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Abstract

Objective: To estimate the cost-effectiveness of prevention of mother to child transmission (MTCT) of HIV with lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') compared to ART during pregnancy or breastfeeding only unless clinically indicated ('Option B'). Design: Mathematical modelling study of first and second pregnancy, informed by data from the Malawi Option B+ programme. Methods: Individual-based simulation model. We simulated cohorts of 10,000 women and their infants during two subsequent pregnancies, including the breastfeeding period, with either Option B+ or B. We parameterised the model with data from the literature and by analysing programmatic data. We compared total costs of ante-natal and post-natal care, and lifetime costs and disability-adjusted life-years (DALYs) of the infected infants between Option B+ and Option B. Results: During the first pregnancy, 15% of the infants born to HIV-infected mothers acquired the infection. With Option B+, 39% of the women were on ART at the beginning of the second pregnancy, compared to 18% with Option B. For second pregnancies, the rates MTCT were 11.3% with Option B+ and 12.3% with Option B. The incremental cost-effectiveness ratio comparing the two options ranged between about US$ 500 and US$ 1300 per DALY averted. Conclusion: Option B+ prevents more vertical transmissions of HIV than Option B, mainly because more women are already on ART at the beginning of the next pregnancy. Option B+ is a cost-effective strategy for PMTCT if the total future costs and lost lifetime of the infected infants are taken into account.

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... Option B+ was first conceived and implemented in Malawi. Preliminary findings of routine Option B+ PMTCT programme in a rural district in Malawi showed a fivefold increase in ART initiation and 88% client retention in the first quarter of its implementation in 2011 [9][10][11]. ...
... Overall service quality was assessed by combining input, process, and output service quality items. Facilities were categorized rendering good input service quality, if the average weighted score of input quality performance standards is 100% [10], and 90% or more for process, output, and overall quality performance standards [10,20]. See the score of each variable for respective quality components (Additional file 1). ...
... Overall service quality was assessed by combining input, process, and output service quality items. Facilities were categorized rendering good input service quality, if the average weighted score of input quality performance standards is 100% [10], and 90% or more for process, output, and overall quality performance standards [10,20]. See the score of each variable for respective quality components (Additional file 1). ...
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Background: Substantial improvements have been observed in coverage and access to maternal health services in Ethiopia. However, the quality of care has been lagging behind. Therefore, this study aimed to assess the level of quality of Option B+ PMTCT in Northern Ethiopia. Methods: A facility based survey was conducted from February to April 2016 in Northern Ethiopia. Twelve health facilities were enrolled in the study. Mixed method approach was used in line with Donabedian (Input- Process-Output) service quality assessment model. Data of 168 HIV positive mothers & their infant were abstracted from registers, and follow up charts. During the Option B+ service consultation, a total of 60 sessions were involved for direct observation. Of which, 30 clients and 12 service providers were subjected for exit and in-depth interview respectively. Facilities were categorized rendering good service quality based on predetermined quality judgment criteria. Reasons of good and bad service quality were thematically fitted with each quality component based on emerging themes (TM1-TM3), and categories (CA1-CA6). Results: Of the total 12 study health facilities, 2(16.7%) were achieved the desired level of service quality based on the three quality components. The input quality was better and judged as good in 33.3% health facilities. However; process and output service quality were realized in one - fourth of them. Conclusion: Insignificant numbers of facilities fulfilled the aspired level of service quality. Quality of care was found influenced by multiple inputs, processes, and output related barriers and facilitators. Comprehensive Program monitoring is needed based on three quality components to improve the overall service quality.
... Hình 1. Quy trình tìm kiếm các nghiên cứu đưa vào phân tích tổng quan Đặc điểm các nghiên cứu chi phí hiệu quả thuốc ARV Trong 33 nghiên cứu được phân tích, có 20 nghiên cứu (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) sử dụng ARV với mục đích điều trị, chiếm tỉ lệ 60%, và 13 nghiên cứu (21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33) sử dụng ARV với mục đích dự phòng, chiếm tỉ lệ 40%. Quan điểm được nghiên cứu thông dụng là quan điểm người cung cấp dịch vụ (39,4%). ...
... Mô hình tĩnh xem xét tỉ lệ lây nhiễm bệnh của quần thể nghiên cứu là không đổi trong thời gian nghiên cứu đã được 11 nghiên cứu ứng dụng, gồm có mô hình cây quyết định (1,11,15,2411,29) , mô hình Markov và semi-Markov (2,17,21,32,33) . Có 22 nghiên cứu sử dụng mô hình động, là mô hình giả thiết tỉ lệ lây nhiễm luôn thay đổi trong thời gian nghiên cứu, bao gồm mô hình CEPAC (3,6,13,20,26,28) , mô hình ARAMIS (12,18) mô hình mô phỏng vi mô (5,16,23,31,33) mô hình ngăn (22,33) , và các mô hình toán học khác (1,4,6,8,9,25,27,30) . 5 trong số 33 nghiên cứu tìm được có phân tích kịch bản (5,7,9,28,31) và 21 nghiên cứu có time horizone dài trên 5 năm. ...
... Có 22 nghiên cứu sử dụng mô hình động, là mô hình giả thiết tỉ lệ lây nhiễm luôn thay đổi trong thời gian nghiên cứu, bao gồm mô hình CEPAC (3,6,13,20,26,28) , mô hình ARAMIS (12,18) mô hình mô phỏng vi mô (5,16,23,31,33) mô hình ngăn (22,33) , và các mô hình toán học khác (1,4,6,8,9,25,27,30) . 5 trong số 33 nghiên cứu tìm được có phân tích kịch bản (5,7,9,28,31) và 21 nghiên cứu có time horizone dài trên 5 năm. ...
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Nghiên cứu tổng quan chi phí - hiệu quả thuốc ARV trong điều trị và dự phòng HIV/AIDS giai đoạn 2014-2019 Background: Although using cART therapy has extended the life span of HIV/AIDS patients, the high cost of ARVs is an economic burden to be concerned. Research studies on the cost-effectiveness of ARVs will help managers to optimize the use of ARVs in prevention and treatment. Method: This review collected all scientific papers which had the same study interest in the cost-effectiveness of ARVs use from PubMed database combined with MeSH in the period of 01/2014-06/2019. Data were aggregated in Excel 2016 and the research results were analyzed according to target population, research perspective, implementation method, type of model applied, ARV drug, acceptance threshold, and unit of effectiveness of ARV drugs. Results: Of the 33 papers collected, ARVs were used for treatment purposes in 20 papers (60%) and for the purpose of prophylaxis in 13 papers (40%). The common research perspective was based on the payers (39.4%), 22 studies (66.7%) used dynamic models while 11 studies used static models. One-variable sensitivity analysis method was applied in 51.5% of papers. Cost-effectiveness research mainly focused on integrated enzyme inhibitors (39.5%) and protease inhibitors (15.2%), with the effectiveness determined by either QALYs (60.6%), the rate of successful treatment (18.2%), LYs (12.1%), or DALYs (9.1%). The acceptance threshold of less than $50.000 was recorded in 54.5% of papers. Conclusion: This review found important information on the acceptance threshold and the unit of effectiveness in preventing and treating HIV/AIDS with ARVs from different perspectives. These findings created a basis for patients and healthcare providers to make appropriate decisions on using ARVs in the most costefficient way. Keywords: ARV, cost-effectiveness, HIV/AIDS, systematic review
... The cost and cost-effectiveness outcomes from this study indicate that there is a robust economic case for pursuing the Option B+ approach in Swaziland and similar settings such as South Africa. This is one of the first studies to present an empirical economic evaluation using primary patient level data as opposed to modelled data as has been done in the recent past [7,[13][14][15][16][17][18][19][20]. ...
... Results from Malawi [18], Rwanda [25] and Cameroon [26] differ from our study findings as they modelled estimates, are from settings other than Swaziland and have differing time horizons. In the five papers reviewed by Karnon and Orji, cost inputs in the models for Option A ranged from US $16 to 76, while costs for Option B+ varied from US $114 to 470 per year [6], which are lower than our estimates. ...
... In this study, the total cost for PMTCT in the five sites during the study period was US $680 508 under Option A and US $868 426 under Option B+. In comparison, the total programme costs for Option B+ as simulated by Tweya et al., [18] in Malawi were US $431 910 for a first pregnancy and US $662 074 for a woman's second pregnancy. ...
