Cost-Effectiveness Analysis of Option B+ + for HIV
Prevention and Treatment of Mothers and Children in
Olufunke Fasawe1, Carlos Avila2*, Nathan Shaffer3, Erik Schouten4, Frank Chimbwandira5, David Hoos6,
Olive Nakakeeto7, Paul De Lay8
1Master of International Health Management, Economics and Policy Program, SDA Bocconi School of Management, Milan, Italy, 2Senior Health Economist, Principal
Associate, Abt Associates, Bethesda, Maryland, United States of America, 3PMTCT Technical Lead, HIV Department, World Health Organization, Geneva, Switzerland, 4HIV
Advisor, Management Sciences for Health, Lilongwe, Malawi, 5Director of the HIV and AIDS Department, Ministry of Health, Lilongwe, Malawi, 6Assistant Professor of
Clinical Epidemiology, Senior Implementation Director, ICAP, Columbia University, Mailman School of Public Health, New York, New York, United States of America,
7Health Economist, Independent Consultant, Saint-Genis-Poully, France, 8Deputy Executive Director, Joint United Nations Programme on HIV/AIDS (UNAIDS), Geneva,
Background: The Ministry of Health in Malawi is implementing a pragmatic and innovative approach for the management
of all HIV-infected pregnant women, termed Option B+, which consists of providing life-long antiretroviral treatment,
regardless of their CD4 count or clinical stage. Our objective was to determine if Option B+ represents a cost-effective
Methods: A decision model simulates the disease progression of a cohort of HIV-infected pregnant women receiving
prophylaxis and antiretroviral therapy, and estimates the number of paediatric infections averted and maternal life years
gained over a ten-year time horizon. We assess the cost-effectiveness from the Ministry of Health perspective while taking
into account the practical realities of implementing ART services in Malawi.
Results: If implemented as recommended by the World Health Organization, options A, B and B+ are equivalent in
preventing new infant infections, yielding cost effectiveness ratios between US$ 37 and US$ 69 per disability adjusted life
year averted in children. However, when the three options are compared to the current practice, the provision of
antiretroviral therapy to all mothers (Option B+) not only prevents infant infections, but also improves the ten-year survival
in mothers more than four-fold. This translates into saving more than 250,000 maternal life years, as compared to mothers
receiving only Option A or B, with savings of 153,000 and 172,000 life years respectively. Option B+ also yields favourable
incremental cost effectiveness ratios (ICER) of US$ 455 per life year gained over the current practice.
Conclusion: In Malawi, Option B+ represents a favorable policy option from a cost-effectiveness perspective to prevent
future infant infections, save mothers’ lives and reduce orphanhood. Although Option B+ would require more financial
resources initially, it would save societal resources in the long-term and represents a strategic option to simplify and
integrate HIV services into maternal, newborn and child health programmes.
Citation: Fasawe O, Avila C, Shaffer N, Schouten E, Chimbwandira F, et al. (2013) Cost-Effectiveness Analysis of Option B+ for HIV Prevention and Treatment of
Mothers and Children in Malawi. PLoS ONE 8(3): e57778. doi:10.1371/journal.pone.0057778
Editor: Paula Braitstein, Indiana University and Moi University, United States of America
Received April 19, 2012; Accepted January 29, 2013; Published March 12, 2013
Copyright: ? 2013 Fasawe et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: The authors have no support or funding to report.
Competing Interests: The authors have declared that no competing interests exist.
* E-mail: Carlos_Avila@abtassoc.com
HIV continues to pose a serious health risk for pregnant women
and their children in high prevalence settings. Vertical transmis-
sion, occurring during pregnancy, labour, delivery or breastfeed-
ing , remains the main mode of HIV infection in children. An
estimated 390 000 children globally acquired HIV from their
mothers in 2010 with over 90% of these new infections occurring
in sub-Saharan Africa . While the majority of infants of HIV-
infected mothers do not themselves become HIV-infected, they are
nonetheless at risk of increased mortality and morbidity and
vulnerable to orphanhood . However, the use of antiretroviral
drugs during and after pregnancy is a proven intervention to
virtually eliminate the risk of HIV transmission to infants, as
evidenced in high-income countries where new childhood HIV
infections are now almost non-existent [4,5].
Malawi, a low-income country of 15 million people is one of the
countries with the highest number of HIV-infected pregnant
women; between 57,000 and 76,000 pregnant women (mid-point
estimate 66,500) were HIV-infected and required antiretroviral
prophylaxisfor preventionof mother-to-child transmission
(PMTCT) in 2010 . There are approximately 663,000 annual
PLOS ONE | www.plosone.org1March 2013 | Volume 8 | Issue 3 | e57778
births and a high mortality ratio (510/100,000 births); approxi-
mately 32% of maternal deaths are attributable to HIV .
