In 2009, UNAIDS, the Joint United Nations Programme on HIV/AIDS, made a global call for the elimination of mother-to-child transmission of HIV (eMTCT) by 2015, and there is great impetus to achieve the target as the deadline approaches [1–3]. Coupled with this was a call for a 50% reduction in HIV-related maternal mortality [1]. Elimination is defined as a 90% reduction in the number of new paediatric HIV infections, or a MTCT rate below 5% [1]. Great strides have been made in the field of prevention of mother-to-child transmission (PMTCT), both globally and in South Africa [3]. Rates of HIV transmission to children have decreased substantially – among the 21 Global Plan priority countries in sub-Saharan Africa, including South Africa, MTCT rates have decreased by around a half or more since 2009 [3]. This decrease is largely attributable to the availability of efficacious antiretroviral regimens at high coverage [3]. However, success of PMTCT initiatives depends on more than the availability of antiretrovirals. The World Health Organization’s (WHO’s) comprehensive strategic approach for PMTCT also includes primary prevention of HIV infection; prevention of unintended pregnancies in HIV-infected women; and a family-centred approach to HIV care [4]. There is also a need to integrate PMTCT into routine maternal, neonatal, child and women’s health services [5]. Several studies have demonstrated the benefits of integration of services, in both the delivery and utilisation of services [5].

Patient and health system factors are critical in determining success of PMTCT programmes and attainment of eMTCT goals [6–9]. While there are effective biomedical interventions for HIV and pregnancy prevention, patients need timely access to care and then to utilise the interventions appropriately. Women who are already pregnant need to access healthcare early and if identified as HIV-infected, be initiated on antiretrovirals timeously and also adhere to therapy during the ante- and postpartum periods. While it is well-recognised that the highest risk of MTCT is among women with undiagnosed and/or untreated HIV infection, and also in known HIV-infected women who either do not start or delay treatment, there are still health system factors that fail to address these [10–13]. Also, antenatal and HIV services remain largely segregated, and there is still failure to prioritise pregnant women for initiation of antiretroviral therapy (ART) [12, 13]. Pregnant women may not access antenatal care early; may decline ART; or fail to adhere to antiretroviral regimens. This study thus focused on, and identified key patient-centred risks for MTCT in a high HIV prevalence setting in Johannesburg, South Africa.

This study identified several patient groups at high risk of MTCT. These were patients with unknown HIV status prior to conception; those with unplanned pregnancies; accessing antenatal care after 20 weeks gestation; and having less than 12 years of formal education. Slightly more mothers of HIV-infected infants elected to breastfeed – 11.7% compared to 4.6% of mothers with –uninfected infants, but this difference was not significant. While causality may not be definitively ascertained from this study, the findings highlight several important risk factors that must be targeted for eMTCT; availability of antiretrovirals alone is not enough.

Of women with HIV-infected infants, only 13.0% knew that they were HIV-infected prior to conception. The lowest risk of MTCT is with preconception ART and the duration of ART is directly related to MTCT risk [14, 15]. HIV-infected women who initiate ART prior to pregnancy are more likely to be virally suppressed at the time of delivery – the most important determinant of MTCT. Even if ART is not initiated prior to pregnancy, there is an increased likelihood of women with known HIV status accessing PMTCT care [16]. For those women who initiate ART during pregnancy, earlier initiation of treatment is associated with a decreased risk of MTCT, and each additional week of treatment confers a cumulative reduction in risk [15, 17, 18].

If we are to eliminate MTCT, there needs to be routine HIV testing for all women and men of reproductive age, and ART initiation for those found to be HIV-infected and eligible for treatment. South Africa implemented large population-based HIV-testing campaigns in recent years, but it is uncertain if these have impacted on PMTCT and linkage to care. However, recent unpublished programmatic data from the Soweto PMTCT programme, where this study was conducted, shows an increasing proportion of pregnant women presenting with an already known HIV status, and an increasing number already on treatment. As HIV testing and treatment programmes expand and become functional, more women will know their HIV status preconception. They will however still need to present for antenatal care timeously for early initiation and continuation of appropriate PMTCT interventions. Healthcare services need to be able to manage the increased demand for both HIV testing and initiation of ART in those found to be eligible.

