Clinical Outcomes of Virologically-Suppressed Patients with Pre-existing HIV-1 Drug Resistance Mutations Switching to Rilpivirine/Emtricitabine/Tenofovir Disoproxil Fumarate in the SPIRIT Study^*

^*The SPIRIT study was conducted in accordance with the Declaration of Helsinki. The protocol was reviewed and approved by central of site-specific institutional review boards or ethics committees. All participants gave written informed consent.

Figures & data

Table 1 Baseline characteristics of patients analyzed by proviral DNA genotyping (N = 51).

Characteristic	Median (range) or percent
Age	42 (24–60)
Gender
Male	94.10%
Female	5.90%
Race
White	76.50%
Black or African-American	13.70%
Latino ethnicity	25.50%
Time since first ART (years)	2.4 (0.6–10.8)
Baseline HIV-1 RNA (copies/mL)	<50 (<50–63)
Baseline CD4 Cell Count (cells/uL)	537 (124–1261)

Table 2 Protease and reverse transcriptase drug resistance mutations detected by proviral DNA and historical RNA genotypes at baseline

Patients with resistance mutations at baseline, N (%)	Proviral DNA genotype (N = 51)	Historical RNA genotype (N = 51)
Any primary PR or RT resistance mutations	35 (68.6%)	32 (62.7%)
No PR or RT resistance mutations	16 (31.4%)	19 (37.3%)
NNRTI-associated^a	33 (64.7%)	29 (56.9%)
Average NNRTI resistance mutations	1.6	1.4
NRTI-associated^b	6 (11.8%)	5 (9.8%)
Average NRTI resistance mutations	1.7	1.2
Primary PI-associated^c	4 (7.8%)	3 (5.9%)
Average primary PI resistance mutations	1.5	1

^a Non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations are V90I, A98G, L100I, K101E/H/P, K103N/S, V106A/M/I, V108I, E138A/G/K/R/Q, V179D/F/I/L/T, Y181C/I/V, Y188L/C/H, G190A/E/Q/S, H221Y, P225H, F227C, and M230I/L in RT.

^b Nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance mutations are M41L, E44D, A62V, K65R/N, D67N, T69D/N, T69 insertions/deletions; K70E/R, L74V/I, V75I, F77L, Y115F, F116Y, V118I, Q151M, M184V/I, L210W, T215Y/F, and K219Q/N/E/R in RT.

^c Primary protease inhibitor (PI) resistance mutations are D30N, V32I, L33F, M46I/L, I47A/V, G48V, I50L/V, I54L/M, Q58E, T74P, L76V, V82A/F/L/S/T, I84V, N88S, L90M in protease.

Table 3 Week 48 virologic outcomes of patients with pre-existing NRTI or NNRTI resistance mutations by baseline proviral DNA or historical RNA genotype

Mutation	Number of patients with mutation at baseline			Snapshot outcome at week 48, N (%)
	Proviral DNA genotype (N = 51)	Historical RNA genotype (N = 51)	Total RNA or DNA genotype (N=51)	Virologic success (<50 copies/mL)	Virologic failure	No data in window^a
NNRTI-Associated
V90I	2	3	3	2 (67%)	0	1 (33%)
A98G	1	1	1	1 (100%)	0	0
L100I	1^b	0	1	1 (100%)	0	0
K103 N	20	19	20	18 (90%)	1^c (5%)	1 (5%)
V106I	3	0	3	3 (100%)	0	0
V108I	1	2	2	2 (100%)	0	0
E138A/G/K/Q	7	4	7	6 (86%)	0	1 (14%)^e
E138A	4	3	4	4 (100%)	0	0
E138G	1	0	1	1 (100%)	0	0
E138K	1	0	1	1 (100%)	0	0
E138Q	1	1	1	0	0	1 (100%)^e
V179I	10	7	11	9 (82%)	1^c (9%)	1 (9%)
Y181C	2	0	2	1 (50%)	1^d (50%)	0
G190A	3	3	3	3 (100%)	0	0
H221Y	2	1	2	0	0	2 (100%)^e
NRTI-Associated
M41L	1	0	1	1 (100%)	0	0
D67N	2	1	2	2 (100%)	0	0
T69N	1	1	1	1 (100%)	0	0
K70R	0	1	1	1 (100%)	0	0
V75I	1	1	1	1 (100%)	0	0
V118I	1	1	2	2 (100%)	0	0
M184I	1	0	1	0	1^d (100%)	0
L210W	1	0	1	1 (100%)	0	0
T215Y	1	0	1	1 (100%)	0	0
K219Q	1	1	1	1 (100%	0	0
Total Patients with NNRTI or NRTI Mutations	34	31	35	29 (83%)	2 (6%)	4 (11%)
Total NNRTI and NRTI Mutations Detected	62	46	67

^a All patients with no data in the Week 48 window had HIV-1 RNA <50 copies/mL at their last study visit on RPV/FTC/TDF treatment.

^b The patient with L100I did not have K103N.

^c One patient had K103N + V179V/I.

^d One patient had Y181Y/C + M184I.

^e One patient with E138Q and one patient with H221Y in their historical genotypes were discontinued due to a protocol violation (exclusion mutation) after enrollment.

Figure 1 (A–D) HIV-1 RNA (copies/mL) curves and genotyping results for the four RPV/FTC/TDF-treated patients who experienced virologic failure with emergent resistance. Historical genotype results and timing prior to study enrollment are shown in black boxes. Plasma RNA genotype results from visits on study drug are indicated in white boxes. Proviral DNA genotype results from PBMCs collected during the study are denoted in gray boxes. The baseline visit is indicated as Week 0 with the screening time point occurring within 4 weeks prior. (*) sample was collected after the patient discontinued study drug; (**) result was obtained using an earlier version of the proviral DNA assay that used population sequencing.