Malawi has experienced successful national efforts in reducing
disparities in safe motherhood with reductions in maternal
mortality of approximately 50% in the last decade. More than
90% of pregnant women attend antenatal clinics at least once
during their pregnancy , although the majority first attend
during the second or third trimester. The Government of Malawi
has implemented a decentralized approach to HIV prevention,
care and treatment in order to reach the 85% of Malawi’s
population that live in rural areas . Malawi has also had notable
success in rapidly expanding ART (antiretroviral treatment)
coverage in the general population; the number of ART sites
across the country grew from 9 to 491 between 2003 and 2009,
almost half of which are community-based health centres, and an
estimated 49–57% of HIV-infected adults eligible by clinical or
immunologic criteria were receiving ART by the end of 2010. By
contrast, the coverage of antiretroviral prophylaxis for HIV-
infected pregnant women was still very low in 2010, within the
range of 23–31% . Malawi’s healthcare system remains
overstretched, with one doctor for every 49 000 people and one
nurse for every 1 800 people  which is ten times lower than the
World Health Organization (WHO) recommended minimum
The revised 2010 WHO guidelines for prevention of mother-to-
child transmission of HIV recommend lifelong ART for women
with CD4 counts at or lower than 350 cells/ mL. The guidelines
recommend two prophylaxis regimens for women who are not
clinically or immunologically eligible for ART . Option A
consists of antepartum zidovudine (AZT) from 14 weeks of
pregnancy, single-dose nevirapine (sd-NVP) at the onset of labour
and a dual-drug regimen of zidovudine (AZT) and lamivudine
(3TC) until one week after delivery. The infant receives daily oral
nevirapine from birth until all breastfeeding has ceased. In Option
B, mothers receive triple-drug antiretroviral prophylaxis starting
from 14 weeks of pregnancy until all exposure to breast milk has
ended. Daily oral nevirapine to the infant is provided from birth
until six weeks of age. Determination of which women are eligible
for lifelong ART and which women receive prophylaxis is
primarily through CD4 screening.
The Ministry of Health in Malawi proposed and has recently
begun implementing a new approach termed Option B+ in which
all pregnant women who test HIV positive are placed on ART for
life, from 14 weeks gestation or first antenatal visit, and regardless
of their CD4 count or clinical stage . This simplified approach
would facilitate the achievement of not only the Global Plan target
of elimination of new paediatric HIV infections by 2015 , but
also the target of universal access to HIV treatment for mothers in
a setting where it is difficult to effectively distinguish between those
mothers eligible for treatment and those needing prophylaxis.
While CD4 testing should be available to guide the initiation of
ART , Malawi, like many other low-income countries, suffers
major constraints in the expansion of laboratory capacity, and
specifically regarding access to CD4 testing . The simplifica-
tion of drug regimen options may also help to improve adherence
to therapy and reduce the many bottlenecks within the cascade of
PMTCT interventions as countries adopt the Treatment 2.0
framework of simplified HIV treatment . Implementing
Option B+ may be a more effective PMTCT strategy, as it can
help overcome some of the individual, organizational and societal
barriers associated with achieving high coverage levels of
prophylaxis and treatment, and will ensure that most HIV-
infected pregnant women are placed on treatment immediately
following diagnosis leading to further reduction of MTCT .
The objective of this analysis was to determine if Option B+
represents a cost-effective policy option for the treatment of HIV-
infected pregnant women and for PMTCT, as compared with
WHO Options A and B. We assess the cost-effectiveness from the
Ministry of Health perspective while taking into account the
practical realities and costs of implementing ART services in
A decision analytic model was developed to compare the costs,
health outcomes and cost-effectiveness of WHO PMTCT Options
A and B as well as Option B+ in Malawi for all HIV-infected
pregnant women. The analysis was structured as a probability tree
starting with an HIV-infected pregnant woman entering into
contact with the health system for antenatal care, then receiving a
cascade of interventions towards reducing the risk of transmission
to her infant as well as care and treatment for her own health
(Figure 1). The risk of transmission depends on the background
HIV transmission rates during pregnancy, labour, delivery and
breastfeeding, the efficacy of the antiretroviral drugs in preventing
transmission, prophylaxis and treatment coverage and the level of
adherence. The estimated number of HIV-infected pregnant
women in Malawi was taken as the midpoint of the range reported
for the end of 2010  and this number, 66,500, was then used as
an input to analyse as an annual cohort of HIV-infected pregnant
women that, after surviving childbirth, was followed over a 10-year
time horizon. This time horizon was thought to be sufficiently long
enough to capture the effects of immediate or later access to
treatment and to assess maternal survival outcomes.
The patterns of disease progression in HIV-infected pregnant
women with and without ART were assumed to be similar to that
documented in the general adult population. A Markov model was
developed to simulate the natural history of HIV infection and
project the 10-year maternal outcomes associated with the
different options implemented. The model assumes that women
are treatment naı ¨ve and in one of four transition states: (a) CD4
counts .350 cells/ mL; (b) CD4 counts 350–200 cells/ mL; (c)
CD4 between 199–0 cells/ mL and (d) death, as the absorbing
state. Women starting with high CD4 counts and subsequently
becoming eligible for ART when their CD4 cell counts fall to 350
or below, would access ART services when they move into the
eligible transition state, while women eligible for treatment receive
life-long therapy and are accounted for in the PMTCT
programme. As more women access ART services in the future,
the background survival rates of HIV-infected mothers under
Options A and B improve when compared to the no-treatment
Outcomes assessed include the number of infant infections
averted, cost per infection averted, cost per disability adjusted life
year (DALY) averted for infants, life years gained in HIV-infected
mothers, cost per life year gained for the HIV-infected mothers
and the incremental cost-effectiveness ratios for each outcome.
DALYs were estimated using standard published methods .
