Patients who take a triple nucleoside reverse transcriptase inhibitor (NRTI) combination with abacavir (Ziagen) as their third drug are significantly more likely to experience a rebound in their viral load, even if they achieve durable suppression of HIV, than patients who take the non-nucleoside reverse transcriptase inhibitor (NNRTI) efavirenz (Sustiva) as their third antiretroviral drug. Italian investigators writing in the July 1st edition of The Journal of Infectious Diseases recommend that patients who take abacavir as the third drug as part of a triple NRTI combination with 3TC and AZT, d4T and 3TC or d4T and ddI should change to a more potent antiretroviral regimen, irrespective of whether they have durable viral suppression.
The aim of potent antiretroviral therapy is to achieve and maintain suppression of HIV replication to below 50 copies/ml. It is currently recommended that individuals starting anti-HIV therapy for the first time should take a combination of anti-HIV drugs that includes either an NNRTI or a protease inhibitor - the potency of which is boosted by low dose ritonavir. Although triple NRTI therapy is perceived to have certain advantages, such as low pill burden, general ease of adherence and a tolerable side-effects profile, it is not recommended because it was shown to be less likely to achieve initial suppression of viral load.
Italian investigators wanted to see if patients who took abacavir as a third drug, and who had initially achieved an undetectable viral load, had an increased risk of experiencing subsequent virological failure compared to individuals taking efavirenz-based therapy. They therefore conducted an observational study including 744 patients who were starting anti-HIV therapy for the first time. Virological failure was defined as a rebound of viral load to above 400 copies/ml in two consecutive measurements.
The patients had a median age of 37 years, 27% were female, 26% had a history of injecting drug use and 22% were gay men. A total of 1,140 patient years of follow-up were available for the investigators’ analysis.
Overall, the rebound rate was low at 4.8 per 100 patient years, but the investigators noticed that patients who were treated with abacavir as their third drug had an 85% greater risk of rebound than those who received efavirenz. When the investigators repeated their analysis, adjusting the data for potentially confounding factors, they found that patients who took abacavir as their third drug were still significantly more likely to experience virological rebound than those taking efavirenz (p = 0.02). The researchers also established that virological failure was significantly more likely to be the reason why patients taking the abacavir-based therapy discontinued treatment with their regimen (p = 0.03).
The investigators also compared changes in blood fats between patients taking abacavir-based and efavirenz-based therapy. Patients taking abacavir had a lower risk of experiencing an increase in their total cholesterol, but a higher risk of seeing their LDL or “bad” cholesterol increasing than those taking efavirenz, but the differences were not statistically significant. Both abacavir-based treatment and efavirenz-based therapy had a similar impact on triglyceride levels.
“Our results seem to argue in favour of switching patients who are receiving abacavir and have a viral load that is currently suppressed to below quantifiable level to a more virologically potent therapy”, conclude the investigators. However, they emphasise that their study was only observational in design and that “the limitations of this nonrandomized comparison should be fully understood.”
Cozzi-Lepri, A et al. A comparison between abacavir and efavirenz as the third drug used in combination with a background therapy regimen of 2 nucleoside reverse-transcriptase inhibitors in patients with initially suppressed viral loads. J Infect Dis 194 (online edition), 2006.