Table 3 Association between timing of nirmatrelvir/ritonavir initiation and 28-day viral burden rebound

From: Optimal timing of nirmatrelvir/ritonavir treatment after COVID-19 symptom onset or diagnosis: target trial emulation

All-cause mortality or hospitalization

Cumulative incidence

Absolute risk reductiona

95% CI

Early

Late

  

N

RiskΔ

N

RiskΔ

  

Primary analysis (days 0–1 vs days > 1)

Overall

9128

1.39%

541

0.31%

−1.08%

(−1.55%, −0.46%)

Subgroup analyses

Male

4837

1.62%

296

0.64%

−0.99%

(−1.81%, 0.32%)

Female

4291

1.12%

245

0.00%

−1.12%

(−1.41%, −0.88%)

March–June 2022‡

697

0.59%

100

0.00%

−0.59%

(−1.20%, −0.15%)

July–October 2022‡

4495

1.88%

250

0.57%

−1.31%

(−2.18%, −0.06%)

November 2022–January 2023‡

3936

0.98%

191

0.18%

−0.80%

(−1.18%, −0.36%)

Fully vaccinated or boosted

6366

1.06%

344

0.43%

−0.62%

(−1.10%, 0.25%)

Not fully vaccinated

2762

2.14%

197

0.00%

−2.14%

(−2.52%, −1.69%)

Charlson’s index 0–6

8078

1.24%

478

0.36%

−0.88%

(−1.37%, −0.27%)

Charlson’s index >6

1047

2.57%

63

0.00%

−2.57%

(−3.48%, −1.68%)

Concomitant corticosteroid use

1976

2.20%

128

0.00%

−2.20%

(−2.83%, −1.55%)

No concomitant corticosteroid use

7152

1.17%

413

0.40%

−0.77%

(−1.35%, −0.12%)

Immunocompromised

2112

1.86%

108

0.00%

−1.86%

(−2.57%, −1.42%)

Not immunocompromised

7016

1.25%

433

0.43%

−0.83%

(−1.39%, −0.03%)

Documented symptom onset date as index date

968

1.42%

74

1.36%

−0.06%

(−1.95%, 4.67%)

Date of COVID-19 diagnosis as index date

8571

1.38%

501

0.14%

−1.24%

(−1.58%, −0.83%)

Inpatient users

8861

1.40%

519

0.29%

−1.11%

(−1.56%, −0.55%)

Outpatient users

267

1.18%

22

0.00%

−1.18%

(−2.78%, 0.00%)

Sensitivity analysis (days 0–2 vs days > 2)

Overall

9452

1.38%

217

0.00%

−1.38%

(−1.67%, −1.18%)

Subgroup analyses

Male

5011

1.62%

122

0.00%

−1.62%

(−2.15%, −1.26%)

Female

4441

1.11%

95

0.00%

−1.11%

(−1.41%, −0.86%)

March–June 2022‡

756

0.57%

41

0.00%

−0.57%

(−1.32%, 0.00%)

July–October 2022‡

4645

1.86%

100

0.00%

−1.86%

(−2.20%, −1.47%)

November 2022–January 2023‡

4051

0.98%

76

0.00%

−0.98%

(−1.30%, −0.66%)

Fully vaccinated or boosted

6567

1.06%

143

0.00%

−1.06%

(−1.30%, −0.81%)

Not fully vaccinated

2885

2.11%

74

0.00%

−2.11%

(−2.54%, 0.00%)

Charlson’s index 0–6

8363

1.24%

193

0.00%

−1.24%

(−1.47%, −1.02%)

Charlson’s index >6

1086

2.49%

24

0.00%

−2.49%

(−3.34%, 0.00%)

Concomitant corticosteroid use

2044

2.12%

60

0.00%

−2.12%

(−2.72%, −1.45%)

No concomitant corticosteroid use

7408

1.18%

157

0.00%

−1.18%

(−1.50%, −0.92%)

Immunocompromised

2173

1.79%

47

0.00%

−1.79%

(−2.35%, 0.00%)

Not immunocompromised

7279

1.26%

170

0.00%

−1.26%

(−1.50%, −1.03%)

Documented symptom onset date as index date

1018

1.50%

24

0.00%

−1.50%

(−2.23%, −0.66%)

Date of COVID-19 diagnosis as index date

8864

1.37%

208

0.00%

−1.37%

(−1.63%, −1.11%)

Inpatient users

9173

1.39%

207

0.00%

−1.39%

(−1.76%, −1.14%)

Outpatient users

279

1.10%

10

0.00%

−1.10%

(−2.91%, 0.00%)

Sensitivity analysis (days 0–3 vs days > 3)

Overall

9580

1.39%

89

0.00%

−1.39%

(−1.68%, −1.19%)

Subgroup analyses

Male

5081

1.63%

52

0.00%

−1.63%

(−2.16%, −1.26%)

Female

4499

1.12%

37

0.00%

−1.12%

(−1.41%, −0.86%)

March–June 2022‡

779

0.57%

18

0.00%

−0.57%

(_1.33%, 0.00%)

July–October 2022‡

4705

2.04%

40

0.00%

−2.04%

(−2.45%, −1.63%)

November 2022–January 2023‡

4096

0.97%

31

0.00%

−0.97%

(−1.31%, −0.66%)

Fully vaccinated or boosted

6651

1.06%

59

0.00%

−1.06%

(−1.30%, −0.81%)

Not fully vaccinated

2929

2.14%

30

0.00%

−2.14%

(−2.58%, 0.00%)

Charlson’s index 0–6

8482

1.24%

74

0.00%

−1.24%

(−1.47%, −1.03%)

Charlson’s index >6

1095

2.76%

15

0.00%

−2.76%

(−3.81%, 0.00%)

Concomitant corticosteroid use

2075

2.10%

29

0.00%

−2.10%

(−2.78%, −1.37%)

No concomitant corticosteroid use

7505

1.18%

60

0.00%

−1.18%

(−1.50%, −0.92%)

Immunocompromised

2200

1.79%

20

0.00%

−1.79%

(−2.35%, 0.00%)

Not immunocompromised

7380

1.26%

69

0.00%

−1.26%

(−1.50%, −1.03%)

Documented symptom onset date as index date

1034

1.48%

8

0.00%

−1.48%

(−2.25%, −0.62%)

Date of COVID-19 diagnosis as index date

8986

1.38%

86

0.00%

−1.38%

(−1.64%, −1.11%)

Inpatient users

9294

1.40%

86

0.00%

−1.40%

(−1.76%, −1.14%)

Outpatient users

286

1.07%

3

0.00%

−1.07%

(−2.85%, 0.00%)

  1. CI confidence interval.
  2. ΔRisk represents the incidence of 28-day viral burden rebound after inverse probability weighting (IPW) between the two treatment groups against baseline covariates.
  3. aAbsolute risk reduction >0 (or <0) and relative risk <1 (or >1) indicate early initiators (day 0–1) had a lower (higher) risk of the designated outcome compared to late initiators (days ≥2).
  4. ‡Omicron subvariant BA.2 was dominant from March to June 2022, BA.2 and BA.4/BA.5 from July to October 2022 and BA.5, BA.2.75, and BQ.1 from November 2022 to January 2023.
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