Strategies being compared
We analyzed four strategies including; (1) Current practice in
2010, (2) Option A, (3) Option B, and (4) Option B+. For the
current practice, we modelled the mix of interventions in Malawi
including HIV testing and counselling and ARV prophylaxis for
HIV-infected pregnant women at the reported coverage levels as
of the end of 2010 .We modelled an ante-natal care (ANC)
coverage of 91% according to the World Health Statistics report
Cost-Effectiveness Analysis of PMTCT
PLOS ONE | www.plosone.org2 March 2013 | Volume 8 | Issue 3 | e57778
 with an HIV testing and counselling coverage of 66% in
pregnant women . Using data derived from a direct report from
the Ministry of Health (MOH) in Malawi, of the 45% of HIV-
infected pregnant women who received antiretrovirals for
PMTCT in 2010, 38% received single-dose nevirapine (NVP),
25% received a dual-drug regimen containing zidovudine (AZT),
22% received triple-drug ARV prophylaxis and 15% received full
ART . These coverage rates were modelled as the current
practice in 2010, prior to the start of the B+ programme. The
options analysed and their components are shown in Table 1. In
Option A, pregnant women not eligible for ART based on the
disease stage were modelled to receive zidovudine from 14 weeks,
a single dose of nevirapine at the onset of labour and a dual-drug
regimen of zidovudine and lamivudine (AZT+3TC) for one week
after delivery. In Option B, pregnant women not eligible for ART
were modelled to receive triple-antiretroviral prophylaxis of
tenofovir, lamivudine and efavirenz (TDF+3TC+EFV: this is the
regimen adopted by Malawi) from 14 weeks until one week after
all breastfeeding has stopped. In Option B+, treatment decisions
are not based on CD4 count and therefore all HIV-infected
pregnant women who receive HIV testing and are positive based
on the prevalence rate assumptions, were modelled to initiate and
continue lifelong ART. Infants receive prophylaxis with nevir-
apine until one week after all breastfeeding has stopped in Option
A, while they receive nevirapine for six weeks after birth with
current practice, Options B and B+.
For all strategies, it was assumed that 42% of HIV-infected
pregnant women have CD4 counts at or less than 350 cells/ mL
and are eligible for ART, based on findings of a population-based
study in Malawi . Therefore women eligible for ART under
WHO Options A and B receive ART initially in the model and
women who later become eligible after delivery and breastfeeding
will start to receive ART according to their disease progression
and at the coverage of ART in the general population . For this
analysis, full ANC coverage was assumed, and all pregnant women
were assumed to receive HIV testing and counselling while ARV
coverage rates for prophylaxis and treatment were assumed to be
90% for the three options while the 2010 coverage levels reported
by the MOH were modelled for the current practice.
All the input parameters are presented in Table 2. For perinatal
transmission rates, we used the recently revised mother-to-child
transmission rates by the UNAIDS epidemiology reference group
for use in Spectrum  along with published findings from the
multicentre Kesho Bora study with rates of 2.7% for Option A and
1.7% for Options B and B+ for the postnatal transmission in all
options . Breastfeeding can contribute as much as 42% to the
overall mother-to-child transmission . The 2010 Demographic
Health Survey for Malawi reports a mean breastfeeding duration
of 23 months among all mothers  and study findings from
Malawi report a median breastfeeding duration of 11.5 months
among HIV-infected women. . In this analysis, we assumed
Figure 1. Abbreviated decision tree summarizing the analytical approach, policy options and results.
Cost-Effectiveness Analysis of PMTCT
PLOS ONE | www.plosone.org3March 2013 | Volume 8 | Issue 3 | e57778
that HIV-infected mothers would breastfeed for an average of 12
months. The monthly risk of postnatal HIV transmission through
breastfeeding, in the absence of any intervention was assumed to
be 1.04% which is the average of the rates reported for
transmission in eligible and non-eligible women by the UNAIDS
epidemiology reference group .
Survival estimates from the model were calibrated with results
from the ART-LINC, which reported data from 36,615 patients
on ART from 17 cohorts in Africa, Asia and South America .
Transition probabilities between adjacent states for untreated
women were assumed to be similar to reported findings in other
populations and were estimated from the published natural history
studies [23–28] and calculated as the reciprocals of the mean
waiting times in each CD4 cell state . For women receiving
ART, the transition probabilities from one state to the next lower
one were calculated by applying the reported relative risk of
disease progression with treatment compared to no treatment of
0.27 . Weighted averages from studies reporting ART survival
in low-income settings were used to determine the mortality rate in
each state . Women receiving ART could also progress from
lower to higher states based on study findings on CD4 cell
recovery for people on treatment , but these women are
assumed to remain on treatment. The model incorporates possible
treatment failures, which can result from poor adherence and loss
to follow up (LTFU) during treatment. For the purpose of this
analysis, an adherence rate of 90% was used, as reported
adherence rates in resource-limited settings are comparable to
those in developed countries [33–34].
The cost per patient-year in each Markov state was calculated
by multiplying health care utilization by the cost per person per
year, based on recent cost estimates in Malawi. All costs are shown
in US dollars. The cost of rapid HIV testing was $3.50 per test and
all pregnant women are assumed to undergo at least one HIV test
during the first antenatal visit for Options A, B and B+ while the
coverage rates for ANC and HIV testing and counselling were
applied for the current practice. HIV-infected pregnant women
undergo CD4 cell count testing with the Current Practice, Options
A and B to determine eligibility for ART at a cost of US$ 20 per
test. Costs of ARVs for Options A and B included 6 months during
pregnancy and 12 months during breastfeeding. The cost of drugs
per woman receiving Option A for 6 months of prophylaxis is US$
76.20, consisting of $60 for AZT and AZT+3TC, $0.20 for NVP
and $16 for infant Nevirapine for 12 months of breastfeeding. The
annual cost of drugs per woman receiving Option B or Option B+
is US$ 193.60 per woman. Based on the percentage distribution of
regimens under the current practice as previously described, the
same costs of the various regimens were applied to the current
practice. Total costs of ARV prophylaxis and ART for all options
are calculated for the entire period of 10 years.
