Secondary Logo

Journal Logo

Supplement Article

Eliminating Preventable HIV-Related Maternal Mortality in Sub-Saharan Africa

What Do We Need to Know?

Kendall, Tamil PhD*; Danel, Isabella MD, MS; Cooper, Diane PhD; Dilmitis, Sophie§; Kaida, Angela PhD; Kourtis, Athena P. MD, PhD; Langer, Ana MD*; Lapidos-Salaiz, Ilana MBChB, MPH; Lathrop, Eva MD, MPH#; Moran, Allisyn C. PhD**; Sebitloane, Hannah MBChB, FCOG, MMed††; Turan, Janet M. PhD‡‡; Watts, D. Heather MD§§; Wegner, Mary Nell EdM, MPH*

Author Information
JAIDS Journal of Acquired Immune Deficiency Syndromes: December 1, 2014 - Volume 67 - Issue - p S250-S258
doi: 10.1097/QAI.0000000000000377
  • Open

Abstract

INTRODUCTION

Nearly 18 million women are living with HIV worldwide, and more than 90% of pregnant women living with HIV (WLWH) reside in sub-Saharan Africa.1,2 Globally, HIV and complications related to pregnancy remain the 2 leading causes of death for women of reproductive age.3 Global maternal mortality has been reduced from an estimated 543,000 deaths in 1990 to 287,000 deaths in 2010. However, in the same period, maternal mortality seems to have increased in 8 sub-Saharan African countries with high HIV prevalence.4 Without timely antiretroviral therapy (ART), WLWH in sub-Saharan Africa are approximately 8 times as likely to die during pregnancy or the postpartum period as HIV-negative women.5–7 Before wider availability of ART, about 1 quarter of pregnancy-related deaths in the region were attributable to HIV.6 International commitments to eliminate preventable maternal mortality8 and reduce HIV-related deaths among pregnant and postpartum women by 50%9 will not be achieved without a better understanding of the links between HIV and poor maternal health outcomes and improved health services for the care of WLWH during pregnancy, childbirth, and postpartum.

Research, monitoring, and evaluation are needed to understand the relationships between HIV and increased maternal morbidity and mortality, track progress, motivate adoption of and sustained support for interventions that work, and generate solutions that address persistent barriers to the maternal health of WLWH. The context for the questions identified in this research and evaluation agenda includes impressive but uneven progress on providing antenatal HIV testing and ART to prevent vertical (mother-to-child) HIV transmission in sub-Saharan Africa.10 Additionally, new treatment guidelines recommend earlier initiation of ART for all adults, and a growing number of countries are moving towards initiation of lifelong treatment for all pregnant and breastfeeding WLWH, regardless of CD4 count (Option B+).11 The impact of these treatment changes on maternal mortality and morbidity is still unclear. At the same time, significant numbers of treatment-eligible women who learn they are living with HIV during pregnancy in sub-Saharan Africa do not begin ART,12,13 and for those who do, retention in care14,15 and postpartum ART adherence16 are suboptimal. The current situation suggests that services better aligned to women's needs and enabling social environments are critical for more women to begin and remain in care.

Beyond ART, coverage of interventions necessary to improve the maternal health of all women, but which are particularly crucial for WLWH, such as screening and treatment for tuberculosis17 and malaria18 and provision of contraceptive information and services,19 is insufficient. Pregnancy and HIV both increase women's susceptibility to acquiring malaria and to developing active tuberculosis disease.20–22 Coinfection with HIV and either malaria or tuberculosis are also associated with increased risk of maternal death compared with women who have tuberculosis or malaria but are not living with HIV.23,24 Reducing unintended pregnancies among WLWH constitutes primary prevention of vertical transmission and maternal mortality and morbidity, but although 66%–92% of WLWH in sub-Saharan Africa report not wanting another child (now or ever), only 20%–43% are using contraception.25 Finally, although the efficacy of ART for preventing sexual26 and vertical HIV transmission27 holds promise for safer reproductive opportunities for WLWH, limited attention has been focused on strategies to support safer conception among HIV-serodiscordant couples in resource-constrained settings.28,29

Identification of the Research and Evaluation Priorities

In June 2013, 56 international maternal health and HIV researchers and policy implementers were convened by the Maternal Health Task Force, the United States Agency for International Development, and the United States Centers for Disease Control and Prevention to share emerging evidence and identify priority knowledge gaps for improving programmatic responses to maternal health in contexts of high HIV prevalence. After this 2-day meeting, 30 researchers and policy implementers participated in a day-long meeting dedicated to reaching consensus on research and evaluation priorities for HIV and maternal health in sub-Saharan Africa. In addition to experience and technical expertise in HIV and maternal health, criteria for selecting the invited experts included representation of institutions from sub-Saharan Africa, North America, and Europe and a range of disciplinary backgrounds. Please see www.mhtf.org to consult the meeting agenda, presentations, and participant list. After a facilitated discussion of research and evaluation priorities, the experts divided into 3 groups tasked with reaching consensus on 4 priority areas for research and evaluation. Repetition of identified priorities allowed clustering in 3 broad areas for research and evaluation that were agreed on by consensus: (1) clinical management of pregnant and postpartum WLWH to address the leading causes of maternal death and evaluate the impact of expanded ART on maternal mortality and morbidity, (2) integrated service delivery models that simultaneously provide HIV screening and/or treatment and address malaria, tuberculosis, and/or the reproductive health of WLWH to optimize maternal health outcomes, and (3) an enabling social environment for women to begin and remain in care. The international working group that authored this article was formed to further develop the research and evaluation agenda and a conceptual framework (Fig. 1). Subsequently, narrative reviews of the peer-reviewed literature, relevant international guidelines and selected documents from the gray literature were conducted for each of the identified subtopics to summarize the existing evidence and knowledge gaps and generate additional specific research questions. The full working paper provides a comprehensive review of the literature and a detailed discussion of the proposed research and evaluation agenda.30 This article synthesizes broad research and evaluation questions that should be addressed to improve the maternal health of WLWH and provides illustrative examples. Table 1 outlines additional research questions.

