Treatment switches becoming less common, side-effects still the key reason for switching

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The number of people who need to change their antiretroviral drug regimen has declined significantly in recent years, Alison Boyle of the Chelsea & Westminster Hospital, London told the British HIV Association (BHIVA) conference in Birmingham last week.

Pharmacists and doctors at the hospital conducted a retrospective analysis of all patients who changed their antiretroviral drugs over an 18-month period in 2009-2011. During this period, 722 of 6211 patients (12%) switched drugs, occasionally more than once.

The annual switch rate was 8% – considerably lower than the 20% rate seen in 2006, when a similar exercise was conducted.

Glossary

toxicity

Side-effects.

retrospective study

A type of longitudinal study in which information is collected on what has previously happened to people - for example, by reviewing their medical notes or by interviewing them about past events. 

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). 

nucleoside

A precursor to a building block of DNA or RNA. Nucleosides must be chemically changed into nucleotides before they can be used to make DNA or RNA. 

clinical trial

A research study involving participants, usually to find out how well a new drug or treatment works in people and how safe it is.

Half the switches (49%) were motivated by concerns about side-effects. This is slightly less than in 2006, when 61% of switches were for this reason. 

Other major reasons for switches were to simplify a regimen (15%), to join a clinical trial (8%), because of virological failure (8%) or to avoid drug-drug interactions (4%).

The researchers calculated the ‘observed toxicity switch ratio’ (OTSR) for each drug. This takes into account both the number of people who switch drugs due to side-effects and the total number of days that a drug was taken by Chelsea & Westminster patients.

The figure is expressed ‘per 1000 patient years’. If a drug has an observed toxicity switch ratio of 15, this means that if 1000 patients had taken the drug for one year, 15 patients would have stopped taking it due to the experience of side-effects or concern about possible side-effects.

Observed toxicity switch ratios were markedly high for three older drugs which relatively few patients took, precisely because of their side-effect profiles.

 

Observed toxicity switch ratio

Lopinavir (a component of Kaletra)

69.1

AZT (zidovudine, Retrovir and a component of Combivir)

43.5

Saquinavir (Invirase)

96.1

The other results were much more encouraging, with no other prescribed drug having an OTSR above 30.

For example, for the nucleoside and nucleotide reverse transcriptase inhibitors tenofovir, FTC and 3TC the scores were 6.4, 1.2 and 1.4 respectively. For abacavir, the rate was a little higher at 18.6. Boyle commented that this was largely due to concerns about cardiovascular risk, but that clinicians’ views on this are changing.

In terms of third agents, switch rates for efavirenz (Sustiva), etravirine (Intelence) and atazanavir (Reyataz) were similar at 27.8, 25.7 and 27.2 respectively.

Rates appeared to be lower for darunavir (Prezista), raltegravir (Isentress) and maraviroc (Celsentri) at 15.0, 15.0 and 5.2 respectively. 

References

Boyle A et al. An investigation into the frequency and reasons why patients switch antiretroviral therapy and which antiretrovirals are commonly implicated in toxicity. 18th Annual Conference of the British HIV Association, Birmingham, abstract O28, 2012. See abstract here.