Table 1.
Selected Model Input Parameters
| Variable | Value | Data Sources | |||
|---|---|---|---|---|---|
| Clinical Model Input Parameters | |||||
| Baseline Maternal Cohort Characteristics | |||||
| Age, mean, y (SD) | 24 (5) | MOHCW [21] | |||
| Mortality during pregnancy | 0.7% | MOHCW [8] | |||
| Proportion ART eligiblea | 36% | ZVITAMBO trial [24] | |||
| CD4 count, cells/µL (SD) | |||||
| Total cohort | 451 (50) | ZVITAMBO trial [24] | |||
| ART-eligible women | 275 (50) | ZVITAMBO trial [24] | |||
| Non-ART-eligible women | 550 (50) | ZVITAMBO trial [24] | |||
| Uptake of PMTCT services and postnatal care | |||||
| PMTCT uptakeb | 100% (sensitivity analyses: 56%, 80%, 95%) | WHO [1] | |||
| Sensitivity of clinical assessment of ART eligibility | 36% | MTCT-Plus Cohort [47] | |||
| Probability of linking to pediatric HIV diagnosis, care, and ART | 100% (sensitivity analysis: 36%) | WHO/UNICEF [48] | |||
| Probability of linking to postnatal maternal HIV-related care | 100% (sensitivity analyses: 87% if ANC received, 43% if no ANC received) | After ANC: Mean of published values [49–54] No ANC: assumption | |||
| Loss to follow-up from postnatal maternal care | 0% per year (sensitivity analyses: 16% [year 1]; 6% per year [years ≥2]) | [30–32] | |||
| Base Case Value (range for sensitivity analysis) |
|||||
| Maternal HIV Status | |||||
| Mother-to-Child Transmission Risks | PMTCT Regimen Received | ||||
| Intrauterine/intrapartum period (one-time risks) | |||||
| No ARVs | sdNVP | Antenatal ZDVc | 3-Drug Regimen | Data Sources | |
| ART eligible at conception | 0.273 (0.199–0.322) | 0.176 (0.082–0.264) | 0.136 (0.091–0.157) | 0.033 (0.011–0.041) | [24, 55–69] |
| Non-ART eligible at conception | 0.175 (0.127–0.206) | 0.073 (0.033–0.109) | 0.036 (0.024–0.041) | 0.01 (0.004–0.028) | [24, 55–64] [66, 67, 69–71] |
| Postnatal period (rate per 100 person-years among HIV-uninfected infants aged 4-6 weeks) | |||||
| No ARVs | Extended Infant NVP | 3-Drug Regimen | Data Sources | ||
| ART eligible | 9.1 (EBF); 15.4 (MBF) (5.7–28.4) | NA | 4.0 (0–6.4) | [24, 57, 59, 65, 67, 69–72] | |
| Non-ART eligible | 2.9 (EBF); 4.8 (MBF) (1.8–8.8) | 2.7 (1.4–3.7) | 2.2 (0–6.4) | [24, 52, 59, 67, 70–77] | |
| Infant Mortality and Life Expectancy | |||||
| Probability of live birth | 95.7%–98.0% | MOHCW [21] | |||
| Relative increase in infant mortality if maternal death occurs | 2-fold increase | [78–81] | |||
| Short-term mortality risks, % | 1-year risk | 2-year cumulative risk | |||
| HIV-exposed, uninfected children | 7.4 [82] | 9.2 [82] | |||
| HIV-infected children, no ART | |||||
| Intrauterine/intrapartum infection | 51.0 [83] | 65.0 [83] | |||
| Postpartum infection | 24.0 [83] | 38.0 [83] | |||
| HIV-infected children, on ART | 9.5 [84] | 12.0 [85] | |||
| Life-expectancy estimates, y | Base Case Value | Range for Sensitivity Analyses | |||
| HIV-exposed, uninfected children (from weaning) | 50.0 (assumption) | 43.0–67.0 [86, 87] | |||
| HIV-infected children, no ART | |||||
| Intrauterine/intrapartum infection (from birth) | 1.1 [83] | 1.1–2.0 (assumption) | |||
| Postpartum infection (from time of infection) | 9.4 [83] | 5.0–10.0 (assumption) | |||
| HIV-infected children, on ART | |||||
| Intrauterine/intrapartum infection (from birth) | 20.0 (assumption) | 10.0–25.0 (assumption) | |||
| Postpartum infection (from time of infection) | 20.0 (assumption) | 10.0–25.0 (assumption) | |||
| Maternal Disease Progression Parameters | Value | Data Source | |||
| Impact of antiretroviral therapy | |||||
| Efficacy, % HIV RNA suppression at 24 wk | |||||
| First-line ART, TDF/FTC + (NVP or EFV) | |||||
| Initiated during pregnancy | 90% | [88] | |||
| Initiated postpartum, no sdNVP exposure | 90% | OCTANE trial [89] Difference: [90–92] | |||
| Initiated postpartum, with sdNVP exposure | 85% (difference assumed vs no sdNVP, 5% [88]) | ||||
| Second-line ART (ZDV/3TC/LPV/r) | 72% | [93] | |||