Other itemized costs for all the options and the current practice
include early infant diagnosis testing, and cotrimoxazole prophy-
laxis for HIV-exposed infants. Ninety percent of all infants born to
an HIV-infected mother are assumed to be tested with DNA PCR
at a cost of US$ 32.50 . Cotrimoxazole prophylaxis was
assumed to be given to all HIV-exposed infants for a period of 12
months at a cost of US$5 per person per year to account for the
time it takes to receive early-infant diagnosis (EID) results and
place HIV-infected infants on treatment [36–37].
Costs are shown in Table 3. Cost estimates and prices were
obtained directly from the Ministry of Health of Malawi, and
supplemented with additional cost data from the World Health
Organization Global Price Reporting Mechanism . All costs
are expressed in US dollars at a 2010 price base. Costs and
benefits were discounted at 3% annually. The three options were
compared to the current practice using incremental cost-effective-
ness ratios, of US dollars per life-year gained and per disability-
adjusted life-year averted.
Sensitivity analysis was performed to assess the robustness of the
results to changes in the assumptions made. The efficacies of ARV
prophylaxis and ART on reducing peripartum and postnatal
Table 1. ARV regimens for HIV prevention and treatment of mothers and children compared in the analysis - Current Practice 2010,
WHO Option A, WHO Option B and Malawi’s Option B+.
ARV regimens for mothers who do not need treatment for their own healthAll HIV-infected mothers
Current Practice 2010Option AOption BOption B+ +
Depending on availability and
setting, single-dose nevirapine
(NVP), or dual-drug regimen
containing zidovudine (AZT),
or triple-drug ARV prophylaxis
until cessation of breastfeeding
Antepartum twice-daily AZT starting
from as early as 14 weeks of gestation
and continued during pregnancy. At
onset of labour, sd-NVP and initiation
of twice daily AZT+3TC for 7 days
postpartum (Note: If maternal AZT was
provided for more than 4 weeks
antenatally, omission of the sd-NVP
and AZT+3TC tail can be considered;
in this case, continue maternal AZT
during labour and stop at delivery).
Triple ARV prophylaxis starting from
as early as 14 weeks of gestation
and continued until delivery, or, if
breastfeeding, continued until 1
week after all infant exposure to
breast milk has ended. Regimen:
Antiretroviral therapy starting from as
early as 14 weeks of gestation and
continued for life. Preferred regimen:
Irrespective of mode of
infant feeding: Daily NVP or
twice daily AZT from birth
until 4 to 6 weeks of age.
For breastfeeding infants: Daily NVP
from birth for a minimum of 4 to 6
weeks, and until 1 week after all exposure
to breast milk has ended. Infants
receiving replacement feeding only:
Daily NVP or sd-NVP+twice2daily AZT
from birth until 4 to 6 weeks of age.
Irrespective of mode of infant
feeding: Daily NVP or twice daily
AZT from birth until 4 to 6 weeks
Irrespective of mode of infant
feeding: Daily NVP or twice daily AZT
from birth until 4 to 6 weeks of age.
Cost-Effectiveness Analysis of PMTCT
PLOS ONE | www.plosone.org4March 2013 | Volume 8 | Issue 3 | e57778
transmission rates were varied using ranges reported in the
literature to take into account clinical practice situations where
adherence may be lower than reported in clinical trials.
Using the current PMTCT practice and coverage in Malawi in
2010 as our base case, a cohort of HIV-infected pregnant women
would result in an estimated 16,217 infant infections (24.4%
transmission rate) after one year and an estimated 28% survival
among HIV-infected mothers after ten years. Our counterfactual
analysis showed that without any PMTCT interventions, an
estimated 20,681 infections (31.1% transmission rate) would occur
after 12 months of breastfeeding. In addition, if no antiretroviral
treatment is provided to HIV-infected mothers, the natural HIV
progression results in a 3% survival rate after 10 years or an
estimated 1,920 women surviving from the initial cohort of HIV-
Cost-effectiveness analyses: preventing new paediatric
Table 3 shows the costs, outcomes and cost-effectiveness of
different strategies modelled to prevent new child infections in the
HIV-infected pregnant women. Our base case represents the
current PMTCT practice and coverage in Malawi in 2010; at
reported coverage levels, this resulted in 4,503 infections averted
among infants, with a generalized cost effectiveness ratio of US$
816 per infection averted.
If fully implemented, Option A averts 391 infections fewer than
Options B and B+ and has a generalised cost-effectiveness ratio of
$ 844 per infection averted; Option B, a generalised cost-
effectiveness ratio of $1,331 per infection averted and Option B+
a generalised cost-effectiveness ratio of US$ 1,265 (from savings
attributable to not carrying out CD4 testing). Generalized cost-
effectiveness analysis for the three approaches resulted in costs per
DALY of US$ 37 for Option A, US$ 60 for Option B and US$ 57
for Option B+.
The incremental cost effectiveness per DALY when compared
to the current practice as the base case resulted in ratios of US$ 38
for Option A, US$ 68 for Option B and US$ 64 for Option B+.
With comparable coverage and implementation, Option A
emerges as the most cost-effective option to prevent new child
infections among HIV-infected pregnant women following deliv-
ery and 12 months of breastfeeding.
