Table 3. Resistance-associated mutations in reverse transcriptase at week 8 after interruption of NNRTI-based ART, according to the interruption modality, HIV-1 RNA load at interruption, and NNRTI concentrations at week 4 post-interruption.
| Interruption modality | Interrupted ART regimen | Viral load (copies/ml) | NNRTI concentration (ng/ml) | Resistance-associated mutationsa |
| Simultaneous | ZDV/3TC NVP | 216 | 3.2 | NNRTI: G190A |
| ZDV/3TC NVP | <400 | <0.25 | NNRTI: Y181C | |
| ZDV/3TC NVP | <50 | 1.0 | NNRTI: K103N | |
| TDF/FTC NVP | <50 | 1.3 | NNRTI: K103N | |
| TDF/FTC EFV | <50 | 16 | NNRTI: K103N | |
| TDF/FTC EFV | <75 | 64 | NNRTI: Y188C | |
| TDF 3TC NVP | <75 | NA | NNRTI: K103N (21) Y181C (6) G190A (4) | |
| TDF 3TC NVP | <50 | NA | NNRTI: K101E Y181C G190S | |
| D4T 3TC EFV | <75 | 41 | NNRTI: V179D (10) Y188L (19); NRTI: M184V (15) | |
| ABC 3TC EFV | <400 | NA | NNRTI: K103N; NRTI: L74V | |
| TDF ZDV NVP | <50 | NA | NNRTI: K103N G190S | |
| DDI NVP IDV | <400 | >250 | NNRTI: Y181C; NRTI: M41L D67E T69ins M184V L210W T215Y | |
| TDF DDI EFV | 357 | NA | NNRTI: L100I (6) K101E (2) K103N (98) G190A (14); NRTI: K65R | |
| Staggered | ZDV/3TC NVP | <400 | 49 | NNRTI: L100I (3) K101E (8); NRTI : M41L D67N M184V (3) L210W T215Y |
| ZDV/3TC NVP | <50 | 1.6 | NNRTI: Y181C; NRTI: M184V K219Q | |
| ZDV/3TC EFV | <400 | 15 | NNRTI: A98G K103N | |
| ZDV/3TC EFV | <50 | <5 | NNRTI: K103N (5) V179D (10); NRTI: K70R | |
| DDI D4T NVP | <400 | NA | NNRTI: Y181C | |
| DDI D4T EFV | 238 | 67 | NNRTI: K103N Y181C Y188L G190A; NRTI: Q151M M184I T215F | |
| DDI NVP NFV | 375 | NA | NNRTI: G190A | |
| TDF EFV LPV/r | <75 | NA | NNRTI: G190EQR; NRTI: D67N T69A K70R T215F K219Q | |
| Switched | ZDV/3TC NVP | <50 | 0.6 | NNRTI: K103N |
Each row gives data for a single patient.
Resistance-associated mutations (RAMs) in reverse transcriptase (RT) were detected by Sanger sequencing, allele-specific PCR (AS-PCR) and ultra-deep sequencing (UDS). AS-PCR targeted the NNRTI-RAMs K103N, Y181C, Y188L and G190A (the latter only in samples with K103N), and the following NRTI-RAMs: thymidine analogue mutations (M41L, D67N, K70R, L210W, T215Y/F, K219Q), K65R, Q151M, and 184V/I. Mutation-specific cut-offs ranging between 0.3% and 1% were used for AS-PCR interpretation as previously described [15]. UDS targeted the RT amino acid region 100–190; a detection limit of 1% was chosen to avoid the high probability of technical artifacts below this threshold [19]. RAMs detected by sensitive testing but not by Sanger sequencing are indicated in bold; RAMs detected by RT100–190UDS but not by AS-PCR are underlined; where RT100–190UDS results were obtained the frequency (%) of the mutant is given in brackets. Only samples with NNRTI-RAMs are shown; an additional 15 samples had NRTI-RAMs only, without NNRTI-RAMs. NNRTI = non-nucleoside reverse transcriptase inhibitor; ART = antiretroviral therapy; ZDV = zidovudine; 3TC = lamivudine; NVP = nevirapine; TDF = tenofovir; FTC = emtricitabine; EFV = efavirenz; D4T = stavudine; ABC = abacavir; DDI = didanosine; IDV = indinavir; NFV = nelfinavir; LPV/r = lopinavir/ritonavir; NA = not available.