F1-12
FIGURE 1:
Conceptualization of research and evaluation priorities for eliminating HIV-related maternal mortality.
T1-12
TABLE 1-a:
Priority Research and Evaluation Questions to Improve the Maternal Health of WLWH
T2-12
TABLE 1-b:
Priority Research and Evaluation Questions to Improve the Maternal Health of WLWH

The 3 thematic areas focus on different levels of the social and programmatic context relevant for HIV and maternal health (Fig. 1) as follows: (1) the “individual” level is focused on the clinical management and maternal health outcomes of WLWH; (2) the “health system” level considers how multiple priority health needs can best be addressed in resource-constrained health systems; and (3) at the “society” level, the intent is to assess how interventions that address gender and HIV-related discrimination and create a supportive social environment affect women's linkage to and retention in health services. Evidence-based interventions will resonate positively across all 3 levels. For instance, better information about the causes of maternal death among WLWH can inform clinical management and health system resource allocation. Subsequent reductions in maternal deaths can create more community demand for services, creating a positive cycle. Similarly, when the social context enables women to access and continue HIV care and adhere to ART, individual morbidity and mortality, sexual and vertical HIV transmission, and development of antiretroviral resistance will be reduced. Individual and community health outcomes and the sustainability of ART programs will be improved.

IMPROVING DATA AVAILABILITY AND QUALITY

Three overarching issues were identified regarding data availability and quality: the lack of good quality data on the causes of maternal death, the need for enhanced program monitoring to better track coverage and effects of programmatic interventions for pregnant and postpartum WLWH, and the need for program evaluation to report on health outcomes in addition to process indicators. To improve availability and quality of maternal death data, recording all maternal deaths that occur in facilities and improving the quality of death certificates is a priority.31 Implementing maternal death surveillance and response, which links facility- and community-based notification and investigation to national health information systems and includes a multidisciplinary process for making recommendations, is strongly advised.32 The existence of significant errors in descriptions of cause of maternal death (even at tertiary level facilities) indicates the need for more autopsy studies. In addition, the large numbers of women who deliver outside of facilities in most countries in sub-Saharan Africa points to the need for further development of minimally invasive autopsies and improvement of verbal autopsy tools for use in the community.

Harmonized monitoring that identifies whether women are (1) living with HIV and (2) pregnant or postpartum would permit evaluation of the effects of programs on the maternal health of WLWH. Tuberculosis provides an example of the value of this approach. Ensuring that people living with HIV are screened for tuberculosis and given prophylactic treatment is a core activity for HIV treatment and tuberculosis control programs. Pregnant WLWH have an elevated risk of developing tuberculosis disease and of maternal death, but many information systems for monitoring tuberculosis prevention and treatment among people with HIV do not identify pregnant and postpartum women.

Finally, evaluation research tends to report on process outcomes, such as coverage, rather than health outcomes, and in general, does not report on relatively rare events, such as maternal mortality. The expert meeting and literature review identified the need to increase reporting of maternal health outcomes as part of program evaluation. Indeed, many of the interventions identified as priorities for evaluation have had a positive impact on proximate outcomes, such as use of contraceptives or reduction of intimate partner violence (IPV), but have not been evaluated for their effects on maternal morbidity and mortality among WLWH.

INDIVIDUAL: CAUSE OF MATERNAL DEATH AND CLINICAL MANAGEMENT OF PREGNANT AND POSTPARTUM WLWH

How Will Rates and Causes of Morbidity and Mortality During Pregnancy and the Postpartum Period be Affected by Increased Availability of ART for WLWH?

Tracking maternal health outcomes to assess the impact of ART on excess maternal morbidity and mortality is a priority as millions of WLWH begin and remain on treatment. Evidence from sub-Saharan Africa indicates that earlier initiation and longer duration of ART reduces the risk of maternal death among WLWH. When South Africa began initiating ART at a CD4+ cell count of ≤350 cells per microliter rather than at ≤200 cells per microliter, an 18% reduction in the institutional maternal mortality ratio for WLWH was observed during the first year.33 In Mozambique and Malawi, more than 30 days of ART before delivery has been associated with reduced risk of death during childbirth and postpartum.34 However, data from South Africa indicate higher maternal mortality rates among WLWH compared with HIV-negative women even when they are receiving ART,35 and results from a prospective cohort study of women initiating ART in Uganda found elevated risk of pregnancy-related mortality when pregnancy and the 1-year postpartum period were treated as a time-dependent risk factor.36 Data from the United States also indicate a persistently elevated risk of maternal morbidity and mortality among WLWH in the ART era.37 More studies, including cohort studies that allow valid comparisons by controlling for the health status of different groups of WLWH and that allow adjusted comparisons with HIV-negative women, are needed to tease out the relationships between HIV, pregnancy, time on ART, immune status, and maternal morbidity and mortality. As more countries offer lifelong ART for all pregnant and breastfeeding WLWH, it is critical to develop surveillance systems to track potential negative and positive effects of ART on women and infants.

