As of December 2013, an estimated 35 million persons were living with HIV; approximately two thirds of these people were living in sub-Saharan Africa.1 The response to the HIV pandemic in Africa and in other low- and middle-income regions of the world has consisted of a variety of bilateral and multilateral support from donor agencies, and local support from countries. A majority of the support has been directed toward HIV care and treatment.
Accordingly, the past 10 years have witnessed a remarkable increase in the number of HIV-infected persons receiving antiretroviral therapy in low- and middle-income countries (LMIC)—from 300,000 in 2003 to 11.7 million in 2013.2,3 Expanded access to ART in these countries has led to significant increases in the proportion of eligible persons enrolled on ART, reaching coverage rates as high as 61% globally based on the World Health Organization (WHO) treatment guidelines' eligibility criteria of CD4 <350 cells per microliter in 2012.4 In 2013, WHO revised its guidelines to indicate eligibility at CD4 <500 cells per microliter; under these criteria, only 34% of eligible persons were on ART in 2013.2 Nevertheless, these changes in access to ART were estimated to have averted 4.2 million deaths through 2012.4
HIV prevention, care, and treatment programs in LMIC have been supported by a variety of sources, including over US $41 billion through the US President's Emergency Plan for AIDS Relief (PEPFAR)5 from 2004 to 2013, in addition to nearly US $9 billion in PEPFAR funds to support HIV, tuberculosis (TB), and malaria programs through the Global Fund to Fight AIDS, Tuberculosis and Malaria during this period.6 PEPFAR programs are coordinated by the US Department of State's Office of the US Global AIDS Coordinator and Health Diplomacy (OGAC) in Washington, DC and concentrated in 36 countries and regions in sub-Saharan Africa, South and Central Asia, Eastern Europe, Central America, and the Caribbean. Oversight, accountability, and support of in-country PEPFAR programs are accomplished through the US government (USG) interagency teams. PEPFAR “country operating plans” and budgets are submitted annually for review at OGAC with ultimate approval by the US Congress.
In HIV care and treatment, PEPFAR supports a range of care and support services besides ART including clinical (eg, monitoring to determine eligibility for ART and prevention and treatment of opportunistic infections) and nonclinical (eg, psychological, social, and preventive) services.7 Programming implemented with PEPFAR support in each country is determined through a dialog between the USG and host governments.
In 2013, the US Institute of Medicine (IOM), in its evaluation of PEPFAR, called attention to the wide range of non-ART care and support services supported by PEPFAR, and challenged PEPFAR to assess the impact of these services on key outcomes.8 The IOM recommended prioritizing care and support services that should be funded in PEPFAR country portfolios based on their impact—a recommendation consistent with the current focus of PEPFAR on “accountability, transparency, and impact.”8,9 In response, the PEPFAR Adult Care and Support interagency technical working group (TWG) reviewed available evidence on the impact of non-ART adult care and support interventions on key outcomes to assist PEPFAR country teams as they make care and support program decisions. This article presents the general approach and methods used in these reviews.
In late 2013, the PEPFAR Adult Care and Support interagency TWG undertook a review of the literature on each of 11 non-ART adult care and support services commonly funded by PEPFAR to evaluate the impact of each intervention on 5 outcomes: mortality, morbidity, retention in HIV care, quality of life, and prevention of ongoing HIV transmission. A 12th intervention—TB screening and treatment—was not reviewed because of the abundance of information on this intervention and its recognized importance (and separate budget allocations) in PEPFAR programming. A list of the 12 care and support interventions (including TB screening and treatment) is shown in Table 1.
Review teams were constituted from the PEPFAR Adult Care and Support TWG based on expertise and experience as related to the respective intervention. Where needed, subject matter experts who were not members of the TWG were invited to join the review teams. Each review team included at least 3 reviewers with subject matter expertise. These review teams constitute the authorship of the 11 intervention-specific articles in this supplement for which literature reviews were conducted.
The following databases were searched to perform this literature review: Medline, Global Health, and Embase through Ovid; Cumulative Index to Nursing and Allied Health Literature (CINAHL) through EBSCO; Sociological Abstracts (SOCA) through ProQuest; and African Index Medicus (AIM) through the WHO. Databases were assessed by librarians for their capability to perform complex searches. Aspects of databases considered included strength of controlled vocabulary and indexing, advanced search capabilities, and number of citations indexed by the database. According to capability, simple searches were performed in SOCA and AIM, searches of moderate complexity were performed in CINAHL, and searches of the highest complexity were performed in Medline, Embase, and Global Health. Search terms used to perform the review were agreed on by members of the review teams and 2 Centers for Disease Control and Prevention (CDC) librarians who performed the searches (G.B. and E.W.). Terms were intentionally chosen to produce a broad scope of results relating to HIV/AIDS and the selected interventions.
Base search strategies were created by the librarians to use across all 11 interventions for which the literature was reviewed. These strategies varied according to the capabilities of the databases in which they were performed. Simple base strategies, used in AIM and SOCA, used variations of the terms HIV, human immunodeficiency virus, AIDS, Acquired Immunodeficiency Syndrome, and HIV Infections to create filters that addressed HIV/AIDS. More complex base strategies, used in CINAHL, built on the simple base by introducing a filter that addressed the outcomes of interest, including mortality, morbidity, retention in care, quality of life, HIV transmission, and cost-effectiveness (see Appendix 1, Supplemental Digital Content, http://links.lww.com/QAI/A620). Base strategies of the highest complexity, used in Medline, Embase, and Global Health, further added developing countries or resource-limited settings' filter in an effort to limit citations to countries and socioeconomic groups of interest to the reviewers (see Appendix 2, Supplemental Digital Content, http://links.lww.com/QAI/A620). Additionally, base strategies used in Medline and Embase applied a humans-only filter that was not available in other databases. Further intervention-specific terms were applied to these base strategies depending on the intervention and database used. These additional terms are listed in the articles relating to the individual interventions in this supplement. All strategies were initially limited to a date range of January 1995–July 2013 (Several authors updated their literature searches in May 2014; see the intervention-specific articles for details). Results were inclusive of all publication types and languages.
