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South Africa has a national antenatal HIV prevalence of 30.2% (Republic of South Africa Department of Health 2010a) and more people living with HIV than any other country in the world (UNAIDS 2010). In an ongoing effort to improve care for pregnant women with HIV and to prevent mother-to-child transmission (PMTCT), South Africa's 2010 HIV treatment guidelines called for lifelong ART to be initiated for all pregnant women with a CD4 value ≤350 cells/μl (Republic of South Africa Department of Health 2010b) and PMTCT guidelines mandated AZT prophylaxis from 14 weeks of pregnancy (Republic of South Africa Department of Health 2010c). However, implementation of these guidelines remains inadequate, with pregnant women in South Africa commonly presenting for their first ANC visit well into their second trimester or later, delaying HIV diagnosis, AZT prophylaxis and lifelong ART initiation (Black et al. 2008; Hoffman et al. 2010; Stinson et al. 2010).
In addition to late presentation for ANC services, some studies suggest that pregnant women have poorer retention in HIV care than men and non-pregnant women (Kaplan et al. 2008; Wang et al. 2011). Retention in HIV care is paramount, as HIV-positive patients require routine management and daily adherence to ART once initiated (Republic of South Africa Department of Health 2010d); mortality is high among patients who drop out of ART programmes (Brinkhof et al. 2009; Fox et al. 2010), and HIV/AIDS contributes to nearly half (43.7%) of maternal deaths in South Africa, far overshadowing deaths due to other obstetric complications such as haemorrhage or sepsis (National Committee on Confidential Enquiries into Maternal Deaths 2008). An analysis of nearly 30 000 women initiating antiretroviral therapy (ART) in South Africa found loss was 54% higher in pregnant than in non-pregnant women (aHR 1.54; 95% CI 1.38–1.72), despite lower mortality (Myer et al. 2012a). The reasons for these differences are still being identified and may include lower rates of immunosuppression and a lack of perception of need for treatment (Wang et al. 2011; Solarin & Black 2012), heavier financial burden (Wang et al. 2011), travel or relocation during pregnancy (Hoffman et al. 2010; Wang et al. 2011; Ferguson et al. 2012a) and stigma (Thorsen et al. 2008; Hoffman et al. 2010; Ferguson et al. 2012b). In South Africa, antenatal coverage is widespread and nearly all births occur in healthcare facilities (Shisana et al. 2009), but there is still great difficulty in ensuring an unbroken continuum of HIV care between antenatal care at a primary health clinic (PHC), labour and delivery at a hospital and between post-natal care and ongoing HIV care returning at the PHC.
To date, investigations of retention in HIV care among pregnant women have provided an estimate of loss to follow-up between specific milestones, such as HIV testing to ART initiation (Kaplan et al. 2008; Stinson et al. 2010; Ferguson et al. 2012a) or ART initiation to between 6 months and 3 years on treatment (Kaplan et al. 2008; Wang et al. 2011; Myer et al. 2012a), without evaluating the impact of delivery on loss. While studies from the United States demonstrate that ART adherence often declines in the post-partum period compared to during pregnancy (Turner et al. 2000; Ickovics et al. 2002; Tedaldi et al. 2002; Mellins et al. 2008), few studies have documented post-partum attendance in HIV care in sub-Saharan Africa in routine clinic settings (Nassali et al. 2009). We hypothesise that loss to follow-up may differ before and after delivery given that women's motivations for seeking care may change during these time periods. This analysis of data from a cohort of newly diagnosed HIV-positive pregnant women examines loss to follow-up through early stages of HIV care to better understand how loss to follow-up is influenced by delivery.
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Clinical and demographic characteristics at HIV testing of the 273 pregnant women are summarised in Table 1. The median (IQR) age at the first ANC visit was 27 years (24–31), and the median CD4 count at the time of HIV testing was 357 cells/μl (238–500). Overall, almost half of the cohort (44.7%) was born outside of South Africa, most notably in Zimbabwe (89.3% of those foreign born).