Cost-effectiveness analysis: maternal health outcomes
(10-year analysis of cohort of HIV-pregnant women)
Table 4 presents the assessment of the different options in terms
of costs and maternal outcomes for the original annual cohort of
HIV-infected pregnant women followed over a ten-year horizon.
The total discounted cost of the current practice (limited coverage)
amounts to US$ $14.3 million, which is a fraction of the most
costly Option B+, at US$ 97.7 million. The current practice in
2010 results in a survival rate of 27.5%, with 18,267 of 66,500
HIV-infected mothers remaining alive after ten years and 66,289
life-years saved. Options A and B result in 152,966 and 171,543
Table 2. Input parameters and plausible ranges used for sensitivity analysis and relevant references for the Malawi analysis (US $
1. Number of HIV-infected pregnant women 66,500 (57,000–76,000) 
2. Percentage of pregnant women with CD4 count .350 cells/ mL (%)58
3. Percentage of pregnant women with CD4 count 349–200 cells/ mL (%)22 Same as above
4. Percentage of pregnant women with CD4 count ,200 cells/ mL (%)20Same as above
MTCT transmission rates
5. Background transmission rate without intervention (peripartum)%22 
6. Monthly post-natal transmission, no prophylaxis, breastfeeding (12 months)%1.04
7. Peripartum transmission, Option A %2.7 
8. Monthly post-natal transmission with infant prophylaxis, breastfeeding (as per Option A)%0.2
9. Peripartum transmission, Option B, Option B+ and eligible women on ART %
10. Monthly postnatal transmission with ART, breastfeeding (Options B and B+ and women on ART)%
11. HIV Testing and counselling
$3.50 MOH Malawi
12. CD4 Screening
$20.00 MOH Malawi
13. Follow-up visit/clinical monitoring (per visit)
$2.00 MOH Malawi
14. Single-dose NVP
15. AZT (6 months) and AZT+3TC (7 days)
16. TDF+3TC+EFV (per year)
17. Infant NVP including syringes (per year)
18. Early infant diagnosis
19. Cotrimoxazole prophylaxis (per year)
21. Discounted lifetime cost for an HIV infected child on ART
$ 3195 [39,40]
Cost-Effectiveness Analysis of PMTCT
PLOS ONE | www.plosone.org5March 2013 | Volume 8 | Issue 3 | e57778
life-years saved respectively. However, Option B+ improves the
survival and results in 249,576 life-years saved. The ICER per life-
year gained, when each option is compared to the current
practice, is US$ 314 for Option A, US$ 338 for Option B and US$
455 for Option B+.
We evaluated a range of possible scenarios with increasing levels
of service coverage for ARV prophylaxis and ART with the
different Options and estimated the incremental cost-effectiveness
among next best alternative strategies for Malawi. Figure 2
presents the relationship between level of investment and the
effectiveness of the intervention expressed in Life Years Gained
(LFG). The upward-sloped line represents the boundary and it is
called the ‘efficient frontier’. The efficient frontier offers the
highest expected return for a given level of investment. The ICERs
shown represent the incremental ratios from one alternative to the
next best alternative outlined at the frontier line. Current practice
represents our base case scenario or the status quo in 2010 and
results in the lowest health gains. In terms of outcomes; Option A
reaches the efficiency frontier by requiring fewer resources than
option B and producing almost comparable outcomes. Full
Table 3. Costs and paediatric outcomes from preventing mother to child transmission programmatic interventions for 18 months
of prophylaxis and treatment*(US $ 2010).
Current Practice Option A Option BOption B+ +
HIV testing and counseling
Cost of ARVs for prophylaxis and treatment
Early infant diagnosis
Total PMTCT programme cost (18 months)
Number of infants infected***
Number of infections averted4,503 15,606 15,99715,997
Lifetime costs of averted ART and hospital care
DALYS averted101,308351,139 359,930359,930
Cost per infection averted
Cost per DALY averted
ICER per DALY (compared to the current practice)
*Assumes 663,000 pregnant women, 66,500 HIV-infected pregnant women annually, and 90% (59,850) of those women reached by Option A, B and B+.
**Assumes no needed CD4 to start ART under the Malawi Option B+ approach; however, in practice some HIV-infected pregnant women will have access to CD4 testing
as part of staging and response to treatment
***Background infections if no ARV interventions=20,681
Table 4. Costs, maternal health outcomes and cost-effectiveness ratios of options A and B and Malawi’s Option B+ for the ten-year
horizon (US $ 2010).
Current PracticeOption AOption BOption B+ +
PMTCT costs (first 18 months)
Cost of ART for eligible women (subsequent years)
Cost of follow up and monitoring
Total programme costs (10 years)
Number of HIV infected women on ART and alive after ten years 18,26728,567 30,05742,137
Life years gained in HIV infected mothers after ten years 66,289 152,966 171,543249,576
ICER per life year gained (compared to the current practice)-
Cost-Effectiveness Analysis of PMTCT
PLOS ONE | www.plosone.org6March 2013 | Volume 8 | Issue 3 | e57778
implementation of Option A coupled with the provision of ART to
all eligible women results in rapid health gains, with 250 thousand
life years over an investment of US$ 50 million. Doubling the
investments to US$ 100 million, by providing full Option B+,
results in an increase of 120 thousand life years gained.
Sensitivity analysis was performed to assess the robustness of the
results. For infant outcomes, Option A remained the most cost-
effective option with changes in the efficacy of antiretroviral drugs,
changes in transmission rates and costs of antiretroviral drugs. The
cost of ARVs was varied by 50% below and above the reported
price. One-way sensitivity analyses were performed on key model
parameters with the model being robust to most of the changes.
