PI Perspective #24

April 1998     View PDF

Lower Dose Maintenance Therapy

Two recent studies asked whether it is possible to switch to a “less potent” maintenance anti-HIV regimen after sustaining HIV RNA levels below 200 copies for at least 2 months. The hope would be that once initial HIV RNA levels are brought under control, “maintaining” viral suppression with a less potent antiviral approach could offer the potential to decrease the complexity of regimens that people are taking for the long-term.

Overall, the “less potent” maintenance regimens were not as effective at sustaining viral suppression compared to a three-drug, highly active antiretroviral therapy regimen. One study followed 509 people with a median CD4+ cell count of 450 and a median viral load of about 20,000 copies HIV RNA who had not previously been on 3TC or a protease inhibitor. Forty-three percent had previously been on AZT. All participants received AZT + 3TC + indinavir for six months. If the participants had HIV RNA levels decrease to below 200 at 16, 20 and 24 weeks, they then received either AZT + 3TC, indinavir alone or stayed on AZT + 3TC + indinavir as a maintenance regimen. At the time of the preliminary analysis, 316 people were on the maintenance phase. Viral rebound was defined as any return of viral load above 200 copies HIV RNA. The results were as shown in Table A.

A European study, known as TRILEGE showed similar results. Three hundred and seventy-one people with an average CD4+ cell count of 363, and a viral load of about 30,000 copies of HIV RNA, who have not been on any prior anti-HIV therapies participated in this study. Volunteers received AZT + 3TC + indinavir for three months and then either AZT + 3TC, AZT + indinavir or AZT + 3TC + indinavir if they had fewer than 500 copies of HIV RNA after the second month of the induction phase. Two hundred and seventy-seven people went onto the maintenance phase of the study. The results were as shown in Table B.

These results raise as many questions as they answer. They must be taken at face value, namely that switching to maintenance therapy after 24 weeks (the U.S. study) or after as little as twelve weeks (the European study) greatly increases the risk of viral rebound. However, it would be a mistake to believe that these studies answer the broader question of maintenance therapy. Other studies have shown that the peak level of viral response is seldom reached in eight weeks, and not always even in 24 weeks, and that the peak response cannot be measured solely in the bloodstream. Tissue reservoirs of HIV take longer to clear. Moreover, these studies did not use the newer, more sensitive viral load tests which can distinguish between people with hundreds of copies of HIV RNA and people with less than 50 or 20. People who become “undetectable” on the more sensitive assays respond differently over time than those who never reach such levels. Finally, other studies have shown that the peak level of immune restoration in response to HAART is seldom if ever reached in six months. Taken together, these considerations argue that the switch to maintenance therapy in these studies occurred far earlier than it should have. For now, all that can be said is that an early switch to maintenance therapy is not warranted. Whether switching at a later time will work, after peak responses to HAART are attained, is uncertain, but it is not ruled out by the current data. Further study is warranted.