Efficacy of Antiretroviral Drugs in Reducing Mother-to-Child Transmission of HIV-AID - Essay Example

Antiretroviral drugs (ARVs) have been regarded as efficacious in the promotion of Prevention of Mother to Child Transmission (PMTCT) of HIV.However, minimal studies have been conducted to ascertain its effect in Sub-Saharan Africa, especially Zambia. The proposed review will be used in estimating the effectiveness of ARVs in reducing the prevalence of Mother to Child Transmission (MTCT) of HIV in Zambia. EMBASE, Medline and Cochrane Library will be researched for information related to MTCT of HIV and use of ARVs by the pregnant Zambian women. The metameter that will be used will be the cumulative incidence of HIV transmissions through recognition of each arm within a trial as the data point. The sample size will be directly determined from the sources. Transmission of 4-6 weeks postpartum will be chosen to reflect the combined intepartum and intrapartum transmission. Publication will be assessed through constructing a publication funnel plot while using Duval and Tweedie’s trim and fill process in ascertaining the number of the publications missing in the event of a bias. A one-study-removed analysis will be run for both the placebo and the ARV use group to determine if there was a study with a disproportionate effect to the combined estimate. A cumulative meta-analysis of the chronological arrangement of the sources will also be conducted to determine the period when the conclusive evidence of the ARV efficacy was available. Table of Contents Abstract 1 Background/Rationale 4 Methods of the Review 6 Search Strategy 6 Study Selection Criteria and Procedures 7 Evaluating the research evidence 7 Methodology 7 Definition of the Evidence Threshold 8 Study Quality Assessment Checklists and Procedures 9 Data Synthesis 10 Measuring the Review Outcome 11 Challenges 12 Recommendations 13 References 13 Systematic Review on the Efficacy of Antiretroviral Drugs in Reducing Mother-to-Child Transmission of HIV/AIDS Sub-Saharan Africa (Zambia) According to Gisselquist et al. (2009), HIV pandemic has evolved in various characteristics and paces since its identification in 1983. The pandemic has grown to unprecedented levels in most sub-Saharan countries with most studies affirming that the disease is more prevalent in females than males (UNAIDS, 2008). Some of the factors identified by Boerma and Weir (2005) as controlling the spread dynamics of HIV/AIDS include individual factors such as biological susceptibility and behaviour as well as broader factors that include urbanisation and modernisation. The 2008 Report on the Global AIDS Epidemic indicates that an estimated 22 million people were infected with HIV/AIDS in sub-Saharan Africa (UNAIDS, 2008). Out of these people, 2 million are children, with the main cause of infection being mother-to-child transmission. The risk factors for the transmission include high viral load with a low CD4 count, breastfeeding, vaginal delivery that may cause lacerations and infections resulting from prolonged rapture of membranes (UNAIDS 2008; Carael et al, 2004; Brahmbhatt et al, 2006; Bravo-Garcia, Magis-Rodriquez and Saavedra, 2006; Brucková et al, 2007; Bradshaw et al, 2004). Some of the interventions for the reduction of mother-to-child transmission include caesarean delivery, use of antiretroviral drugs (ARVs) and avoiding breastfeeding (Stringer et al, 2005). The most feasible strategy as suggested by Stringer et al (2005) is the use of ARVs that reduces the viral load. The population that will be affected by the review will be children and women. The systematic review will focus on the sources i.e. studies and reports containing information on use of antiretroviral drugs in Zambia, whose evaluation and analysis ranges from 2005 to 2012. According to Patrikios et al (2010), several studies and intervention strategies have been published and reported since HIV/AIDS was introduced in Zambia. In view of the urgency to improve the effectiveness of the use of ARVs in minimising HIV/AIDS pandemic in Zambia as well as the recent availability of research and evaluation findings, it is convenient to re-evaluate and re-assess the past studies on the strategy. Background/Rationale According to MacIntyre and Carey (2009), resources involved in the prevention of HIV/AIDS in Zambia are inadequate. The country is also characterised by competing and conflicting programs and activities as well as the increased demand for treatment services. This indicates that treatment resources should be distributed and used effectively. It is also apparent for the government to ensure that all the strategies of enhancing preventive attitudes among citizens are incorporated in the policy frame work. The results of this review can be applied in ascertaining the use of antiretroviral drugs to enhance their effectiveness in minimising mother to child transmission of HIV/AIDS in Zambia. The focus of this review has been enhanced by the rising number of infections among children (UNAIDS, 2008). It is important to review literature related to use of ARVs in identifying