Efficacy trials

While all drugs and vaccines have to be tested on animals to establish their safety, testing them to establish their effectiveness is a different matter.

HIV is a retrovirus specific to humans (hence the name ‘Human Immunodeficiency Virus’), which means it is not naturally found in any other animal. Some African primates, such as chimpanzees and a few species of monkey, are naturally infected with SIV (Simian Immunodeficiency Virus), which is believed to be the virus from which HIV originated. Chimpanzees can also be artificially infected with HIV in a laboratory. However most monkeys and chimpanzees have very efficient immune responses to SIV (and HIV), and do not develop AIDS, even after many years of infection. This can make it very difficult to assess whether a drug or vaccine actually works, so primates are not used as widely as human substitutes as they once were.

This said, there is one primate still commonly used to conduct efficacy testing: the Rhesus macaque monkey. Because Rhesus macaques originate from Asia, rather than Africa, they have never been exposed to SIV, and thus have no natural immune responses to it. A Rhesus macaque that is infected with SIV will therefore develop AIDS type illnesses in a relatively short time ².

For this reason (and because they are not an endangered species like some other Asian primates), macaques are often used in HIV research. A few HIV drugs, such as AZT and tenofovir (see our Introduction to Antiretroviral Treatment page for more information about these), have been tested on macaques for efficacy, though stricter rules on the use of primates in animal testing, and greater knowledge of HIV, mean that more modern antiretrovirals are generally only tested on animals for safety reasons.

Vaccine development on the other hand makes extensive use of primates. Because it could be seen as unethical to give a healthy human a vaccine, and then expose them to HIV to see if the vaccine works (if it doesn’t, they’ll end up with HIV), animals can be used as substitutes to establish whether a vaccine is effective or not. This method can also be used to test the usefulness of current AIDS drugs (such as tenofovir) in preventing HIV infection. Such work of course raises significant questions over whether it is any more ethical to give a monkey HIV than a human, when it too may become sick with AIDS and die.

A fundamental problem with using macaques in vaccine research has been that they have different immune systems to humans. This means they cannot be infected with HIV-1 (although they are susceptible to certain strains of HIV-2), however they can be infected with SIV, or an SIV-HIV combination (‘chimeric’ virus) known as SHIV. A drug or vaccine that is effective in Rhesus monkeys infected with SIV or SHIV may not therefore be effective in humans with HIV. Conversely, a drug or vaccine that may be effective in an HIV positive human may be dropped because it appears ineffective in animals. Scientists have now constructed a simian strain of HIV-1 that differs from the human virus by only one gene and mimics early HIV infection, however the infected macaques did not develop AIDS³. Further research on this genetically engineered virus is necessary, however if successful this may make testing vaccines in primates potentially more reliable.

Monkey research has yielded significant discoveries about HIV in recent years⁴, including major findings that have strengthened understanding of early SIV and HIV infection