... In this context, engagement in care for the women during the pre-natal phase and for the mother-infant pair during post-partum are of paramount importance to guarantee important milestones of PMTCT care such as rapid maternal viral control before delivery, EID testing at 6-8 weeks and final HIV infant testing at 12-18 months post-partum ( Figure 2.1) [97,98]. Furthermore, compared to previous PMTCT regimens (Options A or B), lifelong ART provided to pregnant women under Option B+ has the additional public health benefit of guaranteeing viral suppression for subsequent pregnancies while keeping mothers alive [99]. Thus, disengagement from PMTCT care share the common consequence as for the general 'Test and Treat all' approach of poor viral control for the HIV-positive women but adds-in the failure of elimination of MTCT of HIV. ...
... A. Near universal healthcare access i.99.9% of Thai citizens have government supported insurance ii. Additional 1.4 million non-Thai migrants have health insurance B. All PMTCT services (ANC, screening and treatment for HIV and syphilis) financed through national budget with free access for migrantsThe 'Global Plan' was recognized as one of the greatest public health achievements of recent times. ...
Thesis
In 2015, the World Health Organization published new guidelines for the prevention of motherto- child transmission (PMTCT) of HIV and recommended that all seropositive pregnant and breastfeeding women be provided with lifelong anti-retroviral therapy (ART) (option B+).However, there are rising concerns about the effectiveness of the strategy in truly reducing the number of vertical HIV transmissions; there are indeed programmatic challenges related to its implementation; in particular, the sub-optimal levels of engagement in care of mother/infantpairs observed mainly in sub-Saharan Africa. The aim of the present thesis was to discuss, from a public health perspective, the programmatic challenges of engagement in care under option B+ strategy, with the example of Mozambique, a country known to have one of the highest HIVprevalence figures in the world. More specifically, we focused on three important aspects of engagement in care: the antenatal cascade of care, the maternal ART retention and the HIV exposed infant (HEI) testing coverage.We observed a high uptake of HIV testing, significant improvement in ART coverage over time and a better acceptance of ART at initiation in HIV+ pregnant women. Retention in care by the end of the first year of ART in HIV+ pregnant women and HIV testing coverage in HEI remainsub-optimal. Therefore, interventions to improve the mother-infant pair’s engagement in care should be systematically promoted. Finally, we underscore the considerable heterogeneity of definitions of outcomes used across various PMTCT programs.This work has highlighted the gaps in optimal engagement care of the mother-infant pair and its consequences on achieving virtual elimination of MTCT of HIV. We also highlighted the importance of having a consensus approach to measure PMTCT programme outcomes to allow national and international comparisons. Efforts to retain women under lifelong ART, ensuring their HIV-exposed infants receive the expected PMTCT services at the right moments along the continuum until final HIV status is determined, is the cornerstone of achieving an AIDS free generation by 2030.
... Countries such as Malawi, Zambia, and South Africa with a high HIV burden have introduced option B+. 45 This approach has clinical benefits to the mother's own health through early initiation of ART and reduced vertical transmission. 46,47 However, client refusal and drop out have been demonstrated to be among other obstacles that threaten the success of option B+. 46 Although there is a policy shift toward treating all HIV-infected pregnant women irrespective of CD4 count, CD4 count still remains a useful tool for monitoring patient's response to treatment in settings where VL monitoring is limited. 48 Point-of-care technologies for CD4 count are available, [49][50][51][52] and studies have demonstrated that POC CD4 testing can overcome challenges associated with laboratory-based CD4 testing. ...
... Countries such as Malawi, Zambia, and South Africa with a high HIV burden have introduced option B+. 45 This approach has clinical benefits to the mother's own health through early initiation of ART and reduced vertical transmission. 46,47 However, client refusal and drop out have been demonstrated to be among other obstacles that threaten the success of option B+. 46 Although there is a policy shift toward treating all HIV-infected pregnant women irrespective of CD4 count, CD4 count still remains a useful tool for monitoring patient's response to treatment in settings where VL monitoring is limited. 48 Point-of-care technologies for CD4 count are available, [49][50][51][52] and studies have demonstrated that POC CD4 testing can overcome challenges associated with laboratory-based CD4 testing. ...
Article
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Point-of-care (POC) testing can improve health care provision in settings with limited access to health care services. Access to POC diagnostic services has shown potential to alleviate some diagnostic challenges and delays associated with laboratory-based methods in low-and middle-income countries. Improving accessibility to POC testing (POCT) services during antenatal and perinatal care is among the global health priorities to improve maternal and child health. This review provides insights on the availability of POC testing designed for diagnosing HIV, syphilis, and malaria in pregnancy to improve maternal and child health. In addition, factors such as accessibility of POC testing, training of health work force, and the efficiency of POC testing services delivery in low-and middle-income countries are discussed. A framework to help increase access to POC diagnostic services and improve maternal and child health outcomes in low-and middle-income countries is proposed.
... Infant infections averted was the most common outcome measure among all the studies. While two studies [25,27] applied a fixed time horizon of 10 years, the other studies applied a lifetime horizon [24,28,29]. ...
... However, if Options B and B+ led to a larger increase in DALYs, this may merely imply both strategies have a higher ICER than Option A and not necessarily that either is 'less cost-effective'. Tweya et al. [28] evaluated the cost-effectiveness of Option B+ (lifelong ART) relative to Option B in Malawi. Their study used an individual-based simulation model to simulate 10,000 women and their infants. ...
Article
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Introduction: The 2016 World Health Organization (WHO) consolidated guideline recommends lifelong antiretroviral therapy (ART) for all HIV-infected pregnant and breastfeeding women for preventing mother-to-child HIV transmission (PMTCT). Ambiguity remains about the cost-effectiveness of this strategy in resource-limited developing countries. Areas Covered: We reviewed model-based studies on the cost-effectiveness of lifelong ART (formerly Option B+) relative to previous WHO guidelines for PMTCT. Our search using PubMed, Medline and Google Scholar for articles on Option B+ resulted in the final inclusion of seven studies published between 2012 and 2016. The Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist was used to assess the quality of reporting. Outcomes of interest, which included infant infections averted, maternal quality and length of life, and the Incremental Cost Effectiveness Ratio (ICER), were used in comparing cost-effectiveness. Expert Commentary: Despite most model-based studies favouring lifelong ART (Option B+) in terms of cost-effectiveness in comparison to Options A and B, inclusiveness of the evidence remains weak for generalization largely because setting specificity for providing lifelong ART to all pregnant and breastfeeding women may differ significantly in each setting. Therefore, future cost-effectiveness studies should be robust, setting-specific, and endeavor to assess the willingness and ability to pay of each setting.
... A number of studies have since provided evidence supporting the policy decisions around Option B + [56,57]. However, stakeholders should be mindful that implementation of strategies like Option B + raises concerns since many of these studies do not take into account initial costs and upfront investment required to scale up PMTCT programs to a level that can be considered cost-effective over an extended time period [61,75]. Additionally, while the majority of PMTCT studies included in this review focused on Prong III, only one study addressed PMTCT Prong II by studying the expansion of family planning services as a cost-effective method to avert HIV infections through the prevention of unintended pregnancies [47]. ...
Article
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Background: Sub-Saharan Africa carries the highest HIV burden globally. It is important to understand how interventions cost-effectively fit within guidelines and implementation plans, especially in low- and middle-income settings. We reviewed the evidence from economic evaluations of HIV prevention interventions in sub-Saharan Africa to help inform the allocation of limited resources. Methods: We searched PubMed, Web of Science, Econ-Lit, Embase, and African Index Medicus. We included studies published between January 2009 and December 2018 reporting cost-effectiveness estimates of HIV prevention interventions. We extracted health outcomes and cost-effectiveness ratios (CERs) and evaluated study quality using the CHEERS checklist. Findings: 60 studies met the full inclusion criteria. Prevention of mother-to-child transmission interventions had the lowest median CERs ($1144/HIV infection averted and $191/DALY averted), while pre-exposure prophylaxis interventions had the highest ($13,267/HIA and $799/DALY averted). Structural interventions (partner notification, cash transfer programs) have similar CERs ($3576/HIA and $392/DALY averted) to male circumcision ($2965/HIA) and were more favourable to treatment-as-prevention interventions ($7903/HIA and $890/DALY averted). Most interventions showed increased cost-effectiveness when prioritizing specific target groups based on age and risk. Interpretation: The presented cost-effectiveness information can aid policy makers and other stakeholders as they develop guidelines and programming for HIV prevention plans in resource-constrained settings.
... To simplify the cascade and improve PMTCT services, the World Health Organization introduced Option B+ in 2013 by which HIV-positive women initiate lifelong antiretroviral therapy (ART) during pregnancy regardless of CD4 count [15]. Since then, studies have found Option B+ to be cost-effective [16][17][18][19]. A study in Malawi found that Option B+ not only prevented infant infections, but also increased the mother's 10-year survival rate by more than 4-fold compared with the standard of care [19]. ...