One area that is under-researched, but increasingly shown to be important in the success of PMTCT interventions, is male partner involvement [19–21]. Encouraging male partners to be involved in antenatal care, including routine HIV testing for themselves, has been shown to increase the likelihood of HIV-infected pregnant women accessing and adhering to treatment [19, 20]. More importantly, it has been linked with a decreased risk of MTCT, and increased HIV-free survival in HIV-uninfected infants [21]. In our study, less than half of the women with infected infants knew their partners’ HIV status, and of the known, the majority were HIV-infected; the proportions were marginally better for women with HIV-uninfected infants, but still suboptimal. There are several barriers to male partner involvement in PMTCT programmes, and more broadly in sexual and reproductive health services. Some of the most pertinent barriers identified include the cultural perception, and often societal norm, that men do not participate in reproductive health services and that the facilities where these are offered are not male-friendly [22]. Various strategies have been utilised to encourage more male partner participation, and amongst them, healthcare provider-driven initiatives to invite men to be part of reproductive and PMTCT programmes, and community-based strategies which include male peer support groups and community campaigns [22, 23].

Rates of unplanned pregnancies were high, especially amongst women who had infected infants – 83.1% of the pregnancies were unplanned. Family planning, and consequently prevention of unintended pregnancies, has long been the most underutilised PMTCT intervention, with only modest progress to date [24]. In addition to decreased risk of MTCT, planned pregnancies are also associated with better obstetric outcomes, with decreased maternal morbidity and mortality [24]. There remains a high unmet need for contraception among HIV-infected women, and even in those who have access to reproductive health services, rates of unplanned pregnancies remain high [25, 26]. Integration of reproductive health and PMTCT is one of the suggested strategies for improving the reproductive health outcomes of HIV-infected women [27]. There is however a need for stronger programmatic efforts and implementation research for integration to work [27].

Timing of antenatal care influences diagnosis and appropriate management of maternal HIV infection. In our study, accessing antenatal care beyond 20 weeks gestation was associated with an increased MTCT risk. This is consistent with findings from other studies where late presentation for antenatal care delayed initiation of appropriate PMTCT interventions, increasing the risk of perinatal transmission [16, 17]. Lack of integration of antenatal and HIV services also contributes to the delay in HIV-infected women initiating treatment [28]. There are several reasons why pregnant women either do not access antenatal care, or delay doing so, and these include lack of access to care; poor knowledge about timing and need to present for care; and unavailability of services [29]. It is also important that once HIV-infected women access antenatal care, they remain in care. While adherence to ART has been shown to be higher prenatally than postpartum, there is still significant loss to follow-up in the PMTCT continuum of care, and patient and health system factors have been identified as contributing factors [16]. There is a need for targeted interventions, both prenatally and postpartum, to ensure that HIV-infected women remain in care.

While there is increased public knowledge of HIV infection, stigma remains a reality for many, especially women. In our study, there were women who knew that they were HIV-infected, but still did not access antenatal care due to fear of being stigmatised by either health workers or family. There’s a need to address stigma at all levels, as it has been shown to impact health-seeking behaviour and adherence to treatment [30]. Patient information on PMTCT interventions should be simplified and reinforced at every opportunity; understanding and adherence to treatment need not depend on level of education. A low level of formal education was one of the risk factors for MTCT identified. Inadequate knowledge of PMTCT interventions among health workers was also highlighted in a cross-sectional survey assessing quality of care within the same Soweto programme as this study [31].

Despite the challenges identified, the study provides several reassuring findings. Routine early infant diagnosis, and ART initiation in those found to be HIV-infected were timeous. At the time of the study, 94.8% of the HIV-infected infants had already been initiated on ART, and the mean age at ART initiation was 10.8 weeks.

While this study makes an important contribution to our knowledge of the requirements for an effective PMTCT programme, and highlights the importance of patient factors as we work towards elimination of MTCT, there are limitations. Causality cannot be inferred between the negative patient factors identified and risk of MTCT. There was also a lag period between the interviews of cases and that of controls, and this could have contributed to recall bias amongst the controls as they were interviewed at a much later period post-delivery. The sample of controls might also not have been representative as there was a high percentage that could not be reached, and some of the infants might have died during the lag period as it is a recognised fact that despite being uninfected, the morbidity and mortality rate in HIV-exposed infants remains significant. We also relied on self-reported information, but this was found to be reliable when compared to hospital records.

Despite the limitations, the study provides important insights as we work towards eMTCT. As much as availability and implementation of efficacious PMTCT interventions are key in preventing HIV infection in children, individual patient factors are also important and need to be targeted. Undiagnosed maternal HIV infection prior to conception, unplanned pregnancies, delays in accessing antenatal care, and low levels of education were the most significant patient risk factors associated with MTCT in our study. The focus in resource-constrained settings has largely been on establishing functioning systems to facilitate implementation of efficacious PMTCT interventions, and great strides have been made in this regard, including in South Africa [24, 32]. While continued strengthening of health systems is crucial, our study highlights the considerable importance of individual patient factors for further reducing paediatric HIV infections. There is a need for further research on why rates of unplanned pregnancies, and consequently considerable delays in accessing antenatal care, remain high. Also, why the rates of preconception HIV testing remain low in resource-constrained settings, despite the availability of interventions to address these factors.