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Objective To investigate highly active antiretroviral therapy (HAART) initiation among pregnant women and the optimum model of service delivery for integrating HAART services into antenatal care.
Methods We analysed clinic records to reconstruct a cohort of all HIV-infected pregnant women eligible for HAART at four antenatal clinics representing three service delivery models in Cape Town, South Africa. To assess HAART coverage, records of women determined to be eligible for HAART in pregnancy were reviewed at corresponding HIV treatment services.
Results Of 13 208 pregnant women tested for HIV, 26% were HIV-infected and 15% were HAART-eligible based on a CD4 cell count of ≤ 200 cells/μl. Among eligible women, 51% initiated HAART before delivery, 27% received another prevention of mother-to-child transmission (PMTCT) intervention and 22% did not receive any antiretroviral intervention before delivery. The proportions of women initiating HAART between the different service delivery models were comparable. The median gestational age at first presentation was 26 weeks, and early gestational age at first presentation was the strongest predictor of being on HAART by delivery. Of the women who did not initiate HAART in pregnancy, 24% started treatment within 2 years postpartum.
Conclusions In this setting with clear PMTCT and HAART protocols, services failed to prioritize and initiate a high proportion of eligible pregnant women on HAART. The initiation of HAART in pregnancy requires strengthened antenatal and HIV services that target women with advanced stage disease.
Initiation de la thérapie antirétrovirale hautement active chez les femmes enceintes à Cape Town en Afrique du Sud
Objectif: Investiguer l’initiation du HAART chez les femmes enceintes pour un modèle optimal des prestations des services intégrant les services HAART dans les soins prénataux.
Méthodes: Nous avons analysé les dossiers cliniques afin de reconstituer une cohorte de toutes les femmes enceintes infectées par le VIH admissibles au HAART dans quatre cliniques prénatales représentant trois modèles de prestation des services à Cape Town en Afrique du Sud. Afin d’évaluer la couverture HAART, les dossiers des femmes identifiées pour être admissibles au HAART pendant la grossesse ont été examinés dans des services correspondants de traitement du VIH.
Résultats: Sur 13.208 femmes enceintes testées pour le VIH, 26%étaient infectées et 15%étaient admissibles au HAART sur base d’un taux de CD4 ≤ 200 cellules/μl. Parmi les femmes admissibles, 51% ont débuté le HAART avant l’accouchement, 27% ont reçu une autre intervention de PTME et 22% n’ont reçu aucune intervention antirétrovirale avant l’accouchement. La proportion de femmes initiées au HAART entre les différents modèles de prestation de services, étaient comparables. L’âge gestationnel médian à la première présentation était de 26 semaines et l’âge gestationnel précoce à la première présentation était le meilleur prédicteur du fait de demeurer sous HAART à l’accouchement. Parmi les femmes qui n’ont pas entamé le HAART pendant la grossesse, 24% ont commencé un traitement post-partum dans les deux ans.
Conclusions: Dans cet endroit avec une PTME et des protocoles HAART bien définis, les services n’ont pas réussi comme prioritéà initier une proportion élevée de femmes enceintes admissibles au HAART. L’initiation au HAART pendant la grossesse nécessite un renforcement des services prénataux et du VIH qui ciblent les femmes atteintes du stade avancé de la maladie.
Iniciación de una terapia antirretroviral altamente activa entre mujeres embarazadas de Ciudad del Cabo, Sudáfrica
Objetivo: Investigar la iniciación de la terapia antirretroviral altamente activa (HAART) entre mujeres embarazadas, con el fin de buscar un modelo óptimo de entrega del servicio a la hora de integrar el HAART en los cuidados prenatales.
Métodos: Hemos analizado las historias clínicas de mujeres embarazadas infectadas con VIH, con el fin de reconstruir una cohorte de mujeres elegibles para recibir HAART en cuatro clínicas prenatales que representan tres modelos de entrega de servicio en Ciudad del Cabo, Sudáfrica. Para evaluar la cobertura del HAART, se revisaron las historias clínicas de mujeres determinadas como elegibles para recibir HAART durante el embarazo, en cada uno de los servicios para el tratamiento de VIH.
