Most side-effects occur after a person has been taking the drug for one or two weeks, although there is no strict pattern to this, and some people will suffer problems after their first dose.

Some side-effects are worst for the first month or two of taking a drug, but may then lessen or disappear altogether. This is often the case with the nausea, vomiting and headaches that can affect people starting AZT.

Side-effects such as nausea, vomiting, diarrhoea, bloating, abdominal discomfort, headache and dizziness tend to be associated with the time at which drug levels reach their peak in the blood. This is why side-effects may occur regularly at certain times of day. It may be possible to minimise the inconvenience of these side effects by adjusting the time at which you take particular medications, although this may also depend on your eating schedule and the need to take your medication with food or on an empty stomach.

The reason why more intense side-effects occur in the first few months of treatment is not because your body is being poisoned, but because especially high levels of the drug are present in your bloodstream. After a few weeks the peaks and troughs in blood levels of the new drug become less pronounced, and side-effects wear off. This is why some treatments, such as ritonavir, are dose-escalated

If you have decided that it is worth taking a particular treatment, this is an important reason to put up with the side-effects for a few weeks (as long as your doctor feels that this is safe) even if at first the side-effects seem unacceptable. During this period you may need to take other treatments to deal with the side-effects, such as anti-nausea or anti-diarrhoea medicines.

For a few drugs, the risk of side-effects depends on the cumulative dose you have taken. In other words, you may experience few or no side-effects during the first weeks or months of treatment, but once the total amount of drug you have taken passes a certain level, the risk of side-effects increases. This is the case with several cancer chemotherapy drugs such as bleomycin and doxorubicin.

Other side effects associated with long-term use of antiretrovirals include lipodystrophy, wasting of the arms, legs and face, and metabolic abnormalities including high blood lipids, insulin resistance and high lactate levels. The latter may lead to a serious condition called lactic acidosis. See the section Body fat and metabolic changes whilst on treatment for further details.

People with advanced HIV disease seem to be more prone to side-effects associated with the nucleoside analogues (NRTIs eg. d4T, ddI, AZT) such as peripheral neuropathy, pancreatitis and fat wasting. For instance, the HOPS cohort individuals who began treatment with CD4 cell counts below 100 cells/mm³ were significantly more likely to develop peripheral neuropathy. Experts have speculated that immune activation during advanced disease leads to higher drug concentrations within cells, which in turn causing greater toxicity.