the reasons why the intervention strategy is still inefficient. Objectives The aim of the review is to undertake a systematic review of all the published reports and trials using ARV in the prevention of mother to child transmission The main objective of interest will be identification of the challenges facing the HIV/AIDS prevention policy and suggest improvement measures that can be applied in curbing the challenge. The prominent goal of this report is to systematically review ARV use in the prevention of mother transmission of HIV in Zambia; a constituent country of the Sub-Saharan Africa. The literary sources that will be reviewed should have analysed or laid emphasis on the information related to use of ARVs in PMTCT. Although the review evaluates the HIV/AIDS Prevention Policy in Sub-Saharan Africa (Zambia), the recommendations will be related to the strategies that can be applied in overcoming the challenges for inclusion in the policy framework. This review focuses on the recent literature from a wide range of electronic databases (Cleary, Hunt and Horsfall, 2009). These sources will be chosen depending on their information status related to HIV/AIDS prevention policy in Zambia. PICOD Elements for the Review Participants The participants will be mothers diagnosed with the HIV/AIDS, which will include the pregnant and breastfeeding mothers. The review will also focus on the children whose mothers are infected with HIV. The review will also focus on the studies of the mixed diagnosis if the outcomes if the outcomes were reported separately for the women with HIV. Intervention and Counter-intervention The interventions will focus on any measure or combination of measures related to the use of ARVs in the prevention of mother to child transmission of HIV/AIDS. Outcomes The outcomes will be any clinical outcome including (but not restricted to) child and mother survival, body response to the use of ARVs and the effective strategies for the prevention of mother to child transmission. The review will also recommend improvement strategies that can be applied by the policy makers, donors and programmers to improve the significance of the prevention policy to a higher level, suggest evidence-based additions to the currently proposed preventive strategies, and suggest recommendations for research priorities. Study Design The metameter that will be used will be the cumulative incidence of HIV transmissions through recognition of each arm within a trial as the data point. The sample size will be directly determined from the sources. Transmission of 4-6 weeks postpartum will be chosen to reflect the combined intepartum and intrapartum transmission. Publication will be assessed through constructing a publication funnel plot while using Duval and Tweedie’s trim and fill process in ascertaining the number of the publications missing in the event of a bias. Methods of the Review Search Strategy The review will involve the selection of relevant databases from the list of more than 120 available databases. These databases contain a wide range of information on HIV/AIDS which is not specific to use of ARV. The search will involve a computerised search of the following databases: the Embase, GlobalHealth, ERIC, Cochrane, Medline, PsychINFO and Web science of databases because they normally focus on publishing information related to medical health (Jesson, Matheson and Lacey, 2011). The sources should not be too old i.e. from 2005 to 2012. The geographical spread of the study should also be restricted in Sub-Saharan Africa without putting any barriers related to language. Even non-published sources will be included in the review to avoid the bias related to publication. Additionally, the review will involve cross-checking information from other studies i.e. published or evaluated before 2005 in cases where the sources import information from older sources. This enhances clarification and minimise errors. The search strategy will be constantly cross-checked to ensure that the pre-chosen sources fulfil the time requirements. In addition to the databases, other electronic sources will also be accessed e.g. HIV Prevention Trials Network (HPTN), Zambian National HIV/AIDS/STI/TB Council, UNAIDS, WHO and the government of Zambia websites. The review may also involve direct communication with authors if the information contained in the studies identified as sources is not complete. The references from all the relevant studies will be examined for additional citations. Study Selection Criteria and Procedures Evaluating the research evidence This section will involve the evaluation of the evidence related to the effectiveness of ARV use in PMTCT strategies. The preventive strategies are normally complex and contain conflicting and complicated opinions. The review attempts to utilise these diverse views in coming up with an effective workable strategy that can reduce the increased spread of the disease in Zambia. Some of the strategies target individuals while others target communities and groups. It is anticipated that the effectiveness and generalisability of the findings will