More than twice the risk of failure for patients starting on abacavir with low CD4s or high viral loads, compared with tenofovir

A study published at the Conference on Retroviruses and Opportunistic Infections (CROI 2011) in February has found that patients starting therapy who either have viral loads over 100,000 copies/ml, or who have a CD4 count under 50 cells/mm³, are more than twice as likely to experience viral load failure in the first 2.75 years of therapy if they start on abacavir/3TC (Kivexa), compared with patients who start on tenofovir/FTC (Truvada).

The study, by the US AIDS Clinical Trials Group, has relevance to the UK in terms of recent decisions on prescribing practice in London.

A5202 is a long-lasting series of trials which, in the past, have found significant differences between abacavir and tenofovir in terms of blood lipids and heart attack risk.

In the current study, 1857 patients starting therapy were randomised into two groups: they either took Kivexa with a dummy (placebo) Truvada pill, or Truvada with a Kivexa placebo. These two groups were then further randomised either to take efavirenz (Sustiva) or boosted atazanavir (Reyataz plus Norvir), though these were open-label and they did not take efavirenz or atazanavir placebos. There were therefore four treatment groups.

Patients in this study had a mean age of 38 and only 17% were women. There was racial balance, with 40% of the group of white ethnicity and 33% African-American.

The average CD4 count on starting therapy was 230 copies/mm³, with 43% starting therapy with a CD4 count below 200 and 18% with a count below 50 copies/mm³. 

The average viral load when people started therapy was 50,000 and 25% started with a viral load over 100,000 copies/ml. In terms of treatment results, patients were stratified by baseline viral load and CD4 count and these were related to the proportion who failed treatment – which meant the proportion who, once virally suppressed, then returned to having a viral load over 200 before the end of this period of study (192 weeks or about two years, nine months).

Broadly speaking, rates of treatment failure in patients on Truvada were similar regardless of CD4 count or viral load, with approximately 20-25% of patients having experienced viral failure by week 192, and no viral load or CD4 group differing by more than 5-6% from these rates.

Rates of treatment failure in patients on Kivexa differed across treatment arms. Failure rates were approximately 20% in patients with baseline viral loads below 100,000 copies/ml and CD4 counts over 50 copies/mm³, and were similar to patients on Truvada. These are the only patients who should not be prescribed Kivexa under the new London arrangements.

As has been previously documented, failure rates were higher in patients with baseline viral loads over 100,000 copies/ml, averaging 20-25% in patients with CD4 counts over 50 copies/mm³. A high viral load will be a specific contra-indication for Kivexaunder the new arrangements.

What was also observed, however, was that failure rates were especially high in patients who started on Kivexa with a CD4 count below 50 cells/mm³. Forty per cent of this group of patients failed therapy if they had viral loads over 100,000 copies/ml, and 35% of those with viral loads under this figure.      

Treatment success can be influenced by confounding factors that may also influence the drugs they are given. Hypothetically, for instance, failure rates on abacavir might be higher if more African-American patients were given it (because they tend to get more kidney problems and tenofovir can exacerbate them), but the failure rates might be related to the kidney problems, to their ethnicity, or both, rather than the drugs taken.

In multivariate analysis that took account of this by weeding out the influence of ethnicity, gender and age, patients on Kivexa with viral loads over 100,000 copies/ml were 134% more likely to experience viral load failure during the 192 weeks than patients with lower viral loads, whereas patients on Truvada with high viral loads were no more likely.  In univariate analysis, patients on Kivexa with baseline CD4 counts under 50 cells/mm³, regardless of viral load, were 144% more likely to experience treatment failure, and Truvada patients no more likely. In multivariate analysis Kivexa patients with CD4 counts under 50 cells/mm³ remained 75% more likely to fail treatment, though this became just statistically non-significant (95% confidence interval 0.99-3.11).

Grant P et al. Association of Baseline Viral Load, CD4 Count, and Week 4 Virologic Response with Virologic Failure in ACTG Study A5202. Eighteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 535, 2011.

You can view the abstract and a PDF of the poster presentation from this research on the official conference website:

Abstract 535: http://www.retroconference.org/2011/Abstracts/41175.htm

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