July 14, 2003
Hyperlipidemia (elevation of blood fats) is a common and important complication of antiretroviral therapy, and different features of hyperlipidemia have been described with NRTIs, NNRTIs and protease inhibitors. The relative occurrence of these side effects is an important consideration when selecting an initial antiretroviral regimen especially in people who have baseline elevations in lipids and those who have other risk factors for coronary artery disease.
Kuma, et al. compared the development of hyperlipidemia in antiretroviral-naive patients who had initiated treatment with either Trizivir (3TC [lamivudine, Epivir] + AZT [zidovudine, Retrovir] + abacavir [ABC, Ziagen]) or Combivir (3TC + AZT)/nelfinavir (NFV, Viracept), or with d4T (stavudine, Zerit)/3TC/nelfinavir.
This was an open-label study that enrolled 261 patients, 50 percent of whom were women and 79 percent people of color. The primary endpoint was change in LDL cholesterol from baseline at week 96. Participants from the Trizivir arm had lower LDL and total cholesterol than either of the nelfinavir arms at week 96. The HDL cholesterol did not change significantly from baseline in any of the three arms. Triglycerides, however, were elevated from baseline in all three arms and were most elevated in the arm containing d4T. Blood lactate levels were elevated more often in the d4T arm compared to the Trizivir or Combivir/nelfinavir arms (14 percent vs. 1 percent vs. 5 percent, respectively).
The virologic efficacy of these regimens was a secondary endpoint and it is difficult to interpret because treatment intensification was allowed in all three arms for incomplete viral suppression. The proportion less than 50 copies/mL at week 96 was 76 percent, 72 percent and 66 percent, respectively, in the as-treated analysis (missing subjects are removed from the analysis) and 49 percent, 39 percent and 33 percent, respectively, in the intent-to-treat analysis (missing subjects are considered virologic failures). Unfortunately, 34 percent of participants withdrew early for administrative reasons (i.e., lost-to-follow-up, withdrew consent, protocol violation or "other").
The results of this study are consistent with the current understanding of hyperlipidemia and antiretrovirals. Previous studies have documented hyperlipidemia associated with both nelfinavir and d4T.
When choosing an initial antiretroviral regimen, it is important to balance virologic efficacy with possible side effects and toxicities. Nelfinavir has difficulties on both accounts. Previous studies have repeatedly shown it to be inferior to other antiretrovirals, and this study reinforces its problems with hyperlipidemia. The more difficult issue is the use of Trizivir as initial therapy. ACTG 5095 found that Trizivir had inferior virologic efficacy compared to either of two efavirenz-based regimens. However, many clinicians and persons living with HIV may continue to use it because of its convenience and tolerability and this study documents the relatively small impact of Trizivir on blood lipids, an important side effect of many other antiretroviral regimens.
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