Methodology

Over the past five years, in addition to a wide array of research, advocacy and position papers focusing on the needs of women and girls, there has been an increase in the number of strongly evaluated published interventions that have proven effective in reaching various groups of women and girls and caring for their particular needs. The focus of this document is to gather the evidence of what programs have positive outcomes for women in HIV/AIDS prevention, treatment and care. This document reviews the evidence available on interventions and provides a summary of the evidence, along with the supporting research that documents the effectiveness of interventions designed to address the needs of women and girls.

The Complexities of Measuring What Works

Measuring “what works” is complicated since the outcomes and impacts of interventions depend on a number of biological and proximate determinants (Boerma and Weir, 2005). Understanding the epidemiology of HIV, how it is spread and who is at risk is critical for developing and evaluating successful interventions (Chin, 2007). The epidemiological concept of the reproductive number for HIV, R_0,[1]is a key component in understanding the epidemic in any given population. R₀ “is the number of secondarycases which one case would produce in a completely susceptiblepopulation [which] depends on the duration of the infectious period,the probability of infecting a susceptible individual duringone contact, and the number of new susceptible individuals contactedper unit of time” (Dietz, 1993: 23). Not surprisingly, the reproductive number for HIV varies considerably within and across countries and among groups within countries. For this reason, interventions need to be carefully tailored for various groups.

Operating in specific socioeconomic, cultural (including gender), and demographic settings, interventions, such as counseling and testing, must affect “proximate determinants” such as number of concurrent partners, condom use, blood safety practices, etc., which must act through biological determinants (exposure, efficiency of transmission per contact and duration of infectivity) to affect HIV transmission. “The distinction between underlying and proximate determinants is important for the conceptualization of pathways through which underlying determinants, including interventions, may affect infection” (Boerma and Weir, 2005: S64). Thus, when interventions are determined to work in this compendium of evidence, they have been shown to work through a pathway to affecting HIV – or at least a proximate determinant, such as partner reduction or condom use. Yet, a word of caution is due unless biological outcomes are measured. For example, it is possible for an intervention to increase condom use but “the effect of such an increase would depend on the extent to which condoms were used during sexual contact between infected and susceptible partners” (Boerma and Weir, 2005: S66). In this compendium, examples of interventions that improve proximate determinants with no impact on HIV are noted.

Rates of HIV prevalence reflect infections that have happened in the past. Therefore, it is important that programs and policies be based on the question: “Where will the next 1,000 infections occur?” (Bertozzi et al., 2008: 833). Policy and program responses to this question must be based on a clear understanding of the epidemiology of HIV, an understanding of the contexts in which women and girls live and the factors that make them vulnerable to HIV infection and evidence of what works.

Search Methodology

To search for relevant interventions that had been evaluated, SCOPUS[2] searches were conducted for 2005-2009, using the search words HIV or AIDS and wom*n. Additional topics were researched using “syphilis and HIV;” “gender and HIV;” “malaria and HIV;” “breastfeeding and HIV;” and “abortion and HIV.” For the years 2005 to 2009, a total of 7,744 citations were generated. Of these citations, approximately 2,500 articles were reviewed in full. If the article title indicated that there might be an intervention that could be replicated; then the article was obtained and reviewed. The lead author read and reviewed all the articles obtained and determined if there was sufficient information to be included in “What Works” and that the intervention took place in Asia, Africa, Latin America and the post-Soviet states. Key interventions that had taken place only in the US, Europe, Japan and Australia were included only if the authors determined that they could be relevant for developing country contexts but had not yet been initiated in developing countries. For example, many of the studies on the safety of contraceptive options for HIV positive women have been conducted in developed countries but are relevant for women throughout the world. Likewise, much of the scientific evidence base for harm reduction for intravenous drug users (IDU) comes from developed country contexts. If studies met the criteria that they included an intervention which had an outcome and had been evaluated for effectiveness, one of the authors read and wrote up the intervention in a standard format: study year, country where the study took place; the numbers included in the study (N); study design; the intervention; and the outcome.

From 2001 to 2005, searches on women and AIDS were conducted using Popline and Medline. Few studies prior to 2005 have been included and only when more recent data are not available. Studies prior to 2005 were included if they were key articles with more robust methodologies, and data than studies in more recent years; or more recent data did not exist. For example, all the studies on treatment options for occupational exposure to HIV were done in the 1990s, so these were included.

In addition, the authors searched the gray literature by reviewing documents from some key websites. Key websites reviewed included: UN agencies, UNAIDS, World Health Organization (WHO), The Cochrane Collaboration; OSI; ICRW; Population Services International (PSI); The Population Council; ICW; World Bank; Family Health International (FHI); AIDStar I, and the Guttmacher Institute.

