Table 1.
Resistance at first-line failure and predicted activity of NRTIs prescribed in second-line protease inhibitor and NRTI regimen
| Total |
Number of predicted-active NRTIs in second-line regimen |
||||
|---|---|---|---|---|---|
| 0 | 1 | ≥2 | |||
| Baseline genotype results available | 391 | 230 | 128 | 33 | |
| GSS of prescribed NRTIs | 0·25 (0–1; 0–3) | 0 (0–0·25; 0–0·5) | 1 (0·5–1; 0·5–1·25) | 2 (2–2; 1–3) | |
| Country | |||||
| Malawi* | 37 (9%) | 17 (7%) | 8 (6%) | 12 (36%) | |
| Uganda | 253 (65%) | 154 (67%) | 87 (68%) | 12 (36%) | |
| Zimbabwe | 84 (21%) | 56 (24%) | 21 (16%) | 7 (21%) | |
| Kenya | 17 (4%) | 3 (1%) | 12 (9%) | 2 (6%) | |
| Age (years) | 37 (31–43) | 37 (31–43) | 37 (31–45) | 36 (24–41) | |
| Years on first line ART | 4·0 (2·8–5·4) | 4·1 (2·9–5·5) | 4·2 (2·7–5·3) | 2·8 (2·3–5·0) | |
| Viral load (copies per mL) | 68 359 (23 200–181 887) | 83 634 (34 800–222 514) | 47 733 (13 683–94 293) | 113 982 (10 683–325 122) | |
| >100 000 | 158 (40%) | 110 (48%) | 29 (23%) | 19 (58%) | |
| CD4 (cells per μL) | 69 (28–136) | 47 (21–98) | 116 (64–183) | 91 (50–177) | |
| ≤100 | 247 (63%) | 174 (76%) | 54 (42%) | 19 (58%) | |
| Number of NRTI mutations | 4 (2–5) | 5 (4–5) | 2 (2–3) | 0 (0–1) | |
| Any NRTI mutation | 370 (95%) | 230 (100%) | 128 (100%) | 12 (36%) | |
| Any TAM1 mutations | 211 (54%) | 173 (75%) | 38 (30%) | 0 | |
| Any TAM2 mutations | 220 (56%) | 159 (69%) | 60 (47%) | 1 (3%) | |
| Most common NRTI mutations | |||||
| Met184Val | 355 (91%) | 217 (94%) | 126 (98%) | 12 (36%) | |
| Met41Leu | 170 (43%) | 158 (69%) | 12 (9%) | 0 | |
| Thr215Tyr | 167 (43%) | 137 (60%) | 30 (23%) | 0 | |
| Asp67Asn | 150 (38%) | 126 (55%) | 24 (19%) | 0 | |
| Lys70Arg | 125 (32%) | 81 (35%) | 43 (34%) | 1 (3%) | |
| Leu210Trp | 118 (30%) | 110 (48%) | 8 (6%) | 0 | |
| Thr215Phe | 97 (25%) | 75 (33%) | 22 (17%) | 0 | |
| Lys219Gln | 66 (17%) | 42 (18%) | 24 (19%) | 0 | |
| Lys219Glu | 44 (11%) | 40 (17%) | 4 (2%) | 0 | |
| Lys65Arg | 29 (7%) | 25 (11%) | 4 (2%) | 0 | |
| Most common NRTI mutation pattern | |||||
| 41Leu, 184Val, 210Trp, 215Tyr | 40 (11%) | 40 (17%) | 0 | 0 | |
| 184Val | 38 (10%) | 1 | 27 | 10 | |
| 41Leu, 67Asn, 184Val, 210Trp, 215Tyr | 26 (7%) | 26 | 0 | 0 | |
| 67Asn, 70Arg, 184Val, 219Gln | 18 (5%) | 1 | 17 | 0 | |
| 184Val, 215Tyr | 15 (4%) | 0 | 15 | 0 | |
| First-line NRTIs used | |||||
| Zidovudine | 275 (70%) | 177 (80%) | 86 (67%) | 12 (36%) | |
| Tenofovir | 39 (10%) | 19 (8%) | 16 (13%) | 4 (12%) | |
| Initial second-line NRTIs prescribed | |||||
| Tenofovir, lamivudine/emtricitabine | 279 (71%) | 159 (69%) | 105 (82%) | 15 (45%) | |
| Tenofovir, zidovudine, lamivudine/emtricitabine* | 36 (9%) | 17 (7%) | 8 (6%) | 11 (33%) | |
| Abacavir, didanosine | 51 (13%) | 40 (17%) | 5 (4%) | 6 (18%) | |
| Abacavir, lamivudine/emtricitabine | 12 (3%) | 9 (4%) | 2 (2%) | 1 (3%) | |
| Zidovudine, lamivudine/emtricitabine | 10 (3%) | 2 (1%) | 8 (6%) | 0 | |
| Didanosine, lamivudine/emtricitabine | 2 (1%) | 2 (1%) | 0 | 0 | |
| Zidovudine, didanosine | 1 (<1%) | 1 (<1%) | 0 | 0 | |
Data are median (IQR) or median (IQR; range), and number of patients and % of those with baseline genotypes available in each group. Predicted-active NRTIs are prescribed NRTIs with no more than low-level resistance on baseline genotype. ART=antiretroviral therapy. NRTI=nucleoside reverse-transcriptase inhibitor. GSS=genotypic susceptibility score. TAM=thymidine analogue mutation.
An NRTI regimen of three NRTIs (tenofovir, zidovudine, and lamivudine) was initially prescribed in Malawi, but this was reduced to two NRTIs (usually tenofovir and lamivudine) after a median of 45 weeks from randomisation when national guidelines changed.