July 14, 2003
HIV vaccine development is an area of intense research, primarily for the prevention of HIV acquisition. These vaccines are also being studied as a novel treatment strategy for persons chronically infected with HIV and are termed "therapeutic vaccines" when used for this purpose. To date, no therapeutic vaccines have been proven to be useful for the treatment of persons with HIV. Given that there are limited research grants, the IAS conference organizers posed the question, "Is there a prospect for a therapeutic vaccine?" Drs. Yves Lévy and Jonathan Weber provided the pro and con positions, respectively.
Currently, antiretroviral therapy is administered lifelong once it is started. Treatment interruptions are a viable option only for people who started antiretroviral therapy at a higher CD4 count, or only for brief periods. A therapeutic vaccine would allow longer periods of time off antiretroviral therapy, reducing toxicity and cost. A therapeutic vaccine could be used in many different ways. It could be administered to patients chronically infected with HIV to enhance their immune response to HIV and thereby slow disease progression and delay time to initiation of antiretroviral therapy. Another strategy is to administer a therapeutic vaccine to patients who are suppressed and stable on antiretroviral therapy in order to boost their immune response to HIV (which diminishes after antiretroviral therapy is started). When antiretroviral therapy is then interrupted, the boosted immune response would lead to improved control of HIV replication, and slow disease progression. A final strategy is to use therapeutic vaccines in conjunction with antiretroviral therapy -- without interruption of treatment -- to improve the long-term response and prevent treatment failure.
Yves Lévy began his argument by reminding us of the importance of the immune system in the long-term control of HIV.
Dr. Lévy believes that the HIV-specific immune response is not destroyed during primary infection with HIV. However, the HIV-specific immune response does fade away during antiretroviral therapy because there is very little HIV to stimulate the immune system. Administering a therapeutic vaccine to someone who is virologically suppressed allows the immune response to fully develop and expand prior to treatment interruption. Dr. Lévy asserts that this could lead to better virologic control of HIV after interrupting therapy. He says that a proof-of-concept is needed to validate therapeutic vaccines as a viable clinical strategy.
He pointed to a study of ALVAC-VIH 1433, HIV Lipopeptide (Lipo-6T) and interleukin-2 (IL-2) in patients chronically infected with HIV-1 (ANRS 093) presented at the 10th Conference on Retroviruses and Opportunistic Infections. Patients who were stably suppressed on antiretroviral therapy for at least one year were randomized to HAART alone or HAART with ALVAC/Lipo-6T followed by IL-2. Then all participants stopped HAART. Twelve weeks after stopping, 5 percent of the HAART-alone group remained off antiretroviral therapy compared to 24 percent of the vaccinated group. The time to viral rebound was longer in the vaccinated group (42 days versus 29 days). He believes this provides hope for therapeutic vaccines.
Dr. Weber followed with an opposing view. He acknowledged the importance of the immune system in the long-term control of HIV. He pointed to a study of macaques whose CD8 cells, which are an important part of the immune system, were temporarily deleted. CD8 depletion led to a loss of SIV (simian immunodeficiency virus) control that was reversed when the CD8 cells were restored. His primary argument was that the immune response to HIV is genetically pre-determined. In other words, a person's genetic make-up dictates the strength and breadth of their immune response. While the immune response is tremendously important, he believes that it is not able to be modified in any meaningful way by therapeutic vaccines.
He pointed to a myriad of previous studies on therapeutic vaccines that found negative results, including the Swiss-Spanish Interruption Trial where participants were "vaccinated" with their own virus by interrupting antiretroviral therapy. No benefit was observed for participants interrupting therapy. Indeed, the ALVAC/Lipo-6T trial found that vaccinated participants had a delay in viral rebound of two weeks, which is probably not clinically meaningful and did not result in a substantial time off antiretroviral therapy.
The number of people living with HIV in developed countries is continuing to grow because of the continued transmission of HIV and effective antiretroviral therapies that have lowered the death rate from HIV/AIDS. There has been substantial progress in bringing these therapies to developing countries. Once these therapies are begun, the number of people on antiretroviral therapy and the associated cost in these countries will continue to grow even when reserving antiretroviral therapy for those having a CD4 count less than 200 cells/mm3. Any strategy that can reduce the time on antiretroviral therapy and save money will lead to more people having access to these lifesaving medications. Consequently, therapeutic vaccines will continue to be a vigorous area of research.
|Please note: Knowledge about HIV changes rapidly. Note the date of this summary's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this summary. For a complete listing of our most recent conference coverage, click here.|