HIV:The mutant enemy

>From a virus point of view, HIV is a great survivor. Even the scientists trying to combat the Aids epidemic admire their mutant enemy.

HIV is not particularly infectious, it’s not very hardy outside its host and it is susceptible to sterilising treatment like bleach. But it has a lengthy, hidden incubation period, and its main route of transmission is through one of the host’s fundamental biological drivers: sex.

Behavioural changes such as using condoms and reducing one’s number of sexual partners have largely failed to contain the spread of HIV. And so a vaccine is still seen as the most likely way to curb the epidemic. However, doctors are turning their hopes from vaccines that totally prevent infection with HIV to those that help the patient’s body subdue the virus.

Ask researchers if they think a vaccine will be developed and they usually say yes. Ask how long and they say “seven to 10 years” the same answer that was given a year ago, two years ago, seven years ago. Over the years it has became clear how difficult it is to isolate HIV. Its high rate of mutation means it can swiftly become resistant to drugs, which is why multiple drug therapy is the only successful way to help patients in the long(ish) term.

There are four types of registered anti-retroviral drugs that prevent the virus from reproducing: nucleoside analogue reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and nucleotide reverse transcriptase inhibitors.

Reverse transcriptase inhibitors prevent HIV from using the reverse transcriptase enzyme to hijack the host cell’s DNA to duplicate itself.

Protease inhibitors were the last great breakthrough in anti-retroviral therapy. Introduced into clinical use in 1996, they stop the reproduction of HIV by blocking the way the virus proteins are processed. Protease inhibitors have helped anti-retroviral therapy to reduce deaths of children with HIV by about two-thirds, according to a United States study.

Earlier this year the US Centre for Disease Control revised its guidelines on anti-retroviral therapy, saying it should be started when patients are closer to developing full-blown Aids. This change from the “hit early and hit hard” attitude of blasting was partially an acknowledgement that HIV cannot be eradicated by current drug therapy and the side effects of taking the drugs can be debilitating and damaging. On the other hand, not taking them can result in an even more final result death.

Different combinations of anti-retrovirals can keep people alive and healthy for years. But side effects and developing immunity mean new drugs are needed.

Nucleotides are the latest weapon in the arsenal. Only one, Tenofovir, has been registered for use. It prevents the virus from manipulating the host cell’s DNA, preventing it from reproducing. A great hope for the future is a fusion inhibitor T-20. These drugs could help patients whose HIV is immune to all other existing drugs.

It is important that the medication is easy for patients to take. Combivir, two drugs in one, means one only need take two pills a day. Trizivir contains three nucleoside reverse transcriptase inhibitors in one tablet.

A great hope is microbicides or chemical condoms, that would line the vagina, creating a chemical or physical barrier to the virus.

The health of HIV-positive people can be improved by such things as access to clean water and adequate sanitation. Simple measures like the provision of vitamins and basic antibiotics to prevent infections can improve their quality of life. And, when drugs fail, adequate palliative care, including painkillers such as morphine, can provide a humane end for someone living with HIV and help those trying to care for them. Belinda Beresford


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