Cost-effectiveness of option B+ in prevention of mother-to-child transmission of HIV in Yunnan Province, China

The recommendations of the World Health Organization (WHO) on the prevention of mother-to-child transmission (PMTCT) of HIV infection have evolved significantly over time. Up to 2011, the WHO recommended that all pregnant women with HIV infection and CD4 count below 350 cells/mm³ initiate antiretroviral therapy(ART) at gestation week 14 and continue until one week post-partum. This strategy became known as PMTCT Option A [1, 2]. In the same year, the guidelines also commanded the other strategy, Option B, which extended ART for mothers out through the end of breastfeeding [1, 2]. Then, in light of new, compelling evidence that early ART improved treatment outcomes and sustained viral suppression reduced odds of onward sexual transmission [3‐7], the WHO introduced a new strategy in 2013, Option B+,which utilized a new ART. PMTCT Option B+ is providing life-long ART to all pregnant women who once tested HIV positive regardless of CD4 counts or clinical stage [8]. In theory, Option B+ was expected to not only achieve the Global Plan Target of new pediatric HIV infections elimination in 2015, but also achieve the universal access to HIV treatment for mothers to keep mother alive [2].

Option B+ has already been adopted by a range of low- and middle-income countries, including Malawi, Zambia,Tanzania, South Africa and Kenya [1, 6, 8, 9]. Early studies indicate the incremental cost of switching from Option B to Option B+ in PMTCT programs ranged from US$92,813 to US$605,739 per 1000 women [10] and the Incremental cost-effectiveness ratio (ICER) was US$1370 per year of life saved compared with Option B [3] and ranged from US$6000 to US$23,000 per infection averted compared with Option A [6]. Although the most analyses have identified the likely cost-effective of Option B+, a recent review of published cost-effectiveness analyses of Option B+ for prevention of mother-to-child transmission of HIV in developing countries demonstrated whether Option B+ was dominant, cost-effective or non cost-effective depended on the differences of the decision model structure and input parameter values. So decision makers still need additional analyses of model to inform the local funding decision [11].

PMTCT programs became a key public health priority in China in 2002 [12] and Option B+ began to implement in PMTCT programs in 2015 [13]. China’s Yunnan Province, currently has the highest prevalence of HIV infection nationwide. PMTCT programs have been operating since 2003. It’s reported that HIV prevalence in antenatal care (ANC) in Yunnan province is estimated at 0.3%, which translates to approximately 2000 new HIV-exposed infants born to pregnant women with HIV each year. Because HIV counseling and testing has been included in ANC nationwide in China since 2011 [14], and because there is nearly 100% uptake of ANC in Yunnan, pregnant women who have HIV infections are relatively easily identified. Next step, the effective ART is critical. Presently, Option B + is also offered to HIV-infected pregnant women in Yunnan, which means the more expensive second-line ART and life-long ART. Option B+ may be more costly than Option A and Option B while it may provide more health benefits, but it keeps unclear currently in Yunnan province. Therefore, we aimed to project the clinical outcomes and cost-effectiveness of the Option B+ from short-term and long-term respectively in Yunnan Province so as to help inform the funding evidence for the decision making of the optimal ART regimen for PMTCT and HIV/AIDS prevention and therapy.

The methodology we applied in the study was in accordance with the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement guidelines [15].

In the short-term(PMTCT period), our study found that when the ART regimen transferred from Option B to Option B+,comparing with Option B, Option B+ had an less cost when getting the same effect,which demonstrated Option B+ is dominant. We consider that Option B+ responses a dominant strategy in preventing new infections among infants.

In the long-term (10 years starting from the date of PMTCT services concluded), our study found that although the total discounted cost, cost per life-year saved and cost per QALY gained for mothers of Option B+ (lifelong ART regardless of CD4)were more than Option B (ART eligibility based on CD4 count) in 10 years, Option B+ resulted in a survival rate of 89.2%, a better survival outcomes than Option B, with a survival rate of 69.7%. For their partners at 10 years, Option B+ resulted in a cost of US$ 7655.70 per infection averted, which was lower than Option B. If we considered the benefits of the maternal survival and serodiscordant infections, Option B+ could show a higher cost-effective. Otherwise the ICER per life-year gained and QALY acquired was US$5183.96 and US$5355.42 respectively, when compared to Option B for mothers. Using the WHO standards for determining the cost-effectiveness of a strategy [3], the ICER per life-year saved and QALY acquired of Option B+ was less than the 3 × Yunnan’s per capita GDP(US$13,000) threshold, we found that Option B+ responses a cost-effective strategy in keeping mother alive and preventing new serodiscordant infections among their partners.