be affected by cultural differences among Zambians, the legal implication of the strategy to the Zambian legal framework as well as the availability of the resources required for the implementation of the strategy and integrating it into the legal framework (Jesson, Matheson and Lacey, 2011). The findings will also be affected by stigma, knowledge of HIV/AIDS, sexual behaviour, male circumcision, poverty, population, and mobility as well as alcohol and drug abuse. The HIV/AIDS related stigma in Zambia is a widespread problem, with adverse cases being witnessed in homes and health care centres. Serious gaps still exist on the HIV/AIDS awareness levels among Zambians. This undermines the increased government’s commitment to improve awareness. Methodology 1. Source selection will be determined based on the pre-defined inclusion or exclusion criteria i.e. they should be closely related ARV use or PMTCT programmes. The information sources will be subjected to critical review once identified. 2. Information on the two concepts will be presented depending on the available empirical literature. The strength of each one of them is dependent on the factors such as the study design, evaluation of the concept, analysis and the feasibility of the concept in enhancing the effectiveness of the prevention policy. This is then compared with the current situation i.e. the theoretical evidence threshold. 3. The comparison provides evidence based recommendations that address the main aspects of the review topic. Flow Diagram of the Study Selection Process Definition of the Evidence Threshold The range of sources as well as evidence required in the analysis of the various components is dependent on the complexity of the concept. For example, the recommendations would not require a wide range of sources compared to preventive policies because most of its information will be outsourced from the other concepts. Considerations for defining the threshold in this report include feasibility, potential negative outcomes, cost, acceptability, and potential size of the effect as well as social benefits (Higgins, Green & Cochrane Collaboration, 2008). Feasibility defines the human resources and logistics required in the implementation of the recommended preventive strategy. Effective strategies require low costs for implementation. The preventive strategies that may lead to any form of property loss or harm to the health of a person are considered unfeasible. The potential for adverse outcomes of the proposed recommendation increases the strength or evidence reviewed. This promotes the establishment of effective strategies that can minimise the negative impact. If the potential for negative outcomes following application of the recommendation are low, the threshold of the information required will be low. The higher the acceptability, the lower the amount of information required for the analysis of an aspect. The proposed prevention strategies should be widely accepted by the recipients i.e. community, religious leaders, donors or politicians. The effect of the proposed preventive strategy should also be estimated through theoretical evaluation using information from past research. The aspects with a higher potential effect requires low threshold of evidence. In addition to its effect on HIV/AIDS prevention, a recommendation would be plausible if it holds an aspect of health or social benefits. Study Quality Assessment Checklists and Procedures The source should fulfil the required conditions for inclusion in the review (Higgins, Green and Cochrane Collaboration, 2008). The information source will fulfil the time requirements, possess a succinct analysis and contain viable and specific information on the HIV/AIDS prevalence in Zambia or Sub-Saharan region. Evaluation on the potential studies will be conducted on a minimum of 100 individuals with a vivid explanation of any source of errors that could arise in the course of the study. The relevant citations will be evaluated first before acceptance for inclusion in the review, for example, on the basis of abstract, title or key words (Bell, 2007). Irrelevant sources such as letters or policy documents will not be included in the review. The reviewers will be more than one to ensure quality. The first reviewer will review and document the sources that directly fulfil the inclusion criteria and then discuss with other reviewers before including them in the final review. The second or other reviewers will be involved in reviewing the sources whose illegibility is unconfirmed and discuss their opinions with the first reviewer for consideration. More than two reviewers will be required to act as the neutralising agents for any disagreements between the first and the second reviewers. The inclusion criteria 1. Evaluation of the use of ARVs in preventing mother to child transmission of HIV/AIDS Sub-Saharan region, specifically Zambia 2. Dates: 2005-2012 3. Study based on an individual, community or government 4. Representative study population 5. Does the source represent change in the information it contains? 