Table 1. Characteristics of the study participants (N = 273)
|Continuous variables, median (IQR)|
|Age at HIV testing||27 (24–31)|
|First CD4 value (cells/μl)||357 (238–500)|
|Weeks of gestation at first ANC visit||26 (21–30)|
|Categorical variables, n (%)|
|Age at HIV testing|
|18–24 years||78 (28.6%)|
|25–29 years||98 (35.9%)|
|30 years and older||97 (35.5%)|
|First CD4 value|
|<50 cells/μl||4 (1.5%)|
|50–199 cells/μl||48 (17.6%)|
|200–350 cells/μl||83 (30.4%)|
|>350 cells/μl||136 (49.8%)|
|Born in South Africa||143 (52.4%)|
|Born outside of South Africa||122 (44.7%)|
|Not employed||167 (61.2%)|
|Gestation at first ANC visit|
|≤20 weeks||59 (21.6%)|
|>20 weeks||214 (78.4%)|
The median (IQR) gestational age at first ANC visit was 26 weeks (21–30), and the median (IQR) time from HIV testing to delivery was 3.1 months (2.1–4.1). AZT monotherapy as part of PMTCT was almost universally implemented. During pregnancy, 98.0% received at least one 30-day supply of AZT, all but one of whom (99.7%) started AZT on the day of testing HIV positive.
Retention during antenatal care
Figure 1 shows retention of pregnant women through early HIV care, contingent on completing earlier stages. Roughly half of all women were ART eligible at the time of testing; median (IQR) CD4 at HIV testing was 244 cells/μl (171–299) among ART eligible and 500 cells/μl (420–599) among ART-ineligible women. Completing CD4 staging prior to delivery was high at 84.9% (95% CI: 80.2–88.8%) overall and varied little by ART eligibility (87.1% vs. 82.7%). Of those who were ART eligible and who completed CD4 staging prior to delivery (n = 115), most (80.9%; 95% CI: 72.9–87.3%) went on to initiate lifelong ART prior to delivery. These women spent a median (IQR) of 27 days (17–41.5) from HIV testing to ART initiation and a median (IQR) 9.5 weeks (5.1–14.2) on ART prior to delivery. Of the remaining 22 ART-eligible women who completed CD4 staging but did not initiate ART prior to delivery, most (n = 18, 81.8%) never returned for ART initiation, one returned but left before initiation, one required further counselling, one refused ART and one completed the initiation visit but was rescheduled to return for initiation a week later and did not return. Of all 139 ART-eligible women, 66.9% (95% CI: 58.8–74.3%) initiated treatment prior to delivery.
Retention after delivery
The proportion of patients returning for at least one visit after delivery was highest among those who were eligible for ART and initiated treatment prior to delivery (n = 90) at 76.7% (95% CI: 67.1–84.5%) with most of these women (82.8%; 95% CI: 72.1–90.6%) retained in ART care for at least 6 months. Although the numbers of women who completed CD4 staging and were eligible for but did not initiate ART were small (n = 22), only 31.8% (95% CI: 15.1–53.1%) returned at any point after delivery, and less than half of those who did (42.9%; 95% CI: 12.3–78.4%) initiated ART within 6 months of delivery. The picture was much different for those ineligible for ART at the time of testing positive. Among those ART ineligible who completed CD4 staging (n = 112), less than half (49.1%, 95% CI: 39.9–58.3%) returned for any visits after delivery. Of these 50 women, only half (52.0%, 95% CI: 38.2–65.5%) received a repeat CD4 count after delivery.
Cumulative retention in HIV care
Figure 2 shows cumulative retention for ART-eligible women from HIV testing through delivery and 6 months on ART as well as for ART-ineligible women through a post-delivery repeat CD4 count. Cumulatively, less than half (40.5%, 95% CI: 32.3–49.0%) of ART-eligible patients who tested HIV positive during pregnancy completed CD4 staging, initiated ART prior to delivery, returned after delivery and completed 6 months on ART. Cumulative retention was even lower among those ineligible for ART at the time of HIV testing: only 22.6% (95% CI: 15.9–30.6%) of patients ineligible for ART continued in care to the point of a repeat CD4 count after delivery.