What Are the Safest and Most Effective Clinical Protocols to Address the Leading Causes of Maternal Morbidity and Mortality Among WLWH?

Tuberculosis, malaria, pneumonia, and sepsis are the leading causes of maternal death among WLWH.38–40 Prevalence of anemia among pregnant WLWH is high and contributes to poor maternal and infant health outcomes.41–43 Data about greater incidence of hypertension or obstetric hemorrhage and outcomes for pregnant WLWH are inconclusive.44–49 Research to improve the prevention and clinical management of the leading causes of maternal morbidity and mortality among WLWH is needed. To exemplify, WLWH have 3 times the risk of puerperal sepsis as compared with HIV-negative women and a 6-fold greater risk when delivery is by caesarean.44 Maternal death audits in South Africa have identified an institutional maternal mortality ratio due to sepsis of 24.2 among WLWH as compared with 4.1 per 100,000 live births for HIV-negative women.50 Results from studies that examined provision of prophylactic antibiotics to WLWH before or during delivery have been mixed.51,52 Additional research is needed to inform sepsis prevention for WLWH during labor and delivery and as part of postpartum and postabortion care, as well as to elucidate the relationships between puerperal sepsis, immune status, and ART. Similar questions exist for other causes of maternal morbidity and mortality among WLWH (Table 1).

HEALTH SYSTEM: INTEGRATED HEALTH SERVICE DELIVERY

What Are the Most Effective Models for Providing Integrated Services and How Will Integrated Services Affect the Maternal Health of WLWH?

The promise of integrated service delivery is that meeting women's multiple health needs at a single point-of-care, possibly during a single visit and potentially by the same providers, can optimize women's contact with the health system and more effectively use scarce human and financial resources. Providing ART within maternal health services and eliminating barriers to ART initiation, for example by offering point-of-care CD4 testing53 or eliminating CD4 testing before initiation of ART,54 has been shown to dramatically increase uptake of ART among pregnant and breastfeeding women.55,56 Reviews of integration of interventions needed to prevent vertical HIV transmission with other maternal and child health (MCH) services have identified generally positive results in terms of coverage, but few studies provide information on health outcomes.57,58 Similarly, provision of contraceptives in HIV services and as a routine part of postnatal care has shown increased uptake by WLWH,59–61 but information about how these interventions affect unintended pregnancies or other health outcomes is lacking.62 Despite the overall positive impact, individual studies that identify negative effects in some settings, for instance, drops in child immunization rates in rural clinics when offer of HIV testing was added to immunization visits,63 deserve attention. There are also outstanding questions about the point on the MCH and HIV care continuum at which to provide services. For example, if WLWH begin ART in MCH services, when and how is the transition to chronic HIV care most successfully accomplished? Research and evaluation priorities include monitoring to ensure that service integration does not compromise the quality and coverage of core MCH and HIV services and medium-term assessment of health outcomes. Studies that evaluate the impact of adding other care components to MCH and HIV services, such as safer conception and contraceptive services, and malaria and tuberculosis prevention and treatment are also needed.

Increasing the quality of services and the number of interventions provided requires strengthening MCH and HIV services and ensuring adequate human resources. This strengthening is particularly important in the context of increased demands for ART provision to greater numbers of pregnant and breastfeeding WLWH and guidelines recommending earlier initiation of treatment for all people living with HIV. In addition, the skills required to deliver different services, for instance, HIV treatment adherence counseling or diagnosis and management of tuberculosis may differ from the skills required to deliver high-quality antenatal and obstetric care. As task shifting is implemented, evaluation is needed to assess health care staffing needs and skill level and optimal provider mix to deliver interventions safely and effectively while retaining health care providers on the job and pregnant and postpartum women in care.

Preconception counseling and safer conception strategies for women affected by HIV provide examples of the type of research and evaluation needed to guide the integration of service delivery. When and where on the continuum of MCH and HIV services should information about biomedical and behavioral interventions and services to support safer conception be offered to WLWH and to serodiscordant couples? How prepared are different cadres of HIV and MCH health care providers and community members to provide safer conception strategies? What facility- and community-based models are feasible and what resources are needed to ensure quality and coverage? Implementation research is needed to answer these questions and to assess the impact of information and service provision on reproductive behaviors, vertical and sexual HIV transmission, and maternal health outcomes. Additional questions about integrating interventions to support the reproductive choices of WLWH and to prevent, diagnose, and treat tuberculosis and malaria with MCH and HIV services are noted in Table 1.

SOCIETY: CREATE AN ENABLING ENVIRONMENT FOR WOMEN TO BEGIN AND CONTINUE IN MCH AND HIV CARE

Do Programs Designed to Reduce Disrespect and Abuse in Maternity Care, HIV-Related Stigma and Discrimination, IPV, and Increase Supportive Involvement of Male Partners Improve Maternal Health Outcomes?