Resultados: De 13,208 mujeres embarazadas que se hicieron la prueba para VIH, 26% estaban infectadas con VIH y 15% eran elegibles para HAART basándose en un conteo de CD4 de ≤200 células/μl. Entre las mujeres elegibles, un 51% inició HAART antes del parto, 27% recibió otra intervención para la prevención de la transmisión vertical (PMTCT) y 22% no recibió ninguna intervención antirretroviral antes del parto. La proporción de mujeres que iniciaron el HAART entre los diferentes modelos de entrega de servicios era comparable. La mediana de la edad gestacional al momento de presentarse en el centro médico era de 26 semanas y una edad gestacional temprana al momento de acudir por primera vez al centro sanitario era el mejor vaticinador de estar recibiendo HAART en el momento del parto. De las mujeres que no iniciaron HAART durante el embarazo, un 24% comenzó tratamiento dentro de los dos años siguientes al parto.
Conclusiones: En este lugar con protocolos claros de PMTCT y HAART, los servicios no fueron capaces de priorizar y de iniciar el HAART en una proporción alta de mujeres embarazadas elegibles. La iniciación del HAART en el embarazo requiere de unos servicios prenatales y de VIH especialmente sólidos, que prioricen mujeres en un estadio avanzado de la enfermedad.
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The use of antiretroviral (ARV) prophylaxis during pregnancy and labour can dramatically reduce the risk of vertical transmission of HIV infection. Highly active antiretroviral therapy (HAART) has the greatest efficacy in reducing mother-to-child transmission (MTCT) of HIV and has significant direct benefits for maternal health (Cooper et al. 2002). Results from recent studies of improved regimen combinations, earlier treatment start in pregnancy and continued ARV support for mother and infant during breast feeding in the postpartum period have led to significant changes in the recommendations for managing pregnant HIV-infected women (Chasela et al. 2009; Kesho Bora Study Group 2009; Shapiro et al. 2009; Taha et al. 2009). In the light of new evidence, WHO recently released revised guidelines for the management of HIV-infected women in pregnancy, which recommend initiating lifelong HAART earlier in pregnant women and raising the eligibility criteria from a CD4 cell count threshold of ≤ 200 cells/μl to ≤ 350 cells/μl or WHO clinical staging 3 or 4, irrespective of gestational age (World Health Organization 2009).
Despite the importance of HAART during pregnancy, there are significant patient-related and service-related challenges to the implementation of HAART services as part of antenatal care. In many settings, high HIV seroprevalence among women of reproductive age results in a sizeable proportion of HIV-infected pregnant women accessing limited antenatal and HIV care services (Stringer et al. 2008). Patient-driven barriers include lack of knowledge of serostatus prior to conception; reluctance to test in pregnancy; fear of disclosure and denial post-diagnosis; and under-utilization of antenatal care during pregnancy (Abrams et al. 2007; Bolu et al. 2007; El-Sadr & Abrams 2007; Tlebere et al. 2007). Service delivery approaches impact on the accessibility and availability of treatment services for HIV-infected pregnant women. Prevention of mother-to-child transmission (PMTCT) services for women who do not have advanced HIV disease, but who require short-course prophylactic regimens, are generally integrated within routine antenatal health services managed by midwives. Presently, there are a few such integrated services for pregnant women who are eligible for HAART (Schneider et al. 2006). As a result, these women may need to access antenatal care and stand-alone doctor-driven HAART services that may be geographically separate. The integration of HAART into antenatal services has been proposed and is underway in selected settings, yet little is known about the operational experience of different models of service delivery in resource-constrained contexts (Abrams et al. 2007).
Cape Town health services were among the first in the region to offer both PMTCT (1999) and HAART (2001), with protocols providing for universal access to HAART for eligible pregnant women since 2003 (Abdullah et al. 2001; Draper & Abdullah 2008). A number of service models for delivering HAART to pregnant women developed during this period providing an opportunity to explore the relationship between these models and the uptake of HAART. Although HAART has been available for eligible HIV-infected pregnant women in Cape Town since 2003, little is known about HAART coverage in pregnancy. The objectives of this study were to describe HAART coverage in a cohort of eligible women accessing antenatal services and to evaluate different service models for providing HAART.
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This analysis demonstrates substantial missed opportunities to initiate HAART among pregnant women with advanced HIV disease within public sector antenatal care services. Only 51% of HAART-eligible women initiated treatment before delivery, while another 27% received a short-course PMTCT regimen, and more than one-fifth of women received no intervention. Importantly, there were no significant differences in these proportions between the integrated service in which antenatal care and HAART were co-located, the proximal service with separately run services on the same premises and the distal model with off-site antenatal HAART provision.