Figure 2. Cumulative patient retention from HIV diagnosis through 6 months on ART for 131 HIV positive ANC patients eligible for ART and through repeat CD4 testing after delivery for 123 HIV-positive ANC patients ineligible for ART.
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The median (IQR) person-time contributed in the antenatal period was 2.8 months (1.7–3.9) and 4.5 months (1.5–6.0) in the post-natal period. Using time-to-event analysis and analysing all women regardless of ART eligibility at the time of testing, 20.5% (95% CI: 16.0–25.6%) of women were lost to follow-up prior to delivery. Among women in care at delivery, 47.9% (95% CI: 41.2–54.6%) were lost within 6 months after delivery, for a cumulative loss to follow-up of 57.5% (95% CI: 51.6–63.3%).
Table 2 presents the results of multivariate analysis of factors associated with loss within the antenatal and post-natal time periods. Presenting late for the first ANC visit (after 20 weeks of gestation) was associated with twice the likelihood of loss prior to delivery after adjusting for age, initial CD4 count and nationality (aHR 2.00; 95% CI 1.00, 4.02) but late presentation was not associated with loss during the post-natal period (aHR 1.09; 95% CI 0.65–1.83). ART ineligibility at the time of HIV testing based on a CD4 count >350 cells/μl was strongly associated with loss to follow-up following delivery (aHR 3.30; 95% CI: 1.95–5.58), while pregnant women aged 30 years and older were less likely to be lost after delivery (aHR 0.49; 95% CI: 0.30–0.81). Our results suggest that women born outside of South Africa may be more likely to be lost after delivery (aHR 1.36; 95% CI: 0.90–2.06) than women born in South Africa.
Table 2. Multivariate analysis of factors associated with loss to follow-up before and after delivery among 273 newly diagnosed HIV-positive antenatal patients
| ||Antenatal care period (n = 273)||Postnatal care period (n = 211)|
|n (%)a||Crude HR (95% CI)||Adjusted HR (95% CI)||n (%)a||Crude HR (95% CI)||Adjusted HR (95% CI)|
|Age at HIV testing|
|18–24 years||19 (24.4)||1.26 (0.66, 2.40)||1.25 (0.64, 2.42)||31 (54.4)||0.96 (0.61, 1.52)||0.91 (0.57, 1.43)|
|25–29 years||18 (18.4)||1||1||45 (57.7)||1||1|
|30 years and older||19 (19.6)||0.94 (0.54, 1.63)||1.08 (0.55, 2.11)||25 (32.9)||0.50 (0.31, 0.82)||0.49 (0.30, 0.81)|
|First CD4 value|
|<200 cells/mm3||10 (19.2)||1.12 (0.51, 2.47)||1.24 (0.56, 2.78)||16 (41.0)||1.71 (0.87, 3.36)||1.72 (0.87, 3.42)|
|200–350 cells/mm3||16 (19.5)||1||1||18 (27.3)||1||1|
|>350 cells/mm3||28 (20.4)||0.95 (0.51, 1.75)||1.03 (0.55, 1.94)||67 (63.2)||3.00 (1.78, 5.05)||3.30 (1.95, 5.58)|
|Born in South Africa||31 (21.7)||1||1||48 (44.9)||1||1|
|Born outside of South Africa||25 (20.5)||1.05 (0.62, 1.78)||0.99 (0.57, 1.72)||52 (54.2)||1.33 (0.90, 1.97)||1.36 (0.90, 2.06)|
|First ANC visit >20 weeks gestation|
|No||14 (23.7)||1||1||18 (40.9)||1||1|
|Yes||42 (19.6)||2.11 (1.07, 4.19)||2.00 (1.00, 4.02)||83 (49.7)||1.29 (0.77, 2.14)||1.09 (0.65, 1.83)|
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Pregnant women diagnosed with HIV during antenatal care require effective care interventions to ensure the prompt initiation of PMTCT and ART, but also must be linked to HIV care that is sustainable beyond the point of delivery. We found that overall loss to follow-up within 13 months of HIV testing among pregnant women recently diagnosed with HIV was staggeringly high at 57.5% (95% CI: 51.6–63.3%). Unlike studies that begin reporting loss to follow-up at ART initiation, our findings span the period from testing HIV positive through both the pre-ART and early post-ART periods, periods of high attrition. Patients who initiate ART have already successfully been retained through several visits and thus may be more inclined to continue in care. Few reports exist of retention of all patients – both ART eligible and ineligible. Our loss to follow-up proportion, which includes this early loss, is much higher than the 12%-32% among pregnant women after 6 months to 3 years on ART reported elsewhere, which only focuses on the on-treatment period (Kaplan et al. 2008; Wang et al. 2011; Myer et al. 2012a).
