Patterns of engagement in HIV care during pregnancy and breastfeeding: findings from a cohort study in North-Eastern South Africa

In sub-Saharan Africa (SSA) mother-to-child transmission (MTCT) rates ranged from 1.9% in Botswana to 31.9% in Somalia in 2019 [1]. The risk of MTCT starts at conception and continues until breastfeeding cessation, which ranges from 18 to 24 months in SSA countries [2‐4]. Without intervention, MTCT risk is estimated at 5–10% during pregnancy, 10–15% during delivery, and 5–20% during breastfeeding, with the cumulative risk being 30–45% for infants who are breastfed for 18–24 months [5]. The adoption of Option B+ by most treatment programmes in SSA, including South Africa in 2015, has led to large reductions in MTCT rates [6, 7]. Option B+ has dramatically increased the number of pregnant women initiating ART, however retention is challenging, particularly in the postnatal period [8]. Reasons for disengagement include still feeling healthy, transition from PMTCT to adult ART services, stigma, and denial of HIV status [9‐12]. In 2019, the United Nations Children’s Emergency Fund (UNICEF) released their roadmap for the elimination of mother-to-child transmission of HIV (EMTCT) [13], which identified missed opportunities for EMTCT including failure to prevent seroconversion during pregnancy or breastfeeding, mothers living with HIV (MLHIV) who do not receive antiretroviral therapy (ART), MLHIV who previously started ART and stopped, and MLHIV who started ART late in their pregnancy.

An increase in the proportion of people initiating ART shortly after being diagnosed with HIV, as per World Health Organisation (WHO) guidance [14], has in turn led to an increased spectrum of engagement in care patterns, with treatment interruption, reengagement in care and clinic transfers becoming increasingly prevalent [15‐18]. Previous studies have used cohort and cross-sectional data to focus on the occurrence of specific events along the care cascade including linkage to care, ART initiation, and ART discontinuation [7, 19, 20]. However, these snapshots do not always capture the complexity of individual care trajectories. Monitoring these trajectories and understanding the factors that underlie patterns of disengagement and reengagement in care is becoming increasingly important to inform interventions to accelerate progress towards the second and third targets of the UNAIDS 95–95-95 goals and to reduce MTCT [21].

To inform interventions to address missed opportunities for EMTCT, we investigated HIV testing and engagement in care for pregnant and breastfeeding women in north-eastern South Africa. Using linked demographic surveillance and health facility data, we report on HIV testing events, identify periods of ART engagement and discontinuation during the pregnancy and postpartum periods for women living with HIV (WLHIV), and investigate factors associated with ART resumption during the MTCT risk period.

Using linked demographic surveillance and health facility data, we investigated patterns of HIV testing and engagement in care for pregnant and breastfeeding women. Our findings showed a reduction in the number of women testing positive each year during the MTCT risk period. We also identified four patterns of engagement in care during the MTCT risk period representing varying times of seroconversion and different levels of care stability following ART initiation, with women’s age, marital status, baseline CD4 and the year of delivery predicting these patterns. We also found that following discontinuation of HIV care, ART resumption was more likely for women who had a new pregnancy.

An estimated 15% of pregnancies resulting in a live birth recorded in the Agincourt HDSS were to women who had utilised HIV-related healthcare. Of the pregnancies linked to HIV-related healthcare utilisation, 51% were to previously diagnosed women and 49% had no previous HIV-related healthcare data and were presumed to be new diagnoses. Although some of the women who were previously diagnosed had disengaged from care, encouragingly most resumed treatment over the study period.

Reengagement in care is becoming a more common phenomenon as more healthy patients initiate ART [15]. Our finding that a new pregnancy was associated with an increased probability of resumption was probably due to increased interaction with the health system, as well as a desire to protect their baby. Whilst about half of these women resumed ART before delivery, research shows that ART initiation early in the pregnancy is most effective at reducing MTCT risk [14, 39]. Furthermore, whilst ART resumption is a positive outcome, it represents a programmatic failure of Option B+ which aims to keep women on ART for life and extend protection throughout subsequent pregnancies. Treatment interruptions may also contribute to drug resistance [40, 41]. We found that 66.1% of WLHIV who were LTFU when they became pregnant and 51.5% of WLHIV but not on ART when they became pregnant were still not on treatment by delivery, indicating that ART programmes still have much work to do to initiate and keep less compliant patients on ART.