A break-even point between Option B+ and Option A occurs
when the annual cost of antiretroviral treatment and care is
reduced and reaches $387, with Option B+ becoming the more
cost-effective option to prevent new infant infections and
producing an ICER of $52.4 per DALY averted in infants.
However, when considering outcomes for HIV- infected mothers,
the model is sensitive to changes in the coverage of CD4 testing,
ARV coverage among HIV-infected pregnant women, ART
coverage in the general population and the cost of ART. Results
are shown in Table 5. As the coverage of ART in the general
population increases, the cost-effectiveness ratio of Option B+
increases while Options A and B become more cost-effective.
Option B becomes the most cost-effective strategy when the
coverage of CD4 testing is lower than 73% and if the cost of ART
is reduced by 40%; with resultant ICERs of $320, and $217 per life
year gained respectively. Figure 3 highlights results for the
variables found to have the most effect on the ICER of Option
B+ considering life years gained in HIV-infected mothers.
We assessed the cost-effectiveness of the 2010 WHO mother-to-
child transmission prevention strategies: Options A and B, and
Malawi’s Option B+. Analyzing both infant infection outcomes
and long-term maternal health outcomes allows us to make a
distinction between strategies to prevent mother-to-child trans-
mission whose impact improves only child outcomes and those to
treat mothers whose impacts improve both survival in HIV-
Table 5. Results from sensitivity analyses on input parameters affecting outcomes in HIV-infected mothers; US$ per life year
gained (compared to the current practice) and paediatric outcomes; US$ per DALY averted.
Model parametersOption AOption BOption B+ +
Base case (US$/LYG in HIV-infected mothers)314.1337.6455.3
ARV coverage among HIV-infected pregnant women
Best case 100%312.8 333.6 446.7
Worst case 30%341.2443.7751.5
Coverage of CD4 testing
Best case 90%314.1 337.6455.3
Break-even point–73% 320.1320.4455.3
Worst case 30%328.1305.0 455.3
Cost of Triple-drug regimen (ART)
Best case $96.8194.8188.1241.1
Break-even point - $ 105.6217.8 217.0 282.5
Worst case $290 433.3487.2 669.4
ART coverage in the general population
Best case 90% 310.9357.9519.4
Worst case 49%314.4 335.6449.3
Base case (US$/DALY averted- infants)37.269.064.3
Background transmission rate used (22%)
Best case–15% 47.183.778.0
Worst case-40% 25.446.143.0
Peripartum transmission rate with Option A (2.7%)
Best case–1.3%36.268.1 63.5
Perinatal transmission rate with ART (1.7%)
Best case–0.7%37.765.3 60.9
Worst case–4.0%38.975.7 70.5
Cost of ART (US$ 193.60)
Best case-$96.830.640.5 69.0
Worst case-$ 290.445.595.857.9
Break-even point-$38752.9 123.4 52.4
Cost-Effectiveness Analysis of PMTCT
PLOS ONE | www.plosone.org7 March 2013 | Volume 8 | Issue 3 | e57778
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
Figure 2. Cost effectiveness of various strategies for the prevention of new pediatric infections and the treatment of HIV-infected
mothers in Malawi. Current practice represents our base case scenario or the status quo in 2010. The next set of scenarios highlight the cost
effectiveness of incrementally expanding program implementation and service delivery coverage, and ranges from PMTCT only to the addition of
integrated ART-ANC services for eligible pregnant women, both identified immediately and at a later time. Universal coverage implies the availability
of HIV services for mother and children at any point of needing treatment. Option B+ offers ART to pregnant women regardless of CD4 count.
Figure 3. Tornado diagram for the ICER of Option B+ +, base case is $455 per life year gained shown with the dotted line.
Cost-Effectiveness Analysis of PMTCT
PLOS ONE | www.plosone.org8March 2013 | Volume 8 | Issue 3 | e57778
recent study compares WHO option B with short course
prophylaxis in Nigeria and reported an ICER of $111 per DALY
averted if there was full PMTCT coverage among pregnant
From an economic perspective, each of the three options
analyzed here results in enormous cost savings by averting new
paediatric infections; thereby yielding significant returns on
investment. For every dollar invested in the PMTCT programmes,
between 2.5 and 4 dollars would be obtained in return from
averted lifetime pediatric care, equivalent to saving nearly US$ 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
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/ mL  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/ mL . Finally, evidence shows that women on
ART before pregnancy can have lower mother-to-child transmis-
sion 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
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 [10,50].
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.
Conceived and designed the experiments: CA OF PDL. Performed the
experiments: OF CA. Analyzed the data: OF CA NS. Contributed
reagents/materials/analysis tools: OF CA ON. Wrote the paper: OF CA
NS ES FC DH ON PDL.
1. UNAIDS (2011) Outlook Report: 30 years into the AIDS epidemic. Available:
2. WHO UNAIDS, UNICEF (2011) Global HIV/AIDS Response. Epidemic
update and health sector progress towards Universal Access. Available: www.
who.int/hiv/pub/progress_report2011/en/index.html.Accessed 2011 Nov 30.
3. Kuhn L, Kasonde P, Sinkala M, Kankasa C, Semrau K, et al. (2005) Does
Severity of HIV Disease in HIV-Infected Mothers Affect Mortality and
Morbidity among Their Uninfected Infants? Clin Infect Dis 41:1654–1661.
