TABLE 1.
Summary of design, conduct and findings of the Strategic timing of antiretroviral therapy and TEMPRANO ANRS 12136 (Early antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults) randomised controlled trials.
| Trial | TEMPRANO | START |
|---|---|---|
| Countries | Cote d’Ivoire | 35 countries (21% of participants enrolled in Africa) |
| Enrolment years | 2008–2012 | 2009–2013 |
| Number of participants | 2056 | 4685 |
| Inclusion criteria | ≥ 18 years old | ≥ 18 years old |
| HIV-1 (or dual HIV-1 and 2) | ART naive | |
| CD4 < 800 | No history of AIDS | |
| Not meeting WHO criteria for starting ART at the time (these criteria changed during the course of the trial) | General good health | |
| - | 2 CD4 counts > 500 | |
| Comparison arms | Immediate ART | Immediate ART |
| ART deferred until WHO criteria for starting ART met (these criteria changed over the course of the trial) | ART deferred until CD4 ≤ 350, AIDS diagnosis or other indication for ART (e.g. pregnancy) | |
| Composite primary endpoint | AIDS, non-AIDS cancer, non-AIDS invasive bacterial disease or death | Serious AIDS-related event, serious non-AIDS-related event or death |
| Duration of follow-up | 30 months for each participant | Mean 3.0 years (trial stopped early by DSMB) |
| Number of primary events | Immediate arm: 64 | Immediate arm: 42 |
| Deferred arm: 111 | Deferred arm: 96 | |
| Primary endpoint finding | 44% reduction with immediate ART (aHR = 0.56, 95% CI = 0.41–0.76) | 57% reduction with immediate ART (HR = 0.43, 95% CI = 0.30–0.62) |
| Among patients with baseline CD4 ≥ 500, there was also a 44% in primary endpoint (aHR = 0.56, 95% CI = 0.33–0.94) | - | |
| Main contributors to finding | Reduction in AIDS events (50%, mainly TB [50%]) and invasive bacterial disease (61%) | Reduction in AIDS events (72%, including TB [71%]), serious non-AIDS events (29%), cancers (64%) and bacterial infections (62%) |
| Deaths | Immediate arm: 21 | Immediate arm: 12 |
| Deferred arm: 26 | Deferred arm: 21 | |
| Not significant: aHR = 0.60, 95% CI = 0.34–1.09 | Not significant: p = 0.13 | |
| Viral load suppression | Viral load < 100 at 12 months on ART | Viral load < 200 at 12 months on ART |
| Immediate arm: 84% | Immediate arm: 98% | |
| Deferred arm: 80% | Deferred arm: 97% | |
| Adverse events | Overall, the 30-month probability of a Grade 3 or 4 AE did not differ between arms although it was 2.6 times higher in the immediate ART arm for the first 6 months | No difference between arms in terms of grade 4 events and hospitalisations for reasons other than AIDS |
Note: In the TEMPRANO trial, there was a separate randomisation of participants to 6 months isoniazid preventive therapy (IPT) versus no IPT.
WHO, World Health Organization; DSMB, Data and Safety Monitoring Board; aHR, adjusted hazard ratio; CI, confidence interval; HR, hazard ratio; AE, adverse event.