Cost-effectiveness of human T-cell leukemia virus type 1 (HTLV-1) antenatal screening for prevention of mother-to-child transmission

Abstract

Background: Human T-cell leukemia virus type 1 (HTLV-1) causes adult T-cell leukemia-lymphoma (ATL) and HTLV-1-associated myelopathy-tropical spastic paraparesis (HAM/TSP) with a poor prognosis. This study aimed to evaluate the cost-effectiveness and health impact of HTLV-1 antenatal screening.

Methodology/principal findings: A state-transition model was developed for HTLV-1 antenatal screening and no screening over a lifetime horizon from a healthcare payer perspective. A hypothetical cohort of 30-year-old individuals was targeted. The main outcomes were costs, quality-adjusted life-years (QALYs), life expectancy life-years (LYs), incremental cost-effectiveness ratios (ICERs), HTLV-1 carriers, ATL cases, HAM/TSP cases, ATL-associated deaths, and HAM/TSP-associated deaths. The willingness-to-pay (WTP) threshold was set at US$50,000 per QALY gained. In the base-case analysis, HTLV-1 antenatal screening (US$76.85, 24.94766 QALYs, 24.94813 LYs, ICER; US$40,100 per QALY gained) was cost-effective compared with no screening (US$2.18, 24.94580 QALYs, 24.94807 LYs). Cost-effectiveness was sensitive to the maternal HTLV-1 seropositivity rate, HTLV-1 transmission rate with long-term breastfeeding from HTLV-1 seropositive mothers to children, and the cost of the HTLV-1 antibody test. HTLV-1 antenatal screening was cost-effective when the maternal HTLV-1 seropositivity rate was greater than 0.0022 and the cost of the HTLV-1 antibody test was lower than US$94.8. Probabilistic sensitivity analysis using a second-order Monte-Carlo simulation showed that HTLV-1 antenatal screening was 81.1% cost-effective at a WTP threshold of US$50,000 per QALY gained. For 10,517,942 individuals born between 2011 and 2021, HTLV-1 antenatal screening costs US$785 million, increases19,586 QALYs and 631 LYs, and prevents 125,421 HTLV-1 carriers, 4,405 ATL cases, 3,035 ATL-associated deaths, 67 HAM/TSP cases, and 60 HAM/TSP-associated deaths, compared with no screening over a lifetime.

Conclusion/significance: HTLV-1 antenatal screening is cost-effective and has the potential to reduce ATL and HAM/TSP morbidity and mortality in Japan. The findings strongly support the recommendation for HTLV-1 antenatal screening as a national infection control policy in HTLV-1 high-prevalence countries.

Fig 1. Simplified schematic depiction of a state transition diagram.

The health states in the model are shown to be oval. In a yearly model cycle, transition paths occur between the health states and other health states, as represented by the arrows. HTLV-1, human T-cell leukemia virus type 1; ATL, adult T-cell leukemia-lymphoma; HAM/TSP, HTLV-1-associated myelopathy-tropical spastic paraparesis.

Fig 2. ICER tornado diagram for HTLV-1 antenatal screening versus no screening.

HTLV-1 antenatal screening is cost-effective compared with no screening at a WTP threshold of US$50,000 per QALY gained when the maternal HTLV-1 seropositivity rate is greater than 0.0022, HTLV-1 transmission rate with long-term breastfeeding from HTLV-1 seropositive mothers to children is greater than 0.154, HTLV-1 transmission rate with short-term breastfeeding from HTLV-1 seropositive mothers to children is greater than 0.043, HTLV-1 transmission rate with bottle feeding from HTLV-1 seropositive mothers to children is lower than 0.044, the health utility value of HTLV-1 carriers is lower than 0.77, and the cost of HTLV-1 antibody test is lower than US$94.8. ICER, incremental cost-effectiveness ratio; WTP, willingness-to-pay; QALY, quality-adjusted life-year; HTLV-1, human T cell leukemia virus 1; ATL, adult T-cell leukemia-lymphoma; HAM/TSP, HTLV-1-associated myelopathy-tropical spastic paraparesis.

Fig 3. Two-way sensitivity analysis for the maternal HTLV-1 seropositivity rate and the proportion of long-term breastfeeding.

HTLV-1 antenatal screening is optimal in the blue region which includes the base-case result (x). No screening is optimal in the orchid region. This figure shows that HTLV-1 antenatal screening is more cost-effective the higher the maternal HTLV-1 seropositivity rate and the higher the proportion of long-term breastfeeding. WTP, willingness-to-pay; HTLV-1, human T cell leukemia virus 1.

Fig 4. Cost-effectiveness acceptability curve.

The probabilistic sensitivity analysis analyzes 1000 simulations of the model in which input parameters are randomly varied across pre-specified statistical distributions. The x-axis represents the WTP threshold. The acceptability curve showed that HTLV-1 antenatal screening is 81.1% cost-effective at a WTP threshold of US$50,000 per QALY gained. CE, cost-effectiveness; QALY, quality-adjusted life-year; WTP, willingness-to-pay; HTLV-1, human T cell leukemia virus 1.

Fig 5. ICE scatterplot with a 95% confidence ellipse at a WTP threshold of US$50,000 per QALY gained.

Each dot represents a single simulation for a total of 1000 simulations. The ICE scatterplot showed that HTLV-1 antenatal screening is dominant in 811 trials to no screening in 1000 trials. ICE, incremental cost-effectiveness; QALY, quality-adjusted life-year; WTP, willingness-to-pay; HTLV-1, human T cell leukemia virus 1.