Changes in HIV incidence in a randomised controlled trial

Changes in HIV incidence are the ‘gold standard’ when it comes to measuring the efficacy of a measure to prevent HIV, and other outcome measures may provide misleading evidence as to the ultimate usefulness of the intervention. For example:

  • Changes in the incidence of other STIs, though they certainly correlate with risky sex, may not correlate with changes in HIV incidence, especially if there is widespread ‘serosorting’ in the population.
  • Changes in reported behaviour are susceptible to poor recall or social desirability bias in study subjects.
  • Condom uptake does not necessarily mean condom use, and certainly not consistent use.
  • Changes in knowledge and attitudes may not lead to changes in behaviour.
  • A programme can reach, and be recognised by, large numbers of people while having no effect on them at all, or even a negative one.

So HIV incidence is the ‘real deal’. However, for a number of reasons, HIV incidence has only been measured in a minority of studies.

Firstly, even in a high-incidence population, HIV infections are relatively rare events. This means that studies have to be extremely large to generate statistically meaningful differences in incidence between control and intervention arms. If incidence in the population is 4% a year, for instance (typical of some urban gay communities and some African populations) and the intervention produces a 25% reduction in risky sex leading to infection, then in a study of 200 people there would be four HIV infections in the control arm and three in the intervention arm – not a statistically meaningful result.

The study size needed to produce a meaningful result depends on a number of factors. These include baseline HIV incidence in the population, baseline risk behaviour, whether that risk behaviour is homogeneous or heterogeneously spread between individuals with low and high risk, the projected efficacy of the method being tested and projected behaviour of subjects within the study. It is usually expressed as a probability of observing a probability - the likelihood of the study producing a statistically significant result if the ‘true’ efficacy is above a certain number.

In the recent iPrEx study of pre-exposure prophylaxis, for instance, it was determined that the study was 80% likely to establish a statistically significant finding of more than 30% efficacy if the true efficacy of Truvada PrEP (the ‘as treated’ efficacy, not taking adherence or drop-outs into consideration) was 60% or more. This would be the case if at least 85 HIV infections occurred in 2500 trial subjects. In the end, there were 100 infections during the study, the efficacy detected was 42%, which was highly statistically significant (p = 0.005), and the as-treated efficacy was estimated as 92 to 95%.

This was in a high-incidence population. However, the RV144 vaccine study, which took place in a low-incidence population, needed 16,395 subjects to allow the finding of 31% efficacy which was barely statistically significant (p = 0.04).

Secondly, HIV tests have to be done fairly frequently in order to get a true measure in changes in incidence. A screening test at baseline and one at follow-up some time after the end of the intervention may fail to capture short-term effects of the intervention.

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.