6. Evaluation conducted in more than the minimum number of sample proposed by the review i.e. 100 7. Study provides sufficient details that portray consistency in the past and the present status of the topic being addressed 8. The evaluation provides the inclusion or the exclusion criteria used during its preparation 9. Analysis appropriately conducted Data Synthesis The studies will be classified according to the study concepts i.e. use of ARVs in PMTCT and recommendations. The criteria will consider the contribution of the study to the review goals and its significance to the efforts geared towards enhancing HIV/AIDS prevention. The sources will be classified according to their level of contribution to the concepts of the study to ensure that a wide range of information is obtained from the sources (Scott et al, 2011). This provides the wide range of opinions and ideas required for an intervention or preventive strategy to be viable. Classification also ensures that all the selected sources provide specific information on the seemingly wide topic. Some of the studies will analyse multi-components e.g., it is expected that most of them will provide varying recommendations in addition to other review components. Therefore, it is the obligation of the reviewers to decipher what is relevant for the study from the various recommendations present in the sources. They identify the relevant information from two conflicting sources of information through discussions and referring to the studies that presents the evidence to the issue that is causing conflict. All sections will start with the summary of the main findings from the review sources. The information will be paraphrased and in text citations included to indicate the sources of the ideas. The evidence will be organised from the old to new. Summary and combined recommendations of the all reviews will then be presented. The results for the relevant studies will be presented in the comprehensive study descriptions. A significant p-value will also be considered for simplicity purposes. Measuring the Review Outcome It is not meaningful to statistically summarise the efficacy among studies in different comparison groups because each differ from the regimen or duration. The metameter that will be used will be the cumulative incidence of HIV transmissions through recognition of each arm within a trial as the data point. The sample size will be directly outsourced from the sources. Transmission of 4-6 weeks postpartum will be chosen to reflect the combined intepartum and intrapartum transmission. For the sources that did not reflect the data for the transmissions occurring between 4-6 weeks , the data that will be used will be close to four weeks but not less than three weeks because this might miss intrapartum transmission (Balasubramanian and Lagakos, 2001). The sources that produced multiple publications, the estimate reported once will be used because a cumulative metaanalysis will be used showing when the data was first available. The data will then be converted into standard rate and event error. Some of the heterogeneity that might be evident before the analysis includes differing durations, application of different regimen and the end point measured between 4-6 weeks. In conducting the summary statistics, the studies that use the ARV regimen will be separated from the ones that do not use the ARV regimen (placebo), where the analysis will later be conducted. The qualitative sensitivity of the model will be determined through the use of Mantel–Haenszel fixed effects model (Mantel and Hanszel, 1959). A one-study-removed analysis will be ran for both the placebo and the ARV use group to determine if there was a study with a disproportionate effect to the combined estimate. A cumulative meta-analysis of the chronological arrangement of the sources will also be conducted to determine the period when the conclusive evidence of the ARV efficacy was available. Publication will be assessed through constructing a publication funnel plot while using Duval and Tweedie’s trim and fill process in ascertaining the number of the publications missing in the event of a bias (Appendix 1; Reinwein, 2012). Challenges According to MacIntyre and Carey (2009) & UNAIDS (2008), HIV/AIDS use of ARVs as preventive strategies in Zambia are faced with various challenges. Some of the challenges include inadequate resources for purchase, dysfunctional government system and poor translation of the government regulations related to use of ARVs (UNAIDS 2008). According to Patrikios et al., (2010), the Zambian culture denies women the power to negotiate or contribute their opinions in matters related to marriages and/or sex. This may have far reaching effects on the practice for the use of ARVs among women. In conclusion, these challenges would be avoided if the systematic review will be carried out because the causes will be identified and appropriate solutions will formulated. Recommendations National and international collaboration should be applied in enhancing the use of ARVs among the pregnant women as well as the general population. The government should also increase