ICAAC 2009: Nevirapine (Viramune) and Boosted Atazanavir (Reyataz) Produce Comparable Early Virological and Immunological Response

Early virological response has been proposed as a marker of efficacy of antiretroviral therapy (ART). In the ARTEN trial, nevirapine (Viramune) showed similar efficacy to ritonavir-boosted atazanavir (Reyataz), but with a more favorable lipid profile after 48 weeks. Results from a sub-analysis of the ARTEN trial looking at early virological and immunological response were presented last week at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009) in San Francisco last week.

As previously reported, the ARTEN trial included 569 treatment-naive patients who were randomly assigned to receive 300/100 mg once-daily (QD) atazanavir/ritonavir, or nevirapine administered either 200 mg twice-daily (BID) or 400 mg once-daily, each in combination with the fixed-dose once-daily tenofovir/emtricitabine combination pill (Truvada). At 48 weeks, 66.8% of patients who received nevirapine achieved viral load < 50 copies/mL on 2 consecutive tests, compared with 64.8% of those who received atazanavir/ritonavir.

In the sub-analysis presented last week, investigators analyzed early viral decay, percentage of patients with HIV RNA < 50 copies/mL at each visit, and CD4 cell count increases within the first 12 weeks of treatment.

Time to treatment response (TTR) was defined as time from the start of treatment until the first measurement of the first confirmed virological response.

Results

• 62.8% of of 376 patients in the combined (200 and 400 mg) nevirapine arm and 65.8% of the 193 patients in the atazanavir/ritonavir arm had viral load > 100,000 copies/mL at baseline.
• At 8 weeks, 26.3% of patients taking nevirapine and 23.8% of those taking atazanavir/ritonavir achieved vial load < 50 copies/mL
• At 12 weels, the corresponding percentages were 44.2% and 39.4%, respectively.
• Distributions of TTR were significantly better for nevirapine than for atazanavir/ritonavir.

Table: Early virological and immunological response

Parameter	Nevirapine combined	Atazanavir/ ritonavir	ANCOVA
Mean HIV-RNA (log10) (SD) Baseline	5.12 (0.64)	5.12 (0.66)
Change from baseline at Week 4 (log10) (SD)	-2.32 (0.58)	-2.16 (0.53)	P=0.004
Change from baseline at Week 12 (log10) (SD)	-2.98 (0.83)	-2.94 (0.64)	Non-significant
Mean CD4 cell count (SD) Baseline	193 (95)	193 (96)
Change from baseline at Week 4 (SD)	+78 (94)	+86 (94)	Non-significant
Change from baseline at Week 12 (SD)	+121 (113)	+114 (117)	Non-significant

Conclusions

• Nevirapine and atazanavir/ritonavir, both combined with fixed-dose tenofovir/emtricitabine, led to comparable virological and immunological responses.
• However, viral load decay within the first 4 weeks and time to treatment response were significantly better for nevirapine.
• Non-inferiority between nevirapine and atazanavir/ritonavir (both combined with tenofovir/emtricitabine) with regard to treatment response at week 48 was established.
• The ARTEN study confirms that the combination of nevirapine and tenofovir/emtricitabine is effective in treatment-naive patients, including those with high viral load at baseline.
• The study demonstrates that nevirapine is an effective and well tolerated drug for first-line therapy, when used in accordance with the guideline-recommended CD4 cell count thresholds for nevirapine of < 250 cells/mm³ for women and < 400 cells/mm³ for men.

Royal Free Hospital, London, UK; Hosp. Carlos III, Madrid, Spain; Ruhr-Univ. Bochum, Bochum, Germany; St Mary's Hosp., London, UK; Boehringer Ingelheim, Ingelheim, Germany.

9/22/09

Reference

M Johnson, V Soriano, N. Brockmeyer, and others. Early Virological and Immunological Response is Comparable for Nevirapine and RTV-boosted Atazanavir: An ARTEN Sub-analysis. 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009). San Francisco. September 12-15, 2009. AbstractH-924c.