Table 2.
Protease Inhibitor Resistance at Failure of Second-line Antiretroviral Therapy
| Reference | Study Design | Year | Location | Total Population, No. |
Second-line ART Duration, mo, Median (IQR) | Viral Load Threshold for Sequencing, Copies/mL | Failure Population, No. (%) |
Resistance Analysis Population, No. (%) | Protease Resistance, No. (% of At-Risk Population)a |
Protease Resistance, No. (% of Those Sequenced)b |
Major Protease Mutation (No.) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Prospective studies | |||||||||||
| Paton [18] | RCT | 2010–14 | Uganda, Kenya, Malawi, Zimbabwe, Zambia | 426 | 24 | 1000 | 46 (10.7) | 41 (89.1) | 8 (2.1)c | 8 (19.5)c | M46I (8), I54V (7), L76V (3), V82AF (6) |
| Boyd [14] | RCT | 2010–14 | Nigeria, South Africa | 100 | 12 | 500 | 8 (8.0) | 8 (100) | 0 (0) | 0 (0) | … |
| Ciaffi [15]d | RCT | 2010–13 | Cameroon, Burkina Faso, Senegal | 451 | 12 | 1000 × 2 | 29 (6.4) | 5 (17.2) | 0 (0) | 0 (0) | … |
| Boender [25] | POC | 2007–11 | Kenya, Nigeria, South Africa, Uganda, Zambia, Zimbabwe | 205 | 12 | 1000 | 21 (10.2) | 17 (81.0) | 2 (1.2) | 2 (11.8) | M46I (2), I54V (2), L76V(1), V82A (2), L90M (1) |
| 177 | 24 | 1000 | 26 (14.7) | 21 (80.8) | 6 (4.2) | 6 (28.6) | M46I (5), I54V (4), L76V(2), V82A (4), I84V (1) | ||||
| 90 | 36 | 1000 | 8 (8.9) | 3 (37.5) | 2 (5.9) | 2 (66.7) | M46I (2), I50V (1), I54V (1), V82A (2) | ||||
| Johnston [30] | POC | 2003–8 | South Africa | 417 | 12 | 400 | 112 (26.8) | 15 (13.4) | 0 (0) | 0 (0) | … |
| Cross-sectional observational studies | |||||||||||
| Schramm [39] | CS | 2014–15 | Kenya | 355 | 27 (23–36) | 500 | 65 (18.3) | 65 (100) | 16 (4.5) | 16 (24.6) | NA |
| Inazule [38] | CS | 2010–15 | Kenya | NS | 37 (23–55) | 1000 | 126 (…) | 123 (97.6) | 39 (…) | 39 (31.7) | M46I/L (30), I54V (27), V82ATFS (25) |
| Court [32] | CS | 2009–13 | South Africa | NS | 20 (13–34) | 1000 | 164 (…) | 134 (81.7) | 28 (…) | 28 (20.9) | M46I (22), I47VA (2), I50V (1), I54VTALM (24), L76V (19), V82A (22), I84V (2), L90M (1) |
| Maiga [34] | CS | 2012 | Mali | 913 | 24 (6–48) | 500 | 106 (11.6) | 93 (87.7) | 23 (2.9) | 23 (24.7) | M46I (15), I47V/A (6), I54V (12), L76V(11), V82A (8), I84V (10), L90M (3) |
| Ndahimana [37] | CS | 2012 | Rwanda | 74 | 31 (18–46) | 1000 | 35 (47.3) | 30 (85.7) | 5 (7.9) | 5 (16.7) | L33F (2), M46I (4), I54V (5), L76V (2), V82A (4), I84V (2), |
| Levison [33] | CS | 2009 | South Africa | 322 | 17 (18)e | 1000 × 2 | 43 (13.3) | 33 (76.7) | 0 (0) | 0 (0) | … |
| Reynolds [35] | CS | 2004–9 | Uganda | 65 | 6 (6–14) | 2000 | 8 (12.3) | 6 (75.0) | 0 (0) | 0 (0) | … |
| Wallis [36] | CS | 2008 | South Africa | NS | 16 (7–18) | 5000 × 2 | 75 (…) | 75 (100) | 5 (…) | 5 (6.7) | L33F (2), M46I (4), I54SV (2), L76V (2), V82A (1), I84V (2), L90M (1), |
Abbreviations: ART, antiretroviral therapy; CS, cohort study; IQR, interquartile range; NA, genotype not available; NS, not specified; POC, prospective observational cohort; RCT, randomized controlled trial.
aAs proportion of total at-risk population; adjusted for proportion who underwent sequencing. Major protease resistance mutations as defined by the Stanford HIV drug resistance database [9].
bAs proportion of failure population; adjusted for proportion who underwent sequencing.
cResistance refers to intermediate or high-level resistance to lopinavir only.
dAll patients received lopinavir/ritonavir apart from participants in the Ciaffi et al study [15]; 33% were randomized to darunavir/ritonavir, and the remainder received lopinavir/ritonavir.
eStandard deviation.