An estimated 38 million people were living with HIV worldwide in 2019 [1]. These large numbers reflect higher longevity in people with HIV due in part to improvements in the management of HIV infection by early detection and early treatment with antiretroviral therapy. One obstacle to the effectiveness of antiretroviral therapy is drug resistance, as it limits the number of effective drugs, increases the potential for onward transmission, and compromises survival [2,3].

Drug resistance to antiretroviral therapy may be acquired when there is viral replication in the presence of a drug [4]. In some individuals, drug-resistant viral strains are already present prior to the start of antiretroviral therapy, referred to as pretreatment drug resistance [5]. This type of resistance can arise due to infection with a drug-resistant viral strain, also referred to as “transmitted drug resistance,” or due to prior exposure to antiretroviral treatment (eg, women and children exposed to treatment as part of prevention programs and people who abandoned prior treatments) [6].

HIV drug resistance is a recognized global health problem [7]. People with drug resistance are more likely to experience treatment failure, discontinue treatment, and develop new drug-resistant strains [5]. The rise in drug resistance is one of the greatest threats to global health—without urgent attention, it could result in millions of deaths, an increase in new harder-to-treat strains of HIV, and higher health care costs [8]. The prevalence of HIV drug resistance varies worldwide, and it can be as high as 25% in some countries [9], likely due to the efforts to expand widespread availability of antiretroviral therapy in these settings. Understanding the levels of HIV drug resistance is important to researchers, clinicians, and policy makers because this information can inform guidelines on how treatment should be tailored and what drugs should be used as first-line treatments. For example, in 2020, a total of 21 of the 30 World Health Organization (WHO) drug resistance surveys reported drug resistance to nevirapine or efavirenz in populations initiating first-line antiretroviral therapy above 10% [10].

The prevalence of drug resistance varies among people living with HIV, but is higher in certain high-risk populations such as men who have sex with men, sex workers, transgender people, people who inject drugs, people in prisons, pregnant women, and adolescents and children; resistance prevalence also varies by sex, ethnicity, and HIV subtype due to differences antiretroviral exposures [11-14]. The pooled prevalence estimate of HIV drug resistance is high among men who have sex with men (13.0%, 95% CI 11.0%-14.0%), sex workers (17.0%, 95% CI 6.0%-32.0%), and people in prisons (18.0%, 95% CI 11.0%-25.0%) [15]. Overall, men who have sex with men are more likely to have any drug resistance compared to the general population (odds ratio 1.28, 95% CI 1.13-1.46) [15].

Adequate monitoring of HIV drug resistance across countries and populations is often challenged by heterogenous and inadequate data reporting. In our previous systematic review of pretreatment drug resistance in key populations, we found that the quality of reporting in studies of HIV drug resistance prevalence is low [16]. This compromises the accuracy, interpretation, and usability of prevalence estimates, especially if key data are not reported, including precision of the estimates, representativeness and diversity of the participants included, techniques used to measure resistance, participants’ transmission risk group, prior exposure to treatments, and class of drug for which resistance was tested [15]. Our recent methodological study concluded that while reporting has improved over time [8], guidance is needed to ensure complete and uniform reporting to improve the interpretation of study findings, generalizability, and comparability of prevalence estimates, while accounting for differences in geographical settings and populations [17].

In 2010, Moher et al [18] published guidance for researchers seeking to develop health research reporting guidelines, outlining a strategy emphasizing the importance of using robust and widely accepted methodologies. In accordance with this strategy and to initiate the process of developing reporting guidelines for studies of HIV drug resistance prevalence, our prior work evaluated the completeness of reporting of HIV drug resistance prevalence literature, the results of which supported the need for reporting guidelines [15,17]. We have registered this guideline project on the EQUATOR (Enhancing the Quality and Transparency of Health Research) network as CEDRIC-HIV (ChEcklist for studies of Drug ResIstanCe in HIV) [19].

The objective of this study is to develop a reporting item checklist for prevalence studies of HIV drug resistance by achieving agreement among experts on items that should be reported in studies of HIV drug resistance prevalence. This mixed methods study includes (1) a quantitative phase with survey methodology to identify a list of reporting items considered by participants to be essential, (2) focus group methods to identify emergent themes on reporting items that are essential to HIV drug resistance prevalence studies, and (3) data integration methods to explain discrepancies between quantitative and qualitative data as well as the rationale behind what makes a reporting item important to HIV drug resistance research.

We will conduct a sequential explanatory mixed methods study (QUAN → qual) among authors of studies of HIV drug resistance. This design comprises two phases: a cross-sectional electronic survey (quantitative phase) and subsequent focus group discussions (qualitative phase). The results of the survey will be used to develop an initial list of potential reporting items and additionally suggested reporting items, which will be evaluated, revised, and expanded upon in the qualitative phase. Transcripts from the focus group discussions will provide key agreement-based insights on why these items are important to report.

Mixed methods suit research objectives that cannot met by either qualitative or quantitative methodologies alone [20,21]. The sequential explanatory design is well suited for this research as the quantitative phase provides the recommended reporting items and the qualitative phase provides the rationale for reporting these items. Each of these will inform the guidance and elaboration document that will accompany the checklist.

