Table 1.
Main characteristics of the three early ART randomized controlled trials (HPTN052, Temprano ANRS 12136, START)
| HPTN052 | Temprano | START | |
|---|---|---|---|
| First enrolment–last visit | June 2007–May 2011 | March 2008–Jan 2015 | April 2009–May 2015 |
| Protocol | |||
| Study design | Open label RCT | Open label RCT | Open label RCT |
| CD4 inclusion criterion | 350 < CD4 < 550 | 250/350 < CD4 < 800b | >500 |
| ART initiation CD4 thresholda | 250 | 200–350–500b | 350 |
| Composite primary outcome | Death, WHO stage 4, non-AIDS cancers, tuberculosis, severe bacterial infections, serious cardiovascular, diabetes mellitus | Death, AIDS, non AIDS cancers severe bacterial infections | Death, AIDSc, non AIDS cancer, serious cardiovasculard, renal failure, liver failure |
| Number of participants | |||
| Enrolled/analyzed | 1763/1761 | 2076/2056 | 4588/4585 |
| Early ART | 886 | 1033 | 2326 |
| Deferred ART | 875 | 1023 | 2359 |
| Geographical origin | |||
| Africa | 54 % | 100 % | 21 % |
| Europe, USA, Australia, Israel | – | – | 46 % |
| Asia | 30 % | – | 7 % |
| Latin America | 16 % | – | 25 % |
| Baseline characteristics | |||
| % of women | 49 % | 79 % | 27 % |
| Age, median (IQR) | 33 (27–39) | 35 (29–42) | 36 (29–44) |
| CD4 count, median (IQR; Max) | 436 (364–522; 550) | 463 (366–572; 1456e) | 651 (584–765; 2296) |
| Positive serum HBs Ag | 5 % | 9 % | NA |
| Follow-up characteristics | |||
| Received IPT during trial follow-up, % | 3 % | 45 % | NA |
| Follow-up, year, median (IQR) | 2.1 (1.5–2.9) | 2.5 (2.5–2.5) | 2.8 (2.1–3.9) |
RCT randomized controlled trial; IPT isoniazid prophylaxis for tuberculosis
aART-start CD4 threshold for asymptomatic patients randomized to the deferred ART strategy
bFor ethical reasons, the Temprano investigators considered that the WHO revised guidelines had to be followed as soon as they were released
Therefore, they adopted the WHO 2010 guidelines in December 2009 as soon as the WHO rapid advice was released; and further adopted the WHO 2013 guidelines in August 2013. The 2010 and 2013 guidelines revisions impacted the trial procedures at two levels: the eligibility criterion ‘no WHO criteria for starting ART’, and the criteria for starting ART in participants assigned to the Deferred-ART strategy:
Asymptomatic patients were considered having ‘no WHO criteria for starting ART’ and therefore eligible for the trial: between the trial start and November 2009: if they had more than 250 CD4/mm3; Between December 2009 and July 2012: if they had more than 350 CD4/mm3; As enrolment was completed in July 2012, the WHO 2013 guidelines revision did not impact the eligibility criteria
Asymptomatic participants assigned to the Deferred-ART strategy started ART: between the trial start and November 2009: whenever they met the WHO 2006 criteria for starting ART (CD4 count <200/mm3); Between December 2009 and July 2013: whenever they met the WHO 2010 criteria for starting ART (CD4 count <350/mm3); Between August 1st 2013: whenever they met the WHO 2013 criteria for starting ART (CD4 count <500/mm3; or stable partnership with an HIV-negative individual)
cExcluding HSV and oesophageal candidiasis
dMyocardial infarction, stroke, or coronary revascularization
eTemprano, patients were eligible for the trial if the pre-inclusion CD4 count (measured within 1 months prior to randomization) was below 800/mm3. The “baseline” CD4 count distribution shown here is the distribution of values measured at inclusion (ie after informed consent), not the pre-inclusion value that determined eligibility. This explains why some patients had CD4 counts higher than 800/mm3 at baseline