Our analysis also suggests that the focus on cumulative loss to follow-up among pregnant women is missing important trends over time with implications for when to intervene. Loss to follow-up prior to delivery was much lower than after delivery (20.5% vs. 47.9%). The antenatal period is a time of reasonable compliance with HIV care, likely because women are already attending care for another reason for which they have motivation to continue. Our results suggest that many women are not returning to the PHC after delivery. Among HIV-positive pregnant women, the challenge is ensuring HIV care extends beyond the period of pregnancy and continues for the lifetime of the mother. In South Africa, infants are to accompany their mothers to the first three post-natal care visits, so failure to attend these visits also suggests a failure to link infants to post-natal care, including PCR testing for HIV and immunisations.
In addition to a high rate of loss to follow-up, we also found that pregnant women presented for their first ANC visit and HIV testing well after the recommended gestational age of 14 weeks for AZT initiation. The median gestational age at HIV testing of 26 weeks in our study matched that found by Stinson et al. (2010) and represents delayed PMTCT efforts. Half of the pregnant patients in our cohort were ART eligible at their first ANC visit, yet despite the overall trend of late presentation, 66.9% (95% CI: 58.8–74.3%) of those eligible initiated ART prior to delivery. The median time from first visit to ART initiation of 27 days indicates that patients are being initiated promptly after the first visit, but as the median time on ART is 9.5 weeks, they are not presenting early enough to obtain maximal effectiveness of ART for PMTCT, which is reached around 13–15 weeks of duration prior to delivery (Patel et al. 2007; Chibwesha et al. 2011). The median duration on ART prior to delivery in our study is consistent with findings of 7.6–10.7 weeks in other studies in South Africa (Black et al. 2008; Fitzgerald et al. 2010; Hoffman et al. 2010; Stinson et al. 2010). Additionally, nearly one-third (31.1%, 95% CI 25.7–41.2%) of ART-eligible women should have initiated before delivery but did not. Recognition of the problem of late presentation to ANC care and its impact on delayed ART initiation, as well as poor linkage to care prior to ART, has spurred interest in rapid or same-day ART initiation among pregnant women using point-of-care CD4 testing (Myer et al. 2012b).
South African ANC patients receive a government-mandated ANC card at their first ANC visit and must present it at the hospital labour ward prior to delivery. There has been speculation that women only attend one ANC visit to get this card but do not return for additional care. Our data do not support this idea. Among pregnant women in our cohort, 15.1% failed to complete CD4 notification (i.e. attended only one clinic visit), which is half the proportion (30.2%) of non-pregnant adults who did not complete CD4 staging during this same period (Clouse et al. 2013). Our finding of sufficient linkage to care among pregnant women is consistent with that of Kranzer et al. (2010), who found CD4 completion was highest among antenatal care patients in Cape Town when compared to patients of other clinic services. This suggests that many women are making repeat visits while pregnant but many then stop after delivery.
