight weeks of anti-HIV therapy followed by two weeks off therapy, for a total of four cycles. At the end of the four cycles (week 40) everyone stops anti-HIV therapy, which is then only restarted if viral loads rise above 5,000 copies at week 52.
During the first two-week interruption, 28 people had no detectable viral load, in other words all had less than 50 copies HIV RNA during the two weeks off anti-HIV therapy. However, fifteen people had a high rebound in viral load (reaching over 100,000 copies HIV RNA) during the interruption. A preliminary analysis of the first 56 people who completed all four cycles showed no general trends in patterns of response. Almost equal numbers of people had widely differing responses during each interruption (some had roughly the same viral load levels during each interruption, others had viral loads that increased with each interruption, still others had viral loads that decreased with each interruption). Of note, there were eight people with no viral load rebounds, whatsoever, during the four interruptions. There is no known reason why these eight people responded differently than the rest of the group. The final results from this study are expected by the end of this year.
Another ongoing STI study is being conducted at the NIH. Seventy people are participating with half taking an STI and the other half taking continuous anti-HIV therapy. The STI cycle for this study is two months on and one month off therapy. Early results suggest that there is a trend towards a lower rebound of viral load with each interruption. These results are, at least for now, different than what has been seen in the SSITT study.
Further analysis of the results from the SSITT study and the STI study from the NIH is needed to try to understand whether there is a reason some people seem more likely to benefit from this kind of treatment strategy or whether their success if merely a coincidence.