Gender discrimination and HIV-related stigma violate human rights and contribute to poor health outcomes, in part by creating barriers to women's utilization of essential maternity and HIV services. Anticipation or experience of disrespect and abuse in maternity care and HIV-related stigma and discrimination, including internalized stigma, have been associated with avoidance of skilled delivery, refusal of antenatal HIV testing, and for WLWH, not enrolling in HIV services, and reduced adherence to ART for prevention of vertical HIV transmission.64–66 One of the most egregious forms of gender discrimination, Intimate Partner Violence (IPV), is associated with increased likelihood of acquiring and living with HIV66–68 and with poor reproductive health outcomes among all women.69–72 Qualitative research indicates that experiencing IPV can be a barrier to accessing HIV care and ART adherence for women in Africa.73 Studies from the United States and Canada associate IPV with reduced ART adherence, detectable viral load, and less engagement in HIV care.74–76 There is an urgent need to evaluate if facility- and community-based interventions that reduce disrespect and abuse during childbirth, HIV-related stigma, and IPV result in improved uptake and retention in care and better maternal health outcomes.64,77–81 Interventions, such as IMAGE and Stepping Stones, are particularly promising as they have been shown to simultaneously reduce IPV and HIV-related stigma and increase measures of women's empowerment,80,81 indicating the potential to address multiple social determinants simultaneously.

Research and evaluation of male involvement in HIV and MCH care is a related priority. When men attend prenatal care visits with their female partners and choose to test for HIV or women disclose their HIV status to male partners during pregnancy, male involvement has been associated with improved implementation of interventions to prevent vertical HIV transmission.82–84 Similarly, when women choose to disclose their HIV status, family-centered care has successfully engaged men and supported women to remain in care.85 However, how best to involve men systematically is a knowledge gap. For example, while some models of promoting couple counseling and HIV testing during pregnancy show promise for engaging men and assisting women with safe disclosure,86 others have resulted in half of the pregnant women asked to bring their male partner not returning for antenatal care.87 Research is needed to develop and evaluate programs that involve male partners while safeguarding women's access to and retention in care, safety, and autonomy.

In addition, policymakers and programmers should seriously consider the evidence associating participatory women's groups with reduced maternal mortality,88 and showing that community mobilization and peer support increase supply of, demand for, and implementation of interventions to prevent vertical HIV transmission, in addition to improving pregnant and postpartum WLWH's retention in care.15,89–91 Existing evidence indicates that further investment in and evaluation of strategies that actively involve and engage community members, including people living with HIV, is warranted.

Interventions designed to create an enabling environment for women to begin and remain in care and treatment should be sensitive to the diversity of women's experiences and needs, including those of women who may face additional barriers because of age, civil status, ethnicity, drug use, involvement in sex work, or other factors. Evaluation should consider proximate measures, such as uptake of services, retention in care, disclosure of HIV status, postpartum depression, and adherence to ART, as well as maternal health outcomes.

CONCLUSIONS

Research and evaluation to guide clinical and programmatic practice are urgently needed to make significant progress towards reducing HIV-related maternal deaths and eliminating preventable maternal mortality in sub-Saharan Africa. Research priorities include evaluating the impact of scaled-up access to ART on maternal health outcomes and improving clinical protocols to prevent and treat the leading causes of maternal death among WLWH. To generate this information, causes of maternal death data must be improved, as must facility-based information on pregnancy-related outcomes including HIV status, ART use, and maternal morbidities. Additionally, improving the availability and accuracy of data from routine program monitoring that permits analysis of the outcomes of pregnant and postpartum WLWH is critical.

More evaluation of integrated models of care to understand how HIV testing, care, and treatment during antenatal, labor and delivery, and postpartum care can be better delivered is also important. A nuanced understanding of program models, including community support systems, which improve uptake and retention in care and their effects on maternal morbidity and mortality, is needed. Critical to this understanding is implementation research on how to incorporate screening and treatment for tuberculosis and malaria, preconception counseling, and contraception without sacrificing coverage or quality of other core MCH and HIV services. Disease burden, causes of maternal deaths at the community and country level, and the national policy context need to be considered when identifying which interventions to prioritize. Successful delivery of integrated MCH and HIV services requires further health system strengthening, including implementation research to generate a better understanding of the optimal mix of skills, staffing, and supportive supervision.

There is an increasing body of compelling evidence about the social, structural, and psychosocial barriers WLWH face when deciding to seek and remain in MCH and HIV care. Less information is available about how to overcome these barriers. Reducing IPV, HIV-related stigma, and disrespect and abuse in maternity care, and engaging men hold promise for supporting women to access services and remain in care and should be evaluated for their effects on the maternal health of WLWH.

The expert consultation and literature review described here capture key priorities for research and evaluation to (1) improve identification of and response to leading causes of maternal death among WLWH and evaluate the effects of increasing availability of ART on maternal health outcomes, (2) enhance integrated models for delivery of critical health interventions to WLWH, and (3) identify interventions that contribute to an enabling environment for WLWH to begin and remain in care. Although we endeavored to be comprehensive by addressing different factors that influence maternal health outcomes (clinical care, models of health service delivery, and social context) and by including experts with a broad range of relevant disciplinary backgrounds and institutional affiliations, the scope of the expert consultation and literature review do not preclude the possibility that additional critical areas for research and evaluation have been omitted.

