Paper:Missed Opportunities to Prevent Mother-to-Child-Transmission in sub-Saharan Africa: Systematic Review and Meta-Analysis
Missed Opportunities to Prevent Mother-to-Child-Transmission in sub-Saharan Africa: Systematic Review and Meta-Analysis
Celina WETTSTEIN,1 Catrina MUGGLIN,1 Matthias EGGER,1,2 Nello BLASER,1Luisa SALAZAR,1 Janne ESTILL,1 Nicole BENDER,1 Mary-Ann DAVIES,2Gilles WANDELER,1,3,* and Olivia KEISER1,*
AIDS. Author manuscript; available in PMC 2013 Nov 28.
Published in final edited form as:
Reference:
Wettstein, C., Mugglin, C., Egger, M., Blaser, N., Salazar, L., Estill, J., ... & Keiser, O. (2012). Missed opportunities to prevent mother-to-child-transmission in sub-Saharan Africa: systematic review and meta-analysis. AIDS (London, England), 26(18), 2361.
MY SUMMARY:
The question is what are barriers of accessing PMTCT service?? Even in Sub Saharan,
"uptake of PMTCT interventions and early infant diagnosis is unsatisfactory"?
Abstract
Objectives
To determine magnitude and reasons of loss to programme and poor antiretroviral prophylaxis coverage in prevention of mother-to-child transmission (PMTCT) programmes in sub-Saharan Africa.
Design
Systematic review and meta-analysis.
Methods
We searched PubMed and Embase databases for PMTCT studies in sub-Saharan Africa published between January 2002 and March 2012. Outcomes were the percentage of pregnant women (i) tested for HIV, (ii) initiating antiretroviral prophylaxis, (iii) having a CD4 cell count measured, and (iv) initiating antiretroviral combination therapy (cART) if eligible. In children outcomes were (v) early infant diagnosis for HIV, and (vi) cART initiation. We combined data using random-effects meta-analysis and identified predictors of uptake of interventions.
Results
Forty-four studies from 15 countries including 75,172 HIV-infected pregnant women were analyzed. HIV-testing uptake at antenatal care services was 94% (95% confidence intervals [CI] 92-95%) for opt-out and 58% (95% CI 40-75%) for opt-in testing. Coverage with any antiretroviral "prophylaxis was 70% (95% CI 64-76%) and 62% (95% CI 50-73%) of pregnant women eligible for cART received treatment. Sixty-four percent (95% CI 48-81%) of HIV exposed infants had early diagnosis performed and 55% (95% CI 36-74%) were tested between 12 and 18 months. Uptake of PMTCT interventions was improved if cART was provided at the antenatal clinic and if the male partner was involved.
Conclusions
In sub-Saharan Africa, uptake of PMTCT interventions and early infant diagnosis is unsatisfactory. An integrated family-centered approach seems to improve retention.
Keywords: pre-ART, linkage to care, mortality, loss to follow-up, PMTCT, early infant diagnosis, prophylaxis
IMPORTANT QUOTATION
At each step of the PMTCT cascade, pregnant women and their infants may be lost to follow-up and not benefit from important health-care interventions. The magnitude and reasons for program attrition in sub-Saharan Africa remain poorly understood.
Steps of the prevention of mother-to-child-transmission cascade
Bold arrows represent steps with risk of attrition
ANC=antenatal care, cART=lifelong combination ART, ARVs=antiretroviral drugs, PCR=polymerase chain reaction
AIM: We performed a systematic review and meta-analysis to evaluate the uptake of HIV testing and antiretroviral treatment in pregnant women and their children.
Data sources
We searched Pubmed and Embase databases on March 5th 2012, limiting the search to publications in the English language and studies published since 2002 (i.e. when the scale-up of ART programs in sub-Saharan Africa began) [5]. We used free text words as well as Medical Subjects Headings (MeSH) in Pubmed and Emtree-terms in Embase. We combined the following search terms and their variations: HIV, prevention of mother-to-child-transmission, infection of newborn, pregnancy, prenatal care, postnatal care, antiretroviral agents, eligibility, referral process and loss to follow-up. We examined the references of all included studies. Further details on the search strategy are given in the webappendix.