The cumulative probability of a new HIV diagnosis occurring during the MTCT risk period was estimated as 5.9% during pregnancy, increasing to 7.5% by the breastfeeding cessation. The proportion of women testing positive for HIV during pregnancy increased until 2016, reaching 7%, and then declined in 2017 to 5%. These are likely to be underestimates as some women might have attended private facilities or facilities outside the HDSS. Additionally, while UNAIDS estimated that 90.1% of pregnant women in South Africa were tested for HIV in 2019 [1], without a comprehensive HIV testing database where both negative and positive results are recorded, it is likely that not all seroconversions were captured. Nonetheless, the reduction in the number of women testing HIV positive in 2017 is encouraging. Option B+ and treat all were implemented as part of the paradigm shift towards using treatment as prevention. South Africa national guidelines moved to Option B+ in 2015 and to universal treatment in 2016 [6, 42], all of which have been widely adopted in the area covered by the Agincourt HDSS. Other countries have reported a surge in the volume of pregnant women testing positive and utilising PMTCT services as more women became eligible for ART following the implementation of Option B+ [43]. This was followed by a steady decline as more WLHIV became aware of their HIV status [44]. Our data suggests, there was a further reduction in 2018, however, further research and monitoring of this trend will be needed.

Over half of HIV-exposed pregnancies occurred to women who already knew their HIV status. There is a general recognition that the number of HIV-positive women having children who already know their HIV-status is increasing [44, 45], illustrating the importance of keeping women engaged in care and virally suppressed. Our finding that older age was associated with sustained retention on ART aligns with other studies [46‐49]. Later year of delivery was also found to be associated with early stable ART with the odds of late ART decreasing over time potentially showing the benefits of simplified treatment guidelines under Option B+. We found that married women were more likely to initiate ART late which other studies have reported citing the need for their partner’s support [50‐52]. As such, interventions that improve partner support such as couple testing or joint counselling are important to encourage early ART initiation for married women [10, 53, 54].

Teenage mothers were more likely to have a first positive test recorded postnatally which might suggest late seroconversion, late testing, or poorer health seeking behaviour, all of which have been reported as important factors among this age group in similar settings [55‐57]. Older women were more likely to have already seroconverted or to be on treatment at the beginning of their pregnancy which possibly reflects their longer time at risk for HIV. There were lower odds of postnatal seroconversion in later years, possibly indicating reduced incidence of HIV in the wider population.

This study has some limitations. Firstly, the health facilities used may not capture every sentinel event as a small proportion of HDSS residents receive ART through private facilities or public facilities outside the HDSS. Furthermore, we did not have treatment adherence data. The assumption that a patient was in care until their next scheduled visit might therefore misclassify some patients. During the linkage process a very small proportion of residents declined to be linked and we did not manage to link everyone that claimed to be an HDSS resident. These linkage errors might bias these results downwards. Finally, there are biases arising from using routinely collected data. If women testing positive did not self-report a previous diagnosis, we would have erroneously categorised them as newly diagnosed. Additionally, if a woman tested positive but did not report to the PMTCT clinic to start treatment then she would have been missed as this data would only be available in the testing registers which were not linked to HDSS data. Finally, data from 2018 does not include clinic data past July 2018 or pregnancy data past November 2018, as such HIV incidence reduction seen in our analysis in 2018 might be an effect of the data.

This study also has some strengths. To our knowledge, this is the first study to use linkage of population and clinical records to estimate HIV incidence in pregnant women in SSA. The method of linking routinely collected data to answer this question shows promise and should be considered in future research. The use of multiple data sources also means we were able to crosscheck matching data and had access to new pregnancies data and socioeconomic variables which are not always available in clinical data.

In conclusion, our study shows the importance of new pregnancies in encouraging treatment resumption for women previously LTFU. This coupled with the reduction in the number and proportion of pregnant and postpartum women testing HIV positive should be considered as successes of the Option B+ programme. Our study also shows the growing scale of reengagement in care. Treatment programmes will need interventions to keep pregnant women on ART after delivery and ensure that pregnant women previously in care are reengaged promptly for their own health and to protect their unborn infants.