In conclusion, the availability, acceptability, and quality of maternal health care are life and death issues for pregnant women. The identified research and evaluation priorities focus on the maternal health of WLWH. However, improving the availability of data on maternal causes of death and evaluating how best to integrate service delivery to increase coverage of crucial services and creating an enabling environment for women to begin and remain in care are expected to contribute to the maternal health of all women. The Saving Mothers Giving Life project in Uganda and Zambia indicates how rapidly progress can be made on reducing maternal mortality when HIV is addressed as an integral component of maternal health and resources are pooled to strengthen existing MCH and HIV platforms to improve access to and quality of maternal health care.92

Research and evaluation on maternal health and HIV can increase collaboration on these 2 global priorities, strengthen political constituencies and communities of practice and accelerate progress toward achievement of goals in both areas. The investments made to reduce maternal mortality and increase access to HIV treatment in sub-Saharan Africa are significant. The scope of these investments should be reflected in support for research and evaluation that addresses priority knowledge gaps. As the global community evaluates progress and prepares for new maternal mortality and HIV targets, addressing the needs of WLWH must be a priority now and after 2015.

ACKNOWLEDGMENTS

Florence Anam, Lucy Gati and Jennifer Gatsi-Mallet provided comments on a draft manuscript.

The findings and conclusions in this article are those of the authors and do not necessarily represent the official positions of the United States Government, the CDC, Office of the Global AIDS Coordinator, USAID, the Canadian Institutes of Health Research, the Pierre Elliott Trudeau Foundation, or the Bill & Melinda Gates Foundation.

