About The Study

The objective of this study was to directly compare efavirenz and nevirapine, the two most widely used non-nucleoside reverse transcriptase inhibitors (NNRTI), in combination therapy with 3TC and d4T. The primary endpoint was the proportion of participants with undetectable viral load (< 50 copies/ml) after 48 weeks of treatment. The study also compared the use of nevirapine given once a day with nevirapine given twice a day. Lastly, it evaluated the use of the two NNRTIs given together (2NN) in combination with two nucleoside analogue RT inhibitors (3TC and d4T).

Study Approach

This was a phase III, open-label, randomized comparative international study with a target enrolment of 1200 participants. Volunteers were randomly assigned to receive either nevirapine 200mg twice daily, or nevirapine 400 mg once daily, or efavirenz 600 mg once daily, or nevirapine 400 mg once daily plus efavirenz 800 mg one daily. The numbers to be enrolled in these four arms, were 400, 200, 400 and 200 respectively. In addition, all participants received 3TC and d4T at standard doses.

Population

A total of 1216 patients with a viral load above 5,000 copies/ml and no previous HIV treatment were enrolled by June 2001, from 65 sites in 17 countries. Baseline characteristics were similar in all four arms. The percentage of female and male was 37 and 63 respectively. The average age was 34. The average CD4 count was 190 cells/mm, and the average viral load was 50,000 copies/ml.

Results

Data were presented on percentage of treatment failure defined as either less than 1 log decline in viral load in the first 12 weeks, virologic failure from week 24 onwards, disease progression, or change of allocated treatment.The only significant difference in therapy failure was found when the efavirenz arm was compared to the 2NN arm, caused primarily by increased treatment discontinuations in the 2NN arm. The study showed a higher percentage of participants with at least one adverse event rated severe or lifethreatening in the 2NN arm compared to the efavirenz arm. It also showed a higher percentage of participants with liver associated laboratory adverse events in the nevirapine once daily arm when compared to efavirenz. The CD4 increase was about 160 copies/mm3 in all arms. The proportions of participants with a viral load below 50 copies/ml at 48 week was around 67% in all arms.

Conclusion

Overall treatment failure was similar among the efavirenz and the nevirapine arms, but was highest in the nevirapine plus efavirenz arm, mainly caused by more treatment discontinuations in this arm. This study suggests that nevirapine either once daily or twice daily is a reasonable alternative to efavirenz. Dual non-nucleoside (2NN) appears to offer no advantage.

Note: These results were taken from an abstract presented at the 10th Conference on Retroviruses and Opportunistic Infections, Boston, February 2003 (Abstract 176), as well as from NATAP and CATIE conference reports.

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