Table 2:
Organic indirect effects of curative HIV treatments that shift the distribution of the HIV reservoir measures downwards. The estimated probability of virologic suppression without treatment was 63/124 or 51% (week 4) and 17/122 or 14% (week 8).
| Mediator | Shift (log10 scale)a | Weekb,c | Indirect effectd | 95% CIe | RRf | 95% CIe |
|---|---|---|---|---|---|---|
| SCA HIV RNAg | 0.5 log10 | 4 | 3% | (−2.5%,7.0%) | 1.0 | (0.96,1.1) |
| SCA HIV RNAg | 1 log10 | 4 | 6% | (−1.3%,13%) | 1.1 | (0.98,1.2) |
| SCA HIV RNAg | ∞i | 4 | 6% | (−1.4%,14%) | 1.1 | (0.97,1.3) |
| CA HIV RNAh | 0.5 log10 | 4 | 7% | (1.7%,13%) | 1.1 | (1.0,1.3) |
| CA HIV RNAh | 1 log10 | 4 | 10% | (2.7%,17%) | 1.2 | (1.1,1.4) |
| CA HIV RNAh | ∞i | 4 | 13% | (3.0%,23%) | 1.2 | (1.1,1.5) |
| SCA HIV RNAg | 0.5 log10 | 8 | 3% | (0.61%,6.3%) | 1.2 | (1.0,1.4) |
| SCA HIV RNAg | 1 log10 | 8 | 5% | (0.92%,10%) | 1.3 | (1.1,1.6) |
| SCA HIV RNAg | ∞i | 8 | 6% | (0.95%,11%) | 1.3 | (1.1,1.7) |
| CA HIV RNAh | 0.5 log10 | 8 | 9% | (3.5%,15%) | 1.7 | (1.3,2.2) |
| CA HIV RNAh | 1 log10 | 8 | 12% | (4.9%,19%) | 1.9 | (1.4,2.5) |
| CA HIV RNAh | ∞i | 8 | 16% | (6.8%,26%) | 2.1 | (1.6,2.9) |
Downwards shift of the mediator distribution, given the common cause C, on the log10 scale, relative to no curative treatment a = 0.
For the week-4 analysis, analyzing viral rebound in the first 4 weeks after ART treatment interruption, C is NNRTI-based (versus not).
For the week-8 analysis, analyzing viral rebound in the first 8 weeks after ART treatment interruption, C is the nadir CD4 count (categorized as ≤ 500 versus > 500). Not available in 2 patients, who were excluded from the week-8 analysis.
Difference in probability of virologic suppression that is mediated, expressed as a percentage.
95% Confidence Interval, calculated by bootstrap with 5000 replicates using Efron’s percentile method (Van der Vaart (1998)39 page 327). This leads to consistent coverage because of the bootstrap Z-estimator master theorem, Theorem 10.16 from Kosorok (2008).40
Indirect effect effect on the Risk Ratio (RR) scale.
Single-copy plasma HIV RNA, on–ART. Analysis restricted to the 94 patients with SCA HIV RNA measured.
Cell-associated HIV RNA, on–ART. All 124 patients had CA HIV RNA measured.
Treatment A which causes all mediator values below the assay limit.