550 - Abstract (11th CROI)

Session 80 Poster Abstracts
Antiretroviral Therapy: Predictors of Response and Virologic Failure
Monday, 1:30 - 3:30 pm
Poster Hall

550
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
F van Leth*¹, S Andrews², B Grinsztjen³, E Wilkins⁴, M Lazanas⁵, J Lange^1,6, J Montaner⁷, and for the 2NN study group
¹Intl. Antiviral Therapy Evaluation Ctr., Amsterdam, The Netherlands; ²Brooklyn Med. Ctr., Cape Town, South Africa; ³Ctr. de Pesquisa Hosp. Evandro Chagas, Rio de Janeiro, Brazil; ⁴North Manchester Gen. Hosp., UK; ⁵Gen. Hosp. 'Korgialenio-Benakio-Hellenic Red Cross', Athens, Greece; ⁶Academic Med. Ctr., Univ. of Amsterdam, The Netherlands; and ⁷St. Paul's Hosp., Vancouver, Canada

Background: The 2NN study was the first large randomized trial to compare efficacy and safety of the two most widely used non-nucleoside reverse transcriptase inhibitors, nevirapine (NVP) and efavirenz (EFV). The present study looks in-depth at the influence of the number of CD4⁺ cells and the plasma HIV-1 RNA concentration (plasma viral load) at baseline on the risk of virologic failure.

Methods: We enrolled 1216 therapy-naive patients who were randomized to NVP (once or twice daily), EFV, or NVP+EFV, in combination with stavudine and lamivudine. Broad strata of CD4 and plasma viral load were derived after collapsing multiple smaller strata, based on statistical inference or clinical relevance. CD4 strata: <25, 25-200, and >200 cells/mm³, plasma viral load strata: <100,000 and ≥100,000 copies/mL. Subsequently, CD4 and plasma viral load strata were combined to define 6 combination strata. The relationship between initial stratum and virologic failure was assessed by Cox regression analysis. The association between virologic failure and study arm in each combination stratum was assessed by Kaplan Meier analysis. Virologic failure was defined as never a plasma viral load <400 c/mL, or a rebound to 2 consecutive plasma viral load >400 c/mL. NVP arms were combined because of similar efficacy in the main study. A 400 copy plasma viral load cut-off was chosen for comparisons with earlier studies. Patients were censored when discontinuing the study or study medication.

Results: Patients with a CD4 count <25 (n = 140) had a significant higher risk of failure (HR: 1.5; p = 0.04) compared to patients with a CD4 count >200 cells/mL (n = 592), while those with a CD4 count between 25-200 (n=484) had not (HR: 1.02; p = 0.92). Patients with a baseline plasma viral load ≥100,000 copies/mL (n = 398) had a significantly higher risk of failure compared with those with a lower plasma viral load (n = 818) (HR: 1.5; p = 0.004).

CD4	Plasma Viral Load	NVP		EFV		p-value
		n	prop. fail	n	prop. fail	NVP vs EFV
<25	≥100.000	48	0.33	31	0.26	0.58
	<100.000	25	0.20	16	0.19	0.96

25-200	≥100.000	104	0.22	79	0.22	0.96
	<100.000	135	0.16	81	0.16	0.86

>200	≥100.000	39	0.16	27	0.23	0.56
	<100.000	256	0.19	166	0.17	0.47

In each CD4 stratum, patients with a plasma viral load ≥100.000 copies/mL had a higher risk of virologic failure (except in CD4 stratum >200 for NVP). In none of the combined CD4 and plasma viral load strata was there a significant difference in virologic failure between NVP and EFV. The same was true for the arm that combined NVP and EFV.

Conclusions: Only baseline CD4 count <25 cells/mm³ was associated with a significantly higher risk of virologic failure, as was a baseline plasma viral load ≥100,000 copies/mL. Risk of failure was not statistically different between NVP- and EFV-treated patients at any of the strata evaluated here.

Keywords: CD4 count; non nucleoside reverse transcriptase inhibitor; 2NN