Study selection
We included all studies on pregnant women (with either unknown or positive HIV status) and their HIV-exposed infants who attended PMTCT programs in sub-Saharan Africa. We selected studies that reported the number of participants who were given access to at least one of the following interventions: initiation of antiretroviral prophylaxis for HIV positive pregnant women; assessment and initiation of lifelong cART; or HIV testing in infants. We excluded qualitative studies, randomized controlled trials, modeling studies, studies where uptake of interventions was assessed by interview, and cost-effectiveness studies. Abstracts were screened according to a list of inclusion and exclusion criteria. Two reviewers independently assessed the eligibility of articles. Discrepancies were resolved by consensus.
Data extraction
Data extraction was performed in duplicate by eight reviewers using a standardized extraction sheet. The following data were extracted: characteristics of programs (setting, location, country) and participants (age, gestational age at first antenatal care visit), eligibility criteria for cART initiation and the number of participants completing the following steps: (i) HIV-testing of pregnant women; (ii) initiation of antiretroviral prophylaxis for mothers; (iii) CD4 cell count testing; (iv) initiation of cART in eligible women; (v) HIV diagnosis of the exposed infants around 6 weeks by PCR and between 12 and 18 months by PCR or antibody test; and (vi) cART initiation in infected infants (Figure 1).
RESULT
Antiretroviral prophylaxis for PMTCT
In six of these nine studies, some women received sdNVP even though dual or triple ART was available. The reason for this was that the women received sdNVP at their first visit but never returned for an assessment of ART eligibility [15, 22]. In three of the 34 studies the antiretroviral regimen was not specified. Information on predictors of sdNVP uptake was available in six studies [10, 13, 17, 19, 20, 23]. Uptake was better when the male partner was involved [20] and when women delivered at the health care facility [19] (webappendix Table S2).
Eligibility assessment and cART initiation
Six studies assessed whether women with CD4 cell measurements returned to collect the results: an estimated 72.6% (95% CI 62.5-82.7%; PrI 35.5-100%) returned to the clinic.
Linkage between PMTCT services, infant HIV diagnosis and cART initiation
The mean percentage of infants tested for HIV by PCR around 6 weeks based on 12 studies was 64.4% with 95% CI and PrI of 47.5-81.2% and 0%-100%, respectively (Figure 4, webappendix Table S3). Predictors for early infant diagnosis were reported in three studies [26-28]. These showed positive associations between uptake of testing and proximity to the clinic [26], large family size [26], early HIV diagnosis of the mother [27], or having received antiretroviral prophylaxis for PMTCT [27]
The risk of mother-to-child HIV transmission can be dramatically reduced by preventive measures including antiretroviral prophylaxis for the mother and the child [2]. According to a recent WHO update, the use of cART during pregnancy is preferable to mono- or dual therapy [4]. Our analysis showed that some women received sdNVP at their first visit and were then lost before dual or triple prophylaxis or cART could be initiated. In other cases it was unknown why the optimal regimen had not been provided even though it was available. Significantly, about one third of patients did not receive any type of antiretroviral prophylaxis, and 40% of cART eligible women did not initiate treatment. This finding is in line with recent systematic reviews on retention in HIV care, which reported that between 38% and 88% of pregnant women [30], and 32% and 37% of eligible patients from the general HIV infected population never started cART [31, 32]. An important difference between pregnant women and the general, HIV-infected population is that a substantially lower proportion of pregnant women were eligible for cART at first presentation (23% and 40% [31], respectively). This shows that with systematic HIV testing during pregnancy HIV infection can be diagnosed earlier, providing opportunities to initiate cART before patients present with advanced disease.
30. Ferguson L, Grant AD, Watson-Jones D, Kahawita T, Ong’ech JO, Ross DA. 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 [PubMed]
31. Mugglin CEJ, Wandeler G, et al. Linkage to Care from HIV Diagnosis to Start of ART in sub-Saharan Africa: Meta-analysis; 19th Conference on Retroviruses and Opportunistic Infections (CROI 2012); Seattle, WA. 2012.
