Table 3.
Selected 1-Way Sensitivity Analyses of Genotype vs No Genotype at First-line Antiretroviral Therapy Failure in South Africa
| Undiscounted Life Expectancy (mo) | Discounted Life Expectancy (mo) | Discounted Cost ($) | Cost-effectiveness ($/YLS) | Clinical Thresholda | Cost-effectiveness Thresholdb | |
|---|---|---|---|---|---|---|
| Prevalence of WT virus at first-line ART failurec (base case = 20%) | WT virus >11% | WT virus ≥12% | ||||
| Prevalence = 5% WT virus | ||||||
| No genotype | 135.4 | 108.4 | 16 550 | … | ||
| Genotype | 133.3 | 106.7 | 16 600 | Dominatedd | ||
| Prevalence = 30% WT virus | ||||||
| No genotype | 130.1 | 104.6 | 16 230 | … | ||
| Genotype | 137.6 | 109.3 | 16 500 | 700 | ||
| CD4 count at first-line ART failure (base case = 173 cells/µL) | >80 cells/µL | >80 cells/µL | ||||
| CD4 count = 25 cells/µL | ||||||
| Genotype | 91.9 | 74.0 | 13 450 | … | ||
| No genotype | 100.5 | 81.4 | 14 440 | 1600 | ||
| CD4 count = 500 cells/µL | ||||||
| No genotype | 151.2 | 118.6 | 15 770 | … | ||
| Genotype | 154.7 | 120.8 | 15 800 | 200 | ||
| Genotype-associated delays in ART switching (base case = 3 mo) | <5 mo | <5 mo | ||||
| Delay = 1 mo | ||||||
| No genotype | 132.3 | 106.1 | 16 360 | … | ||
| Genotype | 139.3 | 110.5 | 16 730 | 1000 | ||
| Delay = 12 mo | ||||||
| Genotype | 125.5 | 101.0 | 16 120 | … | ||
| No genotype | 132.3 | 106.1 | 16 360 | 600 | ||
| Efficacy of continued NNRTI-based ART after first-line ART failuree (base case = 45%) | Efficacy >10% | Efficacy >17% | ||||
| Efficacy = 20% | ||||||
| No genotype | 132.3 | 106.1 | 16 360 | … | ||
| Genotype | 133.2 | 106.6 | 16 530 | 3900 | ||
| Efficacy = 70% | ||||||
| No genotype | 132.3 | 106.1 | 16 360 | … | ||
| Genotype | 140.0 | 110.9 | 16 550 | 500 | ||
| Efficacy of PI-based second-line after continued NNRTI-based ARTe (base case = 60%) | Efficacy >38% | Efficacy >38% | ||||
| Efficacy = 20% | ||||||
| Genotype | 129.5 | 104.1 | 16 210 | … | ||
| No genotype | 132.3 | 106.1 | 16 360 | 900 | ||
| Efficacy = 70% | ||||||
| No genotype | 132.3 | 106.1 | 16 360 | … | ||
| Genotype | 137.5 | 109.4 | 16 620 | 900 | ||
| Available third-line ART, $254/mo | … | Cost-saving | ||||
| Genotype | 203.6 | 149.0 | 37 100 | … | ||
| No genotype | 202.5 | 148.8 | 38 120 | Dominatedd | ||
| Probability of “late” failuref (base case = 1.3%) | ≥0.25% | 0.25%–0.9%g | ||||
| Probability = 0.1% | ||||||
| Genotype | 197.2 | 138.6 | 17 600 | … | ||
| No genotype | 198.1 | 139.0 | 17 840 | 5100 | ||
| Probability = 30% | ||||||
| No genotype | 82.1 | 73.2 | 13 980 | … | ||
| Genotype | 86.0 | 76.1 | 14 460 | 1900 | ||
| Genotype test cost (base case = $300) | … | <$100g | ||||
| Genotype test cost, $50 | ||||||
| Genotype | 135.9 | 108.3 | 16 310 | … | ||
| No genotype | 132.3 | 106.1 | 16 360 | Dominatedd | ||
| Genotype test cost, $600 | ||||||
| No genotype | 132.3 | 106.1 | 16 360 | … | ||
| Genotype | 135.9 | 108.3 | 16 850 | 2700 |
Abbreviations: ART, antiretroviral therapy; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; WT, wild-type; YLS, years of life saved.
a Clinical threshold represents the threshold value where genotype imparts increased clinical benefit, measured as increased life expectancy, compared with standard of care, no genotype.
b Cost-effectiveness threshold represents the threshold value where genotype is very cost-effective compared with no genotype. Guided by the World Health Organization, we consider an incremental cost-effectiveness ratio <1 times the South Africa per capita gross domestic product as “very cost-effective.”
c ART failure = 2 consecutive HIV RNA with >1 log increase.
d A strategy is “dominated” if it is less effective and more costly than the comparator strategy.
e ART efficacy expressed as week 24 HIV RNA <400 copies/mL
f “Late” failure = monthly probability of virologic failure after 24 weeks on suppressive ART.
g Cost-effectiveness threshold here represents the threshold value where genotype is cost-saving compared with no genotype. A strategy is cost-saving if it imparts more clinical benefit for less money than the comparator strategy.