Abacavir matches tenofovir in Canadian patients with high viral load

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The abacavir/3TC nucleoside combination is as potent as tenofovir/FTC, Canadian investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.  The study involved patients starting HIV therapy for the first time.

There was no difference in the risk of virologic failure between the two combinations. Importantly, the study showed that abacavir/3TC (usually combined in the pill Kivexa) and tenofovir/FTC (co-formulated in Truvada and with efavirenz in Atripla) had similar virologic efficacy in patients with a pre-treatment viral load above 100,000 copies/ml.

The investigators believe that their results show that abacavir/3TC should be reinstated alongside tenofovir/FTC as a “preferred” nucleoside backbone in US guidelines for patients starting HIV therapy.

Glossary

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. 

treatment failure

Inability of a medical therapy to achieve the desired results. 

first-line therapy

The regimen used when starting treatment for the first time.

confounding

Confounding exists if the true association between one factor (Factor A) and an outcome is obscured because there is a second factor (Factor B) which is associated with both Factor A and the outcome. Confounding is often a problem in observational studies when the characteristics of people in one group differ from the characteristics of people in another group. When confounding factors are known they can be measured and controlled for (see ‘multivariable analysis’), but some confounding factors are likely to be unknown or unmeasured. This can lead to biased results. Confounding is not usually a problem in randomised controlled trials. 

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. 

Results of the study will provide reassurance for patients in London where abacavir/3TC is now routinely prescribed as the nucleotide component of first-line antiretroviral therapy.

There has been recent controversy about the effectiveness of abacavir-containing HIV therapy. The ACTG 5202 study showed that patients who had a baseline viral load above 100,000 copies/ml when they started abacavir/3TC had a shorter time to virologic failure than patients treated with tenofovir/FTC.

Doubts have also been cast over the safety of abacavir. Some observational studies found an association between the drug and an increased risk of heart attack (however, a recent analysis of randomised studies failed to replicate these findings).

Because of these concerns, the status of abacavir/3TC downgraded in US treatment guidelines from a “preferred” to an “alternative” regimen for patients starting HIV therapy. However, it still remains a preferred first-line option in Europe.

Canadian investigators wished to establish a clearer understanding of the virologic efficacy of abacavir/3TC.

They therefore undertook a retrospective study involving patients who started HIV therapy for the first time after 2000.

A total of 1764 individuals were included in their analysis, with 588 receiving abacavir/3TC, and 1176 tenofovir/FTC. The patients took these nucleoside backbones in combination with a third antiretroviral drug. The analysis excluded patients who were injecting drug users.

Data were gathered on a number of virologic outcomes, including the risk of treatment failure, time to treatment failure, baseline viral load and the risk of failure, and treatment changes.

Treatment failure was defined as either:

  • a viral load above 1000 copies/ml after week but before week 24

  • A viral load above 200 copies/ml at or after week 24

  • Switching the nucleoside pair for any other reason.

  • The researchers also considered each of these definitions separately.

There were important baseline difference between the abacavir/3TC- and tenofovir/FTC-treated patients.

Abacavir-treated patients were significantly more likely than those taking tenofovir to have a viral load at the start of treatment above 100,000 copies/ml, and these patients also started antiretroviral therapy a median of two years earlier than those taking tenofovir/FTC.

The first set of analyses showed that treatment with abacavir/3TC was associated with a modest but still significant increase in the risk of virologic failure (HR = 1.19; 95% CI, 1.01-1.39).

However, this association disappeared when the investigators took into account a number of potentially confounding factors (aHR = 0.96%; 95% CI, 0.80-1.17). These confounding factors comprised sex, province, third antiretroviral drug, province and year of treatment initiation.

There was no association between abacavir therapy and an increased risk of virologic failure for patients who had a baseline viral load above 100,000 copies/l (aHR = 0.92; 95% CI, 0.69-1.22).

Analysis also showed that there was no difference in the time to virologic failure between the two regimens (abacavir/3TC: aHR = 0.84; 95% CI, 0.58-1.20).

The time to switching or changing nucleoside drugs was comparable between abacavir and tenofovir-containing regimens.

Concerns about the cardiovascular safety of abacavir were first reported in February 2008. The investigators therefore looked at the calendar date patients stopped or switched therapy. The median month of treatment change for patients treated with abacavir/3TC was May 2006, and June 2008 for individuals taking tenofovir/FTC.

After 24 weeks of therapy, abacavir/3TC- and tenofovir/FTC-treated patients had a similar probability of achieving an undetectable viral load (0.55 and 0.60 respectively). The median time to the achievement of this outcome was four weeks for both regimens.

The investigators noted increased rates of treatment failure associated with either nucleoside pair in women, and in patients resident in Ontario or Quebec provinces, and  a higher risk of virologic failure in patients also receiving a boosted protease inhibitor.

“We detected no statistically significant differences in the time to regimen failure, virologic failure, switching or stopping antiretroviral agents for non-virologic failure reasons, or virologic suppression according to NRTI backbone,” write the investigators, who conclude “these results support the use of either NRTI backbone in initial therapy of ART-naïve patients, and would support continuing ABC/3TC as a ‘preferred’ NRTI option.”

References

DHS Tan et al. Comparison of abacavir/lamivudine and tenofovir/emtricitabine among treatment-naive HIV-infected patients initiating therapy. J Acquir Immune Defic Syndr, online edition, doi: 10.1097/QAI.0b013e3182282cfc, 2011 (click here for the free abstract).