Article
Full-text available
Background: Prevention of mother-to-child HIV transmission (PMTCT) care cascade failures drive pediatric HIV infections in sub-Saharan Africa. As nurses' clinical and management role in PMTCT expand, decision-support tools for nurses are needed to facilitate identification of cascade inefficiencies and solutions. The mobile phone-based PMTCT cascade analysis tool (mPCAT) provides health facility staff a quick summary of the number of patients and percentage drop-off at each step of the PMCTC care cascade, as well as how many women-infant pairs would be retained if a step was optimized.
... To simplify the cascade and improve PMTCT services, the World Health Organization introduced Option B+ in 2013 by which HIV-positive women initiate lifelong antiretroviral therapy (ART) during pregnancy regardless of CD4 count [15]. Since then, studies have found Option B+ to be costeffective [16][17][18][19]. A study in Malawi found that Option B+ not only prevented infant infections, but also increased the mother's ten-year survival rate by more than four-fold compared to the standard of care [19]. ...
Article
Full-text available
Background: Prevention of mother-to-child HIV transmission (PMTCT) care cascade failures drive pediatric HIV infections in sub-Saharan Africa. As nurses' clinical and management role in PMTCT expand, decision-support tools for nurses are needed to facilitate identification of cascade inefficiencies and solutions. The mobile phone-based PMTCT cascade analysis tool (mPCAT) provides health facility staff a quick summary of the number of patients and percentage drop-off at each step of the PMCTC care cascade, as well as how many women-infant pairs would be retained if a step was optimized. Objective: The objective of this study was to understand and improve the mPCAT's core usability factors and assess the health workers' experience with using the mPCAT. Methods: Overall, 2 rounds of usability testing were conducted with health workers from 4 clinics and leading experts in maternal and child health in Kenya and Mozambique using videotaped think aloud assessment techniques. Semistructured group interviews gauged the understanding of mPCAT's core usability factors, based on the Nielsen Usability Framework, followed by development of cognitive demand tables describing the needed mPCAT updates. Post adaptation, feasibility was assessed in 3 high volume clinics over 12 weeks. Participants completed a 5-point Likert questionnaire designed to measure ease of use, convenience of integration into work, and future intention to use the mPCAT. Focus group discussions with nurse participants at each facility and in-depth interviews with nurse managers were also conducted to assess the acceptability, use, and recommendations for adaptations of the mPCAT. Results: Usability testing with software engineers enabled real-time feedback to build a tool following empathic design principles. The revised mPCAT had improved navigation and simplified data entry interface, with only 1 data entry field per page. Improvements to the results page included a data visualization feature and the ability to share results through WhatsApp. Coding was simplified to enable future revisions by nontechnical staff-critical for context-specific adaptations for scale-up. Health care workers and facility managers found the tool easy to use (mean=4.3), used the tool very often (mean=4.1), and definitely intended to continue to use the tool (mean=4.8). Ease of use was the most common theme identified, with emphasis on how the tool readily informed system improvement decision making. Conclusions: The mPCAT was well accepted by frontline health workers and facility managers. The collaborative process between software developer and user led to the development of a more user-friendly, context-specific tool that could be easily integrated into routine clinical practice and workflow. The mPCAT gave frontline health workers and facility managers an immediate, direct, and tangible way to use their clinical documentation and routinely reported data for decision making for their own clinical practice and facility-level improvements.
... To simplify the cascade and improve PMTCT services, the World Health Organization introduced Option B+ in 2013 by which HIV-positive women initiate lifelong antiretroviral therapy (ART) during pregnancy regardless of CD4 count [15]. Since then, studies have found Option B+ to be cost-effective [16][17][18][19]. A study in Malawi found that Option B+ not only prevented infant infections, but also increased the mother's 10-year survival rate by more than 4-fold compared with the standard of care [19]. ...
Preprint
BACKGROUND Prevention of mother-to-child HIV transmission (PMTCT) care cascade failures drive pediatric HIV infections in sub-Saharan Africa. As nurses’ clinical and management role in PMTCT expand, decision-support tools for nurses are needed to facilitate identification of cascade inefficiencies and solutions. The mobile phone-based PMTCT cascade analysis tool (mPCAT) provides health facility staff a quick summary of the number of patients and percent drop-off at each step of the PMCTC care cascade, as well as how many women-infant pairs would be retained if a step was optimized. OBJECTIVE The objective of this study is to understand and improve the mPCAT’s core usability factors and assess the health workers’ experience with using the mPCAT. METHODS Two rounds of usability testing were conducted with health workers from four clinics and leading experts in maternal and child health in Kenya and Mozambique using video-taped ‘think aloud’ assessment techniques. Semi-structured group interviews gauged understanding of mPCAT core usability factors, based on the Neilsen Usability Framework, followed by development of cognitive demand tables describing needed mPCAT updates. Post-adaptation, feasibility was assessed in two high volume clinics over 12 weeks. Participants completed a five-point Likert questionnaire designed to measure ease of use, convenience an integration into work, and future intention to use the mPCAT. Focus group discussions with nurse participants at each facility and in-depth interviews with nurse managers were also conducted to assess the acceptability, use, and recommendation for adaptations of the mPCAT. RESULTS Usability testing with software engineers enabled real-time feedback to build a tool following empathic design principles. The revised mPCAT had improved navigation and simplified data entry interface, with only one data entry field per page. Improvements to the results page included a data visualization feature and the ability to share results through WhatsApp. Coding was simplified to enable future revisions by non-technical staff – critical for context-specific adaptations for scale-up. Health care workers and facility managers found the tool “easy to use” (mean = 4.3/5), used the tool “very often” (mean = 4.1/5), and “definitely” intended to continue to use the tool (mean = 4.8/5). Ease of use was the most common theme identified, with emphasis on how the tool readily informed system improvement decision-making. CONCLUSIONS The mPCAT was well accepted by frontline health workers and facility managers. The collaborative process between software developer and user led to the development of a more user-friendly, context-specific tool that could be easily integrated into routine clinical practice and workflow. The mPCAT gave frontline health workers and facility managers an immediate, direct, and tangible way to use their clinical documentation and routinely reported data for decision making for their own clinical practice and facility-level improvements.
... Our LTFU rate in 2014 was 1.3% (or 202 subjects), which is a very low proportion, demonstrating that successful engagement of patients in care is feasible in resource-limited settings if there is a programme tailored to patient needs. The WHO B+ approach to care, which was pioneered by Malawi in sub-Saharan Africa, has also proved to be cost-effective and successful in enhancing ART use in the HIV-infected patient population [9,10]. The LTFU rate observed in our programme is markedly lower than that reported for other programmes in the same geographical region [11][12][13][14][15][16][17][18][19][20][21][22], albeit that the populations and programmes evaluated were inherently different from our cohort and programme (many were prevention of mother-to-child HIV transmission programmes), as was the methodology in many studies. ...
Article
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Objectives: Retention of subjects in HIV treatment programmes is crucial for the success of treatment. We evaluated retention/loss to follow-up (LTFU) in subjects receiving established care in Malawi. Methods: Data for HIV-positive patients registered in Drug Resource Enhancement Against AIDS and Malnutrition centres in Malawi prior to 2014 were reviewed. Visits entailing HIV testing/counselling, laboratory evaluations, nutritional evaluation/supplementation, community support, peer education, and antiretroviral (ART) monitoring/pharmacy were noted. LTFU was defined as > 90 days without an encounter. Parameters potentially associated with LTFU were explored, with univariate/multivariate logistic regression analyses being performed. Results: Fifteen thousand and ninety-nine patients registered before 2014; 202 (1.3%) were lost to follow-up (LTFU) (1.3%). Nine (0.5%) of 1744 paediatric patients were LTFU vs. 1.4% (n = 193) of 13 355 adults (P < 0.001). Subjects who were LTFU had fewer days in care than retained subjects (1338 vs. 1544, respectively; P < 0.001) and a longer duration of ART (1530 vs. 1300 days, respectively; P < 0.001). Subjects who were LTFU had higher baseline HIV viral loads (P = 0.016) and higher body mass indexes (P < 0.001), were more likely to live in urban settings (88% of patients who were LTFU lived in urban settings) with better housing [relative risk (RR) 2.3; 95% confidence interval (CI) 1.67-3.09; P < 0.001], and were more likely to be educated (RR 1.88; 95% CI 1.42-2.50; P < 0.001). Distance to the centre and cost of transportation were associated with LTFU (RR 3.4; 95% CI 2.84-5.37; P < 0.001), as was absence of a maternal figure (RR 1.57; 95% CI 1.17-2.09; P < 0.001). Viral load, distance index, education and a maternal figure were predictive of LTFU. Conclusions: Educated, urbanized HIV-infected adults living far from programme centres are at high risk of LTFU, particularly if there is no maternal figure in the household. These variables must be taken into consideration when developing retention strategies.
