Table 2. RCTS- ADR and associated risk factors.
| Reference | Cohort description and numbers | Acquired isoniazid resistance (%) | Acquired rifamycin resistance (%) | Acquired MDR TB (%) | Risk factors associated with acquired drug resistance (ADR) |
|---|---|---|---|---|---|
| Algerian Working Group/British MRC 1991 Tubercle [16] | Whole cohort n = 2218 Known baseline drug sensitivity n = 2071 Follow up drug sensitivity n = 1415 | WC = 1/2071 (0.05) WCFU = 1/1415 (0.07) PS = 1/1376 (0.07) MR(S) = 0/40 (0) | WC = 4/2071 (0.19) WCFU = 4/1415 (0.28) PS = 1/1376 (0.07) MR(H/S) = 0/61 (0) PR (H+S) = 3/34 (8.8) | WC = 4/2071 (0.19)WCFU = 4/1415 (0.28) PS = 1/1376 (0.07) MR(H /S) = 0/50 PR(H+S) = 3/33 (9) | -Rifampicin in regimen only during intensive phase -Baseline resistance to INH and STREP |
| Hong Kong TB Research Centre Madras/BMRC Am Rev Resp Disease 1991 [12] | Whole cohort n = 145 Culture proven TB with known baseline sensitivity n = 127 | WCFU 2/127 (1.6) PS = 2/91 (2.2) MR(S/R) = 0/13 (0) | WCFU 5/127 (3.9) PS 1/91 (1.1) MR(H/S) = 1/22 (4.5) PR = 3/9 (33) | WC = 4/127 (3.1) PS = 1/91 (1.1) MR(H/S/R) = 1/25 (4) PR(H+S) = 3/9 (33) | -Baseline drug resistance |
| Lienhardt JAMA 2011 [17] | Culture confirmed smear +ve new TB patients either pan-susceptible or INH monoresistant n = 1170 | WCFU 1/1170 (0.09) PS 1/1005 (0.1) | WCFU 1/1170 (0.09) PS 0/1005 (0) MR(H) 1/127 (0.79) | WCFU 1/1170 (0.09) PS 0/1005 (0) MR(H) 1/127 (0.79) | -None of the factors analysed were associated (see S4 Table) |
| Swaminathan AJRCCM 2010 [10] | New TB cases (baseline MDR excluded) n = 327 Culture confirmed with DST and results at end of treatment n = 212 | WC 7/327 (2) WCFU 7/212 (3.3) PS 7/194 (3.6) ¥ | WC 20/327 (6.1) WCFU 20/212 (9.4) PS 11/194 (5.7) ¥ | WC 17/327 (5.2) WCFU 17/212(8.0) PS 11/194 (5.7) ¥ | -Lower median CD4 lymphocyte count (p 0.054)- Higher median HIV VL (p 0.009) -Non-adherence (adherence <90%) (p 0.000) -Baseline isoniazid resistance (OR 8.43, p 0.002) |
| TB Research Centre IJTLD 1997 [18] | Smear +ve TB n = 1203, Followed up post end of treatment and included in relapse analyses n = 777 | WC 22/1053 (2.1) PS 22/825 (2.7) MR(R) 1/1 (100) | WC 26/1053 (2.4) PS 3/825 (0.3) MR(H) 23/227 (10) | WC 26/1053 (2.4) PS 1/825 (0.1) MR(H/R) 23/228(10) | -Lack of ethambutol in a twice weekly regimen -Baseline drug resistance |
| Vernon Lancet 1999 [8] | Culture confirmed drug sensitive TB, HIV co-infected n = 61 | Not specified | WCFU 4/61 (6.6) PS 4/61 (6.6) ¥ | Not specified | -Once-weekly isoniazid/rifapentine (p 0.05) Baseline CD4 (p 0.02) -Age (p 0.04) -Extrapulmonary + pulmonary disease (p 0.03)—Use of antifungal azoles (p 0.006) |
Abbreviations: WC whole cohort denominator known DST; WCFU denominator f/u DST; PS denominator initial pan-sensitivity; MR denominator initial monoresistance; PR denominator initial polyresistance. H isoniazid S Streptomycin R rifampicin DOT directly observed therapy NTM non-tuberculous mycobacteria MDR multidrug resistant ART antiretroviral therapy BMI body mass index INH isoniazid PZA pyrazinamide.
¥ADR data presented is not stratified by baseline monoresistance and polyresistance as this information cannot be ascertained from the paper.