Responses to first-line antiretroviral therapy (ART) in patients with isolated NNRTI transmitted drug resistance (TDR)

Background: Few data exist to inform the selection of first-line ART in patients with NNRTI-associated TDR.

Methods: The population included HIV-1 infected, ART-naïve adults with major NNRTI drug resistance mutations (DRMs) initiating ART in Kaiser Permanente Northern California. DRMs were detected using standard genotypic resistance testing, and those with PI or NRTI DRMs were excluded. Medical and pharmacy records were reviewed to characterize the population and responses to therapy according to ART regimen. The primary outcome was virologic failure (VF) defined as either (i) failure to achieve HIV-1 RNA level below the limit of quantification within 24 weeks of ART; (ii) ART change before 24 weeks due to persistent viremia; or (iii) ≥2 consecutive HIV-1 RNA levels ≥200 copies/ml after suppression.

Results: Of ~3,300 patients initiating first-line ART between April 2002 and May 2014, 137 (4.2%) had isolated NNRTI-associated TDR. 34 were excluded for either insufficient follow-up (28) or non-standard ART (6), and 103  were eligible for analysis. Patients were 86% male, median age of 40 years, with baseline CD4 count of 341^. cells/mm³and baseline plasma HIV-1 RNA of 4.5 log10 copies/mL. 47% were treated with a PI, 42% with an INSTI and 11% with an NNRTI. The most common NRTI backbone was FTC/TDF (93%). The median duration of follow-up was 120 weeks. VF occurred in 14% of patients in the PI group, 7% in the INSTI group, and 36% in the NNRTI group (Table 1). Of the 10 patients with VF in the PI (7) and INSTI (3) groups, none failed with new DRMs, and 5 subsequently suppressed with no change in ART.

Conclusion: Among patients with isolated NNRTI-associated TDR, response rates were high with PI- and INSTI-based regimens.

 

Table 1. Follow-up and outcomes by ART regimen
Class	Drug	n	Median follow-up (weeks)	VF (%)
PI	Atazanavir	22	230	4 (18)
	Darunavir	19	118	2 (11)
	Lopinavir	8	238	1 (11)
	Total	49	159	7 (14)
INSTI	Raltegravir	28	152	1 (4)
	Elvitegravir	15	48	2 (13)
	Total	43	96	3 (7)
NNRTI	Rilpivirine	4	61	2 (50)
	Etravirine	2	111	0
	Efavirenz	5	34	2 (40)
	Total	11	65	4 (36)
All		103	120	14 (14)