... Further, the overall benefit of SWEN among breastfed HIV-exposed infants needs to be determined in light of 2015 WHO guidelines, which recommend Option B+ (lifelong ART for HIV-infected pregnant and breastfeeding women) for the prevention of HIV MTCT [26]. Recent studies from Malawi and Ghana have reported substantial decreases in vertical HIV transmission to breastfed infants with Option B+ [27,28], and a study from Nigeria reported virtually no HIV MTCT among breastfed infants who also received SWEN prophylaxis [29]. Elimination of HIV MTCT may be achievable with Option B+; however, despite being one of the WHO's 22 global targets for scale-up of PMTCT interventions, India has very recently implemented Option B+ on a national level. ...
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Latest World Health Organization guidelines recommend weight-based nevirapine prophylaxis for all HIV-exposed infants in resource-limited settings, yet low birth weight (LBW) infants (< 2500 g) have been understudied. Using data from the NIH-funded India six-week extended-dose nevirapine (SWEN) study, a randomized clinical trial of SWEN versus single-dose nevirapine (SD) for prevention of breast-milk HIV-1 transmission, we examined the relative impact of SWEN among 737 mother-infant pairs stratified by infant birth weight. Birth weight groups were defined as very LBW (VLBW) ≤ 2000 g, moderate LBW (MLBW) >2000 g and ≤ 2500 g, and normal birth weight (NBW) > 2500 g. Outcomes were HIV-1 infection, HIV-1 infection or death by 12 months, and severe adverse events (SAEs). The Kaplan-Meier method was used to estimate probability of efficacy outcomes in birth weight groups, and differential effects of SWEN by birth weight group were examined using Cox proportional hazards models adjusting for independent risk factors for HIV maternal-to-child transmission and significant covariates. Among 50 VLBW, 249 MLBW, and 433 NBW infants, 50% were randomized to SWEN; median gestational age was 36, 38 and 38 weeks, respectively; and there was no difference in breastfeeding duration (p = 0.99). Compared to SD: SWEN-treated VLBW had lower estimates of HIV-1 infection (13% vs. 38%, p = 0.004) and HIV-1 infection or death (13% vs. 41%, p = 0.002); SWEN-treated MLBW had lower estimated HIV-1 infection (13% vs. 17%, p = 0.042); and efficacy endpoints were similar by treatment arm in NBW. In multivariate analysis, SWEN was associated with reduced risk of HIV-1 infection or death by 83% (p = 0.03) in VLBW versus 45% (p = 0.05) in MLBW. SAE frequency was similar by treatment arm in VLBW (68% vs. 76%, p = 0.53) and MLBW (37% vs. 36%, p = 0.93). SWEN may safely increase HIV-free survival among HIV-exposed LBW infants with greatest protective advantage among infants ≤ 2000 g.
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Utilization of the prevention of mother-to-child transmission of HIV (PMTCT) services remains a challenge as losses to follow-up are substantial. This study explored factors that influence adherence to maternal antiretroviral (ARV) medications among PMTCT mothers in Malawi. We conducted a descriptive qualitative study from September 2016 to May 2017 using purposive sampling among 16 PMTCT mothers and 4 key informant interviews with health-care workers. Data were audio-recorded and analyzed thematically. The factors that influence adherence to maternal ARV medications include the quality of PMTCT services and social support. Factors that impede adherence include suboptimal counseling women receive on ARV medications, cost of travel, and conflicting advice from religious institutions. Adherence to maternal ARV medications will require the use of existing social support systems in a woman’s life as a platform for delivery of the drugs while also maintaining continued and comprehensive counseling on the benefits of maternal ARV medications.
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HIV testing of African immigrants in Belgium showed that HIV existed among Africans by 1983. However, the epidemic was recognized much later in most parts of sub-Saharan Africa (SSA) due to stigma and perceived fear of possible negative consequences to the countries’ economies. This delay had devastating mortality, morbidity, and social consequences. In countries where earlier recognition occurred, political leadership was vital in mounting a response. The response involved establishment of AIDS control programs and research on the HIV epidemiology and candidate preventive interventions. Over time, the number of effective interventions has grown; the game changer being triple antiretroviral therapy (ART). ART has led to a rapid decline in HIV-related morbidity and mortality in addition to prevention of onward HIV transmission. Other effective interventions include safe male circumcision, pre-exposure prophylaxis, and post-exposure prophylaxis. However, since none of these is sufficient by itself, delivering a combination package of these interventions is important for ending the HIV epidemic as a public health threat.
https://cran.r-project. org/web/packages/gems/index.html. [Accessed
  • L Salazar-Vizcaya
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Salazar-Vizcaya L, Blaser N, Gsponer T. https://cran.r-project. org/web/packages/gems/index.html. [Accessed 19 May 2015]
Update: Disability weights for disease and conditions
World Health Organisation. Global Burden of Disease 2004 Update: Disability weights for disease and conditions; 2004. p. 1-9.
Malawi Population Projections
National Statistics Office. Malawi Population Projections 2008-2030. National Statistics Office, Zomba, Malawi: 2008. http://www.nsomalawi.mw/images/stories/data_on_line/ demography/census_2008/Main Report/ThematicReports/Popu lation Projections Malawi.pdf. [Accessed 10 April 2015]
Prevention of HIV-1 infection with early antiretroviral therapy
  • Ms Cohen
  • Yq Chen
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  • Mc Hosseinipour
  • N Kumarasamy
Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011; 365:493–505.
Clinical Management of HIV in Children and Adults: Malawi integrated guidelines for providing HIV services. Lilongwe: Malawi Ministry of Health
  • Malawi Ministry
  • Health
Malawi Ministry of Health. Clinical Management of HIV in Children and Adults: Malawi integrated guidelines for providing HIV services. Lilongwe: Malawi Ministry of Health; 2014.
Clinical management of HIV in children and adults: Malawi integrated guidelines for providing HIV services
  • Malawi Ministry
  • Health
Malawi Ministry of Health. Clinical management of HIV in children and adults: Malawi integrated guidelines for providing HIV services. Lilongwe, Malawi: Malawi Ministry of Health; 2014
gems: An R Package for Simulating from Disease Progression Models
  • Nello
  • Blaser
  • Estill
  • Janne
  • Cindy Zahnd
  • Kalesan
  • Bindu
  • Egger
  • Matthias
  • Olivia Keiser
Nello, Blaser, Estill, Janne, Zahnd, Cindy, Kalesan, Bindu, Egger, Matthias, Keiser, Olivia, et al. gems: An R Package for Simulating from Disease Progression Models. J Stat Software. 2015; 64 http://www.jstatsoft.org/v64/i10/.
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Maternal mortality remains a daunting problem in Mozambique and many other low-resource countries. High quality antenatal care (ANC) services can improve maternal and newborn health outcomes and increase the likelihood that women will seek skilled delivery care. This study explores the factors influencing provider uptake of the recommended package of ANC interventions in Mozambique. This study used qualitative research methods including key informant interviews with stakeholders from the health sector and a total of five focus group discussions with women with experience with ANC or women from the community. Study participants were selected from three health centers located in Maputo city, Tete, and Cabo Delgado provinces in Mozambique. Staff responsible for the medicines/supply chain at national, provincial and district level were interviewed. A check list was implemented to confirm the availability of the supplies required for ANC. Deductive content analysis was conducted. Three main groups of factors were identified that hinder the implementation of the ANC package in the study setting: a) system or organizational: include chronic supply chain deficiencies, failures in the continuing education system, lack of regular audits and supervision, absence of an efficient patient record system and poor environmental conditions at the health center; b) health care provider factors: such as limited awareness of current clinical guidelines and a resistant attitude to adopting new recommendations; and c) Users: challenges with accessing ANC, poor recognition amongst women about the purpose and importance of the specific interventions provided through ANC, and widespread perception of an unfriendly environment at the health center. The ANC package in Mozambique is not being fully implemented in the three study facilities, and a major barrier is poor functioning of the supply chain system. Recommendations for improving the implementation of antenatal interventions include ensuring clinical protocols based on the ANC model. Increasing the community understanding of the importance of ANC would improve demand for high quality ANC services. The supply chain functioning could be strengthened through the introduction of a kit system with all the necessary supplies for ANC and a simple monitoring system to track the stock levels is recommended.