Themes emerged from these write-ups and the authors shaped those themes into an intervention point. These are the numbered interventions in each chapter. It is important to note that these interventions emerged organically from the evidence; the authors did not select interventions and look for supporting data.

Experts were consulted during the writing of the document (see Acknowledgments). A number of these experts provided review comments that were incorporated into the final document. A review meeting was held in Cape Town, South Africa, February 17-19, 2010. Sources for January and February 2010 have been included only if they provide significant new evidence related to the review. Forthcoming material was not included, as there was no systematic way to include such material.

Limitations

One limitation of the methodology used is that the search methodology did not capture other endpoints besides HIV/AIDS. For example, increased education for girls is associated with reduced risks of HIV acquisition. The search did not include program interventions to keep girls in school, for example. The chapter on co-infections, particularly the section on malaria, was not as thoroughly reviewed as other topics in the compendium. Stakeholders should consult the relevant experts for each of those topics. The topic of legal reform related to HIV/AIDS did not receive a systematic review of the legal literature that health related topics received in the public health and HIV/AIDS literature. Stakeholders wishing to work on legal reform should consult with legal experts.

It should be noted that there are likely many valuable interventions that have not been evaluated and/or published in the public peer reviewed literature. Important websites may have been unintentionally missed. Additionally, it is clear that faith-based organizations have played a major role in responding to the AIDS pandemic and they are responsible for a significant proportion of treatment, in addition to care and support, including spiritual support. Their role in prevention has also been strong, although not without controversy. The literature reviewed for this compendium of evidence did not yield many studies based on programs implemented by faith-based organizations that met the criteria for inclusion in this document. Given the role of faith-based organizations, this is a significant gap in the evidence base.

Furthermore, while the authors attempted to undertake a systematic review of the evidence, and to get input from expert reviewers, some key resources here are not an exhaustive list, however, and some important interventions may be inadvertently omitted. This document should be viewed as a living document; to be updated as new information is available.

How Evidence is Included in the Compendium

This website contains research published in peer-reviewed publications and study reports with clear and transparent data on the effectiveness of various interventions for women and girls, program and policy initiatives that can be implemented to reduce prevalence and incidence of HIV and AIDS in developing countries. Basic information, as well as policy issues concerning treatment and care for HIV and AIDS is also included. Biomedical information is included in so far as it is relevant to programmatic considerations. Most evidence in the document comes from developing countries; however, where that was not available, evidence from developed countries is included. Articles in English, Spanish and French were reviewed. However, the vast majority of the literature was in English.

Evidence in the compendium was rated, to the extent possible, using the Gray Scale (Gray, 1997), which lists five levels of evidence.

Table 1. Gray Scale of the Strength of Evidence
Type	Strength of Evidence
I	Strong evidence from at least one systematic review of multiple well designed, randomized controlled trials.
II	Strong evidence from at least one properly designed, randomized controlled trial of appropriate size.
III	Evidence from well-designed trials without randomization: single, group, pre-post, cohort, time series, or matched case-control studies.
IV	Evidence from well-designed, non-experimental studies from more than one center or research group.
V	Opinions of respected authorities, based on clinical evidence, descriptive studies or reports of expert committees.

In the case of abstracts from the latest International AIDS Conference (2008) or from relevant conferences in 2009 or 2010, the Gray Scale was not included since it was not always possible to ascertain the appropriate Gray Scale rating from the abstract. All printed abstracts from the XVII International AIDS Conference in Mexico City, Mexico, August 2008 were reviewed and included if they met the criteria for inclusion. The 2008 XVII International AIDS Conference abstracts were searched online (www.iasociety.org for the 2008 conference) using keywords such as “breastfeed” and “malaria.” Some authors of 2008 abstracts were emailed in 2009 to see if particularly promising data had been published. Where possible, the published articles were included, with the appropriate Gray Scale included. In addition, abstracts from the International Family Planning Conference (http://www.fpconference2009.org), held in Kampala, Uganda in November 2009, were included.

One weakness of the Gray scale is prioritizing randomized controlled trials, as randomized controlled trials are “primarily a vehicle for evaluating biomedical interventions, rather than strategies to change human behavior. Altering the norms and behaviors of social groups can sometimes take considerable time….” (Global HIV Prevention Working Group, 2008: 12). Much of the evidence cited in this document falls in strength levels IV and V; however, many studies fall in strength level III, with growing numbers of systematic reviews (level I) and randomized control trials (level II). Not all of the interventions listed here have the same weight and those that are promising but require further evaluation are identified. It must also be noted that randomized controlled trials—the gold standard of the Gray ratings—are not always ethical or appropriate for certain HIV interventions and therefore should not be the only factor in judging the relative weight of any particular study. Furthermore, many HIV prevention programs that address key issues in novel, context-specific ways are often not rigorously evaluated (Gupta et al., 2008a).

