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First-Line Therapy for HIV-Infected Patients

Virologic suppression is more likely with an efavirenz-based regimen than with a lopinavir/ritonavir-based one.

First-line therapy for HIV infection usually consists of two nucleoside reverse-transcriptase inhibitors (NRTIs) plus either the nonnucleoside reverse-transcriptase inhibitor (NNRTI) efavirenz or a ritonavir-boosted protease inhibitor (PI) such as lopinavir/ritonavir. Which of these two initial regimens is better? Also, NRTIs have been associated with toxicities such as lipodystrophy. Are regimens that do not include NRTIs as effective as ones that do? To answer these important questions, investigators randomized 757 HIV-infected, treatment-naive patients to receive one of three regimens: efavirenz plus two NRTIs (EFV group), lopinavir/ritonavir plus two NRTIs (LPV group), or lopinavir/ritonavir plus efavirenz (NRTI-sparing group).

The rate of virologic failure was 24% in the EFV group, 29% in the NRTI-sparing group, and 37% in the LPV group. Among patients with pretreatment viral loads 100,000 copies/mL, the EFV group had a longer time to virologic failure than did the other groups. However, the LPV and NRTI-sparing groups had larger increases in CD4-cell count at week 96 than did the EFV group. Grade 3 or 4 laboratory abnormalities were most common in the NRTI-sparing group, mainly because of elevated triglyceride levels. Surprisingly, the median increase in limb fat was lower in the EFV group (0.05 kg) than in the LPV group or the NRTI-sparing group (0.7 kg and 1.15 kg, respectively). In patients who had virologic breakthrough, fewer patients in the LPV group than in the EFV group developed multiclass-resistant virus. Mutations associated with NNRTI resistance were more frequent in the NRTI-sparing group than in the EFV group.

Comment: This important trial of first-line therapy shows that the rate of virologic failure is lower in patients taking efavirenz-based regimens than in those taking lopinavir/ritonavir-based ones. However, in those patients who do have virologic failure, multiclass resistance develops more frequently with efavirenz-based regimens than with lopinavir/ritonavir-based ones. What are the take-home lessons? Efavirenz-based regimens are an excellent first choice for most patients with HIV infection. In patients who cannot tolerate efavirenz, lopinavir/ritonavir-based regimens are likely to be effective. Studies are ongoing to compare efavirenz-based regimens with combinations that include newer PIs or agents in novel classes. Much of the interest in NRTI-sparing regimens has faded since the inception of this study because rates of metabolic complications are lower with newer NRTIs than with older ones.

— Rajesh T. Gandhi, MD

Published in Journal Watch Infectious Diseases May 14, 2008

Citation(s):

Riddler SA et al. Class-sparing regimens for initial treatment of HIV-1 infection. N Engl J Med 2008 May 15; 358:2095.

• Original article (Subscription may be required)
• Medline abstract (Free)

Hirschel B and Calmy A. Initial treatment for HIV infection — An embarrassment of riches. N Engl J Med 2008 May 15; 358:2170.

• Original article (Subscription may be required)
• Medline abstract (Free)