In the quantitative phase, we will pilot test our survey. In the qualitative phase, we will use member-checking, audio-video recordings, and duplicate coding to validate our data. During the focus group discussions, moderator bias will be minimized by using a discussion guide.

Consensus will be determined statistically in the quantitative phase using item-specific validity ratios so that the items that at least 50% of participants rated essential are kept in the initial reporting item checklist at the end of the quantitative phase. In the qualitative phase, focus groups will seek agreement on both the reporting item checklist and additionally suggested items generated in the quantitative phase. Agreement is inferred when at least one participant verbally speaks on whether a reporting item was essential or not and there are no verbal objections with the statement. Therefore, agreement also involves the failure to speak up against specific items.

This study received ethics approval from the Hamilton Integrated Research Ethics Board (project number #11558) on November 11, 2020, and received annual renewal approval on September 27, 2021. Only participants who provide informed consent will participate in the study. Participants will be able to stop the electronic survey or withdraw from the focus group discussions at any time.

In this study, we will use mixed methods to produce a reporting item checklist of items to be considered in the process of developing reporting guidelines for studies of HIV drug resistance prevalence. We will explore and highlight the insights gained from using mixed methods to meet our study objectives. An explanatory sequential design was selected for this study to allow for the use of qualitative data to explain results from the quantitative findings, and breadth and depth in the data collected [32,33].

We anticipate that most of the initially proposed reporting items presented in the survey will be rated as essential and go on to be evaluated in the focus group discussions. We also expect additional reporting items will be suggested by survey participants, which will also be evaluated in the focus group discussions. During the focus group discussions, we expect considerable agreement on the inclusion of most reporting items proposed in the quantitative phase, with disagreements on areas of wording, grammar, and relevance to specific types of HIV drug resistance research designs. As the purpose of this study is to develop a reporting item checklist and key insights to inform the development of reporting guidelines, we anticipate participants will discuss important considerations that the complete reporting guidelines must consider to be accessible and relevant to all authors and users of HIV drug resistance prevalence research, including any concerns over data privacy and confidentiality.

The strengths of this study include the integration of both quantitative and qualitative methodologies to elicit consensus and agreement from experts on the items that should be reported in studies of HIV drug resistance. Additionally, validation checks will be made in both phases of the study to improve data quality. Study limitations include the susceptibility to low response rates in the quantitative phase and therefore the potential for response bias. We have estimated a sample size to determine the minimum number of responses required for the quantitative phase. However, we have specifically incorporated approaches to enhancing diversity of views by reviewing the geographic coverage of the quantitative data, and purposefully selecting participants from high- and low-income settings for the focus group discussions and as external reviewers.

The results of this work will be presented as peer-reviewed manuscripts, conference presentations, and as part of a master’s thesis. Participants who express interest in the findings of the study will also be sent the results of this work.

We will incorporate several knowledge translation strategies including engagement of opinion leaders in the agreement discussions (eg, study authors), and through linkage and exchange mechanisms (ie, connecting researchers and knowledge users to facilitate dissemination, for example via educational workshops and project summary briefings to stakeholders) [34]. All focus group participants as well as the individuals who have indicated interest in being informed about the outcomes of this research will be engaged as knowledge user partners to help share the reporting guideline. Additional mechanisms will involve academic media releases (eg, St. Joseph’s Healthcare Hamilton, public health/HIV societies) and web-based social marketing (eg, Twitter). We will also tailor conference meeting presentations to be educational to inform knowledge users (eg, researchers designing HIV drug resistance prevalence studies) about reporting issues and the current gaps at the design stage of HIV drug resistance prevalence studies, and the need for the reporting guideline.

During focus group discussions, we will ask participants about any perceptions of barriers for practice change (eg, at the level of HIV drug resistance prevalence study design) and uptake of the reporting guideline. We will use this feedback to tailor educational activities (eg, conference presentations) and dissemination efforts (eg, preferences for receiving the information) for this audience. For example, to increase awareness about reporting issues and the reporting guideline, we will present findings about the impacts of missing study data, as well as ensure that we target local, national, and international conferences for dissemination activities. We will publish manuscripts arising from this work in open-access journals.

Knowledge translation impact and evaluation will be measured at the level of the HIV research community using the following metrics: reach and use indicators (eg, number of times manuscripts are accessed and cited), collaboration indicators (eg, endorsement by relevant journals in the field), and practice change indicators (eg, improvements in reporting over time) [35]. For example, indicators of uptake will be measured over time in cross-sectional studies to evaluate changes in reporting practices before and after the publication of the reporting guideline.

The checklist of items and agreement-based insights produced by this study will be refined, elaborated, and considered by a writing committee of experts in HIV drug resistance. We will also invite external reviewers from international organizations such as the WHO, the Joint United Nations Programme on HIV/AIDS (UNAIDS), the Elizabeth Taylor Foundation, and the Centers for Disease Control and Prevention (CDC) to provide feedback on the reporting guidelines.

We seek to develop a reporting item checklist for studies of HIV drug resistance prevalence and a better understanding of what makes a reporting item important to HIV drug resistance prevalence research. The forthcoming reporting item checklist will directly inform the explanation and elaboration document that will have detailed justifications and rationale for each reporting item in the checklist.