More bad news on tenofovir/abacavir/3TC

Megan Nicholson
Published: 16 December 2003

Replacing a suppressive anti-HIV regimen with tenofovir/abacavir/3TC is a risky strategy according to a small, retrospective study published in The Lancet this week.

Dutch researchers identified eight people with viral load below 50 copies/ml who switched to tenofovir/abacavir/3TC. The eight had been taking suppressive treatment for an average of 14.2 months and none had previously failed an antiretroviral regimen.

Five people changed to tenofovir/abacavir/3TC because they wanted to simplify their combination while three others switched due to lipoatrophy. Six took the regimen once daily.

After an average of 130 days, five of the eight switchers had experienced viral rebound, including four who had been taking the once-daily regimen. Only three people managed to maintain viral suppression out to 28 weeks.

Four of the five people with treatment failure had the resistance mutations K65R and M184V/I upon viral rebound. The role of these mutations in triggering resistance to all three drugs in the combination may have contributed to the rapid failure of this regimen. In addition, unrecognised drug interactions may have played a part in the poor response.

Those who failed the triple nucleoside regimen had a higher pre-treatment viral load compared with the treatment successes (mean of 445,000 versus 69,000 copies/ml). They also had a lower pre-treatment CD4 count (mean 88 versus 177 cells/microlitre) and had been taking combination therapy for less time (mean 10.8 versus 40.7 months). Although these results were not statistically significant due to the small numbers in the study, they point to a possible greater risk of failure of tenofovir/abacavir/3TC in individuals with more advanced disease.

The study augments recent evidence that once-daily tenofovir/abacavir/3TC is a weak first-line treatment option. The randomised ESS30009 study compared tenofovir/abacavir/3TC and efavirenz/abacavir/3TC and found that 95% of the efavirenz arm had undetectable viral load by week 16 compared with just 29% of the tenofovir group. Click here for details.

American HIV treatment guidelines recently recommended that abacavir/3TC/tenofovir and tenofovir/ddI/3TC should not be offered at any time, due to disappointing results. Click here for details.

The authors of the Dutch switching study reiterate this recommendation, saying: "HIV-infected patients should not be given the abacavir, lamivudine, and tenofovir combination either as initial treatment in treatment-naive patients, or as alternative treatments for successful ART regimens."

References

Hoogenwert M et al. Change to abacavir-lamivudine-tenofovir combination treatment in patients with HIV-1 who had complete virological suppression. Lancet 362(9400):1979-1980, 2003.

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