Abacavir as potent as tenofovir for patients starting HIV treatment with a high viral load

Regardless of baseline viral load, an HIV treatment combination that includes abacavir (Ziagen, also in the combination pill Kivexa) is just as effective at suppressing viral load in the early weeks of HIV treatment as a regimen that includes tenofovir (Viread, also in the combination pills Truvada and Atripla), UK investigators report in the September 1^st edition of the Journal of Infectious Diseases.

The researchers found that falls in viral load in the first eight weeks of HIV treatment were comparable between patients taking the two drugs, and that after between six and twelve months of therapy equal proportions of patients taking abacavir and tenofovir had experienced virological failure.

British HIV treatment guidelines caution against the use of abacavir for individuals starting HIV treatment for the first time who have a baseline viral load above 100,000 copies/ml. This recommendation is based upon results from the ACTG 5202 study that showed that patients taking abacavir-containing regimens with a baseline viral load above 100,000 copies/ml had a greater risk of virological failure than individuals taking tenofovir with a similar viral load.

Investigators from the UK Collaborative HIV Cohort Study wished to see if the results of this study were replicated in their large cohort of patients initiating HIV treatment that included either abacavir or tenofovir. The patients took one of these drugs in combination with either 3TC (lamivudine, Epivir, combined with abacavir in Kivexa, or FTC (emtricitabine, Emtriva, combined with tenofovir in Truvada and tenofovir and efavirenz in Atripla, which were taken with either a non-nucleoside reverse transcriptase inhibitor (NNRTI) or a protease inhibitor.

All the patients were starting HIV treatment for the first time. They were stratified into one of four groups according to their baseline viral load: below 30,000 copies/ml; 30,000 to 100,000 copies/ml; 100,000 to 300,000 copies/ml; and above 300,000 copies/ml. Changes in viral load after two to eight weeks of antiretroviral therapy were monitored according to baseline viral load and the use of abacavir or tenofovir. Rates of virological failure between 24 and 48 weeks after starting treatment were also assessed according to these characteristics.

A total of 1548 patients commencing HIV treatment after January 1^st 2002 were included in the analysis.

Median pre-treatment viral load was 80,000 copies/ml amongst patients initiating therapy with abacavir and 100,000 copies/ml for patients starting treatment that included tenofovir.

Two to eight weeks after starting HIV treatment the mean reduction in viral load was 2.08 log₁₀/ml amongst the patients taking abacavir and 2.14 log₁₀/ml amongst those taking tenofovir. This difference was not significant.

However, viral load before starting HIV treatment did significantly predict the change in viral load in the early weeks of antiretroviral therapy. Mean viral load two to eight weeks after starting treatment was 0.28 log₁₀ lower amongst patients with a baseline viral load above 300,000 copies/ml than it was in patients with a viral load of between 30,000-100,000 copies/ml when they initiated antiretroviral therapy (p < 0.01).

A viral load between 50 copies/ml was achieved by 14% of patients two to eight weeks after starting antiretrovirals. Similar proportions of patients taking abacavir and tenofovir achieved this outcome at this time point.

A total of 1492 patients had their viral load measured between weeks 24 and 48 after treatment initiation. Virological failure (a viral load above 50 copies/ml) was detected in 18% of patients taking abacavir and an identical proportion of individuals treated with tenofovir. Statistical analysis showed no association between baseline viral load and use of abacavir and a risk of this outcome.

“We found that baseline viral load at HAART [highly active antiretroviral therapy] initiation was strongly associated with the change in viral load 2-8 weeks after starting HAART; however no association was found between nucleoside backbone and the change in viral load”, comment the investigators.

They add, “if abacavir has meaningfully lower antiviral potency than tenofovir, then we would expect to have seen a difference in outcomes between drug regimens.”

The researchers conclude, “our findings indicate that patients with high pre-HAART viral loads who initiate HAART with abacavir have short-term viral load reductions comparable to those who initiate HAART with tenofovir, and this should be taken into consideration when deciding which nucleoside should be used as part of a patient’s initial HAART regimen.”