In cases where a majority of the evidence, and particularly strong evidence, exists for an intervention, this was listed in each section as “what works.” Criteria set for “what works” and “promising” were:

What Works: strongly rated studies (Gray I, II or III) for at least two countries and/or five weaker studies across multiple settings.

Promising: studies that were strongly rated but in only one setting or a number of weaker studies in only one country.

Within each intervention, studies are listed in order of Gray Scale, with the strongest studies first (Gray I, II, III, etc.) and abstracts last. In some chapters, such as Chapter 11 that discusses the enabling environment, where structural interventions cannot be linked as directly with impact on HIV infection, the authors, based on comments from reviewers, exercised judgment on “what works,” and promising interventions.

Where an intervention could have both positive outcomes for women and negative outcomes, this was noted. For example: microcredit can reduce HIV-related risk behaviors (Pronyk et al., 2008), but it could also increase violence against women if the intervention is not carefully designed and appropriate to local context (Schuler et al., 1998; Gupta et al., 2008a).

In the course of reviewing the literature to generate “what works,” a number of gaps emerged from the literature:

Gaps: programs that need to be implemented to meet women’s needs related to the HIV/AIDS pandemic but did not exist with evaluated data.

However, no search mechanism was possible to generate gaps. Where gaps emerged in the literature, these were noted. Evidence of a gap is not exhaustive but illustrative, providing a few examples. Evidence of a problem—such as the prevalence of violence against women—is described in the introduction to each section.

No attempt has been made, as is done in the Cochrane Collaboration, to reanalyze the data on interventions. For some interventions, many large-scale studies including some randomized controlled trials are listed; for other interventions, supporting research is available from only one study using a small sample size. With review articles, the original studies are cited as reported in the review. An attempt has been made to use the original studies and primary sources; but where the original could not be located, the authors relied on review articles. Evidence from review articles is noted (e.g., x cited in y).

When possible, objective measures such as a decrease in HIV seroconversion rates or a decrease in rates of other STIs are used as evidence. If these measures are not available, evidence is drawn from studies using self-reported behavior changes such as condom use, monogamy, sexual abstinence and a decrease in number of sex partners. This document does not address fully the issues of cost, equity, or sustainability.

Where possible, we have included sex disaggregated data. Where an interventions is relevant for both men and women, but does not have sex disaggregated data, it is included. For the chapters that are heavily medical interventions, such as those related to treatment and co-infection, only interventions that apply to women are included in the compendium.

In all, the evidence for What Works and Promising interventions includes 455 studies.

Table 2. Number of Studies Supporting What Works and Promising Interventions, by Chapter Topic
Chapter Topic	Number of studies supporting What Works/Promising Interventions†
Prevention for Women	43
Prevention for Key Affected Populations	55
Prevention for Young People	43
HIV Testing and Counseling for Women	47
Treatment	12*
Meeting the Sexual and Reproductive Health Needs of Women Living with HIV	33
Safe Motherhood and Prevention of Vertical Transmission	83
Preventing, Detecting and Treating Critical Co-Infections	17*
Strengthening the Enabling Environment	63
Care and Support	38
Structuring Health Services to Meet Women’s Needs	21
Total	455
† What works is based on strongly rated studies (Gray I, II, or III) for at least two countries and/or five weaker studies across multiple settings. Promising includes studies that were strongly rated but in only one setting or a number of weaker studies in only one country. * Most studies conducted on ARV treatment, tuberculosis and hepatitis do not include sex-disaggregated data although many of the findings are clearly relevant to women as well as men (e.g. the effectiveness of ARV treatment in reducing CD4 counts, strong adherence rates). The studies included attempt to highlight issues women face regarding treatment.

[1] “When, on average, one infected person infects more than one other person, R₀is greater than (>) 1 and the result will be epidemic spread of an agent [HIV]. However, when, on average, one infected person does not infect more than one other person, R₀is less than (<) 1 and the epidemic spread does not occur. When R₀is <1, the infectious agent will slowly disappear and if R₀stays close to 1 the agent will maintain itself in the population with no or minimal growth (i.e., becomes endemic”) (Chin, 2007: 60).

[2]Scopus is the largest abstract and citation database of peer-reviewed literature and quality web sources with smart tools to track, analyze and visualize research (http://info.scopus.com/scopus-in-detail/facts/)