Starting treatment

International guidelines recommend starting ART in all HIV-positive people, regardless of the CD4+ cell count, to reduce the risk of disease progression and to prevent transmission.1–4 These recommendations are based on findings from two large, randomised controlled trials that analysed the optimal time to initiate ART: START5 and TEMPRANO.6,7

The START trial

START included asymptomatic people living with HIV (PLHIV) (N=4685) with CD4+ cell count >500/mm.3 Participants were randomised to immediate antiretroviral therapy (ART) or deferred therapy (CD4+ cell count <350/mm3 or until the development of AIDS-related symptoms).5

In participants who began ART immediately, there was a 56% reduction in the primary outcome (any serious event [AIDS related or non-AIDS related] or death), compared to deferred treatment (hazard ratio [HR]=0.43; 95% confidence interval [Cl]: 0.30,0.62; p<0.001).5

The TEMPRANO trial

TEMPRANO was a multicentre, randomised controlled trial of more than 2000 participants that assessed the effects of early ART, 6 months of concomitant isoniazid prophylaxis (IPT), or both.6,7 People living with HIV with CD4 counts of <800 cells/mm3 were randomised to four treatment arms of either immediate or deferred ART, both with and without IPT.6,7 Early ART significantly reduced the risk of death or severe HIV-related illness by 44% (HR=0.56; 95% CI: 0.41–0.76; p=0.0002) compared with deferred ART.6 Data from the post-trial phase also suggested a 26% reduction in risk of death post 30 months (HR=0.74; 95% CI: 0.48,1.13; p=0.17) with early ART.7

Rapid initiation

There is growing evidence that rapid initiation of ART – starting within 7 days of HIV diagnosis – can provide sustained viral suppression and reduce transmission.2,8–13

In the RAPID programme (an intensive, same-day appointment incorporating a social needs assessment, medical provider evaluation, and initiation of ART), time to virological suppression was shorter in HIV-positive individuals initiated on the same day as diagnosis (n=39) compared with participants treated with a standard initiation protocol (n=47) (median 1.8 months versus 4.3 months; p=0.0001).8 A further retrospective analysis of the RAPID protocol confirmed its efficacy in an urban HIV clinic with high rates of substance use, mental illness, and housing instability:9

  • VL<200 copies/mL at least once by 1 year of follow up: entire group (n=216) 95.8%, early referral (n=190) 96.3% vs delayed referral (n=26) 100% (p=0.40)
  • VL<200 copies/mL at last VL measurement: entire group (n=216) 92.1%, early referral (n=190) 93.7% vs delayed referral (n=26) 80.8% (p=0.022)
  • Under 2% (n=225) declining immediate ART initiation.9

The RapIT trial investigated the effect of an accelerated initiation algorithm that allowed treatment-eligible PLHIV to receive their first supply of ART on the day of their first HIV-related clinic visit on medication uptake and viral suppression.10,11 The uptake of ART and viral suppression in the rapid-initiation arm (n=187) was higher than in the standard-initiation arm (n=190).10 Among patients achieving viral suppression, early initiation came with an additional cost of around 4% per individual than standard initiation.11

In the SABES study, investigators assessed HIV-1 viral load in plasma and semen from 216 participants randomised to initiate ART immediately after diagnosis (n=105) or 24 weeks later (n=111).12 There was no difference in virologic suppression at Week 24 after assigned ART initiation in either arm (64.8 vs 63.1%), but this difference became statistically significant (78.1 vs 63.1%; p=0.016) by Week 48.12 In an as-treated analysis, immune markers after 24 weeks of ART in individuals with deferred ART initiation (>90 days) were less likely to normalise than in those who started ART immediately (within 30 days) (CD4+/CD8+ T-cell ratio: 0.88 vs 1.03; p=0.02). Adverse events were the lowest in PLHIV with the most prompt initiation of ART: 85 in PLHIV starting within 30 days (n=38) vs 163 in PLHIV starting between 31-90 days (n =76) vs 125 in PLHIV starting after 90 days (n=97); p=0.03.12

A number of observational studies have also evaluated the impact of early ART initiation. A study of very early ART and regimen type in newly diagnosed PLHIV (N=86) found that ART initiated at the first visit led to rapid viral suppression in acute, early and chronic HIV infection. Time to viral suppression was significantly shorter in those receiving an integrase inhibitor (n=56) versus a protease inhibitor-based regimen (n=30; p=0.022).13 Of patients with acute HIV infection (n=87) at a sexual health clinic who initiated ART at first appointment, 85% achieved viral suppression within 16 weeks and 99% at 24 weeks.14

Most recently at IDWeek 2020, results from a retrospective study (2016–2018) from a tertiary healthcare system in Michigan showed the percentage of patients with undetectable viral load, recovered CD4 counts and retention in care with rapid start (defined as ART initiation prior to genotype results) was comparable to that of standard of care.15 In patients with ART start (n=40) 85.7% maintained undetectable viral load at 12 months compared to 77.1% of patients in the standard-of-care group (n=146; p=0.3174).15

The week 12 results of a New York prospective, open-label single-centre pilot study using BIC/FTC/TAF as rapid start ART (same day), showed that at participants on BIC/FTC/TAF rapid start (n=26) had a significantly (p<0.001) lower number of days from diagnosis to viral load <50 copies/mL (28 days), compared to the non-rapid start control group (n=24) (187.5 days).16