In for the long haul

This article originally appeared in HIV Treatment Update, a newsletter published by NAM between 1992 and 2013.
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With modern treatment, people with HIV can expect to live for decades and decades. But is this sustainable? How realistic is it to expect the drugs to work over a lifetime and for people to continue to adhere to their treatment regimen throughout? What are the risks of drug resistance and treatment failure occurring during long-term treatment?

Combination therapy has been in use for not even 15 years, so any answers can only be preliminary. But two large British studies, just published, have shed some light on these important questions.


treatment failure

Inability of a medical therapy to achieve the desired results. 

drug resistance

A drug-resistant HIV strain is one which is less susceptible to the effects of one or more anti-HIV drugs because of an accumulation of HIV mutations in its genotype. Resistance can be the result of a poor adherence to treatment or of transmission of an already resistant virus.


In HIV, an individual who is ‘treatment naïve’ has never taken anti-HIV treatment before.


A person who has never taken treatment for a condition.

reverse transcriptase

A retroviral enzyme which converts genetic material from RNA into DNA, an essential step in the lifecycle of HIV. Several classes of anti-HIV drugs interfere with this stage of HIV’s life cycle: nucleoside reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). 

The first gives us a reason to be optimistic. It comes from a single hospital in London (the Royal Free) and tracked adherence in its patients over several years.1

It’s often thought that treatment adherence (in other words, not missing doses nor taking them late) is likely to deteriorate when people take treatment for a number of years. It may be hard to maintain motivation over a long period. What’s more, doctors for a wide range of medical conditions have observed that people tend to be less adherent when they don’t feel unwell (it may not be so obvious why the drugs are needed).

The researchers collected information on just over 2000 patients for an average of four and a half years. Some patients’ adherence was monitored for as long as nine years. Adherence was monitored in six-monthly periods, and calculated as the proportion of days covered by a dispensed prescription for at least three drugs (as correctly taking doses of all drugs in a combination is important).

It’s often said that a minimum of 95% adherence is needed for treatment to be effective. Here, overall, 92% of doses were taken.

Adherence in the group has been better since 2005 than it was in previous years. Compared to gay men, adherence tended to be better in black women and poorer in black heterosexual men.

However, the headline finding was that adherence didn’t drop the longer someone was on treatment. In fact, the reverse: the chances of a patient remaining adherent increased by about 2% each year.

What’s more, the older someone was, the more likely they were to stick to their treatment. Other studies have found that older people are more likely to attend their appointments and to recognise the medical consequences of poor adherence.

But while overall adherence was good, one concern is that half the Royal Free patients experienced at least one period of poor adherence. This was often a one-off event, a few weeks or months when adherence was not as consistent as at other times.

The researchers advocate close monitoring of people’s adherence. The concern is that even a single, relatively short period of poor adherence can, in some cases, give rise to the development of drug resistance.

That finding may help us interpret the results of the second study, which are somewhat less optimistic. The researchers collected data on treatment failure and drug resistance in almost 8000 patients at eleven large HIV clinics in England and Scotland. Data were collected on individuals for up to eight years.2

The researchers defined virological failure as having two consecutive viral load results above 400 copies/ml (but not within the first six months of taking treatment). After eight years, over a quarter (28%) of people had experienced virological failure at least once, and would have needed to change treatment.

The researchers also found that 17% of people had some drug-resistant virus. People who had taken non-nucleoside reverse transcriptase inhibitors (NNRTIs such as efavirenz) were more likely to have resistance than those taking protease inhibitors.

However, as in the previous study, the older someone was, the less likely they were to have drug-resistant virus. Again, women had better results than men.

People who had low CD4 counts and high viral loads when they started treatment (i.e. people who started treatment relatively late) had a much greater risk of having drug-resistant virus than other people.

The researchers express concern that an appreciable number of people have these problems with the drugs that are routinely recommended for people starting treatment. Resistance which emerges today will limit the range of drugs that will be effective in the future.

But is the glass half-full or half-empty? If three out of ten people have treatment failure, that means that seven out of ten don’t. What’s more, in this country, alternative treatment regimens are almost always available. Doctors are right not to be complacent, but these two studies do tell us that a significant number of UK patients are able, over a period of almost a decade, to adhere to their treatment and keep their viral load suppressed.


1. Cambiano V et al. Long-term trends in adherence to antiretroviral therapy from start of HAART. AIDS (online edition), DOI:10.1097/QAD.0b013e32833847af, 2010.

2. UK Collaborative Group on HIV Drug Resistance and UK CHIC Study Group Long-term probability of detecting drug-resistant HIV in treatment-naïve patients initiating combination antiretroviral therapy. Clin Infect Dis 50: 1275-85, 2010.

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