Recently, WHO revised its ARV treatment guidelines to recommend the initiation of HAART in all adults including pregnant women with CD4 cell counts ≤350 cells/μl (World Health Organization 2009). Our study showed very high CD4 cell count testing coverage, and based on our data, shifting to a CD4 cell count threshold of ≤350 cells/μl would have raised the proportion of eligible HIV-infected women from 15% to 44%, amounting to a threefold increase in women eligible for lifelong treatment. While this change in threshold for treatment initiation is likely to yield significant improvements in maternal health outcomes, as well as reduce perinatal transmission, our study points to the challenges of implementing these guidelines and initiating large numbers of women on HAART during pregnancy.
Part of the challenge is likely owing to the difficulty in initiating HAART in a midwife-driven antenatal care service and the subsequent logistical demands of coordinating HIV and antenatal care. As doctors are not routinely available in antenatal clinics in this setting and midwives are not certified to prescribe HAART, eligible women must attend separate HIV services or return to the antenatal clinic when a HAART prescriber is available. Furthermore, at the time of this study, it was reported that the duration of treatment adherence preparation in patients eligible for HAART was 4–6 weeks. The possibility of fast-tracking eligible women onto HAART during pregnancy has been suggested, but there are few reports of such an approach in practice, and its impact, given that the availability of appropriate providers is static. Particular concerns may exist around how patient preparation before HAART initiation influences long-term outcomes, although there are few data evaluating this possibility. The availability of appropriate clinical personnel to initiate HAART in antenatal care has been raised as an additional concern. One option that has been suggested to address this is nurse-driven HAART initiation, which has proven effective and feasible in African settings (Zachariah et al. 2009); in the context of pregnancy, midwives are a potentially valuable human resource for HAART initiation, and the possibility of midwife-driven HAART services deserves consideration (Médicines Sans Frontières et al. 2009).
Meanwhile, the challenge of starting HAART in newly diagnosed pregnant women should not be underestimated. Unknown HIV serostatus in pregnancy and labour has been described as an important factor hindering PMTCT scale up (Bolu et al. 2007). In this setting, where utilization of antenatal care services is high, universal HIV screening was not achieved, with a substantial proportion of women not testing for HIV. Attrition at this point contributes to the pool of infected women of unknown serostatus who will not receive PMTCT programme support in pregnancy and who are consequently at increased risk of MTCT. The integrated model achieved 98% testing coverage, which was most likely attributable to individual provider influences at this site, as the opt-in guidelines were consistent across the sites at the time of the study. By modelling the collective data on 100% testing coverage, it is predicted that a further 70 HAART-eligible women would have been missed as a result of failure at this step in the cascade. Also, recent evidence suggests that services are failing to identify HAART-eligible HIV-infected women through clinical and immunological assessment (McIntyre 2010; World Health Organization 2008).
The psychosocial impact of HIV infection on pregnancy has been documented in women with both pre-conception and post-conception HIV diagnosis, and anxiety during pregnancy is commonly associated with disease-related stigma and fear of the risk of vertical transmission (Jones 2008; Makin et al. 2008; Medley et al. 2004; Sanders 2008). Among non-pregnant adults, psychosocial barriers to HAART uptake and adherence include fear of treatment side effects, stigma and a lack of belief in the efficacy of HAART (Mills 2008). However, little is known about the psychosocial challenges to initiating HAART during pregnancy, particularly among women who are diagnosed with HIV while seeking antenatal care. It is plausible that the combined psychosocial effects of an HIV diagnosis and HAART initiation during pregnancy may be particularly problematic, but this possibility requires further research.
We found no difference in HAART initiation during pregnancy between the integrated, proximal and distal models of antenatal HAART delivery. A priori our hypothesis was that the integrated model would be associated with a significantly greater proportion of women starting HAART during pregnancy through increased access to combined antenatal and HAART services. The fact that the integrated model, which had a higher disease burden and more women eligible for HAART, initiated HAART in more women in absolute terms could be demonstrative of a better model. Other authors have also suggested that the integrated model of antenatal HAART services may be expected to facilitate HAART initiation in pregnancy: for example, antenatal care and HAART integration resulted in an increase in HAART uptake in pregnant women from 46% to 71% in one urban South African hospital (Ramdhial & Ramkissoon 2009).