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Mathematical models of disease progression predict disease outcomes and are useful epidemiological tools for planners and evaluators of health interventions. The 𝖱 package gems is a tool that simulates disease progression in patients and predicts the effect of different interventions on patient outcome. Disease progression is represented by a series of events (e.g., diagnosis, treatment and death), displayed in a directed acyclic graph. The vertices correspond to disease states and the directed edges represent events. The package gems allows simulations based on a generalized multistate model that can be described by a directed acyclic graph with continuous transition-specific hazard functions. The user can specify an arbitrary hazard function and its parameters. The model includes parameter uncertainty, does not need to be a Markov model, and may take the history of previous events into account. Applications are not limited to the medical field and extend to other areas where multistate simulation is of interest. We provide a technical explanation of the multistate models used by gems, explain the functions of gems and their arguments, and show a sample application.
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Background: Women may have persistent risk of HIV acquisition during pregnancy and postpartum. Estimating risk of HIV during these periods is important to inform optimal prevention approaches. We performed a systematic review and meta-analysis to estimate maternal HIV incidence during pregnancy/postpartum and to compare mother-to-child HIV transmission (MTCT) risk among women with incident versus chronic infection. Methods and findings: We searched PubMed, Embase, and AIDS-related conference abstracts between January 1, 1980, and October 31, 2013, for articles and abstracts describing HIV acquisition during pregnancy/postpartum. The inclusion criterion was studies with data on recent HIV during pregnancy/postpartum. Random effects models were constructed to pool HIV incidence rates, cumulative HIV incidence, hazard ratios (HRs), or odds ratios (ORs) summarizing the association between pregnancy/postpartum status and HIV incidence, and MTCT risk and rates. Overall, 1,176 studies met the search criteria, of which 78 met the inclusion criterion, and 47 contributed data. Using data from 19 cohorts representing 22,803 total person-years, the pooled HIV incidence rate during pregnancy/postpartum was 3.8/100 person-years (95% CI 3.0-4.6): 4.7/100 person-years during pregnancy and 2.9/100 person-years postpartum (p = 0.18). Pooled cumulative HIV incidence was significantly higher in African than non-African countries (3.6% versus 0.3%, respectively; p<0.001). Risk of HIV was not significantly higher among pregnant (HR 1.3, 95% CI 0.5-2.1) or postpartum women (HR 1.1, 95% CI 0.6-1.6) than among non-pregnant/non-postpartum women in five studies with available data. In African cohorts, MTCT risk was significantly higher among women with incident versus chronic HIV infection in the postpartum period (OR 2.9, 95% CI 2.2-3.9) or in pregnancy/postpartum periods combined (OR 2.3, 95% CI 1.2-4.4). However, the small number of studies limited power to detect associations and sources of heterogeneity. Conclusions: Pregnancy and the postpartum period are times of persistent HIV risk, at rates similar to "high risk" cohorts. MTCT risk was elevated among women with incident infections. Detection and prevention of incident HIV in pregnancy/postpartum should be prioritized, and is critical to decrease MTCT.
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The Ministry of Health in Malawi is implementing a pragmatic and innovative approach for the management of all HIV-infected pregnant women, termed Option B+, which consists of providing life-long antiretroviral treatment, regardless of their CD4 count or clinical stage. Our objective was to determine if Option B+ represents a cost-effective option. A decision model simulates the disease progression of a cohort of HIV-infected pregnant women receiving prophylaxis and antiretroviral therapy, and estimates the number of paediatric infections averted and maternal life years gained over a ten-year time horizon. We assess the cost-effectiveness from the Ministry of Health perspective while taking into account the practical realities of implementing ART services in Malawi. If implemented as recommended by the World Health Organization, options A, B and B+ are equivalent in preventing new infant infections, yielding cost effectiveness ratios between US$ 37 and US$ 69 per disability adjusted life year averted in children. However, when the three options are compared to the current practice, the provision of antiretroviral therapy to all mothers (Option B+) not only prevents infant infections, but also improves the ten-year survival in mothers more than four-fold. This translates into saving more than 250,000 maternal life years, as compared to mothers receiving only Option A or B, with savings of 153,000 and 172,000 life years respectively. Option B+ also yields favourable incremental cost effectiveness ratios (ICER) of US$ 455 per life year gained over the current practice. In Malawi, Option B+ represents a favorable policy option from a cost-effectiveness perspective to prevent future infant infections, save mothers' lives and reduce orphanhood. Although Option B+ would require more financial resources initially, it would save societal resources in the long-term and represents a strategic option to simplify and integrate HIV services into maternal, newborn and child health programmes.
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Background. In 2010, the World Health Organization (WHO) released revised guidelines for prevention of mother-to-child human immunodeficiency virus (HIV) transmission (PMTCT). We projected clinical impacts, costs, and cost-effectiveness of WHO-recommended PMTCT strategies in Zimbabwe. Methods. We used Zimbabwean data in a validated computer model to simulate a cohort of pregnant, HIV-infected women (mean age, 24 years; mean CD4 count, 451 cells/µL; subsequent 18 months of breastfeeding). We simulated guideline-concordant care for 4 PMTCT regimens: single-dose nevirapine (sdNVP); WHO-recommended Option A, WHO-recommended Option B, and Option B+ (lifelong maternal 3-drug antiretroviral therapy regardless of CD4). Outcomes included maternal and infant life expectancy (LE) and lifetime healthcare costs (2008 US dollars [USD]). Incremental cost-effectiveness ratios (ICERs, in USD per year of life saved [YLS]) were calculated from combined (maternal + infant) discounted costs and LE. Results. Replacing sdNVP with Option A increased combined maternal and infant LE from 36.97 to 37.89 years and would reduce lifetime costs from $5760 to $5710 per mother–infant pair. Compared with Option A, Option B further improved LE (38.32 years), and saved money within 4 years after delivery ($5630 per mother–infant pair). Option B+ (LE, 39.04 years; lifetime cost, $6620 per mother–infant pair) improved maternal and infant health, with an ICER of $1370 per YLS compared with Option B. Conclusions. Replacing sdNVP with Option A or Option B will improve maternal and infant outcomes and save money; Option B increases health benefits and decreases costs compared with Option A. Option B+ further improves maternal outcomes, with an ICER (compared with Option B) similar to many current HIV-related healthcare interventions.
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The World Health Organization (WHO) has called for the "virtual elimination" of pediatric HIV: a mother-to-child HIV transmission (MTCT) risk of less than 5%. We investigated uptake of prevention of MTCT (PMTCT) services, infant feeding recommendations, and specific drug regimens necessary to achieve this goal in Zimbabwe. We used a computer model to simulate a cohort of HIV-infected, pregnant/breastfeeding women (mean age, 24 y; mean CD4, 451/µl; breastfeeding duration, 12 mo). Three PMTCT regimens were evaluated: (1) single-dose nevirapine (sdNVP), (2) WHO 2010 guidelines' "Option A" (zidovudine in pregnancy, infant nevirapine throughout breastfeeding for women without advanced disease, lifelong combination antiretroviral therapy for women with advanced disease), and (3) WHO "Option B" (pregnancy/breastfeeding-limited combination antiretroviral drug regimens without advanced disease; lifelong antiretroviral therapy with advanced disease). We examined four levels of PMTCT uptake (proportion of pregnant women accessing and adhering to PMTCT services): reported rates in 2008 and 2009 (36% and 56%, respectively) and target goals in 2008 and 2009 (80% and 95%, respectively). The primary model outcome was MTCT risk at weaning. The 2008 sdNVP-based National PMTCT Program led to a projected 12-mo MTCT risk of 20.3%. Improved uptake in 2009 reduced projected risk to 18.0%. If sdNVP were replaced by more effective regimens, with 2009 (56%) uptake, estimated MTCT risk would be 14.4% (Option A) or 13.4% (Option B). Even with 95% uptake of Option A or B, projected transmission risks (6.1%-7.7%) would exceed the WHO goal of less than 5%. Only if the lowest published transmission risks were used for each drug regimen, or breastfeeding duration were shortened, would MTCT risks at 95% uptake fall below 5%. Implementation of the WHO PMTCT guidelines must be accompanied by efforts to improve access to PMTCT services, retain women in care, and support medication adherence throughout pregnancy and breastfeeding, to approach the "virtual elimination" of pediatric HIV in Zimbabwe. Please see later in the article for the Editors' Summary.