32. Rosen S, Fox MP. Retention in HIV care between testing and treatment in sub-Saharan Africa: a systematic review. PLoS Med. 2011;8:e1001056.[PMC free article] [PubMed]
In a previous review Hensen et al [33] compared HIV-testing uptake before and after implementation of the opt-out strategy and found a substantial increase in uptake, from 10% to 66%. In our analysis, which included studies with either opt-in or opt-out testing, we found that the mean uptake was 94% with the opt-out strategy
However, the provision of universal opt-out HIV-testing in antenatal care clinics might remove some of the fears related to patient-initiated testing, as it “normalizes” the testing process and integrates it into routine clinical care. As a consequence, women might be less afraid of being stigmatized and judged by their peers. The studies included in this analysis showed enhanced uptake of testing if patients were accompanied by their male partner [20]. Finally, programmatic issues such as staff shortages or the unavailability of test kits might also limit HIV-testing uptake [36].
In order to increase the uptake of PMTCT interventions, our understanding of the individual and program-level factors that limit access to care must improve. Although few studies analyzed barriers to pre-ART care, integration of cART provision into routine antenatal services and reducing the number of visits seems promising. An example of this was the improved uptake of cART when the CD4 count was done on the same day as testing for HIV [8]. Better uptake was also associated with the provision of cART at the same place as PMTCT services [8, 21, 24], or if the distance to the clinic was short [8, 13]. In general, however, there is a lack of data on the effectiveness of integrating prevention of mother-to-child HIV transmission (PMTCT) programs with other health services. This is illustrated by a Cochrane review on this topic [40], which found only one study that matched the inclusion criteria. The involvement of the male partner may also increase the chance of successful interventions [20]. In a study from Côte d’Ivoire a family centered approach (i.e. provision of cART to partner and children; and improved access to contraception) helped to achieve coverage of over 90% from CD4 measurement to EID.
Tudor Car L, van-Velthoven MH, Brusamento S, Elmoniry H, Car J, Majeed A, et al. Integrating prevention of mother-to-child HIV transmission (PMTCT) programmes with other health services for preventing HIV infection and improving HIV outcomes in developing countries. Cochrane Database Syst Rev. 2011:CD008741. [PubMed]
Conclusion
In order to reach the UNAIDS goal of eliminating paediatric HIV infections by 2015 [41], the coverage of PMTCT and cART need to be improved. Even though provider-initiated HIV-testing shows promising results, large gaps in antiretroviral prophylaxis, cART initiation, and infant testing remain. In order to improve retention in care of HIV-infected mothers and prevent new HIV-infections in children, a better understanding of the major barriers is of paramount importance. Further research on the major reasons for the failure of PMTCT programs in sub-Saharan Africa is urgently needed.
OTHER PAPERS
1. Linking women who test HIV-positive in pregnancy-related services to long-term HIV care and treatment services: a systematic review
30. Ferguson L, Grant AD, Watson-Jones D, Kahawita T, Ong’ech JO, Ross DA. 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 [PubMed]
Abstract
ENTHIS LINK GOES TO A ENGLISH SECTIONFRTHIS LINK GOES TO A FRENCH SECTIONESTHIS LINK GOES TO A SPANISH SECTION
Objectives To quantify attrition between women testing HIV‐positive in pregnancy‐related services and accessing long‐term HIV care and treatment services in low‐ or middle‐income countries and to explore the reasons underlying client drop‐out by synthesising current literature on this topic.
Methods A systematic search in Medline, EMBASE, Global Health and the International Bibliography of the Social Sciences of literature published 2000–2010. Only studies meeting pre‐defined quality criteria were included.
Results Of 2543 articles retrieved, 20 met the inclusion criteria. Sixteen (80%) drew on data from sub‐Saharan Africa. The pathway between testing HIV‐positive in pregnancy‐related services and accessing long‐term HIV‐related services is complex, and attrition was usually high. There was a failure to initiate highly active antiretroviral therapy (HAART) among 38–88% of known‐eligible women. Providing ‘family‐focused care’, and integrating CD4 testing and HAART provision into prevention of mother‐to‐child HIV transmission services appear promising for increasing women’s uptake of HIV‐related services. Individual‐level factors that need to be addressed include financial constraints and fear of stigma.
Conclusions Too few women negotiate the many steps between testing HIV‐positive in pregnancy‐related services and accessing HIV‐related services for themselves. Recent efforts to stem patient drop‐out, such as the MTCT‐Plus Initiative, hold promise. Addressing barriers and enabling factors both within health facilities and at the levels of the individual woman, her family and society will be essential to improve the uptake of services.
