Side-effects can be divided into two main types: allergic side-effects and side-effects due to the direct effects of the drug. Allergic side-effects occur when the immune system reacts to a drug or its metabolites (the chemicals into which a drug is broken down in the body) by causing symptoms such as a rash or fever. This is unpredictable - some people can take a drug without developing an allergy, while others suffer severe reactions to it. Sometimes allergies do not occur when a person first takes a drug, but take time to develop.

If you are allergic to a drug, you will probably experience the reactions no matter what dose you take. Often they become more severe each time you encounter the reaction. However, in some cases it is possible to desensitise the immune system to the allergic reactions by starting to take the drug at a very low dose, then gradually building up to the correct dose over time. This strategy has worked well for many people who are allergic to co-trimoxazole (often known by the brand-names Septrin or Bactrim), the commonest form of PCP prophylaxis, but must always be done under medical supervision.

Allergic reactions can sometimes be so serious that they are life-threatening. One of the most serious drug allergies is called Stevens-Johnson syndrome, and is characterised by a blistering rash and ulcers in the mouth, eyes and/or genitals. To reduce the risk of such serious problems, people who develop severe allergic reactions are advised never to take the drug in question again.

Some people may be predisposed to certain types of allergic reactions. For example, people who have experienced a rash when taking sulphur-based medications (e.g. co-trimoxazole) may be more likely to develop an NNRTI-related rash.

Other side-effects may be caused directly by unwanted effects of the drug itself, rather than by the immune system's response. Often the nature of the side-effects will depend on the part of the body which is adversely affected by the drug, or the route by which it is excreted from the body. For example, some drugs damage the cells in the bone marrow which are responsible for producing new blood cells, so may lead to blood abnormalities such as anaemia or neutropenia. Some drugs produce generalised discomfort, such as those that cause nausea, malaise or drowsiness. Reduced sex drive is another common side-effect. Most recently, there have been reports of reduced bone density among people on antiretroviral therapy.

Toxic side-effects are usually dose-related; the more drug that is taken, the greater the risk and/or the severity of the side-effects. So a drug may cause side-effects in only a small proportion of people who take the usual dose, but in a larger proportion of people when it is given at a higher dose.

Some people may be vulnerable to unusual or unpredictable side-effects because of inherited conditions. The most common cases are among people whose genetic make-up means that they produce unusually low levels of certain enzymes. For example, people who are lacking the enzyme glucose-6-phosphate dehydrogenase (G6PD) are more likely to suffer blood toxicities from antibiotics such as dapsone, because the lack of this enzyme allows toxic by-products of the drug to accumulate in the body. At-risk groups can be tested for these genetic deficiencies.

The availability of more and more treatments for HIV infection, as well as opportunistic infections and other HIV-related conditions, increases the choices for people with HIV and their doctors. But as well as their potential benefits, virtually every drug carries the risk of some side-effects in a proportion of patients. Additionally, the more drugs an individual takes, the greater the chance that there will be unwanted interactions between some of them.

Side-effects are sometimes referred to as adverse drug reactions (ADRs), adverse effects (AEs) or simply toxicities. The side-effects of most drugs are well established. Information on toxicities is gathered during clinical trials and from reports from doctors who prescribe the drugs once they are approved.

However, many drugs used by people with HIV are relatively new, and the urgent need for effective medications has meant that many anti-HIV drugs have been released onto the market after only a relatively small number of people have taken them for a relatively short period of time. This means that the information on side-effects and drug interactions is likely to be less complete than with other drugs. The emergence of metabolic and fat disorders associated with protease inhibitors demonstrates that some side-effects take months or years to be identified.

In the age of highly active antiretroviral therapy (HAART), drug side-effects are a common cause of ill-health among people undetectable viral load or asymptomatic HIV disease. A review of HIV admissions at the Chelsea and Westminster Hospital in London between January 1997 and October 1998 found that 10% of all admissions (67 people) had viral load below 400 when admitted to hospital. Sixteen of these admissions were due to complications of HAART, specifically renal problems and extreme nausea. Even mild or moderate side-effects have been found to significantly impact quality of life.

In some cases, it is not clear whether these unwanted effects are a direct side-effect of antiretroviral therapy or whether they are the result of a strengthened immune response to infections. For example, people with HIV and hepatitis C who take anti-HIV drugs are more likely to experience liver toxicity than people who do not have hepatitis C. This may be due to an increased susceptibility to drug-related side-effects among those with HCV, or it may be the result of an improved immune response to HCV leading to liver inflammation.

In addition, people with HIV infection may be more likely to experience side-effects from a drug than uninfected people. For example, co-trimoxazole (Septrin) causes side-effects in about 30% of HIV-positive people, but in only about 10% of those who are HIV-negative. People with advanced HIV infection are more likely to experience side-effects from a given drug than healthier people with HIV. The risk of side-effects from a given drug may also be altered if an individual is taking several other drugs too.