Interrupting HAART; Hydroxyurea; Five+ Drug Therapy--Report from the RIGHT Conference
Jules Levin of the National AIDS Treatment Advocacy Project (NATAP) attended the April 18-19 meeting of the Research Institute for Genetic and Human Therapy (RIGHT), in Washington, D.C. Here is an edited version of his report, reprinted with permission. The full report is on the NATAP Web site, www.natap.org.
Interrupting Therapy
The possibility of interrupting or stopping HAART [highly active antiretroviral therapy] was discussed at length in the conference and in the hallway with researchers. Researchers are fully aware of the need to try and understand why a few individuals were reported at the Retroviruses conference (Chicago, February 1999) to maintain an undetectable viral load after interrupting or stopping HAART. A number of researchers from Europe and the USA told me they are planning or have already started studies to explore this issue.
The U.S. AIDS Clinical Trials Group will begin a study (A5063) on this question. People who have had a viral load below 50 copies will be asked to interrupt therapy, and they will be followed closely. If viral load rebounds to a certain level, they will be placed back on therapy, and interruption will be tried again after a specified period of time.
I know a number of individuals considering doing this on their own. I would not do it; let the researchers try to sort this out. The study is still in planing stages and first must be approved at the National Institutes of Health and by the FDA, so it could be 2 months or more before starting.
Another study likely to start soon will give Remune [the HIV immunogen developed by the late Dr. Jonas Salk] to individuals who have undetectable viral load on HAART. Therapy interruption will be explored in this study.
In France, Dr. Brigitte Autran has started a study exploring HAART interruption.
[Note: AIDS Treatment News published related reports from the Retroviruses conference; see "Restoring HIV-Specific Immunity," issue #312, February 12, 1999.]
Hydroxyurea/ddI Studies
in South Africa
Researchers reported on several open-label observational studies conducted in South Africa using hydroxyurea + ddI or hydroxyurea + ddI + d4T. The results were surprisingly good, with higher than expected percentages of people achieving undetectable viral load. If a person's viral load is relatively low, these combinations may be a viable option for initial therapy--saving the non-nucleoside RT inhibitors, the protease inhibitors, and possibly the RT inhibitor abacavir as options for future use.
Third-Line Therapy with
Five or More Drugs
Possibly the most important data at the meeting was Dr. Michael Youle's update from his study of 63 highly treatment experienced volunteers receiving a very intensive regimen consisting of two protease inhibitors, plus efavirenz (a few switched to nevirapine), ddI, d4T, and hydroxyurea; this study was first reported last December, then again at the Retroviruses meeting.1 Most of the volunteers received ritonavir plus indinavir at various dosing combinations, but some received other protease-inhibitor combinations, since the double protease inhibitor was individualized based on what the person had been able to tolerate when they used these drugs before. The median baseline viral load was 63,000 copies, but many had a much higher viral load, over 750,000 copies.
After 28 weeks with 20 individuals available for analysis, 85% of the volunteers achieved a viral load below 400 copies. The median CD4 increase was 120. But the higher the starting viral load, the less chance it would go below the 400-copy limit. Dr. Youle is now analyzing the results using a more sensitive test with a 50-copy limit.
References
1. Youle M, Mocroft A, Johnson M, and others. Surrogate marker responses to multidrug combinations comprising hydroxyurea, efavirenz, double protease inhibitors and nucleoside analogues in protease inhibitor failures. 6th Conference on Retroviruses and Opportunistic Infections, Chicago, January 31 - February 4, 1999 [abstract 400].
