Reports

This report is based on medical evidence presented at sanctioned medical congress, from peer reviewed literature or opinion provided by a qualified healthcare practitioner. The consumption of the information contained within this report is intended for qualified Canadian healthcare practitioners only.

NEW FRONTIERS - 19th Annual Canadian Conference on HIV/AIDS Research (CAHR 2010)

Saskatoon, Saskatchewan / May 13-16, 2010

New data from the Canadian Cohort Collaboration (CANOC) has further reinforced previous evidence that the combination of abacavir and lamivudine (ABC/3TC) offers similar efficacy and safety when compared to the nucleoside reverse transcriptase inhibitor (NRTI) combination of tenofovir and emtricitabine (TDF/FTC) in treatment-naive patients with HIV. It contributes additional data to suggest that the previously published ACTG A5202 trial, which is the only major study to show a difference between these NRTI combinations, is inconsistent with the preponderance of comparative data. In the CANOC database, which was used to compare these NRTI combinations by three different end points, there was no significant difference between the regimens for any. The data are particularly important, because they appear to provide an accurate reflection of current Canadian practice.

“Among antiretroviral-naive individuals with HIV infection in Canada, there did not appear to be a difference in those initiating ABC/3TC and those initiating TDF/FTC in the time to any of these three outcomes, virologic suppression, switching or stopping any part of the current regimen, or switching or stopping the NRTI backbone,” reported Dr. Darrell Tan, Immunodeficiency Clinic, Toronto General Hospital, University of Toronto, Ontario. “Our findings support the use of either of these two NRTI backbone choices as reasonable first-line NRTI choices. The treatment decision needs to be individualized as always.”

The CANOC database, initiated in the year 2000, is a collaborative effort among centres, including those in Toronto, Vancouver, Montreal and Ottawa, to collect data on the care and outcome of patients living with HIV. After publication of the ACTG A5202 study and the DHHS decision to eliminate ABC/3TC as a preferred NRTI backbone, the CANOC database was employed to consider whether the ACTG A5202 outcome (Sax et al. N Engl J Med 2009;361:2230-40) reflected the experience in Canada. Another large multicentre study, also published last year (Smith et al. AIDS 2009;23:1547-56), found no difference in virologic failure rates when ABC/3TC and TDF/FTC were directly compared. In that trial, called HEAT, which was the first randomized, prospective, placebo-matched comparison of these backbones, the virologic failure rates at 96 weeks were exactly the same, and there was no difference when patients were stratified by baseline load below or above 100,000 HIV RNA copies/mL. Safety and tolerability of the NRTI combinations were also comparable.

Virologic Response

The CANOC database identified 713 treatment-naive patients treated with one of the two NRTI backbones. For entry, all patients had to be at least 18 years old, to be living in Canada and to have had at least two viral load measures available to quantify efficacy. Of the 713 patients, 442 had received ABC/3TC and 271 had received TDF/FTC. The most common anchor among patients receiving ABC/3TC was ritonavir-boosted atazanavir (ATV/r; 41.2%) followed by efavirenz (EFV; 30.1%) and ritonavir-boosted lopinavir (LPV/r; 21.1%). For TDF/FTC, the most common anchor was EFV (42.8%) followed by LPV/r (26.9%) and ATV/r (19.6%). Although there was considerable heterogeneity among patients included in this analysis, the average patient was described as a 41-year-old male without hepatitis C co-infection, not currently using intravenous drugs and having no previous AIDS-related illness. The average follow-up for the ABC/3TC group was 12 months, while the average follow-up on TDF/FTC was six months.

The virologic suppression rates at six months were 69% for ABC/3TC and 63% for TDF/FTC. At 12 months, the rates, respectively, were 93% and 89% (Figure 1). The time to virologic suppression was not significantly different between the backbones or for the backbones among patients with a viral load >100,000 HIV RNA copies/mL at baseline. When a separate statistical analysis was conducted to evaluate an interaction between ABC/3TC and baseline viral load >100,000 copies/mL, none was seen. Using a multivariate analysis, there was a trend for longer time to virologic suppression for every 10-year increase in age (P=0.08), but there were also no significant differences when patients were stratified by the protease inhibitor (PI) or NNRTI with which their backbone NRTI regimen was combined.

Figure 1.

When the two NRTI groups were compared for the time to switching or stopping any part of the initial antiretroviral regimen, there were again no significant differences according to the initial backbone or the baseline viral load. Of other variables considered with multivariable analysis on switching or stopping, males were far less likely to switch or stop than females (P<0.001) and initiating therapy with LPV/r was associated with a far greater increase of switching or stopping (P<0.001). For the time to switching or stopping the initial NRTI backbone specifically, the third outcome assessed with CANOC data, there were no significant differences between ABC/3TC and TDF/FTC. Viral load >100,000 copies/mL had no influence on the similarity of this outcome among backbones, and no interaction was observed when a separate statistical analysis was conducted to evaluate an interaction between ABC/3TC and baseline viral load >100,000 copies/mL.

These results further challenge the decision to drop ABC/3TC from preferred NRTIs in the DHHS guidelines. Although the ACTG A5202 trial was well conducted, it is uncommon to base a change in practice on a single study that is inconsistent with other available evidence, particularly a large, randomized multicentre study with a similar design. The CANOC data further suggest that ACTG A5202 is an outlier in regard to efficacy. In his analysis, Dr. Tan pointed out variables that might have been expected to render ABC/3TC at a disadvantage, including a greater heterogeneity in the ABC/3TC cohort. In Canada, the experience with NRTI backbones suggests that ABC/3TC and TDF/FTC are both appropriate options, which is their current status in the European guidelines.

Summary

New data from CANOC demonstrate that the most commonly used backbones of ABC/3TC and TDF/FTC do not differ for efficacy in treatment-naive HIV individuals when combined with any of the currently used PI or NNRTI anchors. These two backbones were also equally effective in patients with a baseline viral load >100,000 copies/mL whether assessed as time to virologic suppression, proportion virologically suppressed at six and 12 months, time to switching or stopping any part of the antiretroviral regimen or switching or stopping the NRTI components of the antiretroviral regimen. The data support the use of either backbone NRTI combination as part of first-line therapy as defined by the experience of unselected patients treated in Canada.