HIV mutates very readily, which means it can rapidly become resistant to drugs, so patients need to be treated with a cocktail of medicines
Belinda Beresford
People almost never die of HIV, they die from any number of a wide selection of diseases which overwhelm immune systems ravaged by the virus. Thousands of different mutants of the virus replicate and overwhelm the immune system, until eventually it cannot rebuild its defences fast enough to deal with the common illnesses we often don’t even notice. The final constellation of symptoms is called Acquired Immunodeficiency Syndrome (Aids).
Aids and HIV research is a minefield with experts arguing over almost every issue, as the debate – in certain circles – about whether HIV does cause Aids demonstrates.
But the general consensus is that there are two predominant types of the virus, which are about 60% identical. HIV-1 is the most common globally, while HIV-2 is more common in Western Africa. Although the results of infection by the two different types are the same, HIV-2 causes a slower-acting form of Aids.
HIV mutates very readily, producing different strains that are in turn classified into groups and subtypes. These subtypes tend to be geographically located: subtypes A and D predominate in sub-Saharan Africa, while I is found mainly in Cyprus and O in Cameroon.
The differences in the genetic composition of the subtypes of HIV could mean they will respond differently to drugs. It is also possible that some of the HIV variants are more infectious or more virulent than others. There have been suggestions that the different subtypes tend to correlate to different modes of transmission, although this is not certain given the number of variables that have to be taken into account.
HIV is about 1/10 000 of a millimetre in diameter and is classified as a retrovirus. A retrovirus contains RNA, rather than DNA, and an enzyme called reverse transcriptase. This combination allows the virus to introduce its own genetic material into the cell, which is turned into a factory to produce more viruses. The body produces hundreds of millions of these viruses every day. The number increases as the immune system becomes overwhelmed. Initially after infection the body can hold its own and the HIV-infected person stays asymptomatic.
There is no cure for HIV, and at first doctors were restricted to trying to stamp out the opportunistic infections and cancers. However, drugs have been developed that manage to slow down the reproduction of the virus.
One way of understanding the war that takes place within the body is to think of a train hurtling down a track. The length of the track is equivalent to the amount of defence cells (lymphocytes) in the body, while the speed of the train is governed by the amount of virus (viral load). To delay arriving at the end of the track or dying, one either has to lengthen the track (increase the number of lymphocytes) or reduce the speed (cut the viral load). Most drugs do both.
One problem with the virus is its mutability, which means it can rapidly become resistant to drugs. This risk is particularly high if an HIV-positive person is treated with one anti-retroviral on its own. A way around the problem is for patients to be given a cocktail of two or three drugs, working on the theory that if a virus is resistant to one, it will be knocked out by the others.
The most effective combinations appear to hit the virus at two different points of its reproduction by using both reverse transcriptase inhibitors and protease inhibitors.
Currently there is a fair degree of consensus that triple therapy is the best way to help people with Aids combat the disease. Such treatment, called HAART (high activity anti-retroviral therapy), has been said to cause a “Lazarus effect”, where some patients literally return from death’s door.
But there are problems. The war between the virus and the drugs occurs primarily in the bloodstream, where the drugs can concentrate heavily. HAART can force the virus to retreat to so-called sentinel sites, such as the brain and the retina, where the drugs cannot easily penetrate. Stopping the regime can cause an upsurge in the viral load as the sentinel sites shed virus back into the bloodstream.
Anti-retrovirals are expensive – which is itself another point of heated debate – and only about 10 000 people are undergoing triple therapy in South Africa. Doctors say many people are taking a dual therapy regime, which costs about R600/R700 a month, as opposed to the full triple therapy, which costs several thousand rand a month. The actual cost of the regime depends on which combination of the 14 available drugs, fitting into three different categories, you use. Some combinations are considered better – either more effective or longer lasting – than others.
The drugs have to be taken very precisely – at certain times of the day or a given number of hours before or after meals, for example. Neglecting the regime can lead to the virus becoming resistant and the drugs becoming useless. There is an added complication – if the carrier of drug-resistant HIV transmits it on, there is the risk of the relevant drugs eventually becoming useless for everyone.
Work is proceeding in many different countries, including South Africa, on developing a vaccine for HIV. However, the mutability of the virus and other factors make it highly unlikely a viable vaccine will be ready before 2008, if then.