Attacking HIV

• HIV contains nine genes which carry all the information needed to make new viruses.

• Proteins on HIV's outer envelope bind to CD4 receptors on the surface of its target cells. In addition to the CD4 receptors, it also binds to co-receptors called CCR5 or CXCR4.

• After the virus has locked onto these receptors, its outer envelope fuses with the cell's membrane and the virus's genetic material is absorbed into the cell.

• Drugs that stop HIV binding to CD4 T-cells are under development.

• Other drugs, like T-20 (enfuvirtide, Fuzeon), can prevent the fusion process from occurring.

• HIV makes a copy of its genetic information when it is inside the cell. This copy is called a provirus. It uses an enzyme of its own called reverse transcriptase to do this.

• Drugs called reverse transcriptase inhibitors can stop the virus from making these copies. 3TC (lamivudine, Epivir, abacavir (Ziagen), AZT (zidovudine, Retrovir), d4T (stavudine, Zerit), ddC (zalcitabine, Hivid), ddI (didanosine, Videx / VidexEC) and FTC (emtricitabine, Emtriva) are reverse transcriptase inhibitors. Efavirenz (Sustiva) and nevirapine (Viramune) are also reverse transcriptase inhibitors, but work in a different way.

• The provirus is inserted into the genetic code of the cell. HIV uses another of its enzymes called integrase to do this. The provirus is put into the genetic code, or genome, by cutting the genome and slipping in the HIV provirus. Drugs are being developed to stop integrase from doing this.

• Some of HIV 's genes can instruct the cell to use its own machinery to make new viruses. Drugs are being investigated that can stop these genes from sending their instructions.

• When the cell receives these instructions, it makes another copy of the provirus that is bound up in its genetic material, and this copy is then used to generate the production of new viruses from materials supplied by the cell. So, in effect, the cell has been hijacked by HIV and turned into a virus factory. Each cell can produce dozens, if not hundreds, of virions.

• The new viral building blocks need to be chopped up and assembled. An HIV enzyme called protease is produced to do this job. Drugs called protease inhibitors can stop this process. Amprenavir (Agenerase), atazanavir (Reyataz), fosamprenavir (Telzir), indinavir (Crixivan), lopinavir, nelfinavir (Viracept), ritonavir (Norvir) and saquinavir (Invirase / Fortovase) are protease inhibitors.

• If viruses can be assembled they are packaged in the wall of the cell and then push through the wall of the cell to float off into the bloodstream or to pass into other cells. Drugs called maturation inhibitors are being developed which might stop this packaging process.

• Various other approaches are being tested that may prevent HIV from reproducing itself. These include drugs that target human cell factors that are necessary for HIV replication, blockers of other HIV proteins and gene therapy.

• Strategies to kill or remove HIV-infected cells from the body have also been suggested by experts, in order to destroy the copies of HIV that are stored for long periods, hidden within the body's cells. These are experimental approaches at present.

• Treatment with anti-oxidant drugs, including vitamins and minerals, may have a role in reducing HIV viral loads and increasing CD4 cell counts, but the findings from clinical studies are mixed so far.

Combination therapy

• HIV makes lots of mistakes when it copies itself. Unlike human cells it cannot spot the errors or get rid of them. Many of these copies are so faulty that they cannot infect other cells, or they will only reproduce very slowly. But some develop genetic changes which allow them to make copies even when antiretroviral drugs are around. This is called resistance.

• Every antiretroviral drug works against a slightly different part of HIV's enzymes. Each enzyme is made up of a chain of chemicals called amino acids. Sometimes these amino acids are placed in different positions as a result of the development of resistance, and this gives the virus the ability to carry on making copies even when high levels of a drug are present.

• However, another drug which also targets the same enzyme may work on this 'mutant' virus, because its target is a different set of amino acids.

• This is why 'combination therapy' is more effective than using one drug to fight the virus.

• Combination therapy can use different drugs which attack the same enzyme, or it can use a combination of drugs which attack several different enzymes at once. It is not known which approach is best in the long term.

• Combinations of two or more drugs have been shown to substantially reduce the risk of disease progression and death. The best results are usually seen with combinations that include a protease inhibitor or a non-nucleoside reverse transcriptase inhibitor.