Stopping Therapy

Another pressing question in HIV care is whether it is possible to stop all treatment for a period of time in a structured treatment interruption (STI). There are several reasons that STIs may be beneficial. The first is that "autoimmunization" might occur if treatment is stopped. In the absence of therapy, the virus has a chance to replicate, and the immune system is reminded of HIV's presence and may try to fight the virus on its own. Another reason that STIs may be beneficial is that side effects may be reduced when treatment is withheld. A third reason that STIs may be beneficial is that the most common strain of HIV may revert to wild type (fully drug-sensitive virus) in the absence of medication. This could be especially important for people who have exhausted their treatment options and have highly resistant virus.

Studies of STIs have looked at three different groups of patients: those with primary infection (just after the initial infection with HIV), those with chronic infection (infected for more than a few months) with suppressed viral load, and those with chronic infection without suppressed viral load. Mr. Harrington highlighted a study performed by Deeks et al. at the University of California at San Francisco. Nineteen patients experiencing virologic failure (viral load more than 2,500) had an STI that averaged 18 weeks before going back on therapy. Many experienced a sharp drop in CD4 cells and an increase in viral load during their STI. After therapy was restarted, CD4 counts increased, and viral load dropped below 50 in 9 out of the 19 patients. Patients who added a new class of drugs were more likely to have a viral load less than 50 copies than those who didn't add a new class of drugs. Patients who failed their new regimen were likely to develop the same resistance mutations that they had pre-therapy.

Mr. Harrington then discussed a study of patients in primary infection who attempted an STI. The study enrolled ten patients who were within 2 to 5 ½ months of initial infection. All ten patients had an undetectable viral load when they stopped therapy, and four of those ten patients remain off therapy while six have restarted due to virologic failure. In comparing people who remain off therapy to those who had to restart, patients off therapy had a lower initial viral load. Mr. Harrington is optimistic about the utility of STIs in HIV treatment, and encourages patients who are interested in STIs to join a clinical study.

Once a Day, Please

Dr. Roy Gulick gave the second presentation of the evening, focusing on ways to simplify HIV treatment. Adherence to antiretroviral therapy is the key to its success, but life sometimes gets in the way of taking medications exactly the way they are supposed to be taken. The current trend is to create regimens that are as easy to take as possible. Researchers and pharmaceutical companies are aiming for once-a-day regimens that are as effective as twice-a-day regimens. An Italian study of a once-a-day regimen (Sustiva+Videx+Epivir) showed effectiveness (78.3% of patients were undetectable after 48 weeks of treatment) with a low level of side effects. A second option for once-daily therapy was studied by a group of French researchers. The combination of Sustiva, Videx and Coviracil (FTC, an investigational, once-a-day NRTI from Triangle Pharmaceuticals) was shown to be effective and safe over a 64-week study.

Another step in creating simpler regimens is the clinical development of BMS-232632, an investigational once-daily protease inhibitor. Results from AI424-007, a 48-week study of BMS-232632, compared the new protease inhibitor with Viracept (nelfinavir), both in combination with Zerit (d4T) and Videx (ddI), in treatment-naïve subjects. BMS-232632 showed favorable early results and will undergo further clinical trials.

Do you blip?

The scientific term is intermittent viremia, but most of us know them as "blips," the temporary increases in viral load above the level of detection that often go away by themselves. In the second segment of his presentation, Dr. Gulick discussed blips, explaining that some think they may actually be beneficial, as they expose immune system cells to HIV and stimulate HIV-specific immune responses. Researchers from UC San Diego found that over half of 21 patients studied had blips, and that there was no difference in virologic failure rates for patients with or without blips. They did not find evidence of immune "boosting" with the viral load blips.

A study out of Switzerland and Germany also examined blips, and found that about 32% of the 1,858 patients enrolled experienced a blip at some time. A single blip had no impact on whether a patient eventually experienced virologic failure, but a sustained viral load level between 51 and 500 copies was associated with a 4X higher risk of virologic failure and should be followed closely.

Switching Therapy

Making a decision to switch medications can be tough, especially for people with few treatment options. Several presentations at the conference focused on salvage (or rescue) therapy. Dr. Gulick highlighted a study of Kaletra and Sustiva used as salvage therapy in patients with previous experience with at least two protease inhibitors, but no prior NNRTI experience. 57 patients joined the study, and were treated for 48 weeks with Kaletra, Sustiva, and two NRTIs. 68% of patients had virus that was resistant to more than three protease inhibitors when they started the study. The salvage regimen showed good efficacy, with 65% of patients reaching an undetectable viral load.

An up-and-coming treatment from a new class of drugs called fusion inhibitors also received attention at the conference. Fusion inhibitors prevent HIV from fusing with the T-cell membrane and infecting the cell. Researchers studied a combination of Ziagen, Agenerase, Norvir, and Sustiva, given alone or with T-20 (an investigational fusion inhibitor) at one of three doses. Subjects in the study had failed at least one protease inhibitor but had never taken NNRTIs. The addition of T-20 boosted the effectiveness of the antiretroviral therapy, leading to larger drops in viral load and greater CD4 count increases. T-20 must be given as a subcutaneous injection (beneath the skin), and there was a high frequency (65%) of injection site reactions. The drug is currently undergoing further testing in large clinical studies.

Stopping Therapy

Dr. Gulick also commented on STIs. While Mr. Harrington feels that they have potential, Dr. Gulick feels that there is not enough information to draw any conclusions. He has concerns about the safety of STIs, as they can cause a significant drop in T-cells and in some cases have been associated with new clinical illnesses. He feels that the case for STIs is more compelling in primary infection than in chronic infection, but that further research is necessary and that patients should not "try this at home."

We are getting closer to answering some of the big questions in HIV treatment, but more research is necessary to solve the many remaining mysteries. Mr. Harrington and Dr. Gulick were encouraged by the tone of activism at the conference and the continued dedication of researchers and patients working together to find answers.