REFERENCES

1. UNAIDS. Report on the Global HIV/AIDS Epidemic 2013. Geneva, Switzerland: UNAIDS; 2013.
2. UNAIDS. Regional Fact Sheet 2012: Sub-Saharan Africa. Geneva, Switzerland: UNAIDS; 2012.
3. WHO. World Health Statistics 2013. Geneva, Switzerland: WHO; 2013.
4. WHO, UNICEF. Accountability for Maternal, Newborn and Child Survival: The 2013 Update. Geneva, Switzerland: WHO; 2013.
5. Calvert C, Ronsmans C. The contribution of HIV to pregnancy-related mortality: a systematic review and meta-analysis. AIDS. 2013;27:1631–1639.
6. Zaba B, Calvert C, Marston M, et al.. Effect of HIV infection on pregnancy-related mortality in sub-Saharan Africa: secondary analyses of pooled community-based data from the network for analysing longitudinal population-based HIV/AIDS data on Africa (ALPHA). Lancet. 2013;381:1763–1771.
7. Myer L. Maternal deaths and HIV treatment in sub-Saharan Africa. Lancet. 2013;381:1699–16700.
8. United Nations Commission on the Status of Women. Resolution 56/3 Eliminating Maternal Mortality and Morbidity Through the Empowerment of Women in Commission on the Status of Women, Report on the fifty-sixth session. New York, NY; United Nations, 2012;12–22. Available at: http://www.un.org/womenwatch/daw/csw/56sess.htm. Accessed September 19, 2014.
9. UNAIDS. Countdown to Zero: Global Plan Towards the Elimination of New HIV Infections Among Children by 2015 and Keeping Their Mothers Alive. Geneva, Switzerland: UNAIDS; 2011.
10. WHO, UNICEF, UNAIDS. Global Update on HIV Treatment 2013: Results, Impact and Opportunities. Geneva, Switzerland: World Health Organization; 2013.
11. WHO. Consolidated Guidelines on the Use of Antiretroviral Drugs for Treating and Preventing HIV Infection: Recommendations for a Public Health Approach. Kuala Lumpur, Malaysia: WHO; 2013.
12. Ferguson L, Grant AD, Watson-Jones D, et al.. Linking women who test HIV-positive in pregnancy-related services to long-term HIV care and treatment services: a systematic review. Trop Med Int Health. 2012;17:564–580.
13. Stinson K, Jennings K, Myer L. Integration of antiretroviral therapy services into antenatal care increases treatment initiation during pregnancy: a cohort study. PLoS One. 2013;8:e63328.
14. Clouse K, Pettifor A, Shearer K, et al.. Loss to follow-up before and after delivery among women testing HIV positive during pregnancy in Johannesburg, South Africa. Trop Med Int Health. 2013;18:451–460.
15. Tenthani L, Haas DW, Tweya H, et al.. Retention in care under universal antiretroviral therapy for HIV-infected pregnancy and breastfeeding women (“Option B+”) in Malawi. AIDS. 2014;28:589–598.
16. Nachega JB, Uthman OA, Anderson J, et al.. Adherence to antiretroviral therapy during and after pregnancy in low-income, middle-income, and high-income countries: a systematic review and meta-analysis. AIDS. 2012;26:2039–2052.
17. Uwimana J, Jackson D. Integration of tuberculosis and prevention of mother-to-child transmission of HIV programmes in South Africa. Int J Tuberc Lung Dis. 2013;17:1285–1290.
18. Hill J, Hoyt J, van Eijk AM, et al.. Factors affecting the delivery, access, and Use of interventions to prevent malaria in pregnancy in sub-Saharan Africa: a systematic review and meta analysis. PLoS Med. 2013;10:e1001488.
19. Darroch JE, Singh S. Trends in contraceptive need and use in developing countries in 2003, 2008, and 2012: an analysis of national surveys. Lancet. 2013;381:1756–1762.
20. Brentlinger PE, Behrens CB, Micek MA. Challenges in the concurrent management of malaria and HIV in pregnancy in sub-Saharan Africa. Lancet Infect Dis. 2006;6:100–111.
21. Mathad JS, Gupta A. Tuberculosis in pregnant and postpartum women: epidemiology, management, and research gaps. Clin Infect Dis. 2012;55:1532–1549.
22. Zenner D, Kruijshaar ME, Andrews N, et al.. Risk of tuberculosis in pregnancy: a national, primary care-based cohort and self-controlled case series study. Am J Respir Crit Care Med. 2012;185:779–784.
23. Ticconi C, Mapfumo M, Dorrucci M, et al.. Effect of maternal HIV and malaria infection on pregnancy and perinatal outcome in Zimbabwe. J Acquir Immune Defic Syndr. 2003;34:289–294.
24. Khan M, Pillay T, Moodley JM, et al.. Maternal mortality associated with tuberculosis-HIV-1 co-infection in Durban, South Africa. AIDS. 2001;15:1857–1863.
25. Sarnquist CC, Rahangdale L, Maldonado Y. Reproductive health and family planning needs among HIV-infected women in sub-Saharan Africa. Curr HIV Res. 2013;11:160–168.
26. Cohen MS, Chen YQ, McCauley M, et al.. Prevention of HIV-1 infection with Early antiretroviral therapy. N Engl J Med. 2011;365:493–505.
27. Volmink J, Siegfried NL, van der Merwe L, et al.. Antiretrovirals for reducing the risk of mother-to-child transmission of HIV infection. Cochrane Database Syst Rev. 2007:CD003510.
28. Matthews LT, Crankshaw T, Giddy J, et al.. Reproductive decision-making and periconception practices among HIV-positive men and women attending HIV services in Durban, South Africa. AIDS Behav. 2013;17:461–470.
29. Bekker L-G, Black V, Myer L, et al.. Guideline on safer conception in fertile HIV-infected individuals and couples. South Afr J HIV Med. 2011;12:31–44.
30. Kendall T, Danel I. Research and Evaluation Agenda for HIV and Maternal Health in Sub-Saharan Africa. Women and Health Initiative Working Paper No. 1. Boston, MA: Women and Health Initiative, Harvard School of Public Health; 2014. Available at: www.mhtf.org.
31. WHO. The WHO Application of ICD-10 to Deaths During Pregnancy, Childbirth and Puerperium: ICD MM: WHO; 2012. Accessed August 1, 2014.
32. WHO. Maternal Death Surveillance and Response: Technical Guidance Information for Action to Prevent Maternal Death. Geneva, Switzerland: WHO; 2013. Available at: www.who.int. Accessed August 1, 2014.
33. National Committee for Confidential Enquiries into Maternal Deaths. Ninth interim report on the confidential enquiries into maternal deaths in South Africa. Pretoria, South Africa: Department of Health; 2013.