| CD4 cell decline over 6 mo following ART interruption | 139 cells/µL | [36–38] | |||
| Laboratory and medication costs | 2008 US Dollars | Data Sources | |||
| Economic Model Input Parameters | |||||
| CD4 assay, performed once in ANC for Options A, B, and B+ | 9.42 | [33] | |||
| Full blood count, performed once in ANC for Options B and B+ | 9.27 | [94] | |||
| Single-dose NVP, 1 maternal and 1 infant dose | 0.06 | ||||
| Antenatal ZDV, Option Ac | 7.67 per month | [27] | |||
| Antenatal TDF/FTC/NVP, Options B and B+, CD4 count ≤350 cells/µLc | 12.12 per month | [27] | |||
| Antenatal TDF/FTC/EFV, Options B and B+, CD4 count >350 cells/µLc | 16.50 per month | [27] | |||
| Postnatal maternal ART | |||||
| First-line TDF/FTC/NVP; TDF/FTC/EFV | 12.12 per month; 16.50 per month | [27] | |||
| Second line, ZDV/3TC/LPV/r | 45.36 per month | [27] | |||
| Pediatric ART, d4T/3TC/NVP | 4.54 per month | [27] | |||
| Healthcare Resource Utilization and Costs | |||||
| Antenatal care | 2008 US Dollars | Data Sources | |||
| Routine antenatal care, 4 visits | 45.77 | Average of: [95, 96] | |||
| Delivery costs, healthcare facility | 54.50 | [96] | |||
| Routine and urgent health care costs: Children | No. of Inpatient Days per Year | No. of Outpatient Visits per Year | Total Cost per Monthd | Data Sources | |
| HIV-infected children, on ART | 2.14 | 6 | 3.32 | [97] | |
| Intrauterine/intrapartum infection, no ART | 18 | 6 | 16.48 | [98] | |
| Postpartum infection, no ART, aged 0–18 mo | 18 | 6 | 16.48 | [98] | |
| Postpartum infection, no ART, aged >18 mo | 11 | 6 | 10.67 | [98] | |
| HIV-exposed, uninfected children, aged 0–18 mo | 1 | 3.5 | 1.73 | Assumptione | |
| HIV-exposed, uninfected infants aged >18 mo | 0 | 1 | 0.26 | Assumptione | |
| Terminal care, last month of life | 5 | 0 | 49.80 | Assumptione | |
| Routine and urgent health care costs: Mothers | No. of Inpatient Days per Event | No. of Outpatient Visits per Event | Total Cost per Eventd | Data Sources | |
| Care for acute opportunistic infections | Cape Town AIDS Cohort [99] | ||||
| WHO stage 3–4 HIV disease, range by specific disease | 1.3–2.9 | 2.7–3.4 | 21.88–39.36 | ||
| Bacterial infection | 2.8 | 2.4 | 32.28 | ||
| Mild fungal infection | 1.2 | 2.3 | 19.04 | ||
| Tuberculosis | 2.9 | 2.2 | 35.66 | ||
| Terminal care, last month of life | 2.39 | 0.77 | 26.18 | ||
| Routine HIV care costs per month | 1.22–7.18 (range by CD4) | ||||
See Supplementary Table 2 for complete list of parameters.
Abbreviations: 3TC, lamivudine; ANC, antenatal care; ART, antiretroviral therapy; ARV, antiretroviral medications; d4T, stavudine; EBF, exclusive breastfeeding (in first 6 months of life, followed by MBF); EFV, efavirenz; FTC, emtricabine; HIV, human immunodeficiency virus; LPV/r, lopinavir/ritonavir; MACS, Multicenter AIDS Cohort Study; MBF, mixed breastfeeding; MOHCW, Zimbabwe Ministry of Health and Child Welfare; NA, not applicable; NVP, nevirapine; PTMCT, prevention of mother-to-child HIV transmission; SD, standard deviation; sdNVP, single-dose nevirapine; TDF, tenofovir; WHO, World Health Organization; ZDV, zidovudine.
a ART eligibility was defined as CD4 count of ≤350 cells/µL or WHO stage 3–4 disease.
b PMTCT uptake was defined as proportion of HIV-infected, pregnant women accessing PMTCT services by the time of delivery. See Supplementary Appendix text and Supplementary Table 2 for details.
c Two months of antentatal drug are assumed in all regimens for the base-case analysis, based on median gestational age at booking in Zimbabwe of 30 weeks.
d Total care costs for mothers and infants were calculated by multiplying resource utilization (number of outpatient visits and inpatient days) by an average of WHO-CHOICE estimates of costs for these encounters in 7 sub–Saharan African countries [28]. See Supplementary Appendix for details.
e See Supplementary Table 2 for description of assumptions of outpatient healthcare resource utilization.