Suppress viral load

Resistance can emerge if HIV continues to reproduce whilst anti-HIV drugs are being taken. HIV can develop resistance to all available anti-HIV drugs, but if they are taken together in a combination, resistance can be prevented. This is because together, the drugs have a much more powerful effect on HIV, and because it's much more difficult for HIV to emerge which is resistant to all of the drugs in your combination, rather than to only one drug.

If your viral load falls below 50 copies (an undetectable viral load) when you start treatment, and remains below 50 copies, you will have a much lower risk of developing resistance than people whose viral load does not fall that low. Getting viral load below 50 copies/ml is the aim of all anti-HIV treatment. The current standard is for anti-HIV treatment with three drugs. You may receive four or more, for instance if you have taken several anti-HIV drugs already. 

The lowest point to which viral load falls after starting treatment, often called the nadir, predicts the likelihood that viral load will rebound in the future whilst you continue with your treatment. The lower the nadir, the lower the risk of rebound, and therefore the lower the risk of developing resistance.

Take care when changing to new drugs

Adding a single new drug to a combination which is not keeping viral load fully suppressed can allow resistance to that drug to emerge rapidly, because the impact of that one drug is unlikely to be enough to stop HIV reproducing. This means that if you are switching from treatment which is not controlling your viral load, you should replace as many drugs as possible in your combination – ideally all of them – to give the best chance that your new combination will work.

The replacement drugs should be chosen with help from a test to detect whether your HIV is resistant to particular drugs. There is more about this issue in the later section called "Resistance tests."

If you are switching drugs because of side-effects, and your viral load is suppressed, this does not present the same risk of resistance emerging. In this situation, your doctor may change just a single drug.

Switch early

The speed at which resistance to different anti-HIV drugs develops varies. HIV needs only one mutation to become fully resistant to 3TC (lamivudine, Epivir), to efavirenz (Sustiva) and to nevirapine (Viramune). This simple change – just a single mutation – can happen easily even at quite low levels of viral load rebound.

Full resistance to the other drugs may require a particular pattern of several mutations to emerge. This will take a little longer and will happen only if these drugs are taken while there is ongoing HIV reproduction. In other words, this will be more of a risk if you continue to take the drugs while your viral load is rebounding. The higher your viral load rebounds, the greater the risk that a drug resistant pattern of mutations will develop.

For this reason, a rising viral load should signal the need to consider changing to a new combination (so long as you have options to switch to).

Take your HIV treatment as prescribed

It's very important to take anti-HIV drugs exactly as your doctor prescribed them. This means taking every dose on time, and following any guidance about the kind of foods you can or should eat with your dose. Sticking to these instructions is often called adherence.

Missing or delaying doses, or not taking a dose in the right way, will lower the amount of the drug which is active in your body. This reduces your drug combination's attack on HIV. Virus which was suppressed will then begin to reproduce, increasing the risk of resistant viruses emerging. Diagram 2 on page 7 shows how this works.

Missing even a few doses a month may be enough to cause your treatment to fail, which is why it's vital that you're well prepared to start a new combination, and that you continue to be supported whilst you take it. There are many sources of support available – your treatment centre, a local AIDS organisation, friends and family, and other people with HIV.

Choosing a combination which suits the way you live, developing a pill-taking routine, and finding ways to avoid missing doses will all be important. But over time, there may be many other issues which might help or hinder your adherence. If you have any concerns, or if you feel your treatment isn't right for you, speak to someone at your treatment centre. Don't stop your treatment abruptly without seeking advice first – for some combinations this can allow resistant HIV to emerge.

For information see the booklet Adherence in this series.

The effect of missed doses

Before treatment begins, the HIV viral population is a mix of mostly drug-sensitive viruses plus a range of drug-resistant viruses.

1. These peaks and troughs show how drug levels in the body rise and fall as doses are taken, the drug’s anti-HIV effect is maximised and HIV reproduction is minimised.
2. Missed doses allow drug levels to fall. HIV reproduction speeds up again and viral load rises as both drug-sensitive and drug-resistant HIV grows.
3. With the next dose taken, the drug’s anti-HIV effect is restored. Drug-resistant HIV may have gained a foothold, however, and may continue to cause a rise in viral load. One missed dose is unlikely to cause your treatment to fail, but the more doses missed, the greater the risk.