34. Liotta G, Mancinelli S, Nielsen-Saines K, et al.. Reduction of maternal mortality with highly active antiretroviral therapy in a large cohort of HIV-infected pregnant women in Malawi and Mozambique. PLoS One. 2013;8:e71653.
35. Moodley J, Pattinson RC. Saving Mothers 2008–2010: Fifth Report on the Confidential Enquiries into Maternal Deaths in South Africa. National Committee for Confidential Enquiry into Maternal Pretoria, South Africa: Department of Health; 2012.
36. Matthews LT, Kaida A, Kanters S, et al.. HIV-infected women on antiretroviral treatment have increased mortality during pregnant and postpartum periods. AIDS. 2013;27(suppl 1):S105–S112.
37. Kourtis AP, Bansil P, McPheeters M, et al.. Hospitalizations of pregnant HIV-infected women in the USA prior to and during the era of HAART, 1994–2003. AIDS. 2006;20:1823–1831.
38. Moran NF, Moodley J. The effect of HIV infection on maternal health and mortality. Int J Gynaecol Obstet. 2012;119:S26–S29.
39. Onakewhor JU, Olagbuji BN, Ande AB, et al.. HIV-AIDS related maternal mortality in Benin City, Nigeria. Ghana Med J. 2011;46:54–59.
40. Menendez C, Romagosa C, Ismail MR, et al.. An autopsy study of maternal mortality in Mozambique: the contribution of infectious diseases. PLos Med. 2008;5:220–226.
41. Belperio PS, Rhew DC. Prevalence and outcomes of anemia in individuals with human immunodeficiency virus: a systematic review of the literature. Am J Med. 2004;116(suppl 7A):27–43.
42. Mehta S, Manji KP, Young AM, et al.. Nutritional indicators of adverse pregnancy outcomes and mother-to-child transmission of HIV among HIV-infected women. Am J Clin Nutr. 2008;87:1639–1649.
43. Finkelstein JL, Mehta S, Duggan CP, et al.. Predictors of anaemia and iron deficiency in HIV-infected pregnant women in Tanzania: a potential role for vitamin D and parasitic infections. Public Health Nutr. 2012;15:928–937.
44. Calvert C, Ronsmans C. HIV and the risk of direct obstetric complications: a systematic review and meta-analysis. PLoS One. 2013;8:e74848.
45. Kalumba VM, Moodley J, Naidoo TD. Is the prevalence of pre-eclampsia affected by HIV/AIDS? A retrospective case-control study. Cardiovasc J Afr. 2013;24:24–27.
46. Suy A, Martinez E, Coll O, et al.. Increased risk of pre-eclampsia and fetal death in HIV-infected pregnant women receiving highly active antiretroviral therapy. AIDS. 2006;20:59–66.
47. Chen JY, Ribaudo HJ, Souda S, et al.. Highly active antiretroviral therapy and adverse birth outcomes among HIV-infected women in Botswana. J Infect Dis. 2012;206:1695–1705.
48. Powis KM, McElrath TF, Hughes MD, et al.. High viral load and elevated angiogenic markers associated with increased risk of preeclampsia among women initiating highly active antiretroviral therapy in pregnancy in the Mma Bana Study, Botswana. J Acquir Immune Defic Syndr. 2013;62:517–524.
49. Curtis M, El Ayadi A, MKumba G, et al.. Association between severe obstetric hemorrhage and HIV status. Int J Gynaecol Obstet. 2014;125:79–80.
50. Sebitloane TH. HIV and postpartum morbidity/mortality. Paper presented at: Maternal Health, HIV and AIDS: Examining Research Through a Programmatic Lens; 10th June 2013; Boston, MA.
51. Aboud S, Msamanga G, Read JS, et al.. Effect of prenatal and perinatal antibiotics on maternal health in Malawi, Tanzania, and Zambia. Int J Gynaecol Obstet. 2009;107:202–207.
52. Sebitloane HM, Moodley J, Esterhuizen TM. Prophylactic antibiotics for the prevention of postpartum infectious morbidity in women infected with human immunodeficiency virus: a randomized controlled trial. Am J Obstet Gynecol. 2008;18:e181–e186.
53. Wynberg E, Cooke G, Schroufi A, et al.. Impact of point-of-care CD4 testing on linkage to HIV care: a systematic review. J Int AIDS Soc. 2014;17:18809.
54. Chimbwandira F, Mhango E, Makobe S, et al.. Impact of an innovative approach to prevent mother-to-child transmission of HIV, Malawi, July 2011–September 2012. MMWR Morb Mortal Wkly Rep. 2013;62:148–151.
55. Suthar AB, Hoos D, Beqiri A, et al.. Integrating antiretroviral therapy into antenatal care and maternal and child health settings: a systematic review and meta-analysis. Bull World Health Organ. 2013;91:46–56.
56. Tudor Car L, Van Velthoven MH, Brusamento S, et al.. Integrating prevention of mother-to-child HIV transmission programs to improve uptake: a systematic review. PLoS One. 2012;7:e35268.
57. Nutman S, McKee D, Khoshnood K. Externalities of prevention of mother-to-child transmission programs: a systematic review. AIDS Behav. 2013;17:445–460.
58. Lindegren ML, Kennedy CE, Bain-Brickley D, et al.. Integration of HIV/AIDS services with maternal, neonatal and child health, nutrition, and family planning services. Cochrane Database Syst Rev. 2012;9:CD010119.
59. Ngure K, Heffron R, Mugo N, et al.. Successful increase in contraceptive uptake among Kenyan HIV-1-serodiscordant couples enrolled in an HIV-1 prevention trial. AIDS. 2009;23:S89–S95.
60. Grossman D, Onono M, Newmann SJ, et al.. Integration of family planning services into HIV care and treatment in Kenya: a cluster-randomized trial AIDS. 2013;27(suppl 1):S77–S85.
61. McNairy M, Melaku Z, Barker P, et al.. Leveraging progress in prevention of mother-to-child transmission of HIV for improved maternal, neonatal, and child health services. J Acquir Immune Defic Syndr. 2011;57(suppl 2):S83–S86.
62. O'Reilly KR, Kennedy CE, Fonner VA, et al.. Family planning counseling for women living with HIV: a systematic review of the evidence of effectiveness on contraceptive uptake and pregnancy incidence, 1990 to 2011. BMC Public Health. 2013;13:935.
63. Goodson JL, Finkbeiner T, Davis NL, et al.. Evaluation of using routine infant immunization visits to identify and follow-up HIV exposed infants and their mothers in Tanzania. J Acquir Immune Defic Syndr. 2013;57:E77–E84.