funding for ARVs because as Gisselquist et al, (2009) purports, most of the PMTCT programs have failed due to inadequate funding. Education should also be enhanced to minimise the high levels of lack of knowledge related to the dynamics of spread or contraction. The master strategy should involve both the formal and informal community institutions to ensure that the grassroots counsellors and peer educators are well trained on the mechanisms of promoting the use of ARVs among women. References Balasubramanian R. and Lagakos SW. (2001) Estimation of the timing of perinatal transmission of HIV Biometrics, 57: 1048–5108. Bell, S. (2007) Tools every searcher should know and use Online, 31(5), 22-27. Publisher, viewed 12 Jan 2013 from . Boerma, J.T. & Weir, S.S. (2005) ‘Integrating demographic and epidemiological approaches to research on HIV/AIDS: The proximate-determinants framework’ The Journal of Infectious Diseases, vol. 191, pp. 61–7. Bradshaw D et al. (2004) Unabated rise in number of adult deaths in South Africa South African Medical Journal, 94(4):278−279. Brahmbhatt H et al. (2006) Mortality in HIV-infected and uninfected children of HIV-infected and uninfected mothers in rural Uganda Journal of Acquired Immune Deficiency Syndrome, 41(4):504−508. Bravo-Garcia E, Magis-Rodriquez C, Saavedra J (2006) New estimates in Mexico: more than 180,000 people living with HIV XVI International AIDS Conference 13−18 August. Toronto, Ontario. Brucková M et al. (2007) HIV/AIDS in the Czech Republic, 2006 Euro surveillance Weekly Release, 12(4). Carael M et al. (2004) Sexual networks and HIV in four African populations: the use of a standardised behavioural survey with biological markers Oxford, Oxford University Press. Cleary, M., Hunt, G. & Horsfall, J. (2009) ‘Conducting efficient literature searches: strategies for mental health nurses’ Journal Of Psychosocial Nursing & Mental Health Services, vol. 47, no. 11, pp. 34-41. doi:10.3928/02793695-20090930-03 Gisselquist, D., Potterat, J.J., St. Lawrence. J.S., Hogan, M., Arora, N.K. & Correa, M. et al. (2009) ‘How to contain generalized HIV epidemics? A plea for better evidence to displace speculation Int J STD AIDS, vol. 20, pp. 443-446. Higgins, J.T., Green, S. & Cochrane Collaboration (2008) Cochrane handbook for systematic reviews of interventions, Chichester, England, Wiley-Blackwell. Jesson, J.K., Matheson, L. & Lacey, F.M. (2011) Doing your literature review: traditional and systematic techniques, Los Angeles, Calif, SAGE. MacIntyre, K. & Carey, S. (2009) Assessing the contribution of civil society organisations to the national response on HIV & AIDS in Zambia, 2006-2008 Lusaka, Zambia, National HIV/AIDS/STI/TB Council. Mantel N and Hanszel W. (1959) Statistical aspects of the analysis of data from retrospective studies of disease J Natl Cancer Inst 22:719–748. Patrikios, A., Mannathoko, C., Tembon, A., Manda, S., Sarr, B., Drake, L. & Bundy, D. (2010) Accelerating the education sector response To HIV: five years of experience from Sub-Saharan Africa, World Bank. Reinwein, J. (2012) Does the Modality Effect Exist? And if so, Which Modality Effect? Journal of Psycholinguistic Research, 41, 1, 1-32. Scott, S.D., Albrecht, L., OLeary, K., Ball, G.C., Dryden, D.M., Hartling, L., Hofmeyer, A. & Klassen, T.P. (2011) A protocol for a systematic review of knowledge translation strategies in the allied health professions, (BioMed Central Ltd.) BioMed Central Ltd. Stringer, J. S., Sinkala, M., Maclean, C. C., Levy, J., Kankasa, C., Degroot, A., Stringer, E. M., Vermund, S. H. (2005) Effectiveness of a city-wide program to prevent mother-to-child HIV transmission in Lusaka, Zambia Aids (London, England), 19, 12, 1309-15. UNAIDS (2008) Zambia country situation 2008, Available at: . Appendix Duval and Tweedie’s trim and fill process Trim and fill procedure calculates the effect of potential data censoring (including publication bias) on the outcome of the meta-analyses. Nonparametric, iterative technique examines the symmetry of effect sizes plotted by the inverse of the standard error. Ideally, the effect sizes should mirror on either side of the mean. The trim and fill process is as follows 1. The overall mean is calculated in the usual manner. 2. The number of hypothetical missing studies is estimated and their corresponding non-missing effect sizes are “trimmed” from the dataset. 3. The overall mean is re-estimated (excluding the omitted effect sizes). 4. The newly calculated “trimmed” mean is used to re-estimate the number of hypothetical missing studies (as in Step One). 5. Steps Two to Four are repeated until the signed ranks of the effect sizes do not change, and the algorithm is terminated. 6. The original dataset is “filled” with symmetric data points representing the potential omitted studies. 7. The overall mean effect size and confidence intervals are recalculated, incorporating the influence of the hypothetical missing studies 8. The L0 and R0 estimators indicate how many hypothetical, non-published studies with a negative effect size were missing from the meta-analysis (step 6 on the previous slide) Read More