TABLE 1.
Direct analysis of phenotypic resistance of HIV-1 RT activity to 3TC in plasma from 15 HIV-1-infected persons by determination of levels of RT inhibition by 3TC-TPa
| Sample | Week | Treatment | RT activity (U/ml)
|
% Inhibition of RT | Mutations
|
||
|---|---|---|---|---|---|---|---|
| No 3TC-TP | With 3TC-TP (5 μM) | Codon 184 | Other | ||||
| 1B | Preb | AZT-ddC | 1.7 × 10−9 | NDc | 100 | M184 | none |
| 1E | 12 | AZT-3TC | 2.1 × 10−6 | 5.1 × 10−7 | 75.6 | V/M184 | L41, Y215 |
| 1F | 18 | AZT-3TC | 1.3 × 10−7 | 3.3 × 10−8 | 75.9 | V184 | none |
| 2B | Pre | AZT-ddC | 2.2 × 10−6 | 6.3 × 10−9 | 99.7 | M184 | none |
| 2F | 12 | AZT-3TC | 1.5 × 10−6 | 4.7 × 10−7 | 68 | V184 | none |
| 3B | Pre | AZT | 1.8 × 10−6 | 1.7 × 10−8 | 99.4 | M184 | none |
| 3F | 12 | AZT-3TC | 1.6 × 10−8 | 1.2 × 10−9 | 92.3 | M/V184 | none |
| 3G | 21 | AZT-3TC | 5.1 × 10−9 | 1.0 × 10−8 | 0 | V184 | none |
| 4A | Pre | AZT | 1.6 × 10−7 | 1.2 × 10−10 | 99.9 | M184 | R70 |
| 4B | 12 | AZT-3TC | ND | ND | V184 | R70 | |
| 5A | Pre | AZT | 1.2 × 10−8 | ND | 100 | M184 | Y215 |
| 5B | 4 | AZT-3TC | ND | ND | M/V184 | Y215 | |
| 5C | 10 | AZT-3TC | ND | ND | V184 | Y215 | |
| 6A | Basal | Basal | 7.7 × 10−5 | 3.6 × 10−8 | 99.9 | M184 | none |
| 6B | 12 | AZT-3TC | 2.3 × 10−5 | 1.5 × 10−5 | 34.7 | V184 | none |
| 7A | Basal | Basal | 1.2 × 10−8 | ND | 100 | M/I184 | none |
| 7C | 28 | AZT-3TC | ND | ND | V184 | none | |
| 8A | Pre | AZT | 4.4 × 10−5 | 5.7 × 10−8 | 99.9 | M184 | L41, Y215 |
| 8B | 8 | AZT-3TC | 5.0 × 10−5 | 4.3 × 10−5 | 15 | V184 | L41, Y215 |
| 9A | Pre | d4Td | 2.9 × 10−6 | 6.3 × 10−8 | 97.8 | M184 | L41, Y215 |
| 9F | 12 | AZT-3TC | 2.1 × 10−6 | 1.1 × 10−6 | 47 | V184 | L41, Y215 |
| 10A | 4 | AZT-3TC | 8.9 × 10−5 | 9.1 × 10−6 | 87.8 | M184 | none |
| 10C | 12 | AZT-3TC | 1.9 × 10−7 | 1.9 × 10−7 | 0 | M/V184 | none |
| 10G | 52 | AZT-3TC | 2.6 × 10−5 | 3.5 × 10−5 | 0 | V184 | L41, Y215 |
| 11A | 12 | AZT-3TC | 1.9 × 10−7 | 1.3 × 10−7 | 29.1 | V/M184 | R70 |
| 11C | 36 | AZT-3TC | 1.7 × 10−7 | 7.0 × 10−8 | 58.5 | V184 | R70 |
| 12A | Pre | AZT | 2.5 × 10−5 | 9.2 × 10−7 | 96.3 | M184 | none |
| 12E | 28 | AZT-3TC | 1.7 × 10−6 | 5.1 × 10−7 | 70 | V184 | R70, Y215 |
| 13A | Pre | d4T | 1.5 × 10−6 | 6.2 × 10−8 | 95.9 | M184 | N69, R70 |
| 13F | 60 | d4T-3TC-INDe | 6.3 × 10−5 | 7.4 × 10−5 | 0 | V184 | L41, D/N69, R70 |
| 14A | 1 | AZT-3TC | 2.5 × 10−7 | 1.3 × 10−8 | 94.7 | M184 | L41, D69, R70, Y215 |
| 14F | 44 | IND-3TC | 2.9 × 10−9 | 5.1 × 10−9 | 0 | V184 | D69, R70, Y215 |
| 15A | Pre | AZT | 8.9 × 10−5 | 4.0 × 10−6 | 95.5 | M184 | D69 |
| 15D | 40 | AZT-3TC-IND | 1.6 × 10−10 | 2.4 × 10−10 | 0 | V184 | D69, Y215 |
Previous treatments were as follows: patient 9 was on AZT before the first sample was obtained, patient 13 was on AZT-ddC before the first sample was obtained, and patient 14 was on ddI for a period of time between the times that the first and second samples were obtained.
Pre, pretherapy.
ND, not detected.
D4T, stavudine.
IND, indinavir.