For patients on existing suppressive HAART regimens, switching to Kivexa is more likely to result in toxicity-related treatment failure than switching to Truvada, according to a late-breaker presentation on Wednesday at the 4th International AIDS Society Conference on HIV Treatment, Pathogenesis and Prevention in Sydney.
Truvada and Kivexa are fixed-dose combination pills, each of which combines two nucleoside or nucleotide reverse transcriptase inhibitors (NRTIs) into a single-tablet formulation. One Kivexa tablet contains 300mg 3TC (lamivudine) and 600mg abacavir; Truvada is a combination of 200mg FTC (emtricitabine) and 300mg tenofovir.
The open-label Spanish “Bicombo” trial compared the safety and efficacy of Truvada and Kivexa after 48 weeks in patients who had already achieved virological suppression on HAART.
The study group consisted of 335 participants, all of whom were on 3TC-containing HAART regimens at study entry, whose viral loads had been suppressed to below 200 copies/mL for at least six months.
Participants were then randomly assigned to switch the NRTIs in their regimen to either Truvada or Kivexa. Some participants changed from individual drugs to the combination pill that contained the same agents (for example, from separate FTC and tenofovir to Truvada), so strictly speaking these patients did not switch therapy. Participants were not pre-screened for genetic susceptibility to abacavir hypersensitivity.
Baseline characteristics – including age, sex, HIV risk group, liver enzyme levels, fasting lipid profiles, and kidney function indicators (creatinine and GFR) – were comparable in the two groups, and representative of the Spanish HIV-positive population. About three-quarters were men and the median age was 43 years. About one-third were coinfected with hepatitis C. The baseline CD4 cell count was just over 500 cells/mm3 in both treatment arms.
Treatment failure was defined as viral load rebound above 200 copies/ml, discontinuation of the study drug, or progression to a new AIDS-related event or death.
After 48 weeks of follow up, 13% of patients in the Truvada arm experienced treatment failure, compared with 19% in the Kivexa arm - a statistically significant difference.
Virological failure was uncommon in both arms, occurring in four patients (2.4%) taking Kivexa and none of those taking Truvada. CD4 cell counts increased by 44 cells/mm3 in the Kivexa group, while falling by 3 cells/mm3 in the Truvada arm – a slight but significant difference.
However, more patients in the Kivexa arm discontinued therapy prematurely. Whilst nine patients (5.4%) taking Truvada discontinued due to adverse events, 17 (10.2%) did so in the Kivexa arm. In the latter arm, nine patients had suspected abacavir hypersensitivity reactions.
With regard to blood lipid levels, patients taking Truvada had lower fasting triglycerides, total cholesterol and low-density lipoprotein (LDL) cholesterol, which are risk factors for cardiovascular disease. However, they also had lower levels of protective high-density lipoprotein (HDL) cholesterol.
Total body fat and limb fat were measured by DEXA scanning in 47 participants. There were no statistically significant differences in limb fat changes in the two study groups.
Changes in creatinine and GFR, indicators of kidney toxicity, were small and comparable in both arms. This was also the case for changes in bone mineral density. This is an important finding because some studies have linked tenofovir with kidney problems and bone loss.
The investigators concluded that switching the NRTI component of an existing suppressive regimen to Kivexa failed to meet the non-inferiority criteria, relative to switching to Truvada, for overall treatment efficacy, though it did so for virological efficacy.
The difference in overall efficacy was mainly driven by treatment discontinuation due to suspected abacavir hypersensitivity in the Kivexa arm. Retrospective genetic screening showed that three of the nine patients with suspected hypersensitivity carried the HLA B*5701 gene.
This suggests that if clinicians were to use the HLA B*5701 genetic screening test to exclude patients who are prone to abacavir hypersensitivity, Kivexa and Truvada might have shown comparable effectiveness.
Reference:
Martinez E et al. Efficacy and safety of NRTIs switch to tenofovir plus emtricitabine (Truvada) vs. abacavir plus lamivudine (Kivexa) in patients with virologic suppression receiving a lamivudine containing HAART: the BICOMBO study. Fourth International AIDS Society Conference on HIV Treatment and Pathogenesis, Sydney, abstract WESS102, 2007.