TABLE 3.
Haplotype frequencies in ART and partner drug resistance-associated genes observed in at least 1 sampleb
| Drug(s) and gene haplotype(s) | 2003–2005 |
2008–2012 |
2014–2018 |
χ2 P value | |||
|---|---|---|---|---|---|---|---|
| No. of samples with haplotype/total no. of samples | % of samples with haplotype (95% CI) | No. of samples with haplotype/total no. of samples | % of samples with haplotype (95% CI) | No. of samples with haplotype/total no. of samples | % of samples with haplotype (95% CI) | ||
| ART | |||||||
| K13 | |||||||
| G449Ca | 1/141 | 0.7 (0.1–4.9) | 0/68 | 0 | 1/45 | 2.2 (0.3–73.4) | 0.03621 |
| K189T | 94/141 | 66.7 (58.4–74.0) | 42/68 | 61.8 (49.6–73.6) | 25/45 | 55.6 (40.7–73.4) | |
| wt | 15/141 | 10.6 (6.5–17.0) | 16/68 | 23.5 (14.9–73.6) | 3/45 | 6.7 (2.1–73.4) | |
| wt incomplete | 29/141 | 20.6 (14.6–28.1) | 10/68 | 14.7 (8.0–73.6) | 14/45 | 31.1 (19.2–73.4) | |
| Missing | 2/141 | 1.4 (0.4–5.6) | 0/68 | 0 | 2/45 | 4.4 (1.1–73.4) | |
| ubp1 | |||||||
| Q107L and/or K1193T type | 60/141 | 42.6 (34.6–50.9) | 6/68 | 8.8 (4.0–18.4) | 3/45 | 6.7 (2.1–19.0) | <2.2e−16 |
| R1133S type | 21/141 | 14.9 (9.9–21.8) | 7/68 | 10.3 (4.9–20.2) | 1/45 | 2.2 (0.3–14.6) | |
| R1133S + E1011K type | 33/141 | 23.4 (17.1–31.2) | 53/68 | 77.9 (66.4–86.3) | 41/45 | 91.1 (78.3–96.7) | |
| Polyclonal Q107L/K1193T+ R1133S | 3/141 | 2.1 (0.7–6.4) | 1/68 | 1.5 (0.2–9.9) | 0/45 | 0 | |
| wt or wt incomplete | 24/141 | 17.0 (11.6–24.2) | 1/68 | 1.5 (0.2–9.9) | 0/45 | 0 | |
| coronin | |||||||
| V424I | 78/141 | 55.3 (47.0–63.4) | 41/68 | 60.3 (48.2–71.3) | 37/45 | 82.2 (68.0–91.0) | 0.002743 |
| V62M | 29/141 | 20.6 (14.6–28.1) | 5/68 | 7.4 (3.1–16.6) | 0/45 | 0 | |
| wt | 30/141 | 21.3 (15.3–28.9) | 20/68 | 29.4 (19.7–41.4) | 8/45 | 17.8 (9.0–32.0) | |
| Polyclonal | 0/141 | 0 | 1/68 | 1.5 (0.2–9.9) | 0/45 | 0 | |
| Incomplete | 4/141 | 2.8 (1.1–7.4) | 1/68 | 1.5 (0.2–9.9) | 0/45 | 0 | |
| SP | |||||||
| dhfr | |||||||
| Single mutant (S108N) | 98/141 | 69.5 (61.4–76.6) | 6/68 | 8.8 (4.0–18.4) | 0/45 | 0 | <2.2e−16 |
| Double mutant + BR + I164L | 32/141 | 22.7 (16.5–30.4) | 0/68 | 0 | 0/45 | 0 | |
| Triple mutant | 0/141 | 0 | 61/68 | 89.7 (79.8–95.1) | 44/45 | 97.8 (85.4–99.7) | |