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Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. In nine countries, we enrolled 1763 couples in which one partner was HIV-1-positive and the other was HIV-1-negative; 54% of the subjects were from Africa, and 50% of infected partners were men. HIV-1-infected subjects with CD4 counts between 350 and 550 cells per cubic millimeter were randomly assigned in a 1:1 ratio to receive antiretroviral therapy either immediately (early therapy) or after a decline in the CD4 count or the onset of HIV-1-related symptoms (delayed therapy). The primary prevention end point was linked HIV-1 transmission in HIV-1-negative partners. The primary clinical end point was the earliest occurrence of pulmonary tuberculosis, severe bacterial infection, a World Health Organization stage 4 event, or death. As of February 21, 2011, a total of 39 HIV-1 transmissions were observed (incidence rate, 1.2 per 100 person-years; 95% confidence interval [CI], 0.9 to 1.7); of these, 28 were virologically linked to the infected partner (incidence rate, 0.9 per 100 person-years, 95% CI, 0.6 to 1.3). Of the 28 linked transmissions, only 1 occurred in the early-therapy group (hazard ratio, 0.04; 95% CI, 0.01 to 0.27; P<0.001). Subjects receiving early therapy had fewer treatment end points (hazard ratio, 0.59; 95% CI, 0.40 to 0.88; P=0.01). The early initiation of antiretroviral therapy reduced rates of sexual transmission of HIV-1 and clinical events, indicating both personal and public health benefits from such therapy. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 052 ClinicalTrials.gov number, NCT00074581.).
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The most effective highly active antiretroviral therapy (HAART) to prevent mother-to-child transmission of human immunodeficiency virus type 1 (HIV-1) in pregnancy and its efficacy during breast-feeding are unknown. We randomly assigned 560 HIV-1-infected pregnant women (CD4+ count, > or = 200 cells per cubic millimeter) to receive coformulated abacavir, zidovudine, and lamivudine (the nucleoside reverse-transcriptase inhibitor [NRTI] group) or lopinavir-ritonavir plus zidovudine-lamivudine (the protease-inhibitor group) from 26 to 34 weeks' gestation through planned weaning by 6 months post partum. A total of 170 women with CD4+ counts of less than 200 cells per cubic millimeter received nevirapine plus zidovudine-lamivudine (the observational group). Infants received single-dose nevirapine and 4 weeks of zidovudine. The rate of virologic suppression to less than 400 copies per milliliter was high and did not differ significantly among the three groups at delivery (96% in the NRTI group, 93% in the protease-inhibitor group, and 94% in the observational group) or throughout the breast-feeding period (92% in the NRTI group, 93% in the protease-inhibitor group, and 95% in the observational group). By 6 months of age, 8 of 709 live-born infants (1.1%) were infected (95% confidence interval [CI], 0.5 to 2.2): 6 were infected in utero (4 in the NRTI group, 1 in the protease-inhibitor group, and 1 in the observational group), and 2 were infected during the breast-feeding period (in the NRTI group). Treatment-limiting adverse events occurred in 2% of women in the NRTI group, 2% of women in the protease-inhibitor group, and 11% of women in the observational group. All regimens of HAART from pregnancy through 6 months post partum resulted in high rates of virologic suppression, with an overall rate of mother-to-child transmission of 1.1%. (ClinicalTrials.gov number, NCT00270296.)
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Both breastfeeding pattern and duration are associated with postnatal HIV acquisition; their relative contribution has not been reliably quantified. Pooled data from 2 cohorts: in urban West Africa where breastfeeding cessation at 4 months was recommended but exclusive breastfeeding was rare (Ditrame Plus, DP); in rural South Africa where high rates of exclusive breastfeeding were achieved, but with longer duration (Vertical Transmission Study, VTS). 18-months HIV postnatal transmission (PT) was estimated by Kaplan-Meier in infants who were HIV negative, and assumed uninfected, at age >1 month. Censoring with (to assess impact of mode of breastfeeding) and without (to assess effect of breastfeeding duration) breastfeeding cessation considered as a competing event. Of 1195 breastfed infants, not HIV-infected perinatally, 38% DP and 83% VTS children were still breastfed at age 6 months. By age 3 months, 66% of VTS children were exclusively breastfed since birth and 55% of DP infants predominantly breastfed (breastmilk+water-based drinks). 18-month PT risk (95%CI) in VTS was double that in DP: 9% (7-11) and 5% (3-8), respectively (p = 0.03). However, once duration of breastfeeding was allowed for in a competing risk analysis assuming that all children would have been breastfed for 18-month, the estimated PT risk was 16% (8-28) in DP and 14% (10-18) in VTS (p = 0.32). 18-months PT risk was 3.9% (2.3-6.5) among infants breastfed for less than 6 months, and 8.7% (6.8-11.0) among children breastfed for more than 6 months; crude hazard ratio (HR): 2.1 (1.2-3.7), p = 0.02; adjusted HR 1.8 (0.9-3.4), p = 0.06. In individual analyses of PT rates for specific breastfeeding durations, risks among children exclusively breastfed were very similar to those in children predominantly breastfed for the same period. Children exposed to solid foods during the first 2 months of life were 2.9 (1.1-8.0) times more likely to be infected postnatally than children never exposed to solids this early (adjusted competing risk analysis, p = 0.04). Breastfeeding duration is a major determinant of postnatal HIV transmission. The PT risk did not differ between exclusively and predominantly breastfed children; the negative effect of mixed breastfeeding with solids on PT were confirmed.
Article
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A great deal of progress has been made in our understanding of mother-to-child transmission of HIV-1. Standardization of case definitions and transmission rate calculation methodologies, and a broader array of diagnostic options for detection of infant HIV-1 infection, will enhance our ability to evaluate and compare cohorts worldwide. In the next decade, several intervention studies should be completed. Carefully designed intervention studies have the potential both to determine which interventions are effective as well as to add to our understanding of vertical transmission of HIV-1. Regional differences in vertical transmission rates reflect a variety of viral, host, and obstetric factors. Intervention strategies will probably need to be regionally designed, taking into consideration these factors. Further research on timing and correlates of vertical transmission is necessary to determine the extent to which specific clinical trials can be extrapolated to public health policy.
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The optimal duration of zidovudine administration to prevent perinatal transmission of human immunodeficiency virus type 1 (HIV-1) should be determined to facilitate its use in areas where resources are limited. We conducted a randomized, double-blind equivalence trial of zidovudine starting in the mother at 28 weeks' gestation, with 6 weeks of treatment in the infant (the long-long regimen), which is similar to protocol 076; zidovudine starting at 35 weeks' gestation, with 3 days of treatment in the infant (the short-short regimen); a long-short regimen; and a short-long regimen. The mothers received zidovudine orally during labor. The infants were fed formula and were tested for HIV DNA at 1, 45, 120, and 180 days. After the first interim analysis, the short-short regimen was stopped. A total of 1437 women were enrolled. At the first interim analysis, the rates of HIV transmission were 4.1 percent for the long-long regimen and 10.5 percent for the short-short regimen (P=0.004). For the entire study period, the transmission rates were 6.5 percent (95 percent confidence interval, 4.1 to 8.9 percent) for the long-long regimen, 4.7 percent (95 percent confidence interval, 2.4 to 7.0 percent) for the long-short regimen, and 8.6 percent (95 percent confidence interval, 5.6 to 11.6 percent) for the short-long regimen. The rate of in utero transmission was significantly higher with the two regimens with shorter maternal treatment (5.1 percent) than with the two with longer maternal treatment (1.6 percent). The short-short zidovudine regimen is inferior to the long-long regimen and leads to a higher rate of perinatal HIV transmission. The long-short, short-long, and long-long regimens had equivalent efficacy. However, the higher rate of in utero transmission with the short-long regimen suggests that longer treatment of the infant cannot substitute for longer treatment of the mother.
Article
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The Women and Infants Transmission Study is a prospective natural history study that has been enrolling HIV-1-infected pregnant women and their infants since 1989. To evaluate the impact of different antiretroviral regimens on perinatal HIV-1 transmission at the population level. Prospective cohort study. Plasma HIV-1 RNA levels were serially measured in 1542 HIV-1-infected women with singleton live births between January 1990 and June 2000. HIV-1 status of the infant. HIV-1 transmission was 20.0% (95% confidence interval [CI], 16.1%-23.9%) for 396 women who not receiving prenatal antiretroviral therapy; 10.4% (95% CI, 8.2%-12.6%) for 710 receiving zidovudine monotherapy; 3.8% (95% CI, 1.1%-6.5%) for 186 receiving dual antiretroviral therapy with no or one highly active drug (Multi-ART); and 1.2% (95% CI, 0-2.5%) for 250 receiving highly active antiretroviral therapy (HAART). Transmission also varied by maternal delivery HIV RNA level: 1.0% for <400; 5.3% for 400 to 3499; 9.3% for 3500 to 9999; 14.7% for 10,000 to 29,999; and 23.4% for >30,000 copies/mL (p =.0001 for trend). The odds of transmission increased 2.4-fold (95% CI, 1.7-3.5) for every log10 increase in delivery viral load. In multivariate analyses adjusting for maternal viral load, duration of therapy, and other factors, the odds ratio for transmission for women receiving Multi-ART and HAART compared with those receiving ZDV monotherapy was 0.30 (95% CI, 0.09-1.02) and 0.27 (95% CI, 0.08-0.94), respectively. Levels of HIV-1 RNA at delivery and prenatal antiretroviral therapy were independently associated with transmission. The protective effect of therapy increased with the complexity and duration of the regimen. HAART was associated with the lowest rates of transmission.
