To the Editor: Human immunodeficiency virus (HIV) type 1 infection remains a serious and intractable public health problem worldwide. In 2020, there were 37.7 million surviving individuals with HIV infection worldwide and 680,000 HIV-related deaths reported by the Joint United Nations Programme on HIV/acquired immune deficiency syndrome (AIDS) (UNAIDS).[1] To combat the complex HIV epidemic, countries are exploring appropriate antiretroviral therapy (ART) strategies in accordance with actual conditions, striving to ensure that more patients can receive therapy. The initiation time of ART has been constantly adjusted throughout the past decade. The World Health Organization (WHO) proposed the concept of rapid initiation of ART in 2017, explicitly suggesting that HIV-positive individuals start ART within 7 days of diagnosis.[2] Studies have shown that rapid initiation can increase viral suppression and medication adherence[3] and reduce HIV transmission and fatality[4]; thus, it is more advantageous than the conventional therapeutic strategy and contributes to promote HIV prevention and treatment. We collected clinical and cost data to construct decision tree models for cost-effectiveness evaluation of different ART strategies. Our findings will support the rapid initiation of ART in China from the perspective of health economics and serve as a reference for the optimization of medical resource allocation. This study was approved by the Ethics Committee of the Shanghai Public Health Clinical Center (No. 2019-S053-02). Written informed consent was provided by all participants. We collected the medical records of patients who started ART and completed 1 year of follow-up after being newly diagnosed with HIV at the outpatient clinic of the Department of Infection and Immunology at the Shanghai Public Health Clinical Center from January 2019 to December 2019. All patients were >18 years of age, and none of the women included in the study were pregnant. The patients were divided into a rapid ART group (starting ART within 7 days of diagnosis) and a conventional ART group (starting ART more than 7 days after diagnosis). To reduce the influence of differences at baseline, the clinical observation data of the two groups (including age, sex, body mass index [BMI], comorbidities, and coinfections) were matched 1:1 by propensity score matching. The sample size was calculated using the following formula: n = 2p¯q¯ (Zα + Zβ)2/(p1-p2)2, where n is the number of patients in each group; p1 and p2 are 61% (rapid initiation rate) and 39% (conventional initiation rate), respectively, from the preliminary survey of our study; p¯ is the mean of p1 and p2; q¯ is the mean of (1-p1) and (1-p2); the value of Zα is 1.96; and the value of Zβ is 1.28. Finally, the minimum sample size was found to be 108 individuals in each group by this calculation. Propensity score matching was performed using R Studio (https://mirrors.sustech.edu.cn/CRAN/), and the statistical analysis was performed using SPSS version 23 (IBM Corp., Armonk, NY, USA). Data were presented as n (%), median (interquartile range) or mean ± standard deviation. Differences between two groups were assessed by Student's t test, chi-squared test, Fisher's exact test as appropriate. A two-sided P <0.05 was considered as a statistically significant difference. Two ART initiation strategies were compared in terms of cost and effectiveness under Markov simulation. TreeAge Pro V.2011 software (http://www.treeage.com) was used to construct the Markov model, which was used to simulate the development process of HIV in ART status [Supplementary Figure 1, https://links.lww.com/CM9/B508]. In the model, each person had an initial health status. The disease status were divided into four sections in the model: health, HIV/AIDS, viral suppression, and death. The mortality rate, prevalence rate, case fatality rate, direct expenses, and relevant clinical and epidemic parameters of HIV were collected from published literature and the China Health Statistical Yearbook 2019 [Supplementary Table 1, https://links.lww.com/CM9/B508].[5–10] According to the suggestion of the WHO, the willingness-to-pay threshold was set as the gross domestic product per capita of China in 2016 (RNB 53,980 Yuan). The discount rates for both future costs and quality-adjusted life years (QALYs) were set at 3%. Effectiveness of the above two stragies was presented as QALYs. By discounting the cost and effectiveness, the cumulative cost and QALYs of different initiation strategies could be obtained. The incremental cost-effectiveness ratio (ICER) was obtained by the following formula: ICER = (cost of rapid ART group－cost of conventional ART group)/(QALYs of rapid ART group－QALYs of conventional ART group), and was compared with the willingness-to-pay threshold.The ICER less than 53,980 CNY/QALY indicates that compared with conventional ART group, rapid ART group is more cost-effective, that is to say, rapid ART group has a lower cost than conventional ART group for saving 1 QALY. Besides, a probabilistic sensitivity analysis was used for the univariate analysis. Finally, we plotted cost-effectiveness acceptability curves (CEACs) which indicate the likelihood that the intervention is cost-effective for a given value of willingness to pay. During the evaluation period, 457 individuals were enrolled in our study (123 in the rapid group and 334 in the conventional group) [Supplementary Table 2, https://links.lww.com/CM9/B508]. The baseline cluster of differentiation 4 positive (CD4+) T cell count and comorbidities between