We assessed the cost-effectiveness of the 2010 WHO mother-to-child transmission prevention strategies: Options A and B, and Malawi's Option B+. Analyzing both infant infection outcomes and long-term maternal health outcomes allows us to make a distinction between strategies to prevent mother-to-child transmission whose impact improves only child outcomes and those to treat mothers whose impacts improve both survival in HIV-infected mothers and children. Option A is the most cost-effective alternative in our modelling where we have assumed an ideal scenario with universal CD4 screening available and very high rates of ARV coverage for prophylaxis and provision of ART to eligible women. However, in real-world situations such as Malawi, with low access to CD4 testing, and low levels of ART in treatment-eligible women with Option A, the cost-effectiveness favours Option B and B+. Using the WHO commission on Macroeconomics and health criterion for determining the cost-effectiveness of an intervention 
, we found that Option B+ represents a cost-effective strategy not only for preventing new HIV infections among infants, but also for improving the survival of HIV-infected mothers. In a recent programmatic update, WHO has encouraged countries to consider Option B+ 
The lower cost-effectiveness ratios (US $38–68 per DALY averted) derived in our analysis when compared to previous studies can be attributed to the current availability of less expensive and more effective regimens for PMTCT as well as improved coverage of services for HIV-infected mothers modelled here. Sweat and colleagues reported higher cost-effectiveness ratios with SD NVP up to US$ 310 per DALY averted, across eight countries in Sub-Saharan Africa 
. Another study from Tanzania reported an incremental cost-effectiveness ratio of US$162 per DALY averted 
for HAART compared to single-dose Nevirapine. A more recent study compares WHO option B with short course prophylaxis in Nigeria and reported an ICER of $111 per DALY averted if there was full PMTCT coverage among pregnant women 
From an economic perspective, each of the three options analyzed here results in enormous cost savings by averting new paediatric infections; thereby yielding significant returns on investment. For every dollar invested in the PMTCT programmes, between 2.5 and 4 dollars would be obtained in return from averted lifetime pediatric care, equivalent to saving nearly US$ 51 million from each annual birth cohort.
We believe that our study is the first economic evaluation to also assess maternal health outcomes when using ART regimens as part of prevention strategies for mother to child transmission. Integrating HIV services in the context of ‘eliminating new infections among children and keeping their mothers alive’ in Malawi, as the new Global Plan on MTCT elimination recommends 
, results in favourable outcomes for both mothers and infants while still yielding cost effective results. Under ideal settings where most women in need of ART for their own health and HIV-infected pregnant women who need ARV prophylaxis for PMTCT receive adequate drugs and clinical monitoring, the three options, A, B and B+ included in our analysis, when compared directly with the base case will result in incremental cost-effectiveness ratios that are less than three times the 2010 GDP per capita in Malawi of US$ 310 
and can be considered feasible policy options. After ten years of treatment, although Option B+ has significantly higher costs, the wider and earlier use of ART results in greater direct benefits, keeping the most women alive for the longest time, and yielding an incremental cost-effectiveness ratio of US $ 455 per life year gained over the current practice. In the Malawi context, where access to CD4 count and therefore targeted initiation of HIV-infected pregnant women on ART based upon CD4 results is unlikely to be successful given current limitations in CD4 test access, this approach represents a cost-effective policy option to prevent a child from being infected, improve HIV-free survival of infants, save mother's lives and reduce orphanhood.
Increasing access to treatment among pregnant women has several advantages. From a therapeutic point of view, it would reduce morbidity and mortality among HIV infected women. Treatment guidelines in North America and Europe recommend treatment initiation with higher CD4 counts 
than those recommended for resource-limited settings. Recent results from the HPTN 052 study show that ART is 96% effective in preventing transmission to an uninfected sexual partner in discordant couples where the index case has CD4 counts between 350 and 550 cells/ µL 
and ART during pregnancy and after may serve as a preventive strategy among discordant couples and to prevent sexual transmission more generally. Future modelling studies are needed to address the potential benefit of Option B+ as a strategy of early start of ART for prevention of new infections in the general population. Early ART is also known to reduce the risk of developing tuberculosis, the leading cause of mortality in HIV infected individuals, which increases with declining CD4 counts below 500cells/ µL 
. Finally, evidence shows that women on ART before pregnancy can have lower mother-to-child transmission rates compared to those initiating ARV prophylaxis during pregnancy, as low as 0.5% during pregnancy 
as some transmission can occur before the timing of prophylaxis protocols, and as women may often enter into antenatal care, and hence PMTCT late in pregnancy. Therefore, for countries like Malawi, which has a high fertility rate of 5.5 children per woman, the long-term effect of continuous ART would result in many more infections averted during subsequent pregnancies and improve the cost-effectiveness of Option B+.
As in any other modelling exercise, there are a number of limitations in relation to our assumptions. The successful implementation of these programmes rests on the capacity of overcoming many obstacles to increase access, especially in rural Malawi and at primary care level. The assumption about scaling programmes from their current levels to high aspiration targets should be taken with reservation. The costs and challenge of achieving such high coverage may be underestimated as the success of these programmes will require intensified community participation, human resources and the infrastructure necessary for service delivery. We made every effort to make explicit all the assumptions in our model, which we hope will be timely and critical to inform policy options. One simplifying assumption we made was that women would continue to receive the first-line ART regimen; this does not account for the realities that women face in terms of stigma, adherence and treatment failures requiring the switching of women to more expensive second- or third-line regimens. Finally, in the analysis, we have focused on the cost and cost-effectiveness of preventing new paediatric infections and on the health of the mother - we have not modelled the additional benefit and cost-benefit likely to result from the prevention of new adult infections in serodiscordant couples and partners. While we believe that our findings are robust and generalizable for many high burden countries, our results may not be applicable in some settings, particularly those with low prevalence, replacement feeding rather than breastfeeding for HIV-exposed infants and low fertility.
In conclusion, we present an economic analysis for the Malawi approach that places PMTCT within a continuum of care that integrates a comprehensive range of interventions, to make an impact on maternal, newborn and child health outcomes 
. Our analysis suggests that Option B+ is a cost-effective strategy to integrate HIV prevention and treatment efforts towards achieving Millennium Development Goals 4, 5 & 6 
and ensuring universal access to ART. Careful monitoring of the Malawi approach is needed to assess the programmatic implications and will be critical for contributing to the evidence base for future global guidelines revisions. However, from an economic point of view, while this strategy will certainly require additional short-term financial resources, it has the potential to save significant societal resources in the long term.