Treating earlier, spending less: cost-effectiveness and budget impact of immediate versus delayed antiretroviral therapy for HIV in Japan

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Abstract Background. In Japan, lifelong antiretroviral therapy (ART) is funded through the physical disability (immune dysfunction) certification pathway, which requires two laboratory assessments four weeks or more apart. This statutory pathway, rather than clinical need, contributes to a median diagnosis-to-ART interval of about 42 days. We evaluated relaxing or reforming it to permit immediate ART. Methods. We developed a stochastic individual-based microsimulation of HIV in Japan, linked to a payer-perspective cost-effectiveness analysis over a 40-year horizon after a 20- year burn-in, calibrated to national surveillance and cascade data. We compared immediate ART with one-month (primary) and two-month (secondary) delays. Costs and quality- adjusted life-years (QALYs) were discounted at 2% per year; uncertainty was assessed across 200 seeds and by probabilistic and one-way sensitivity analyses. Findings. Against the one-month delay, immediate ART averted 2,991 infections and 1,761 deaths among people with HIV over 40 years, gained 9,071 QALYs, and reduced discounted costs by ¥54·4 billion (net monetary benefit ¥99·7 billion). The two-month comparison saved ¥82·5 billion (4,535 infections, 2,688 deaths averted). Immediate ART was dominant at the base case and in all 1,000 probabilistic sensitivity-analysis iterations; cumulative savings offset the early investment within 11 to 12 years, and sensitivity analyses altered only its magnitude. Interpretation. Permitting immediate ART by reforming the certification pathway was projected to reduce HIV incidence, improve population health, and save public-payer costs within the second decade, supporting consideration of statutory reform. Funding. Health and Labour Sciences Research Grant, Ministry of Health, Labour and Welfare of Japan (21HB1003, 23HB1001, 26HB1001). Research in context Evidence before this study. We searched PubMed and Web of Science from database inception to March 31, 2026, without language restrictions, for studies of rapid antiretroviral therapy (ART) initiation, combining the terms "rapid ART", "same-day ART", "early ART initiation", "test and treat", "HIV", and "cost-effectiveness", and we reviewed the World Health Organization (WHO) 2017 and 2021 HIV guidelines together with successive AIDS Surveillance Committee of Japan and Ministry of Health, Labour and Welfare reports. Randomised trials in sub-Saharan Africa and large implementation programmes, most notably the San Francisco RAPID initiative, have consistently shown that starting ART within one week of diagnosis shortens the time to viral suppression, improves linkage to and retention in care, and reduces onward transmission without increasing early adverse events, and by 2023 99 countries had adopted rapid ART in line with the WHO recommendation. Almost all of this evidence, however, comes from high-prevalence or generalised epidemics; we identified no transmission-dynamic or economic evaluation of rapid ART in a low-prevalence, concentrated epidemic with an already strong treatment cascade such as Japan. Above all, to our knowledge no study had modelled the structural barrier that, rather than any clinical consideration, governs the timing of ART in Japan, namely the statutory immune-dysfunction disability certification required to access subsidised treatment, and earlier Japanese HIV modelling was compartmental and did not represent this pathway. Added value of this study. To our knowledge, this is the first study to represent the Japanese immune-dysfunction certification pathway explicitly and to quantify, over a 40-year horizon, the epidemiological, clinical, and economic consequences of relaxing it to permit immediate ART. Using an individual-based dynamic transmission model calibrated to the contemporary national epidemic and approximating the observed median diagnosis-to-ART interval, we found that, under the modelled assumptions, immediate ART was dominant: it was projected to avert HIV infections and deaths, improve population health, and lower public-payer costs, supported, for the primary comparison, by dominance in 199 of 200 paired per-seed replicates, a positive net monetary benefit in all 200, and dominance in all 1,000 probabilistic sensitivity- analysis iterations; no prespecified one-way health-economic parameter variation reversed dominance. By showing that earlier treatment is simultaneously more effective and cost- saving even where downstream retention and viral suppression are already high, the study adds a setting that has been largely absent from the global rapid ART evidence base. Implications of all the available evidence. Taken together with the existing trial and implementation evidence, our findings indicate that relaxing or reforming the statutory certification pathway (allowing ART at diagnosis irrespective of CD4 count and HIV-RNA) could reduce HIV incidence, prevent deaths among people with HIV, and save public-payer resources in Japan, while bringing national practice into line with the WHO recommended standard. Because the barrier is regulatory rather than clinical, policy reform is a potentially actionable route, warranting consideration and further evaluation. More broadly, the results suggest that, even in low-prevalence concentrated epidemics with high treatment coverage, removing administrative delays to ART initiation may deliver population-level health and fiscal benefits.

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