Table 1.
Selected clinical parameters used in a computer simulation of antiretroviral therapy strategies following exposure to single-dose nevirapine.
| Variable | Base Case Value | Data sources |
|---|---|---|
|
Baseline cohort characteristics |
OCTANE Trial 110 | |
| Age (mean (SD), in years) | 31 (5) | |
| CD4 count (mean (SD),/μL) | 135 (61) | |
| Distribution of initial HIV RNA (% total) | ||
| >100,000 copies/ml | 63 | |
| 30,001–100,000 copies/ml | 23 | |
| 10,001–30,000 copies/ml | 9 | |
| 3,001–10,000 copies/ml | 4 | |
| 501–3,000 copies/ml | 2 | |
| ≤ 500 copies/ml | 0 | |
| Time from sdNVP exposure to ART initiation (median (10th, 90th percentile), in months) | 17 (7, 45) | |
| Proportion (%) with detectable NNRTI resistance (Viroseq standard genotype assay) at baseline | 14 | |
|
Natural history of disease | ||
| Mean monthly decrease in CD4/μL by HIV RNA | Multicenter AIDS Cohort Study47 | |
| >30,000 copies/ml | 6.4 | |
| 10,001–30,000 copies/ml | 5.4 | |
| 3,001–10,000 copies/ml | 4.6 | |
| 501–3,000 copies/ml | 3.7 | |
| 0–500 copies/ml | 3.0 | |
| Monthly risk of severe opportunistic infections (%, range by CD4 count) | Cape Town AIDS Cohort14 | |
| Severe bacterial infection | 0.08–0.71 | |
| Severe fungal infection | 0.02–2.22 | |
| Toxoplasmosis | 0.00–0.06 | |
| Pneumocystis jiroveci pneumonia | 0.00–0.12 | |
| Mycobacterium avium | 0.00–0.30 | |
| Other WHO stage 3–4 condition | 0.25–2.57 | |
| Monthly risk of other clinical conditions (%, range by CD4 count) | Cape Town AIDS Cohort14 | |
| Mild fungal infection | 0.59–3.51 | |
| Tuberculosis (pulmonary or extrapulmonary) | 0.21–1.96 | |
| Herpes simplex, varicella zoster, other mucocutaneous manifestions of HIV | 2.51–3.11 | |
| Monthly risk of HIV-related death (%, range by CD4 count) | Cape Town AIDS Cohort14 | |
| No history of opportunistic infection | 0.09–3.33 | |
| With history of opportunistic infection | 0.30–7.94 | |
|
Antiretroviral therapy | ||
| Efficacy (% HIV RNA suppression at 24 weeks; gain in CD4/μL at 24 weeks on suppressive ARTa (assumed equal to entire cohort for all subgroups and for 2nd-line ART); yearly risk (%) of virologic failure >24 weeks after initiation) | ||
| 1st-line NVP/TDF/FTC | OCTANE Trial 110 | |
| Entire OCTANE cohort (base case) | 85%; 173; 10.61 | |
| No detectable NNRTI resistance at baseline | 89%; 173; 5.95 | |
| Detectable NNRTI resistance at baseline | 60%; 173; 49.41 | |
| ART initiation 6–12 months after sdNVP | 82%; 173; 21.34 | |
| ART initiation 12–24 months after sdNVP | 81%; 173; 7.42 | |
| ART initiation >24 months after sdNVP | 91%; 173; 10.61b | |
| 1st-line LPV/r/TDF/FTC | OCTANE Trial 110 | |
| Entire OCTANE cohort (base case) | 97%; 162; 2.84 | |
| No detectable NNRTI resistance at baseline | 97%; 162; 3.19 | |
| Detectable NNRTI resistance at baseline | 94%; 162; 2.84 b | |
| ART initiation 6–12 months after sdNVP | 97%; 162; 2.84 b | |
| ART initiation 12–24 months after sdNVP | 98%; 162; 3.19 | |
| ART initiation >24 months after sdNVP | 94%; 162; 5.72 | |
| 2nd-line NVP/ddI/ZDV (base case) | 43%; 173; 10.61 | UK, SAfr;26,27 late failure assumed = 1st-line nevirapine |
| 2nd line LPV/r/ddI/ZDV (base case) | 72%; 162; 2.84 | Malawi, SAfr, Uganda;27,28,36,late failure assumed = 1st-line LPV/r |
| 3rd line DRV/r/3TC (sensitivity analysis) | 45%; 162; 29.84 | POWER;33 assumption (CD4 gain = 1st-line LPV/r) |
| LPV/r/3TC after failure of 2nd line ART | 12%; 18 (CD4 gain 1st 12 months only); 27.46 | CPCRA 06424 |
| Relative risk reduction on any ART regimen (%, range by CD4) | ||
| HIV-related death | 55–96 | Cotrimo-CI, ANRS 120325 |
| Acute opportunistic infections | 0–32 | Cotrimo-CI, ANRS 120325 |
| Toxicity risk (%, median time to occurrence) | ||
| Minor/moderate (all regimens) | 0.088; 3 months | ANRS 1203;48 assumption |
| Major/severe (requiring regimen change) | ||
| NVP/TDF/FTC | 12.4; 1 month | OCTANE Trial 110 |
| LPV/r/TDF/FTC | 0.8; 1 month | OCTANE Trial 110 |
| NVP/ddI/ZDV | 22.7; 3 months | Tshepo;49 assumption |
| LPV/r/ddI/ZDV | 13.2; 3 months | Tshepo;49 assumption |
|
Parameter values for “best-case” and “worst-case” scenarios for 1st-line LPV/rc | ||
| Parameter (base case value) | “Best-case” for 1st-line LPV/r | “Worst-case” for 1st-line LPV/r |
| Efficacy of NVP in 2nd-line ART (43%) | 72% (assumption, = 2nd-line LPV/r) | 16%26 |
| Efficacy of LPV/r in 2nd-line ART (72%) | 61%34 | 72% (base case) |
| Yearly risk of virologic failure after 24 weeks on LPV/r-based ART (2.84%) | 2.84% (base case) | 29.84%33 |
| Major/severe toxicity risk attributable to NVP (12.4%) | 12.4% (OCTANE) | 0.8% (Risk attributable to LPV/r in OCTANE) |
SD: standard deviation; NVP: nevirapine; LPV/r: lopinavir/ritonavir; TDF: tenofovir; FTC: emtricitabine; ZDV: zidovudine; ddI: didanosine; DRV/r: darunavir; 3TC: lamivudine, UK: United Kingdom; SAfr: South Africa; CPCRA: Community Programs for Clinical Research on AIDS; ANRS: Agence Nationale de Recherche sur le Sida.
Gain in CD4 cells at 24 weeks on suppressive ART for each OCTANE subgroup was assumed equal to that observed among the entire OCTANE cohort. CD4 gain for 2nd-line ART was assumed equal to that observed for 1st-line ART.
For OCTANE trial subgroups indicated, small numbers of events led to trial-derived risks of late virologic failure of 45.96%; late failure risks from the entire OCTANE cohort were instead included in the analyses.
These scenarios incorporated published or OCTANE-derived data most likely to bias the analysis in favor of or against the 1st-line lopinavir/ritonavir strategy.