64. Bowser D, Hill K. Exploring Evidence for Disrespect and Abuse in Facility-based Childbirth: Report of a Landscape Analysis. USAID-TRAction Project and Harvard School of Public Health University Research Co., LLC; 2010. Available at www.traction.org. Accessed August 1, 2014.
65. Turan JM, Nyblade L. HIV-related stigma as a barrier to achievement of global PMTCT and maternal health goals: a review of the evidence. AIDS Behav. 2013;17:2528–2529.
66. Jewkes RK, Dunkle K, Mduna M, et al.. Intimate partner violence, relationship power inequity, and incidence of HIV infection in young women in South Africa: a cohort study. Lancet. 2010;376:41–48.
67. Shamu S, Abrahams N, Temmerman M, et al.. A systematic review of African studies on intimate partner violence against pregnant women: prevalence and risk factors. PLoS One. 2011;6:e17591.
68. Kouyoumdjian FG, Calzavara LM, Bondy SJ, et al.. Intimate partner violence is associated with incident HIV infection in women in Uganda. AIDS. 2013;27:1331–1338.
69. Pallitto CC, Garcia-Moreno C, Jansen HA, et al.. Intimate partner violence, abortion, and unintended pregnancy: results from the WHO Multi-country Study on Women's Health and Domestic Violence. Int J Gynaecol Obstet. 2013;120:3–9.
70. Stockl H, Filippi V, Watts C, et al.. Induced abortion, pregnancy loss and intimate partner violence in Tanzania: a population based study. BMC Pregnancy Childbirth. 2012;12:12.
71. Goo L, Harlow SD. Intimate partner violence affects skilled attendance at most recent delivery among women in Kenya. Matern Child Health J. 2012;16:1131–1137.
72. Andersson N, Omer K, Caldwell D, et al.. Male responsibility and maternal morbidity: a cross-sectional study in two Nigerian states. BMC Health Serv Res. 2011;11(suppl 2):S7.
73. Kouyoumdjian FG, Findlay N, Schwandt M, et al.. A systematic review of the relationships between intimate partner violence and HIV/AIDS. PLoS One. 2013;8:e81044.
74. Trimble DD, Nava A, McFarlane J. Intimate partner violence and antiretroviral adherence among women receiving care in an urban southeastern Texas HIV clinic. J Assoc Nurses AIDS Care. 2013;24:331–340.
75. Lopez EJ, Jones DL, Villar-Loubet OM, et al.. Violence, coping, and consistent medication adherence in HIV-positive couples. AIDS Educ Prev. 2010;22:61–68.
76. Siemieniuk RAC, Krentz HB, Miller P, et al.. The clinical implications of high rates of intimate partner violence against HIV-positive women. J Acquir Immune Defic Syndr. 2013;64:32–38.
77. Stangl A, Lloyd JK, Brady LM, et al.. A systematic review of interventions to reduce HIV-related stigma and discrimination from 2002 to 2013: how far have we come? J Int AIDS Soc. 2013;16(suppl 2):18734.
78. Ratcliffe H. Creating an Evidence Base for the Promotion of Respectful Maternity Care. Boston, MA: Harvard School of Public Health; 2013.
79. Pronyk PM, Hargreaves JR, Kim JC, et al.. Effect of a structural intervention for the prevention of intimate-partner violence and HIV in rural South Africa: a cluster randomised trial. Lancet. 2006;368:1973–1983.
80. Kim JC, Watts CH, Hargreaves JR, et al.. Understanding the impact of a microfinance-based intervention on women's empowerment and the reduction of intimate partner violence in South Africa. Am J Public Health. 2007;97:1794–1802.
81. Skevington SM, Sovetkina EC, Gillison FB. A systematic review to quantitatively evaluate “Stepping Stones”: a participatory community-based HIV/AIDS prevention intervention. AIDS Behav. 2013;17:1025–1039.
82. Farquhar C, Kiarie JN, Richardson BA, et al.. Antenatal couple counseling increases uptake of interventions to prevent HIV-1 transmission. J Acquir Immune Defic Syndr. 2004;37:1620–1626.
83. Peltzer K, Mlambo M, Phaswana-Mafuya N, et al.. Determinants of adherence to a single-dose nevirapine regimen for the prevention of mother-to-child HIV transmission in Gert Sibande district in South Africa. Acta Paediatr. 2010;99:699–704.
84. Kalembo FW, Zgambo M, Mulaga AN, et al.. Association between male partner involvement and the uptake of prevention of mother-to-child transmission of HIV (PMTCT) interventions in Mwanza District, Malawi: a retrospective cohort study. PLoS One. 2013;8:e66517.
85. Tonwe-Gold B, Ekouevi DK, Bosse CA, et al.. Implementing family-focused HIV care and treatment: the first 2 years' experience of the mother-to-child transmission -plus program in Abidjan, Cote d'Ivoire. Trop Med Int Health. 2009;14:204–212.
86. Osoti AO, John-Stewart G, Kiarie J, et al.. Home visits during pregnancy enhance male partner HIV counselling and testing in Kenya: a randomized clinical trial. AIDS. 2014;28:95–103.
87. Becker S, Mlay R, Schwandt HM, et al.. Comparing couples' and individual voluntary counseling and testing for HIV at antenatal clinics in Tanzania: a randomized trial. AIDS Behav. 2010;14:558–566.
88. Prost A, Colbourn T, Seward N, et al.. Women's groups practising participatory learning and action to improve maternal and newborn health in low-resource settings: a systematic review and meta-analysis. Lancet. 2013;381:1736–1746.
89. Ackerman Gulaid L, Kiragu K. Lessons learnt from promising practices in community engagement for the elimination of new HIV infections in children by 2015 and keeping their mothers alive: summary of a desk review. J Int AIDS Soc. 2012;15(suppl 2):17390.
90. Teasdale CA, Besser MJ. Enhancing PMTCT programmes through psychosocial support and empowerment of women: the Mothers2Mothers model of care. South Afr J HIV Med. 2008;9:60–64.
91. Richter L, Rotheram-Borus MJ, Van Heerden A, et al.. Pregnant women living with HIV (WLH) supported at clinics by peer WLH: a cluster randomized controlled trial. AIDS Behav. 2014;18:706–715.
92. CDC. Saving Mothers, Giving Life Monitoring and Evaluation Report: Executive Summary. Atlanta, GA: Centers for Disease Control and Prevention, US Department of Health and Human Services; 2014.
Keywords:

HIV; maternal health; maternal mortality; research priorities; women's health; pregnancy

© 2014 by Lippincott Williams & Wilkins