Integrating prevention of mother-to-child HIV transmission (PMTCT) programmes with other health services for preventing HIV infection and improving HIV outcomes in developing countries
· Review
· Intervention
Authors
2. Lorainne Tudor Car, Michelle HMMT van-Velthoven, Serena Brusamento, Hoda Elmoniry, Josip Car, Azeem Majeed, Rifat Atun
· 15 June 2011
Abstract
Background
Every year nearly 400,000 children are infected with HIV through mother-to-child transmission (MTCT), which is responsible for more than 90% of HIV infections in children. In high-income countries, the MTCT rate is less than 1% through perinatal prevention of mother-to-child HIV transmission (PMTCT) interventions. In low- and middle-income countries, PMTCT programme coverage remains low and consequently transmission rate high. The World Health Organisation recommends integration of PMTCT programmes with other healthcare services to increase access and improve uptake of these interventions.
Objectives
To assess the effect of integration of perinatal PMTCT measures with other health care services on coverage and service uptake compared to stand-alone PMTCT programmes and healthcare services or partially integrated PMTCT interventions.
Search methods
We searched the following databases, for the time period of January 1990 to August 2010: MEDLINE, EMBASE, the WHO Global Health Library, CAB abstracts, CINAHL, POPLINE, PsycINFO, Sociological Abstracts, ERIC, AEGIS, Google Scholar, New York Academy of Medicine Grey Literature, Open SIGLE, British Library Catalogue, ProQuest Dissertation & Theses Database and U.S. National Library of Medicine Gateway system. We also searched the Cochrane Database of Systematic Reviews (the Cochrane Library 2010, Issue 7), the Cochrane Central Register of Controlled Trials (the Cochrane Library 2010, Issue 7), Database of Abstracts of Reviews on Effects (the Cochrane Library 2010, Issue 7). We also searched for ongoing trials in the WHO International Clinical Trials Registry and Controlled clinical trials (January 1990 to July 2010). We performed ISI Web of Knowledge Cited Reference Search and scanned the reference lists of the included articles for additional relevant studies. We contacted authors to locate additional eligible studies. To maximise sensitivity we did not employ any methodological filters.
Selection criteria
Randomised controlled trials (RCT), cluster-randomised controlled trials (cluster RCT), controlled clinical trials (CCT), controlled before and after (CBA) studies and interrupted time series (ITS) studies comparing integrated PMTCT interventions to non-integrated or partially integrated care for pregnant women, mothers and their infants in low- and middle-income countries.
Data collection and analysis
Two review authors independently ran the searches, selected studies, assessed methodological quality, and extracted data. The third review author resolved any disagreements.
Main results
Only one study met the inclusion criteria. A cluster-randomised trial (12 clusters, n=7664), compared mother-infant nevirapine coverage at labour ward between intervention clinics implementing rapid HIV testing with structured nevirapine assessment and control clinics implementing informal assessment of nevirapine adherence. The authors measured nevirapine coverage in all clinics at baseline and after the implementation of the intervention. An increase of 10% (range of difference in coverage from -10% to +33%) was observed in the intervention sites compared to 10% decline in mother-infant coverage in the control sites (range of difference in coverage from -13% to 0%). The study showed that the probability of nevirapine coverage of mothers and their infants in the intervention arm compared to control arm increased from 0.89 at baseline to 1.22 during the intervention period, representing a multiplicative effect of 1.37 upon the ratio of relative risks at baseline (RR 1.37, bootstrapped 95% CI, 1.041.77). The study had a low risk of bias. No studies were found that evaluated the effectiveness of integrating other perinatal PMTCT interventions with healthcare services.
Authors' conclusions
We found only one study suggesting that integrating perinatal PMTCT interventions with other healthcare services in low- and middle-income countries increases the proportion of pregnant women, mothers and infants receiving PMTCT intervention. The weak evidence base does not enable making any inferences for other countries or contexts. The study that met the inclusion criteria assessed only the impact of integrating PMTCT intervention in labour ward on the proportion of mothers and their infants receiving nevirapine. The study showed significant improvement in intervention coverage but it only addressed the labour ward aspect of PMTCT programme. We did not find sufficient evidence to make definitive conclusions about the effectiveness of integration of these interventions with other health services rather than providing them as stand-alone services. Further research is urgently needed to assess the effect of integrating perinatal prevention of mother-to-child HIV transmission interventions with other health services on intervention coverage, service uptake, quality of care and health outcomes and the optimal integration modality.
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