Important note: Information in this article was accurate in December 2002. The state of the art may have changed since the publication date. 
Treatment for HIV/AIDS is readily available for most citizens and legal residents of high-income countries. However, the highest proportion of PHAs live in tropical, low-income countries where people can barely access these life-prolonging medications. In addition to anti-HIV drugs, many PHAs in low-income countries also need the following:
It may be many years before all of these basic needs are met. During this time, particularly in sub-Saharan Africa, against a backdrop of civil wars and famine, HIV/AIDS will continue to spread, leaving a trail of death, reduced economic output, misery, millions of orphans and grieving, perhaps even disintegrating communities. It should come as no surprise that in the absence of a well-funded worldwide "Marshall Plan," policy planners' best hope for slowing down or stopping the spread of AIDS lies in an effective vaccine.
It has been difficult for researchers to create an effective HIV vaccine because the virus changes or mutates so quickly. Unlike previous attempts at vaccination against other diseases, HIV also infects cells of the immune system that are important in fighting the virus. Many attempts at vaccine design in the 1990s failed — both in monkeys and in people — because HIV is such a difficult target. Nonetheless, immunologists need more funding to test fresh approaches in vaccine design against HIV.
We now report on one different approach to an HIV vaccine that has potential to be used as a form of therapy in PHAs. Such products are called "therapeutic vaccines" and an example of this is a vaccine called DermaVir.
Another aspect of DermaVir that makes it stand out from the crowd of potential HIV vaccines is that instead of being injected, it is applied to the skin. What's in DermaVir? This vaccine is a mix of genetic material from HIV. Once applied to a small patch of skin, DermaVir stimulates immune cells (including CD8+ and langerhans cells) located in the skin. This vaccine may help activate these cells to recognize and fight HIV. The vaccine may therefore be useful in helping to control HIV in PHAs.
A virus called SIV, simian immunodeficiency virus, causes an AIDS-like disease in some monkeys. Before testing vaccines in people, researchers commonly test them in monkeys. So researchers made up a batch of DermaVir using bits of SIV. Initial tests in a few animals showed that exposure to DermaVir was safe but unable to help the immune systems of the monkeys to control SIV.
Putting on their thinking caps, researchers realized that infection with SIV had clearly weakened the immune systems of the monkeys so much so that they were unable to benefit from the vaccine. Some way of bringing down the high levels of virus in the animals was needed so that their immune systems could respond to DermaVir.
The researchers came up with a new idea. They thought that by giving the monkeys HAART to suppress SIV levels, this would give the immune system time to begin repairing itself. But they also came up with a different approach to treatment. HAART would be given to the monkeys in an on/off fashion. This is commonly called a "drug holiday," or STI — structured treatment interruption. The monkeys would receive HAART for three weeks, followed by an STI for three weeks, and then resume therapy. These cycles on and off therapy would continue for several months.
The reasoning behind doing an STI is that during HAART, because SIV is suppressed, the immune system isn't exposed to enough SIV to learn how to fight the virus. By taking an STI, this re-exposes the immune system to SIV and hopefully it relearns to fight SIV.
During the time the monkeys would be on HAART some would also receive DermaVir. Having worked out all these details, the researchers planned and conducted a study in which SIV positive monkeys would receive the following:
The researchers found that, in general, monkeys receiving a combination of DermaVir, HAART and STIs, unlike the other regimens, had decreasing levels of SIV and increasing levels of CD4+ cells.
These promising results have prompted the researchers to design a study of DermaVir using HIV's genetic material for testing in people in the United States. This initial study — called ACTG 5176 — will be small and is designed to examine the safety of DermaVir in 24 HIV positive volunteers who are taking HAART. People in the study must also have a viral load below the 50 copy mark and CD4+ counts of at least 350 cells. Results from this clinical trial may not be available until 2004. The Research Institute for Genetic and Human Therapy (RIGHT), located in Georgetown University in Washington, DC, is developing DermaVir.
REFERENCE
Lisziewicz J, Xu J, Lewis M, et al. DermaVir: a new topical DNA vaccine for the treatment of HIV/AIDS.Sixth International Congress on Drug Therapy in HIV Infection, 17-21 November 2002, Glasgow Plenary lecture 7.2
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Copyright © 2002 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284 http://www.catie.ca
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