While our data suggest that, in this setting, the specific service delivery model may not be a major determinant of HAART initiation in pregnancy, the failure to observe this could be related to the fact that the integrated service was limited to one day a week. Since it was not available to pregnant women during all antenatal service hours, it may not have been optimally ‘integrated’. Despite limited capacity, it is impressive that this model performed as well, if not better than models where the referral service was operating every day. Clearly, health systems need to shift from disease-specific programmes towards strengthening approaches to integrated maternal and child health and HIV services, to increase the uptake of HAART in pregnancy.
This study focused on HAART initiation during pregnancy; it does not address the issues of long-term follow-up of HIV-infected mothers. It is unclear whether a specific model of antenatal HAART initiation may be associated with better long-term retention of mothers in HIV care services postpartum. Specifically, it is plausible that an integrated model of HAART initiation during antenatal care leads to more women starting HAART during pregnancy, but the transition to routine adult HIV services postpartum is more difficult, compared to an antenatal HAART model where pregnant women are referred immediately to routine HIV care services. The postpartum follow-up of women who initiated HAART during pregnancy appeared problematic in one study (Kaplan et al. 2008), but another suggested that initiation during pregnancy is not associated with outcomes that are worse than in non-pregnant women (Toro et al. 2010); clearly, this possibility requires further investigation.
We found that gestational age at first antenatal visit was a major determinant of HAART initiation during pregnancy, with women making their first antenatal visit during the third trimester 75% less likely to start HAART while pregnant. At the time of the study, the PMTCT protocol recommended not initiating HAART in women beyond 36 weeks of gestation, and this guideline in conjunction with late presentation may have impacted on providers’ decisions to initiate treatment close to the time of delivery. However, discussions with local service providers (not presented here) suggested that this guideline was not fully implemented.
As duration of HAART is an important factor in achieving viral suppression and in turn preventing vertical transmission of HIV, late presentation is a significant concern. Our study suggests that of those women who received HAART, less than half received more than 8 weeks of treatment before delivery. Data from the European Cohort Study suggest that at least 8 weeks of HAART are required to achieve viral suppression in women with advanced HIV disease (European Collaborative Study Group 2007), and one study in South Africa demonstrated that in women initiating HAART during pregnancy every additional week of treatment reduced the odds of transmission by 8% (Hoffman et al. 2010). Efforts to encourage women to seek antenatal care earlier in pregnancy are likely to face a host of patient-related and health service–related barriers (Downe et al. 2009; Simhkada et al. 2008). Continued progress towards achieving universal HIV testing, particularly in pre-conception care, could ensure that more women are aware of their serostatus prior to conception. Furthermore, moving towards the adoption of provider-initiated counselling and testing, CD4 cell count enumeration and improved systems of expedited HAART initiation should be explored (Bolu et al. 2007).
These data should be interpreted in the light of several limitations. This research was conducted in a high HIV prevalence urban setting within well-established maternal and child health care services. We may anticipate that the proportion of eligible women initiating HAART during pregnancy may be lower in settings with less robust antenatal care systems. These data are from retrospective reviews of clinic records, rather than purposively collected prospective data. However, the system of clinic registries for antenatal care and HAART services that served as the primary data sources is well established and is frequently used for HIV-related research in this setting (Boulle et al. 2008) and hence unlikely to be an appreciable cause of apparently low uptake of HAART/PMTCT. Also, it is possible that our results do not reflect context-specific differences between facilities, and because we selected only four sites to represent the three service delivery models, inter-clinic variability, rather than inter-model variability, may be an explanation for the observed findings.
These data come from 2005 when the local public sector HAART programme, and its links to antenatal care and PMTCT, was still being established. However, the situation of relatively new HIV care and treatment programmes that are exploring the options of how to interface with more established antenatal care structures, particularly in the light of recent WHO policy developments, is likely to be closer to the norm across most of sub-Saharan Africa (Killam et al. 2010). Thus, these results are valuable in highlighting the significant hurdles facing health care services and HIV-infected women starting antenatal HAART.
In summary, this study illustrates that in this setting with clear PMTCT protocols, a high proportion of eligible women did not initiate HAART before delivery. A range of important health service and patient-level challenges may be associated with initiating HAART in pregnant women. Further research into specific models of care is needed to understand the optimal approaches to linking antenatal care with HAART delivery.