| Incomplete | 3/141 | 2.1 (0.7–6.4) | 0/68 | 0 | 1/45 | 2.2 (0.3–14.6) | |
| Missing | 6/141 | 4.3 (1.9–9.2) | 1/68 | 1.5 (0.2–9.9) | 0/45 | 0 | |
| dhps | |||||||
| Single mutant K540K | 16/141 | 11.3 (7.0–17.8) | 0/68 | 0 | 0/45 | 0 | <2.2e−16 |
| Single mutant A437G | 3/141 | 2.1 (0.7–6.4) | 1/68 | 1.5 (0.2–9.9) | 0/45 | 0 | |
| Double mutant | 14/141 | 9.9 (5.9–16.1) | 0/68 | 0 | 0/45 | 0 | |
| Triple mutant | 2/141 | 1.4 (0.4–5.6) | 48/68 | 70.6 (58.6–80.3) | 30/45 | 66.7 (51.6–79.0) | |
| Incomplete mutant | 7/141 | 5.0 (2.4–10.1) | 13/68 | 19.1 (11.4–30.4) | 12/45 | 26.7 (15.7–41.6) | |
| wt | 80/141 | 56.7 (48.4–64.7) | 4/68 | 5.9 (2.2–14.8) | 2/45 | 4.4 (1.1–16.4) | |
| wt incomplete | 19/141 | 13.5 (8.7–20.2) | 2/68 | 2.9 (0.7–11.2) | 1/45 | 2.2 (0.3–14.6) | |
| CQ and MQ | |||||||
| crt (positions 72–76) | |||||||
| CVMNT | 65/141 | 46.1 (38.0–54.4) | 2/68 | 2.9 (0.7–11.2) | 0/45 | 0 | 8.37e−16 |
| SVMNT | 49/141 | 34.8 (27.3–43.0) | 60/68 | 88.2 (78.0–94.1) | 32/45 | 71.1 (56.1–82.6) | |
| CVMNT/SVMNT polyclonal | 0/141 | 0 | 1/68 | 1.5 (0.2–9.9) | 0/45 | 0 | |
| Incomplete | 27/141 | 19.1 (13.4–26.6) | 5/68 | 7.4 (3.1–16.6) | 13/45 | 28.9 (17.4 to 43.9) | |
| mdr1 (positions 86, 144, 184, 1034, 1042, 1246) | |||||||
| NDFCDD | 61/141 | 43.3 (35.3–51.6) | 1/68 | 1.5 (0.2–9.9) | 0/45 | 0 | <2.2e−16 |
| ND_CDD | 2/141 | 1.4 (0.4–5.6) | 0/68 | 0 | 0/45 | 0 | |
| NDFCDY | 17/141 | 12.1 (7.6–18.6) | 60/68 | 88.2 (78.0–94.1) | 42/45 | 93.3 (81.0–97.9) | |
| NGFSDD | 43/141 | 30.5 (23.4–38.6) | 5/68 | 7.4 (3.1–16.6) | 0/45 | 0 | |
| NG_SDD | 4/141 | 2.8 (1.1–7.4) | 0/68 | 0 | 0/45 | 0 | |
| NDFSDD | 1/141 | 0.7 (0.1–4.9) | 0/68 | 0 | 0/45 | 0 | |
| Polyclonal | 5/141 | 3.5 (1.5–8.3) | 0/68 | 0 | 0/45 | 0 | |
| Incomplete | 8/141 | 5.7 (2.8–11.0) | 2/68 | 2.9 (0.7–11.2) | 3/45 | 6.7 (2.1–19.0) | |
a
One out of 2 samples with G449C was also accompanied by K189T; both cases were polyclonal infections.
b
Note that the ubp1 haplotype with R1133S and E1011K was frequently observed with additional SNP mutations (K764N, K774N, and D777G) and a large insert (EQKY) between amino acid positions 2826 and 2827. dhps double mutant indicates the A437G A581G mutant; dhps triple mutant indicates the A437G A581G K540E mutant. wt, wild type; CI, confidence interval.