Cost-Effectiveness Analysis of PMTCT
PLOS ONE | www.plosone.org9March 2013 | Volume 8 | Issue 3 | e57778
4. Townsend CL, Cortina-Borja M, Peckham CS, de Ruiter A, Lyall H, at al. Download full-text
(2008) Low rates of mother-to-child transmission of HIV following effective
pregnancy interventions in the United Kingdom and Ireland, 2000–2006. AIDS
5. McKenna MT, Hu XH (2007) Recent trends in the incidence and morbidity
that are associated with perinatal human immunodeficiency virus infection in the
United States. Am J Obstet Gynecol 197:S10–S16.
6. WHO UNICEF, UNFPA and World Bank (2010) Trends in Maternal
Mortality:1990–2008; Estimates developed by the WHO, UNICEF,UNFPA
and World Bank. Available: http://whqlibdoc.who.int/publications/2010/
9789241500265_eng.pdf.Accessed 2011 Jun 21.
7. WHO (2011). World health Statictics 2011. Available: http://www.who.int/
whosis/whostat/EN_WHS2011_Full.pdf.Accessed 2011 Aug 25.
8. Ministry of Health Malawi (2010) Making it Happen: Revising national policies
to reflect changes in WHO recommendations for preventing vertical
transmission of HIV. XVIII International AIDS Conference. Vienna.
9. WHO (2010) Antiretroviral drugs for treating pregnant women and preventing
HIV infection in infants: recommendations for a public health approach 2010.
2013 Feb 2.
10. Schouten EJ, Jahn A, Midiani D, Makombe SD, Mnthambala A, et al. (2011)
Prevention of mother-to-child transmission of HIV and the health-related
Millennium Development Goals: time for a public health approach. Lancet
11. UNAIDS (2011) Global plan towards the elimination of new HIV infections
among children by 2015 and keeping their mothers alive. Available: http://
Children_en.pdf.Accessed 2011 Jul 12.
12. Athan E, O’Brien DP, Legood R (2010) Cost-effectiveness of routine and low-
cost CD4 T-cell count compared with WHO clinical staging of HIV to guide
initiation of antiretroviral therapy in resource-limited settings. AIDS 24:1887–
13. McGrath N, Kranzer K, Saul J, Crampin A, Malema S, et al (2007) Estimating
the need for antiretroviral treatment and an assessment of a simplified HIV/
AIDS case definition in rural Malawi. AIDS 21:S105–113.
14. Hirnschall G, Schwartlander B (2011) Treatment 2.0: catalysing the next phase
of scale-up. Lancet 378:209–211.
15. Fox Rushby JA, Hanson K (2011) Calculating and presenting disability adjusted
life years (DALYs) in cost-effectiveness analysis. Health Policy Plan 16: 326–331.
16. Ministry of Health of Malawi (2010). Quarterly HIV Programme Report. April–
17. UNAIDS (2011) Expert group on vertical transmission rates: MTCT
transmission rates for use in Spectrum. Working Paper on Mother-to-Child
HIV Transmission Rates for use in Spectrum Available: http://www.epidem.
org/Publications/MTCTratesworkingpaper.pdf.Accessed 2011 Jul 25.
18. The Kesho Bora Study Group (2011) Triple antiretroviral compared with
zidovudine and single-dose nevirapine prophylaxis during pregnancy and
breastfeeding for prevention of mother-to-child transmission of HIV-1: a
randomised controlled trial. Lancet Infect Dis 11:171–180.
19. The Breastfeeding and HIV International Transmission Study Group (2004)
Late Postnatal Transmission of HIV-1 in Breast-Fed Children: An Individual
Patient Data Meta-Analysis. J Infect Dis 189:2154–2166.
20. National Statistical Office, Zomba, Malawi and ICF Macro, Calverton,
Maryland, USA (2011) Malawi Demographic and Health Survey 2010.
pdf.Accessed 2013 Feb 9.
21. Miotti PG, Taha TET, Kumwenda NI, Broadhead R, Mtimavalye LAR, et al.
(1999) HIV Transmission Through Breastfeeding. JAMA 282:744–749.
22. The eART-linc collaboration (2008) Duration from seroconversion to eligibility
for antiretroviral therapy and from ART eligibility to death in adult HIV-
infected patients from low and middle-income countries: collaborative analysis of
prospective studies. Sex Transm Infect 84:i31–i36.
23. Currier JS, Spino C, Grimes J, Wofsy CB, Katzenstein DA, et al. (2000)
Differences between women and men in adverse events and CD4+ responses to
nucleoside analogue therapy for HIV infection. The AIDS Clinical Trials Group
175 Team. J Acquir Immune Defic Syndr 24:316–324.
24. Ekouevi D, Abrams EJ, Schlesinger M, Myer L, Phanuphak N, et al. (2012)
Maternal CD4+ Cell Count Decline after Interruption of Antiretroviral
Prophylaxis for the Prevention of Mother-to-Child Transmission of HIV. PLoS
ONE 7:e43750. doi:10.1371/journal.pone.0043750
25. Longini IM Jr, Clark WS, Gardner LI, Brundage JF (1991) The dynamics of
CD4+T-lymphocyte decline in HIV-infected individuals: a Markov modeling
approach. J Acquir Immune Defic Syndr 4:1141–1147.
26. Mauskopf J (2000) Meeting the NICE requirements: a Markov model approach.
Value Health 3:287–293.
27. Mauskopf J, Kitahata M, Kauf T, Richter A, Tolson J (2005) HIV antiretroviral
treatment: early versus later. J Acquir Immune Defic Syndr 39:562–569.
