Table 1.
Treatment shortening trials that included patients with HIV8
| Study name | Location | Intervention | % HIV positive |
Results | |
|---|---|---|---|---|---|
| LTBI | CPCRA 004 + ACTG 177 | USA, Brazil, Mexico, Haiti | R1F 600 mg/d + PZA 20 mg/kg/d (2 months) versus INH 300 mg/day | 100% | Completion 80% (intervention) vs 69%; efficacy 2.4% TB disease (intervention) vs 3.3% [19] |
| Haiti | INH 600 mg twice weekly (6 months) versus RIF 450 mg plus PZA 1500 mg twice weekly (2 months) | 100%% | No difference in effectiveness [20] | ||
| Spain | INH 300 mg daily (12 months) versus RIF 600 mg plus INH 300 mg daily (3 months) | 100% | Equivalent TB prevention, fewer safety events for 3HR [21] | ||
| Spain | INH 5 mg/kg daily (6 months) versus RIF 10 mg/kg plus INH 5 mg/kg (3 months) versus RIF 10 mg/kg plus PZA 2000 mg daily (2 months) | 100% | No benefit among TST negative patients in TB prevention [22] | ||
| Spain | INH 5 mg/kg daily (6 months) versus RIF 10 mg/kg plus INH 5 mg/kg (3 months) versus RIF 10 mg/kg plus PZA 1500 mg or 2500 mg mg daily (2 months) | 100% | Similar safety of 2RZ versus 6H and 3RH regimens [23] | ||
| Uganda | INH 30 mg (6 months) versus INH 300 mg pus RIF 600 mg daily (3 months) versus INH 300 mg plus RIF 600 mg plus PZA 2000 mg daily (3 months) | 100% | Reduced TB incidence, no change in HIV progression [24] | ||
| Zambia | INH twice weekly (6 months), RIF/PZA twice weekly (3 months), placebo | 100% | Either regimen effective (RR 0.60, CI 0.36–1.01), protective duration limited < 18 months31 | ||
| PREVENT TB/NCT00023452; NCT00023452, TBTC Study 26 | USA, Brazil, Spain, Peru, Canada, Hong Kong | Weekly rifapentine + INH (3 months) vs INH (9 months) | 2.60%, then 100% | In both studies: 3HP equally effective, higher treatment completion [25, 26] | |
| TEMPRANO | Ivory Coast | 2×2 factorial design for delayed versus immediate ART and 6 months IPT or no IPT | 100% | Immediate ART and 6 months IPT had lower rates of death and severe disease than delayed ART and no IPT [9] | |
| NCT00057122 | South Africa | Weekly 3HP, twice weekly 3RH, daily INH (6 years), daily INH (6 months) | 100% | All effective, no regimens superior to daily INH for 6 mo37 | |
| BRIEF TB/A5279, NCTO1404312 | Haiti, Botswana, Peru, Thailand, South Africa, Brazil, Malawi, Zimbabwe, Kenya, USA | 1HP versus 9H | 100% | 1HP non-inferior in TB prevention with equivalent safety and higher treatment completion [27•] | |
| NCTO0931736 | Australia, Benin, Brazil, Canada, Ghana, Guinea, Indonesia, Saudi Arabia, South Korea | RIF (4 months) versus INH (9 months) | 4% | 4R non-inferior to 9H for prevention; safety and completion superior for 4R [28] | |
| NCT02980016 | South Africa, Ethiopia, Mozambique | Annual 3HP (2 years) versus 3HP (once) versus 6H (once) | 100% | Higher treatment completion (3HP arms), similar TB incidence, and mortality [29] | |
| DSTB | TBTC Study 28 NCT00144417 | USA, Canada, Brazil, South Africa, Spain, Uganda | Moxifloxacin 400 mg OR isoniazid plus RZE | 11% | similar culture conversion at 8 weeks [30] |
| RIFAQUIN, ISRCTN44153044 | South Africa, Zimbabwe, Botswana, Zambia | Moxi plus RZE (2 months) followed by either 2 months twice weekly moxi-rifapentine or 4 months once weekly moxi-rifapentine versus RHZE | 28% | Failed to meet non-inferiority for shortened duration arms [31] | |
| OFLOTUB NCT00216385 | Benin, Guinea, Kenya, Senegal, South Africa | 4 months RHZ-gatifloxacin versus RHZE | 18% | Failed to meet non-inferiority for shortened duration arm [32] | |
| REMoxTB NCT00864383 | South Africa, India, Tanzania, Kenya, Thailand, Malaysia, Zambia, China, Mexico | 4 months RHZ-moxifloxacin, 4 months RZE-moxifloxacin, or RHZE | 7% | Failed to meet non-inferiority for shortened duration arms [33] | |
| NC005 | South Africa, Tanzania, Uganda | BPaZ for 8 weeks followed by RHZE | 15.60% | Enhanced bactericidal activity at 8 weeks in BPaZ arm [34] | |
| DRTB | STREAM | Ethiopia, Mongolia, South Africa, Vietnam | 9–11 months moxifloxacin, clofazimine, ethambutol, pyrazinamide plus kanamycin, isoniazid, prothionamide for first 16 weeks versus 20 months per WHO guidelines | 32.60% | Short-course efficacy non-inferior to long course [35] |
| Nix TB | South Africa | BPaL (6 months) versus historical | 51% | Improved efficacy compared with historical controls [36•] |