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Since the implementation of free maternity services in South Africa from 1994, more maternity services were provided (SA, 1994: 73). These services are however inaccessible to many pregnant women in the rural areas, leading to sub-optimal antenatal health service utilization. Another problem that emerged, is deterioration in antenatal health service rendering throughout the country, as well as a lack of guidelines for the mobilization of pregnant women in order to promote optimal antenatal health service utilization (ANHSU) in the North West Province. The mentioned problems were the reasons for undertaking this research.
Article
Objective: To assess factors, outcomes and reasons for loss to follow-up (LTFU) among pregnant and breastfeeding women initiated on a lifelong antiretroviral therapy (ART) for PMTCT in a large antenatal clinic in Malawi. Methods: We identified all pregnant and breastfeeding women who were initiated on ART between September 2011 and September 2013 and had missed their clinic appointment by at least 3 weeks at Bwaila Hospital, the largest antenatal clinic in Malawi. These women were traced by phone or home visits. Their true status and reasons for ART discontinuation were documented during tracing. Results: A total of 2930 women started ART for PMTCT; 2458 (84%) pregnant and 472 (16%) breastfeeding, of which, 577 (20%) missed a scheduled clinic appointment. LTFU was associated with younger age, being pregnant, and earlier year of ART initiation. We successfully traced 229 (40%), of whom, 10 (4%) had died. Of the 219 women found alive, 118 (54%) had stopped taking ARV drugs, 67 (30%) had self-transferred to another ART clinic, 13 (6%) had collected drugs from other sources, 9 (4%) had treatment interruptions and 12 (5%) had other outcomes. Reasons cited for stopping ART were travel (38%), lack of transport money (16%), not understanding the initial ARV education session (10%), being too weak/sick (10%), ARV side effects (10%) and other reasons. Conclusion: Approximately half of the women who were traced were taking ARVs. The study emphasises the need for enhanced post-test counselling strategies, ongoing psychosocial support, provision of incentives and further decentralisation efforts of PMTCT services.
Article
To explore the levels and determinants of loss to follow-up (LTF) under universal lifelong antiretroviral therapy (ART) for pregnant and breastfeeding women ('Option B+') in Malawi. We examined retention in care, from the date of ART initiation up to 6 months, for women in the Option B+ program. We analysed nationwide facility-level data on women who started ART at 540 facilities (n = 21 939), as well as individual-level data on patients who started ART at 19 large facilities (n = 11 534). Of the women who started ART under Option B+ (n = 21 939), 17% appeared to be lost to follow-up 6 months after ART initiation. Most losses occurred in the first 3 months of therapy. Option B+ patients who started therapy during pregnancy were five times more likely than women who started ART in WHO stage 3/4 or with a CD4 cell count 350 cells/μl or less, to never return after their initial clinic visit [odds ratio (OR) 5.0, 95% confidence interval (CI) 4.2-6.1]. Option B+ patients who started therapy while breastfeeding were twice as likely to miss their first follow-up visit (OR 2.2, 95% CI 1.8-2.8). LTF was highest in pregnant Option B+ patients who began ART at large clinics on the day they were diagnosed with HIV. LTF varied considerably between facilities, ranging from 0 to 58%. Decreasing LTF will improve the effectiveness of the Option B+ approach. Tailored interventions, like community or family-based models of care could improve its effectiveness.
Article
Most countries follow WHO 2010 guidelines for the prevention of mother-to-child transmission (PMTCT) of HIV using either Option A or B for women not yet eligible for antiretroviral therapy (ART). Both of these approaches involve the use of antiretrovirals during pregnancy and breastfeeding. Some countries have adopted a new strategy, Option B+, in which HIV-positive pregnant women are started immediately on ART and continued for life. Option B+ is more costly than Options A or B, but provides additional health benefits. In this article, we estimate the additional costs and effectiveness of Option B+. We developed a deterministic model to simulate births, breastfeeding, and HIV infection in women in four countries, Kenya, Zambia, South Africa, and Vietnam that differ in fertility rate, birth interval, age at first birth, and breastfeeding patterns, but have similar age at HIV infection. We estimated the total PMTCT costs and new child infections under Options A, B, and B+, and measured cost-effectiveness as the incremental PMTCT-related costs per child infection averted. We included adult sexual transmissions averted from ART, the corresponding costs saved, and estimated the total incremental cost per transmission (child and adult) averted. When considering PMTCT-related costs and child infections, Option B+ was the most cost-effective strategy costing between $6000 and $23 000 per infection averted compared with Option A. Option B+ averted more child infections compared with Option B in all four countries and cost less than Option B in Kenya and Zambia. When including adult sexual transmissions averted, Option B+ cost less and averted more infections than Options A and B.
Article
Although previous studies investigated pregnancy rates among women on antiretroviral therapy (ART), incidence of, and factors associated with pregnancy among these women remain poorly understood. We, therefore, conducted a retrospective cohort study at a large public HIV clinic in Lilongwe, Malawi, between July 2007 and December 2010. At each clinic visit, pregnancy status was assessed. Time to event analysis was conducted using Poisson regression. Among 4,738 women, 589 pregnancies were observed. Pregnancy incidence was 9.3/100 person-years. After 6 months on ART, women on ART had similar total fertility rates to women in the urban population. In multivariable analysis, increasing age and advanced WHO clinical stage were associated with decreased probability of becoming pregnant while higher body mass index and longer time on ART were associated with increased probability of becoming pregnant. We recommend that ART clinics integrate comprehensive family planning services to address reproductive health needs among women on ART.
Article
Guidelines for treatment of pediatric HIV have recently changed to recommend that all infants who are identified as HIV-infected should start antiretroviral treatment (ART) immediately, regardless of their immunologic or clinical status. This study aims to assess the likely impact of this change in guideline in South Africa. A mathematical model was developed to simulate mother-to-child transmission of HIV, disease progression, and death of HIV-infected children <15 years of age. The model is calibrated to South African data sources, including prevention of mother-to-child transmission program coverage data, pre-ART survival data, ART program statistics, and pediatric HIV prevalence studies. Relative to what would be expected in the absence of early ART initiation, the number of infant AIDS deaths over the 2010-2025 period is expected to drop by 23.6% (95% confidence interval [CI]: 22.5-24.5%) at current levels of polymerase chain reaction (PCR) diagnosis, and by 34.2% (95% CI: 32.7-35.6%) if PCR diagnosis increases to 80% of perinatally infected infants at 2 months. However, the pediatric HIV disease burden has shifted toward older children in recent years. The effect of early ART on total pediatric AIDS mortality during the 2010-2025 period is therefore modest: a 9.8% reduction (95% CI: 7.9-12.6%) at current levels of PCR diagnosis, and a 14.2% reduction (95% CI: 11.4-18.2%) if PCR coverage increases to 80% of perinatally infected infants. The changes in ART guidelines for infants will have a significant impact on pediatric AIDS mortality at young ages, but further efforts are required to reduce the substantial growing AIDS mortality in older children.
Article
World Development Indicators, the World Bank's respected statistical publication presents the most current and accurate information on global development on both a national level and aggregated globally. This information allows readers to monitor the progress made toward meeting the goals endorsed by the United Nations and its member countries, the World Bank, and a host of partner organizations in September 2001 in their Millennium Development Goals. The print edition of World Development Indicators 2005 allows you to consult over 80 tables and over 800 indicators for 152 economies and 14 country groups, as well as basic indicators for a further 55 economies. There are key indicators for the latest year available, important regional data, and income group analysis. The report contains six thematic presentations of analytical commentary covering: World View, People, Environment, Economy, States and Markets, and Global Links.
