Bibliometric analysis of the top 100 cited articles on HIV/AIDS

Introduction

The human immunodeficiency virus (HIV) epidemic, has been one of the most challenging global health issues ever since the first case was reported over 4 decades ago (1). Although the introduction of antiretroviral treatment has significantly reduced the incidence and mortality associated with HIV, it still places a huge burden on households and communities at large.

In 2019, a total of 32.7 million people had died of HIV related illnesses counting from the beginning of the epidemic, 38 million were living with HIV, and 1.7 million newly infected people were diagnosed (2). As a disease that compromises the patient’s immune system and weakens his defence against infections, it exposes the affected patient to a wide range of health risks. It is a sexually transmitted disease that affects young people and can potentially impair social capital, population structure, and economic growth by affecting the youth of working and reproductive ages (3). The fact is that to date, there is no effective cure that exists. However, scientific research on all aspects of the disease is on the increase with academic specialties emerging from these areas. With the emergence of these academic authorities in HIV, it is imperative to map and assess pathways of knowledge for ease of reference. Bibliometric methods have been identified as an effective tool for the assessment and evaluation of progress in scientific research products as well as to identify the most impactful articles by exploring the ground-breaking of significant contributions (4). Based on the use of bibliometric tools, large amounts of scientific literature have been produced in the world to give a better understanding and to shape future research directions (5-7). To date, according to the Google Scholar database, while some articles on scientific production on HIV/acquired immunodeficiency syndrome (AIDS) research have been published about individual countries (8) or regions (9-11), there is no recent study conducted to analyse and visualize the overall academic structure of global HIV/AIDS research using bibliometric analysis as a technique to develop an overview of large amounts of academic literature in this field. The objective of this study is to evaluate the research on HIV/AIDS by examining the 100 top-cited records indexed in Web of Science Core Collection, including Science Citation Index (SCI) and Science Citation Index Expanded (SCI-E) during the period beginning from 2010 until August 19th, 2020.

Methods

Search strategy

To identify the most frequently cited articles in the HIV/AIDS field, we used the Web of Science (WoS) Core Collection. To collect the bibliographic data, our search was limited to the articles indexed in Sciences Citation Index (SCI) and Sciences Citation Index-Expanded (SCI-E) as standard databases for WoS to screen the relevant articles. The search strategy was designed based on the list of Medical Subject Headings (MeSH) indexing of biomedical literature (https://meshb.nlm.nih.gov/search). The query used to retrieve was as follows: Title: “HIV” OR “HIV1” OR “HIV2” OR “HIV-1” OR “HIV-2” OR “human immunodeficiency virus” OR “Human Immuno-Deficiency Virus” OR “Acquired Immunodeficiency Syndrome” OR “Acquired Immuno-Deficiency Syndrome”. All electronic searches on HIV/AIDS articles were performed by two independent reviewers (GG, THM) on a single day (August 19th, 2020) to avoid as much as possible, any potential changes that could occur in citation rate.

Inclusion and exclusion criteria

The ‘document type’ filter was applied, and only included original investigations for papers published as ‘full research article’. Other types of documents were excluded. No language restriction was applied and we limited our search to articles published from 2010 to August 19th, 2020. This resulted in 69,310 HIV/AIDS-related articles; which were then sorted in descending order by the number of citations in WoS (from most cited to least cited). After ensuring the articles were all relevant to our search, we finally stored the top 100 most cited articles on HIV/AIDS in Excel and plain text file for further analysis.

Bibliometric analysis parameters

Bibliometric indicators such as article title, citation count, year of publication, corresponding author, country of origin, the institution of origin, and journal were extracted for each of the 100 records. The journal impact factors were defined based on the Journal Citation Reports (JCR) Science Edition 2020. The quality HIV/AIDS retrieved publications were assessed using Hirsh-index (h-index) (12).

Statistical analysis

The data was analyzed by using VOSviewer software (van Eck and Waltman 2010), which is freely available on http://www.VOSviewer.com (13); Bibliometrix (an R package) (14); as well as HistCite (15). Furthermore, Spearman correlations between the number of times an article has been cited and the number of years since its publication, as well as the number of authors, institutions, and countries involved, were calculated using the Statistical Package for Social Sciences (SPSS) version 25. Statistical significance was defined as a P value less than 0.05.

Results

Publication year

The publication years for the 100 most-cited articles on HIV/AIDS between 2010 and 2020 ranged from 2010 to Aug. 2017. The highest number of the article published and the number of citations in a single year were 22 and 16,400 respectively and were both recorded in 2011 (Figure 1).

Figure 1 The trend of publication and citation analysis for the top 100 most-cited articles on HIV/AIDS. HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome.