28. Mauskopf J, Lacey L, Kempel A, Simpson K (1998) The cost-effectiveness of
treatment with lamivudine and zidovudine compared with zidovudine alone: a
comparison of Markov model and trial data estimates. Am J Manag Care
29. Johansson K, Robberstad B, Norheim O (2010) Further benefits by early start of
HIV treatment in low income countries: Survival estimates of early versus
deferred antiretroviral therapy. AIDS Res Ther 7:3.
30. Mussini C, Cossarizza A, Sabin C, Babiker A, De Luca A, et al. (2011) Decline
of CD4+T-cell count before start of therapy and immunological response to
treatment in antiretroviral-naive individuals. AIDS 25:1041–1049
31. Lawn S, Little F, Bekker L, Kaplan R, Campbel E, et al. (2009) Changing
mortality risk associated with CD4 cell response to antiretroviral therapy in
South Africa. AIDS 23:335–342.
32. Hunt PW, Deeks SG, Rodriguez B, Valdez H, Shade SB, et al. (2003) Continued
CD4 cell count increases in HIV-infected adults experiencing 4 years of viral
suppression on antiretroviral therapy. AIDS 17:1907–1915.
33. Orrell C, Bangsberg DR, Badri M, Wood R (2003) Adherence is not a barrier to
successful antiretroviral therapy in South Africa. AIDS 17:1369–1375.
34. Lanie `ce I, Ciss M, Desclaux A, Diop K, Mbodj F, et al. (2003) Adherence to
HAART and its principal determinants in a cohort of Senegalese adults. AIDS
35. Stevens W, Sherman G, Downing R, Parsons LM, Ou CY, et al. (2008) Role of
the laboratory in ensuring global access to ARV treatment for HIV-infected
children: consensus statement on the performance of laboratory assays for early
infant diagnosis. Open AIDS J 2:17–25.
36. UNICEF (2010) Cotrimoxazole prophylaxis for HIV-exposed and HIV-infected
infants and children; Practical approaches to implementation and scale up. 2010.
2013 Feb 2.
37. Ryan M, Griffin S, Chitah B, Walker AS, Mulenga V, et al. (2008) The cost-
effectiveness of cotrimoxazole prophylaxis in HIV-infected children in Zambia.
38. WHO (2010) Transaction prices for Antiretroviral Medicines and HIV
Diagnostics from 2008 to March 2010. A summary report from the Global
Price Reporting Mechanism. Available: www.who.int/hiv/amds/gprm/
en.Accessed 2013 Feb 2.
39. Sansom SL, Anderson JE, Farnham PG, Dominguez K, Soorapanth S, et al.
(2006) Updated Estimates of Healthcare Utilization and Costs Among
Perinatally HIV-Infected Children. J Acquir Immune Defic Syndr 41:521–526
40. Orlando S, Marazzi MC, Mancinelli S, Liotta G, Ceffa S, et al. (2010) Cost-
Effectiveness of Using HAART in Prevention of Mother-To-Child Transmission
in the DREAM-Project Malawi. J Acquir Immune Defic Syndr 55:631–634
41. WHO (2001) Commission on Macroeconomics and Health. Investing in Health
for Economic Development. Available: http://whqlibdoc.who.int/publications/
2001/924154550x.pdf.Accessed 2013 Feb 2.
42. WHO (2012). Use of antiretroviral drugs for treating pregnant women and
preventing HIV infection in infants. Programmatic update 2012. Available:
2013 Feb 2.
43. Sweat MD, O’Reilly KR, Schmid GP, Denison J, de Zoysa I (2004) Cost-
effectiveness of nevirapine to prevent mother-to-child HIV transmission in eight
African countries. AIDS 18:1661–1671.
44. Robberstad B, Evjen-Olsen B (2010) Preventing Mother to Child Transmission
of HIV With Highly Active Antiretroviral Treatment in Tanzania-a Prospective
Cost-Effectiveness Study. J Acquir Immune Defic Syndr 55:397–403.
45. Shah M, Johns B, Abimiku Al, Walker DG (2011) Cost-effectiveness of new
WHO recommendations for prevention of mother-to-child transmission of HIV
in a resource-limited setting. AIDS 25:1093–1102
46. Department of Health and Human Services (2011). Guidelines for the use of
antiretroviral agents in HIV-1-infected adults and adolescents, 2011. Available:
pdf.Accessed 2013 Feb 2.
47. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, et al.,
(2011) Prevention of HIV-1 Infection with Early Antiretroviral Therapy.
N Engl J Med 365:493–505.
48. Harries AD, Zachariah R, Corbett EL, Lawn SD, Santos-Filho ET, et al., (2010)
The HIV-associated tuberculosis epidemic: when will we act? Lancet 375:1906–
49. Hoffman RM, Black V, Technau K, van der Merwe KJ, Currier J, et al. (2010)
Effects of highly active antiretroviral therapy duration and regimen on risk for
mother-to-child transmission of HIV in Johannesburg, South Africa. J Acquir
Immune Defic Syndr 54:35–41.
50. Horton R (2009) What will it take to stop maternal deaths? Lancet 374:1400–
51. UNDP. Millennium development goals: 4–5 and 6. Available: http://www.
undp.org/content/undp/en/home/mdgoverview.html.Accessed 2013 Feb 2.
Cost-Effectiveness Analysis of PMTCT
PLOS ONE | www.plosone.org10March 2013 | Volume 8 | Issue 3 | e57778