the two groups were significantly different (all P <0.05), which may have affected the comparison of the outcomes. After 1:1 matching of the two groups by the propensity scoring model, 226 selected individuals were equally divided into the rapid and conventional groups, and the baseline characteristics were not statistically significant between the two groups (all P >0.05)[Supplementary Table 3, https://links.lww.com/CM9/B508]. In the dataset of PSM, most participants were men (93.4%, 211/226) and had a normal BMI (63.3%, 143/226). The median age was 37 years (interquartile range, 30–51 years). The virologic suppression rate was 73.5% (83/113) in the rapid group and 61.1% (69/113) in the conventional group (χ2 = 3.938, P = 0.047). The level of immunological indicators was not statistically different between the rapid group and conventional group (85.0% [96/113] vs. 85.8% [97/113], χ2 = 0.035, P = 0.851). We simulated the development process of HIV with rapid ART strategy or conventional ART strategy for over 20 years in Markov model, and found that the total cost of rapid ART was less than conventional ART and the ICER was –3185.4/QALY [Table 1]. The rapid ART strategy was more effective than conventional ART strategy because it provided more QALYs. The probabilistic sensitivity analysis showed that the average cost of conventional ART strategy was the most strongly influencing factor for the ICER [Supplementary Figure 2, http://linkslww.com/CM9/B508.]. However, no matter how the factors change in Supplementary Figure 2, https://links.lww.com/CM9/B508, the ICER remains less than the the willingness-to-pay threshold. The ICERs were still lower than the willingness-to-pay threshold, and rapid ART was more cost-effective than conventional ART. Furthermore, when the willingness-to-pay threshold was 53,980 CNY/QALY, the probabilities of the cost-effectiveness acceptability curve with conventional and rapid ART were 0% and 100%, respectively [Supplementary Figure 3, https://links.lww.com/CM9/B508]. Table 1 - Cost effectiveness analysis of two ART strategies after simulating for over 20 years in Markov model. ART strategies Cost (Yuan) Utility (QALY) ICER Rapid ART 106.24699 27.00009 –3185.49644 Conventional ART 107.02151 26.99985 – ART: Antiretroviral therapy; QALY: Quality-adjusted life year; ICER: Incremental cost-effectiveness ratio; –: Not avaiable. With the improvement of antiretroviral drugs and patients' higher requirements for treatment effectiveness and quality of life, rapid ART has been effectively promoted among people living with HIV/AIDS (PLWHA). Our study demonstrated that offering the opportunity to patients to start ART within 7 days at their first HIV-related clinic visit has more potential to achieve viral suppression. Furthermore, the Markov model simulation showed that rapid ART strategy was more cost-effective than conventional ART strategy in China. These results are important given the lack of economic evidence in support of rapid ART initiation. Rapid initiation of ART treatment should be accepted as a standard of care worldwide, because it leads to a better health status and lower healthcare burden among PLWHA over the long term than conventional ART strategy.[3,4] The promotion of rapid initiation of ART treatment requires structural adjustment of the diagnosis and treatment model coordinated by multiple institutions and departments (outpatient clinics, government institutions, designated hospitals, and health insurance departments).[11] Professional teams with medical doctors, nurses, social workers, and administrative staff should be built to provide comprehensive services for patients, which will result in higher requirements for medical resources (funds, manpower, and practitioner quality). Additionally, the education of medical staff should be strengthened to improve their ability to treat and care for HIV-infected persons. Recognition of the rapid ART strategy by medical staff should be improved, and standardization of the testing process should be performed. This study has several limitations, the most notable one is that the study design was not a randomized controlled trial. Our study was designed to reflect routine clinical practice in Shanghai as closely as possible, but it is not clear whether the results can be generalized to other parts of China or other countries. Although great efforts have been made to ensure the accuracy and quality of the data included, the sample size limits the generalization. Finally, we estimated the direct individual costs of the two groups of patients in the study, but the actual total costs of the two groups of patients also included indirect costs, which are very complicated and may influence our results. The findings of the presented study support the rapid initiation of ART after an initial HIV diagnosis. Rapid initiation is associated with improved health outcomes for the patients and a reduced likelihood of HIV transmission. Our findings also indicate that promoting rapid ART would substantially reduce costs and improve effectiveness. Future directions include establishing specialist teams in metropolises to provide timely services to patients and extending rapid initiation services to other cities. Funding This study was supported by grants from the Shanghai Science and Technology Committee (No.19YF1441300), the Shanghai Municipal Health Commission (No. 20184Y0007), and the Shenzhen High-level Hospital Construction Fund (Nos. G2021027 and G2022062). Conflicts of interest None.
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