Article
The observation that mother-to-child transmission of HIV-1 can occur through breastfeeding has resulted in policies that recommend avoidance of breastfeeding by HIV-1-infected women in the developed world and under specific circumstances in developing countries. We compared transmission rates in exclusively breastfed, mixed-fed, and formula-fed (never breastfed) infants to assess whether the pattern of breastfeeding is a critical determinant of early mother-to-child transmission of HIV-1. We prospectively assessed infant-feeding practices of 549 HIV-1-infected women who were part of a vitamin A intervention trial in Durban, South Africa. The proportions of HIV-1-infected infants at 3 months (estimated by use of Kaplan-Meier life tables) were compared in the three different feeding groups. HIV-1 infection was defined by a positive RNA-PCR test. At 3 months, 18.8% (95% CI 12.6-24.9) of 156 never-breastfed children were estimated to be HIV-1 infected compared with 21.3% (17.2-25.5) of 393 breastfed children (p=0.5). The estimated proportion (Kaplan-Meier) of infants HIV-1 infected by 3 months was significantly lower for those exclusively breastfed to 3 months than in those who received mixed feeding before 3 months (14.6% [7.7-21.4] vs 24.1% [19.0-29.2], p=0.03). After adjustment for potential confounders (maternal CD4-cell/CD8-cell ratio, syphilis screening test results, and preterm delivery), exclusive breastfeeding carried a significantly lower risk of HIV-1 transmission than mixed feeding (hazard ratio 0.52 [0.28-0.98]) and a similar risk to no breastfeeding (0.85 [0.51-1.42]). Our findings have important implications for prevention of HIV-1 infection and infant-feeding policies in developing countries and further research is essential. In the meantime, breastfeeding policies for HIV-1-infected women require urgent review. If our findings are confirmed, exclusive breastfeeding may offer HIV-1-infected women in developing countries an affordable, culturally acceptable, and effective means of reducing mother-to-child transmission of HIV-1 while maintaining the overwhelming benefits of breastfeeding.
Article
To identify factors affecting HIV-1 breastfeeding transmission. Longitudinal observational cohort study. HIV-1 seropositive pregnant women and seronegative controls were enrolled at a maternity hospital in Nairobi. Women and their children were followed from birth, and data on HIV-1 transmission, breastfeeding, clinical illness, and growth were collected. Specimens for HIV-1 serology and/or polymerase chain reaction were obtained at birth, 2, 6, and 14 weeks, 6, 9, 12, and 18 months, and every 6 months thereafter. Children were classified as HIV-1 uninfected, perinatally, or postnatally infected. Potentially breastfeeding transmission related risk factors were compared between postnatally infected and uninfected children. Among children born to seropositive or seroconverting mothers, 317 were uninfected, 51 infected perinatally and 42 infected postnatally. Identified risk factors for postnatal transmission were maternal nipple lesions (OR = 2.3, CI 95% 1.1-5.0), mastitis (OR = 2.7, CI 95% 1.1-6.7), maternal CD4 cell count < 400 mm3 (OR = 4.4, CI 95% 1.9-9.9), maternal seroconversion while breastfeeding (OR = 6.0, CI 95% 1.8-19.8), infant oral thrush at < 6 months of age (OR = 2.8, CI 95% 1.3-6.2) and breastfeeding longer than 15 months (OR = 2.4, CI 95% 1.2-5.1). All factors, except maternal seroconversion due to its rarity, were independently associated with an increased postnatal transmission risk by multivariate logistic regression analysis. In addition perinatal antiretroviral therapies, public health strategies should address: (i) prevention of maternal nipple lesions, mastitis and infant thrush; (ii) reduction of breastfeeding duration by all HIV-1-infected mothers; (iii) absolute avoidance of breastfeeding by those at high risk, and (iv) prevention of HIV-1 transmission to breastfeeding mothers.
Article
Despite high infant and maternal mortality rates, many Mozambican women with access to prenatal services delay prenatal clinic consultations, limiting opportunity for prevention and treatment of preventable pregnancy complications. Ethnographic research, interviews with health providers and longitudinal pregnancy case studies with 83 women were conducted in Central Mozambique to examine pregnant women's underutilization of clinic-based prenatal services. The study found that pregnancy beliefs and prenatal practices reflect women's attempts to influence reproduction under conditions of vulnerability at multiple levels. Women reported high maternal reproductive morbidity, frequent pregnancy wastage, and immense pressure to bear children throughout their reproductive years. Reproductive vulnerability is intensified by poverty and an intense burden placed on poor, peri-urban women farmers for family subsistence and continuous fertility in a period of economic austerity, land shortages, and increasing social conflict and inequality. In this environment of economic insecurity exacerbated by congested living conditions, women report competing for scarce resources, including male support and income. This vulnerability heightens women's perceptions that they and their unborn infants will be targets of witchcraft or sorcery by jealous neighbors and kin. They respond by hiding pregnancy and delaying prenatal care. Within the context of women's perceived reproductive risks, delayed prenatal care can be seen as a strategy to protect pregnancy from purposeful human and spirit harm. Women mobilized limited resources to acquire prenatal care outside the formal clinic setting. It is concluded that provision of clinical prenatal services is insufficient to reduce reproductive risks for the most socially and economically marginal since it is their vulnerability that prevents women from using available services. Confidential maternity services and social safety nets for greater economic security are recommended.
Article
The Drug Resource Enhancement against AIDS and Malnutrition (DREAM) program is a large antiretroviral therapy treatment program financed by the Treatment Acceleration Program (TAP) of the World Bank. In addition to provision of antiretroviral treatment to individuals infected with human immunodeficiency virus (HIV) in sub-Saharan Africa, one major aspect of the DREAM program is nutritional supplementation and prevention of mother-to-child transmission (PMTCT) of HIV. HIV-positive pregnant women enrolled in the DREAM program receive highly active antiretroviral therapy (HAART) free of charge from the 25th week of gestation, irrespective of clinical stage, CD4 count, and viral load. Their infants receive post-exposure prophylaxis. From 2004 to 2006, women enrolled in the DREAM program in Mozambique, Tanzania, and Malawi received water filters and formula for the first 6 months of lactation. In a second cohort starting in 2005 until 2006 in Mozambique, women received HAART for up to 6 months after delivery and were given the option to breastfeed. We conducted a comparative analysis of the two cohorts of HIV-positive pregnant women followed prospectively and evaluated HIV-1 mother-to-child transmission rates, infant morbidity, and mortality in both cohorts. In the first cohort, 879 live-born children were delivered, with 809 evaluable infants at 1 and 6 months. In the second cohort, 341 infants were delivered and evaluable at 1 month, and 251 infants were evaluable at 6 months. At age 1 month, HIV-1 transmission rates were 4/341 (1.2%) among breastfed infants and 7/809 (0.8%) among formula-fed infants. At age 6 months, HIV-1 mother-to-child transmission rates were 2/251 (0.8%) among breastfed infants of women receiving HAART and 15/809 (1.8%) among formula-fed infants (chi = 0.77, P = 0.38 [NS]). The cumulative incidence rate at 6 months of age was 2.7% for formula-fed infants and 2.2% for breastfed infants (chi = 0.27, P = 0.60 [NS]). There was a trend for HIV-1 infection rates to be slightly greater among formula-fed infants, but overall mother-to-child transmission rates in both cohorts were extremely low. Most infants did relatively well on both feeding regimens. Observed Z scores were greater than among the general infant population in the community. Z scores < or =2.0 for weight by age occurred in 92/809 formula-fed infants (11.4%) and in 28/251 breastfed infants (11.1%). The rates of anemia in the study infant population were also lower than that of the general population. A hemoglobin value <8 g/dl was found in 40/809 formula-fed infants (4.9%) and in 17/251 breastfed infants (6.8%) (chi = 0.92, P = 0.33). The mortality rate at 6 months of age was 27 per 1000 person-years among formula-fed infants and 28.5 per 1000 person-years in breastfed infants--both considerably lower than the rates of 101 per 1000 person-years observed in Mozambique. The DREAM HIV-1 PMTCT protocol was safe and efficacious in reducing transmission in infants of 1 and 6 months of age. Results were comparable to those from developed countries. Breastfeeding among HIV-1 infected mothers receiving HAART posed no additional risk of late postnatal HIV-1 transmission to the infant by 6 months of age.
Article
This paper is a report of a systematic review to identify and analyse the main factors affecting the utilization of antenatal care in developing countries. Antenatal care is a key strategy for reducing maternal mortality, but millions of women in developing countries do not receive it. A range of electronic databases was searched for studies conducted in developing countries and published between 1990 and 2006. English-language publications were searched using relevant keywords, and reference lists were hand-searched. A systematic review was carried out and both quantitative and qualitative studies were included. Twenty-eight papers were included in the review. Studies most commonly identified the following factors affecting antenatal care uptake: maternal education, husband's education, marital status, availability, cost, household income, women's employment, media exposure and having a history of obstetric complications. Cultural beliefs and ideas about pregnancy also had an influence on antenatal care use. Parity had a statistically significant negative effect on adequate attendance. Whilst women of higher parity tend to use antenatal care less, there is interaction with women's age and religion. Only one study examined the effect of the quality of antenatal services on utilization. None identified an association between the utilization of such services and satisfaction with them. More qualitative research is required to explore the effect of women's satisfaction, autonomy and gender role in the decision-making process. Adequate utilization of antenatal care cannot be achieved merely by establishing health centres; women's overall (social, political and economic) status needs to be considered.