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The Body PRO Covers: The 11th Conference on Retroviruses and Opportunistic Infections

Substudy of 2NN Shows Nevirapine and Efavirenz to Be Equal in Potency

February 9, 2004

The 2NN study was first presented at the Retrovirus meeting last year, and it generated much excitement at the time. It was a large (1,216 participants), randomized study of treatment-naive subjects who received either nevirapine (NVP, Viramune), efavirenz (EFV, Sustiva), or both NNRTIs together with a nucleoside backbone of lamivudine (3TC, Epivir) and stavudine (d4T, Zerit). The nevirapine arm was also divided into once-daily and twice-daily groups. The overall results showed similar outcomes in the efavirenz and nevirapine groups, but more toxicity and poorer results in the arm that received both NNRTIs. Overall, there was also more liver toxicity associated with nevirapine compared to efavirenz.

This current poster presentation involved a breakdown of data obtained from the 2NN study. Since the study was presented last year, there continue to be questions regarding the relative potencies of efavirenz and nevirapine, and this analysis attempts to shed some light on this issue.

Subjects were divided into different strata based on their CD4 counts and viral loads. The CD4 count stratum were <25 cells/mm3, 25-199 cells/mm3 and >200 cells/mm3. For viral load, the groupings were less than or greater than 100,000 copies/mL.

For each stratum, the risk of virologic failure was estimated. Virologic failure was defined as never reaching a viral load of <400 copies/mL or a rebound to two consecutive viral loads >400 copies/mL. The proportion of subjects with virologic failure was compared for the nevirapine and efavirenz arm using Kaplan Meier analysis.

There were several significant findings in this investigation. The first was that subjects with a baseline CD4 count <25 cells/mm3 had a 25% rate of virologic failure compared to 17% for those with CD4 counts of more than 200 cells/mm3 (p=0.04). This is consistent with other trials that have shown patients with extremely low CD4+ counts have greater challenges with therapy and may require a more potent regimen.

Another result was that 23% of the subjects with a viral load exceeding 100,000 copies/mL had virologic failure compared with 16% for those with less than 100,000 copies/mL (p = 0.004). Other studies have shown mixed results with regard to high viral load levels and rate of virologic failure in treatment-naive patients. There has been a tendency, though, for less-potent regimens (such as unboosted protease inhibitors) to perform less well than highly potent regimens in this higher-risk group.

There were no differences in the rate of virologic failure in any of the CD4 count and viral load stratum between nevirapine and efavirenz. These observations should help dispel some of the folklore that efavirenz is intrinsically a more potent NNRTI than nevirapine.

However, this does not negate the issue of higher rates of liver toxicity seen with nevirapine in 2NN and other trials. To that point, Boehringer-Ingelheim, the maker of nevirapine, has recently updated its recommendations (PDF) to HIV providers about the risk of nevirapine hepatotoxicity, particularly in women with a CD4+ cell count greater than 250. For any patient who is treated with nevirapine, there must be heightened vigilance for clinical and laboratory evidence of hepatitis.


Abstract: Virologic Failure in Antiretroviral Therapy Naive Patients Is Only Determined by Extreme Low Values of CD4+ Cells or High Values of HIV-1 RNA Concentration, Not by Choice of Treatment With Nevirapine or Efavirenz (Poster 550)
Authored by: F. van Leth, S. Andrews, B. Grinsztjen, E. Wilkins, M. Lazanas, J. Lange, J. Montaner, for the 2NN Study Group
Affiliations: Intl. Antiviral Therapy Evaluation Ctr., Amsterdam, The Netherlands; Brooklyn Med. Ctr., Cape Town, South Africa; Ctr. de Pesquisa Hosp. Evandro Chagas, Rio de Janeiro, Brazil; North Manchester Gen. Hosp., UK; Gen. Hosp. "Korgialenio-Benakio-Hellenic Red Cross," Athens, Greece; Academic Med. Ctr., Univ. of Amsterdam, The Netherlands; St. Paul's Hosp., Vancouver, Canada

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