A nucleoside reverse transcriptase inhibitor (NRTI) backbone of abacavir and 3TC (Kivexa) is just as effective and safe as a backbone of tenofovir and FTC (Truvada) when combined with Kaletra, according to a study presented to the recent Fifteenth Conference on Retroviruses and Opportunistic Infections in Boston.
Patients taking abacavir and 3TC (available in a combination pill, Kivexa) were just as likely to have a viral load below 50 copies/ml after a year of treatment as patients taking tenofovir and FTC (which are combined in Truvada). Both backbones were well-tolerated, with few patients taking either treatment stopping their therapy because of side-effects. But patients taking Kivexa had significantly greater increases in CD4 cell counts.
In HIV treatment guidelines (including those of the British HIV Association) two nucleoside/nucleotide backbones are recommended: Kivexa or Truvada. But there are few data comparing these fixed-dose combination pills.
Investigators therefore designed a study comparing the efficacy and safety of the two products. Called the HEAT study, its objectives were to establish the virologic non-inferiority of Kivexa to Truvada over 48 weeks when the products were combined with the protease inhibitor Kaletra (lopinavir/ritonavir); and to compare the side-effects over three years of treatment.
The double-blind, randomised study involved 688 patients at 72 sites in the US and Puerto Rico.
Patients were defined as having experienced virologic failure if their viral load was not suppressed to below 200 copies/ml in the first six months of treatment, or if their viral load, after being suppressed to below 50 copies/ml then increased to over 200 copies/ml in two consecutive tests.
After 48 weeks of treatment, equal numbers of patients treated with Kivexa (68%) and Truvada (67%) had a viral load below 50 copies/ml. This demonstrated the virologic non-inferiority of Kivexa to Truvada.
When the investigators looked at viral suppression in patients with high baseline viral loads - above 100,000 copies/ml, they once again found that the two products had equal efficacy, with 63% of Kivexa-treated patients with a viral load above this level having an undetectable viral load at week 48 compared to 65% of those taking Truvada.
Comparable proportions of patients taking each product (Kivexa, 12%; Truvada, 11%) experienced virologic failure. This failure was more likely to involve the NRTI-associated M184V mutation in the Truvada-treated patients than in the Kivexa-treated patients.
Median CD4 cell counts after 48 weeks of treatment were 429 cells/mm3 in the Kivexa-treated patients and 370 cells/mm3 in the patients taking Truvada.
Treatment was stopped before 48 weeks by 4% of patients taking Kivexa and 6% of those taking Truvada due to side-effects.
Patients were not screened for allergy to abacavir with an HLA-B*5701 test, and 4% of patients taking Kivexa were diagnosed with a suspected abacavir hypersensitivity reaction as were 1% of patients taking Truvada in the double-blind study (neither patients nor investigators knew which drugs they were taking).
Cholesterol and triglyceride levels increased in both groups of patients, but were marginally higher in patients taking Kivexa.
“Abacavir/3TC is comparable to tenofovir/FTC in virologic efficacy when combined with lopinavir/ritonavir through 48 weeks,” conclude the investigators. They add, “both treatment regimens were well tolerated with few discontinuations due to adverse events in either arm.”
Smith KY et al. Efficacy and safety of abacavir/lamivudine combined to tenofovir/emtricitabine in combination with once-daily lopinavir/ritonavir through 48 weeks in the HEAT study. Fifteenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract 774, 2008.