Additional results from a study comparing three HIV drug regimens indicates that Kaletra® (lopinavir/ritonavir) combined with two nucleoside reverse transcriptase inhibitors (NRTIs) is less likely to cause limb fat loss (peripheral lipoatrophy) than Sustiva® (efavirenz) plus two NRTIs. The new data follow on the heels of preliminary efficacy results from the same study suggesting that Sustiva has a few virologic advantages over Kaletra.

The study (A5142), conducted by the AIDS Clinical Trials Group, compared three drug regimens taken for almost two years: Kaletra plus two NRTIs, Sustiva plus NRTIs, and Kaletra plus Sustiva (without any NRTIs).

As for the NRTIs combined with Sustiva or Kaletra, the vast majority of patients used either Epivir® (lamivudine) or Emtriva® (emtricitabine). Approximately 42% also used Retrovir®, 24% used Zerit® (stavudine), and 34% used Viread® (tenofovir).   

A5142, with an enrollment of 753 treatment-naive patients, is the first large study to compare Kaletra to Sustiva – two reigning standard-of-care options in the United States for HIV-positive people starting treatment for the first time.

The preliminary safety and efficacy analysis was reported at the XVI International AIDS Conference, held in Toronto in July. The metabolic outcomes analysis – involving changes in body fat composition and lipid (fat) levels in the blood – was reported today at the 14th Conference on Retroviruses and Opportunistic Infections (CROI).

According to the preliminary efficacy data reported in Toronto, the three treatment groups were concluded to be effective. However, there was one key difference between the treatment groups: the time to virologic failure – defined as a viral load that increased above 200 after being below this point during the study – was shorter in the Kaletra/NRTI group than in the Sustiva/NRTI group. Additionally, the percentage of patients who experienced virologic failure by week 96 of the study was 33% in the Kaletra/NRTI group, compared to 24% in the Sustiva/NRTI group.  

As for the body fat parameters presented at CROI, a notable difference favored the use of Kaletra over Sustiva. After 96 weeks of treatment, 32% of patients in the Sustiva/NRTIs group had evidence of peripheral lipoatrophy – defined as a 20% loss of limb fat documented using dual-energy x-ray absorptiometry (DEXA) scanning – compared to 18% of patients in the Kaletra/NRTI group. In the Kaletra/Sustiva group, peripheral lipoatrophy was documented in 8% of patients.

While this difference between the Sustiva group and the Kaletra group is significant, it is important to note that the choice of NRTIs clearly played a role in the risk of limb fat loss.  Among all patients using NRTIs in the study, lipoatrophy was documented in 42% of those taking Zerit, 27% of those taking Retrovir, and 9% of those taking Viread.

Among those combining Sustiva and Zerit, lipoatrophy was documented in 51%, compared to 33% among those combining Kaletra and Zerit.  Approximately 40% of those pairing Sustiva with Retrovir experienced peripheral lipoatrophy, compared to 16% of those combining Kaletra and Retrovir. 

As a whole, patients in the Kaletra/NRTI and Sustiva/NRTI groups who used Viread were not statistically more likely to develop lipoatrophy.  However, in the comparison between the two groups, lipoatrophy was seen in 12% of patients taking Sustiva plus Viread vs. 6% of patients taking Kaletra plus Viread.     

Moderate increases in upper body (trunk) fat were seen in all three groups, with no statistically significant differences between the groups.

As for metabolic parameters, total cholesterol levels increased by 33 mg/dL in the Sustiva/NRTI group, 33 mg/dL in the Kaletra/NRTI group, and 57 mg/dL in the Sustiva/Kaletra group. The difference between the Sustiva/Kaletra group, compared to the total cholesterol levels in the Sustiva/NRTI and the Kaletra/NRTI groups, was stastically significant.
 
“Good” HDL cholesterol levels increased by 9, 8, and 16 mg/dL, and “bad” non-HDL cholesterol increased by 21, 26, and 43 mg/dL, respectively. The increases in the Sustiva/Kaletra group, compared to those in the Kaletra/NRTI and Sustiva/NRTI groups, were statistically significant.

With respect to triglyceride levels, increases of 14 mg/dL were seen in the Sustiva/NRTI group, 47 mg/dL in the Kaletra/NRTI group, and 63 mg/dL in the Sustiva/Kaletra group. The differences between the three groups were statistically significant.  

In conclusion, results from A5142 continue to uncover some potentially important differences between Sustiva- and Kaletra-based treatment regimens. While there may be evidence of an efficacy advantage among those taking Sustiva plus two NRTIs as first-line therapy, the increased risk of peripheral lipoatrophy among those taking Sustiva plus two NRTIs is yet another noteworthy finding of this important study comparing two popular first-line treatment options.

Sources:

Haubrich R, Riddler S, DiRienzo G, et al. Metabolic outcomes of ACTG 5142: A prospective, randomized, phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infection [Abstract 38]. 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, 2007.

Riddler SA, Haubrich R, DiRienzo G, et al. A prospective, randomized, phase III trial of NRTI-, PI-, and NNRTI-sparing regimens for initial treatment of HIV-1 infections – ACTG 5142 [Abstract THLB0204]. XVI International AIDS Conference, Toronto, 2006.