Search results were exported into individual EndNote libraries by database and combined into large EndNote libraries by intervention. This enabled the librarians to remove duplicate references across databases while maintaining the result counts from individual databases.
EndNote libraries, without duplicates, were exported to Word Documents or sent directly to the reviewers based on software availability and reviewer preference.
For each HIV care and support intervention, reviewers scanned the citations and abstracts to identify studies that seemed to address the intervention of interest in persons living with HIV and reported on at least 1 of the 5 outcomes of interest (eligible studies). Full-text versions of these studies were obtained and reviewed by the review teams. Studies that, on full review, did not contain this information were excluded from further analysis. Those that did meet these criteria were included in the review (included studies).
Rating the Quality of Evidence for Individual Studies
The quality of the evidence from each of the included studies for each outcome of interest was summarized based on the type of study and other factors such as the number of study participants and the internal and external validity of the study data. The overall quality of evidence for each study was rated by the reviewers as strong, medium, or weak on the basis of these factors as adapted from the US Preventive Services Task Force (Table 2).10
Qualitative studies were rated separately using a scale that took into account the research design and methodology, theoretical framework, sampling process, methods of data collection and analysis, and how authors drew their conclusions.11 Based on this scale, qualitative studies were rated as level 1 (generalizable studies), level 2 (conceptual studies), level 3 (descriptive studies), or level 4 (single case study).
Articles that reported on cost-effectiveness were rated separately by a health economist and rated as level 1—full economic evaluation (includes cost-effectiveness analysis, cost-utility analysis, or cost-benefit analysis); level 2—partial economic evaluations (ie, cost analyses, cost-description studies, cost-outcome descriptions); or level 3—randomized trials and studies [reporting more limited information, such as estimates of resource use or costs associated with the intervention(s) and comparator(s)].
Rating the Quality of the Body of Evidence by Outcome
Because of the nature of the review and the review questions, as well as the heterogeneity of study populations, study methods, settings, and outcomes, we did not attempt quantitative synthesis of study results overall. Rather, for each intervention, reviewers rated the quality of evidence in the individual studies as described above, then grouped the studies by the outcome(s) addressed, and rated the overall quality of the body of evidence for each outcome as good, fair, or poor as adapted from the US Preventive Services Task Force (Table 3).10
Rating the Expected Impact by Outcome
The expected impact of the intervention by outcome was then determined based on the magnitude of effect demonstrated in individual studies, the quality of the body of evidence (all included studies), and consistency across the studies. Expected impact was rated as high, moderate, low, or uncertain based on criteria agreed on by the TWG a priori (Table 4). At least 2 members of each review team participated in assigning expected impact ratings for individual outcomes.
Data from included studies were abstracted and entered into an evidence-rating grid. The data elements included the study identifying information (lead author, title, journal and year published); the type of study [eg, randomized controlled trial, controlled trial without randomization, observational study, systematic review (with or without meta-analysis)]; the quality of evidence for each study; the quality of the body of evidence for each outcome; the magnitude of effect for each study, presented as hazard ratios, odds ratios, or relative risk, and 95% confidence intervals; and the overall expected impact for each outcome. These evidence-rating grids are included in each of the articles in this supplement.
Weekly conference calls coordinated by the Adult Care and Support TWG cochairs allowed reviewers from different groups to share progress to optimize adherence to the same general review approach. Each group was asked to summarize their study selection process and present it as a study flow diagram that included (1) the total number of citations from the CDC Library (and other sources, if applicable); (2) the number of abstracts that were deemed eligible for review of the full-text articles (eligible studies); (3) the number of full-text articles retrieved; (4) the number of studies excluded on full-text review; and lastly (5) the number of studies that fulfilled the inclusion criteria (included studies). These flow diagrams are included in the intervention-specific articles in this supplement.
The results of the 11 literature searches and a summary of the literature about TB screening are included in the 12 intervention-specific articles that are presented in this supplement. Each article contains a definition of the intervention of interest; intervention-specific search terms used in the review; a flow diagram indicating the process that led to the studies included in the review; detailed information on the included studies; and an assessment of the overall quality of evidence and the expected impact of the intervention on each of the outcomes of interest. Each article includes discussion of the limitations of the literature search on a particular topic, informational gaps and research priorities emanating from the reviews, and programmatic considerations related to implementation of the intervention in LMIC.
These literature reviews constitute a unique effort to assess the evidence for impact of PEPFAR-supported interventions on key health outcomes—consistent with the OGAC pillars of accountability, transparency, and impact as noted above.9 The impact pillar broadly aims to demonstrate sustained control of the HIV epidemic and demonstrate lives saved and new infections averted. However, it is the objective of this review and of the participating authors to present information that will be of value not only for PEPFAR in-country USG teams but also for other bilateral and multilateral donors and host governments in LMIC. Furthermore, the authors hope that this information will serve as a resource for discussions on how to prioritize HIV care and support funding to maximize the impact of these interventions on the HIV/AIDS epidemics in these countries.
The authors thank Kerry Dierberg, Rebecca Kahn, Julia Martin, and Douglas Shaffer (from the Office of the US Global AIDS Coordinator and Health Diplomacy) for review of the article and for logistical support in preparation of this supplement.