In our study, women who presented late for their first ANC visit (>20 weeks of gestation) were twice as likely to be lost prior to delivery (aHR 2.00, 95% CI 1.00–4.02), underscoring the difficulty of retaining patients who are initially slow to seek care. Three South Africa-based studies identified fear of HIV testing/diagnosis, confusion over pregnancy status, transport limitations, lack of perceived benefit and clinic booking delays as common reasons for late presentation among ANC patients (Myer & Harrison 2003; Laher et al. 2012; Solarin & Black 2012), highlighting the multilevel barriers that can prevent timely access to and retention in care among pregnant women. Patients with higher CD4 counts (>350 cells/μl) who were ineligible for ART were more likely to be lost post-partum (aHR 3.30; 95% CI 1.95–5.58), emphasising the importance of retention during pre-ART care. South Africa's PMTCT guidelines call for repeat CD4 testing after delivery, but only 22.6% of ART-ineligible women received a repeat CD4 count. Witkoppen has a very high proportion of patients born outside of South Africa, as is now common in PHCs throughout Johannesburg (City of Johannesburg 2011; Faal et al. 2011). These patients may be at greater risk of loss to follow-up after delivery (aHR 1.36; 95% CI 0.90–2.06), likely because of frequent mobility among this group.
Our findings must be considered in the light of the study's limitations. First, we do not know why women ceased care at Witkoppen. Under half (45.2%) of the women who were lost received at least one follow-up phone call. We reviewed the files of 84 pregnant patients who were lost to follow-up whom the clinic had made at least one attempt to contact. Over half (52.3%) were unreachable because their cell phone was off or out of service, and 20.2% were found to have moved out of the area, usually outside Johannesburg's Gauteng Province. This may indicate that women return to rural homes (Hoffman et al. 2010; Wang et al. 2011; Ferguson et al. 2012a) – whether in South Africa or in a neighbouring country – either immediately prior to or after birth. While migration around delivery is typically short term, it disrupts the continuity of care, which likely impairs adherence to ART. Further research is needed to better understand pregnancy-associated migration and its impact on maternal and infant health.
Second, we do not know whether patients who drop out of care at Witkoppen continue in care at other facilities, perhaps in a rural facility or outside South Africa, except for those who request a formal transfer. While this is a limitation shared by most studies of loss to follow-up, it is important to note that loss to follow-up in this study reflects ceasing care at one clinic only, but one that was selected for study due to close integration of antenatal care, post-natal care and HIV services. We also cannot link to hospital data to confirm delivery nor do we have data on infant clinic visits or outcomes. More research is needed into ways to improve linkages across treatment sites and ways to improve patient movement between sites (e.g. providing sufficient supply of antiretrovirals).
Finally, our study data, which were collected retrospectively, were limited to those routinely collected in the patient files, but with very few missing data. Our findings regarding timing of first ANC visit and linkage to care among ANC patients are consistent with previously reported studies from other regions of South Africa (Kranzer et al. 2010; Stinson et al. 2010), suggesting that our results are generalisable to other clinics throughout South Africa.
Further research that examines pregnant women's reasons for dropping out of care, interventions to reduce ante- and post-natal attrition, and follow-up studies to confirm linkages to care among new mothers, is needed urgently. Case management interventions to improve linkages to HIV care have demonstrated success in the United States (Gardner et al. 2005; Craw et al. 2008), and research on implementation of this type of intervention in the southern African setting is warranted.
Our study highlights much room for improvement in the provision of HIV care of pregnant women. We found that pregnant women presented late for their first ANC visit, initiated ART too late to achieve maximal PMTCT effectiveness and had high rates of drop out around the time of delivery. Pregnant women likely have different motivation for attending healthcare services than non-pregnant adults and, likewise, have different reasons why they may become lost. Efforts must be increased to better understand the intentions of pregnant women for seeking healthcare after delivery, understanding their motivations for ceasing HIV care and improve linkages to care after delivery.