The sensitivity analyses verified the robustness of our cost-effective measures after changing a variety of parameters. In the short-term, by the increasing of efficacy of Option B/Option B+ in reducing transmission rates, the cost per infant infection averted and the cost per QALY acquired of Option B + decreased slightly, especially as the goal of elimination of mother-to-child transmission of HIV achieved, Option B+ would be more attractive.In view of the lifetime ART(69.5 years) for the infected children, when the lifetime ATR cost was include into the total cost, Option B+ could dominate the most-effective option to prevent new infant infections in Yunnan Province. In the long-term, sensitivity analyses showed the cost-effective of life-year gained, QALY acquired and serodiscordant infection averted were most sensitive to the coverage of ART. Expanding the coverage of ART to those eligible women appears to be more cost-effective, particularly when the coverage rate of ART researches to 90%, the ICER per life-year gained and per QALY acquired compared with Option B decreased, with US$ 5149.40 and US$ 5319.36 respectively. Especially with the year increasing to 20 years, to implement Option B+ will demonstrate the priorities, all the ICER per life year gained and per QALY acquired have declined less than 1 × GDP, with US$ 3568.22 and US$ 3715.56 respectively. From a comprehensive and long-term perspective, Option B+ would be the optimal strategy in Yunnan province when the goals of “90–90-90” (90% of all people living with HIV will know their HIV status, 90% of all people with diagnosed HIV will receive sustained antiretroviral therapy and 90% of all people receiving antiretroviral therapy will have viral suppression.)and “95–95-95” (95% of all people living with HIV will know their HIV status, 95% of all people with diagnosed HIV will receive sustained antiretroviral therapy and 95% of all people receiving antiretroviral therapy will have viral suppression.) achieved.

In comparison with previous cost-effectiveness studies in low- and middle- income countries, less differences were observed. All the previous studies demonstrated the cost effective of Option B+. A previous modeling study of mother-to-child transmission of HIV in Ghana [26], suggested that Option B+ is a cost-effective use of limited resource. In Uganda, lifelong ART was associated with highly cost-effective for prevention mother-to-child transmission of HIV and acquiring additional public health benefit [27]. In Malawi, when averted infants infections and maternal survival outcomes were considered together, Option B+ represented a more cost-effective policy option [2]. In Nigeria, lifelong ART could provide the greatest incremental benefit to prevent HIV transmission among HIV serodiscordant couples [25]. Our study comprehensively included the benefits of infants, mothers and serodiscordant partners together, overcoming the deficiency of the previous cost-effective analyses of Option B+ to omit the important benefits [11]. In China, there is few study to model the cost-effectiveness evaluation of Option B+. Option B+ is recently endorsed by WHO to scale up the PMTCT programs in countries with high-burden [10]. Our study is the first study to develop the cost-effectiveness models informed by the field data of Yunnnan, China and addressed the potential cost saving associated with Option B+ from short-term and long-term. We hope our study could assist the province to complete a policy switching from previous strategies to Option B+ and supply scientific evidences for the applicability of Option B+ in Yunnan province. Future research efforts in the cost-effective analyses of Option B+ should be directed at providing more evidences in different areas in China and also across different cultures. We believe our study could supply a useful framework to other similar studies.

Our study had some important limitations. Firstly, most the parameters included in the models are based on the Yunnan context. For example, Yunnan province is with the highest HIV prevalence level in China, different HIV prevalence level could address different cost-effective results of Option B+. So applying the results elsewhere should be with more cautions. Secondly, our study adopted a perspective of health care system, because the direct cost is the major component of total cost of implementation of Option B+. A further study should be conducted by using the perspective of societal prevention so that Option B+ could be more preferable as more evidences indicated the possible influence to the family and society. Thirdly, our study didn’t consider the other factors associated with decision making regarding the resource allocation. These factors may include society and culture factors.

In conclusion, we have presented an economic analysis that provides evidence that HIV PMTCT Option B+ is a cost-effective strategy for comprehensive HIV prevention for infants and serodiscordant partners and life-long treatment for mothers in Yunnan Province, China. Option B+ could be implemented in Yunnan province, especially as the goals of eMTCT(MTCT< 2%) and “90–90-90”(coverage rate of ART> 90%) achieved, Option B+ would be more attractive.