• The ADAM study: maintenance therapy after 50 weeks of induction therapy (Poster Presentation TuPpA1154)
  Authored by M.H. Reijers, G.J. Weverling, S. Jurriaans, H.M. Weigel, R.W. Ten Kate, J.W. Mulder, H. Schuitemaker, J.M.A. Lange

• Once-a-day indinavir therapy in virologically controlled HIV-positive persons (Poster Presentation TuPpA1155)
  Authored by F. Maggiolo, M. Rizzi, G. Finazzi, F. Suter

The ADAM study: maintenance therapy after 50 weeks of induction therapy (Poster Presentation TuPpA1154)

Over the past few years there have been numerous studies exploring ways to decrease the number of medications needed after HIV suppression has been achieved. Could someone start on a standard three- or four-drug cocktail, and after the viral load was below 50 copies, decrease the number of medications to just two medications and maintain suppression?

So far, the answer has been no, and this study gives us one more approach that did not work to accomplish this method of simplification. They report on a study which explored an initial four drug combination of d4T, 3TC, nelfinavir and saquinavir. After a period of time, if the viral load was below 50 copies, participants would reduce the number of medications to just two instead of four, and the study monitored to see if viral load rebound would occur. Earlier reports from this study showed rebound if the combination was simplified after just 24 weeks. Here they report that even if we wait until one year of treatment has been completed, and then simplify to just two medications, there is still prompt rebound of virus in those who try to reduce the number of medications in the combination. Indeed, rebound occurred just as fast in those who simplified at week 52 as compared to those who simplified at week 24, in each case there was an average of about six weeks for the return of a viral load over 50 copies.

To date, all of the studies using this approach have not shown us a way to define a combination that can be later simplified by reducing the number of medications used. Waiting for a year on an initial combination is not long enough to allow us to then simplify the combination. It appears from this and other research that defining successful simple combinations at the beginning of treatment is going to be necessary, rather than starting with a more difficult combination at the beginning and planning to simplify it at some later point. Fortunately, in the past few years, there have been a number of examples of simpler combinations that have also been successful at maintaining viral control.

Once-a-day indinavir therapy in virologically controlled HIV-positive persons (Poster Presentation TuPpA1155)

Given that we cannot simplify the number of medications in a cocktail, as shown in the above study (A1154), research has instead focused on ways to simplify the ways in which the medications are taken. A lot of work has explored ways to facilitate once-a-day dosing for all medications. In this study, once-a-day indinavir is studied. This protease inhibitor was originally taken every eight hours. Here, the researchers took patients who had a viral load of <50 on indinavir and changed the way indinavir was taken by changing to 1,200mg of indinavir and adding 100mg of ritonavir. This same approach was taken by several studies in the past few years, as ritonavir prolongs the time indinavir remains in the body. Based on previous studies, this dose appears to maintain an adequate amount of indinavir even when it is taken just once a day.

Twelve participants were enrolled, all of whom had been on indinavir at the standard dose for about 40 months. After 16 weeks, the authors report that all participants maintained a viral load below 500 copies after this new dosing was initiated. Two participants did complain of pain consistent with kidney stones, which is a concern for this approach -- given the higher peak level of indinavir that is seen, since the dose is 1,200mg rather than just 800mg at a time.

This study has interesting preliminary findings, although it is too soon to adopt this dose since only 12 people were followed here for only 16 weeks. More follow up is needed to find out how safe and successful this approach will be. Other studies are already underway to characterize the safety and effectiveness of indinavir when ritonavir is added. There are at least three different ways that this has been done -- either 400mg of both ritonavir and indinavir twice a day, 800mg of indinavir with either 100mg or 200mg of ritonavir twice a day, and now this once a day study. Each approach has potential reasons why it is attractive, and more work is ongoing to better define the ways that indinavir can be dosed. However, it is fair to say that virtually no one needs to take indinavir every eight hours as initially dosed since these other approaches all make indinavir an easier medication to use.