Epzicom and Truvada are the two preferred NRTI options—for use in combination with protease inhibitors (PIs) or non-nucleoside reverse transcriptase inhibitors (NNRTIs)—for HIV-positive people beginning antiretroviral therapy, according to the January 29, 2008 issue of the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents, maintained by the U.S. Department of Health and Human Services (DHHS). Both fixed-dose combination tablets can be used once a day and have been well studied in first-time treatment takers.

GSK’s HEAT study was conducted to compare the efficacy of both NRTIs, when used in combination with Kaletra (lopinavir/ritonavir), over a period of 48 weeks. For the first 48 weeks of the study, Kaletra capsules were used. For weeks 48 through 96—a long-term safety and tolerability extension of the study—Kaletra tablets are being employed.

The 48-week data were presented at CROI by Kimberly Smith, MD, of Rush University Medical Center in Chicago. Ninety-six-week follow-up data will be presented in the future.

A total of 343 patients were randomized to receive Epzicom, and 345 volunteers were allotted to take Truvada. Approximately 50 percent of the study volunteers were white; 36 percent were African American.

Viral loads, at the start of the study, averaged 80,000 copies. Approximately 43 percent of patients in both study groups had pretreatment viral loads in excess of 100,000 copies. Roughly 50 percent of the study volunteers had CD4 counts below 200 cells.

Eighty percent of the Epzicom-treated patients and 76 percent of the Truvada-treated patients completed all 48 weeks of the study, a difference that was not statistically significant. Four percent and 6 percent, respectively, discontinued the study because of side effects.

Fourteen (4 percent) of patients in the Epzicom group switched to Retrovir (zidovudine) plus Epivir (lamivudine) due to a suspected allergic reaction to abacavir (HLA genetic screening for abacavir hypersensitivity was not used in this study). Three patients (1 percent) of patients in the Truvada group also had suspected abacavir hypersensitivity, though it should be noted that this was a blinded study in which neither the patients nor the investigators knew which NRTIs were being given.

Three (1 percent) of patients in the Truvada group switched to Emtriva (emtricitabine) plus another NRTI—other than abacavir—because of kidney toxicity (proximal renal tubule dysfunction).

After 48 weeks of treatment, 68 percent of patients in the Epzicom group, compared to 67 percent of patients in the Truvada group, had viral loads below 50 copies. This slight difference was not statistically significant and, along with other viral load analyses, allowed the researchers to conclude that Epzicom is “non-inferior”—comparable—to Truvada.

In patients with high viral loads—above 100,000 copies—upon entering the study, 63 percent of the Epzicom recipients and 65 percent of the Truvada recipients had viral loads below 50 copies after 48 weeks. Among those with baseline viral loads below 100,000 copies, 71 and 69 percent, respectively, had undetectable viral loads after 48 weeks. Neither of these differences between the two groups was statistically significant.

As for changes in CD4 counts, there was an average 201-cell increase in the Epzicom group and an average 173-cell increase in the Truvada group at 48 weeks. This difference was not statistically significant.

Approximately 45 percent of patients in both study groups experienced a side effect of treatment. Diarrhea was the most common, occurring in 18 percent of the Epzicom recipients and 19 percent of the Truvada recipients. Less common side effects included nausea, elevated triglyceride and cholesterol levels, signs of kidney impairment (decreased glomerular filtration rate), and vomiting—with comparable incidences in both treatment groups.

Dr. Smith and her colleagues concluded that Epzicom is comparable to Truvada in virologic efficacy, at least when combined with Kaletra, through 48 weeks of treatment. Both treatment regimens, they suggested, were well-tolerated with few discontinuations due to adverse events in either group.