Description of main characteristics of the articles

The total number of citations for the top 100 articles was 63,356. The average number of citations per article was 633, with a range of 338 to 4,396. Of the 100 top-cited articles, 77 had 400 or more citations in WoS qualifying to the definition of citation classic (16); 50 were cited more than 500 times, and only 9 were cited over 1,000 times.

The number of articles annual citations representing the number of times the article was cited per year ranged from 43.25 to 628. The top-cited article was published in the New England Journal of Medicine in August 2011 (17) as presented in Table 1.

Table 1 The top 100 cited articles on HIV/AIDS
Full table

Contributing authors

Overall, the 100 publications involved a total of 2,101 authors. Table 2 shows a list of the most frequently appearing authors who contributed with more than six articles each. The top productive authors are Burton DR, affiliated to Scripps Research Institute, and Mascola JR, from the National Institute of Allergy and Infectious Diseases (NIAID), who each had 9 publications.

Table 2 Authors with six or more top-cited articles on HIV/AIDS research
Full table

Journal of publication and impact factors

The top 100 cited articles were published in 32 different journals. Eight journals, all of which were in the top quartiles, had three or more cited publications. Close to half of all the articles (48%) were published in only the top 3 journals, which include: Nature (n=17), New England Journal of Medicine (n=16), and Science (n=15) articles (Table 3).

Table 3 Journals with three or more top-cited articles on HIV/AIDS research
Full table

Institutions & institutions with subdivision

In Table 4, the top institutions and institutions with subdivisions involved in HIV/AIDS publications in the recent 10 years are shown. The University of California San Francisco took the lead institutions with 19,482 citations, followed by NIAID with 18,469 citations, among other reported ones.

Table 4 Top 10 institution and institution with subdivision on HIV/AIDS research
Full table

Funding agencies

The analysis of the main funding agencies revealed that the United States Department of Health Human Services (USA, 82%), the National Institutes of Health NIH (USA, 80%) and NIH National Institute of Allergy Infectious Diseases (USA, 63%) accounted for the highest amount of financial support towards HIV research (Figure 2).

Figure 2 Top 10 agencies funding global HIV/AIDS research. HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome.

Keyword analysis

A keyword analysis was performed to help understand the main searches in the HIV/AIDS field. “Infection” (n=21) was a frequently used keyword plus. Other common ones included “transmission” (n=12), and “therapy” (n=11) (Figure 3). Keywords plus which are different from the keywords chosen by authors are extracted by Thomson Reuters, from the titles of the cited references without being in the title of the article itself. According to Garfield, they offer a greater picture in the exploration of the content of an article or a set of articles (18).

Figure 3 Word-clouds of keywords plus [2010–2020] in WoS for the top 100 most-cited articles on HIV/AIDS. HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome; WoS, Web of Science.

Bibliographic coupling analysis

Bibliographic coupling is a type of bibliometric network that analyses the number of articles that two articles share in their references; a bibliographic coupling strength increases as the number of references cited by both publications increases and that can be used as an indicator of how similar the articles are in their topic or field of research (19,20).

For the purpose of running a bibliographic coupling assessment between authors, countries, and organizations that had a contribution in 100 top-cited articles on HIV/AIDS, we used VOSviewer software to obtain a graphical visualization of networks. In Figures 4-6, the bibliographic coupling between authors, countries, and organizations respectively.

Figure 4 Bibliographic coupling of the authors that contributed to the 100 top-cited articles.

Figure 5 Bibliographic coupling of the countries that contributed to 100 top-cited articles on HIV/AIDS. Countries with a minimum of 4 documents (n=23) are shown. HIV, human immunodeficiency virus; AIDS, acquired immunodeficiency syndrome.

Figure 6 Bibliographic coupling of the organizations that had a contribution in 100 top-cited articles.

Authors

Out of 850 authors, those with a minimum of 2 documents were selected. That resulted in 88 authors included in this coupling (Figure 4). The total links strength (TLS) of bibliographic coupling links with other authors were calculated. The overall links between the authors were 1,462, and that made a TLS of 50,000. The top 5 authors accounting for the highest rates of TLS included: Julien JP (TLS =3,629), followed by Wilson IA (TLS =3,629), Burton DR (TLS =3,389), Ward AB (TLS =3,239), and Cupo A (TLS = 2,915).

Countries

Authors with a minimum of 2 documents were considered.

Figure 5 shows the bibliographic coupling between countries. A minimum of 4 documents per country was considered and 23 countries, subdivided into 3 clusters, met the thresholds. The 23 countries make up 253 Links, and the Total Link strength is equal to 31,169. In a similar way we did for authors, we also report the top 5 countries with the highest TLS. The first country was the USA (TLS =11,847), followed by South Africa (TLS =5,690), England (TLS =4,608), Netherlands (TLS =3,030), and France (TLS =2,929).

Organizations

Figure 6 shows institutions with a minimum of 7 documents. Out of 398 organizations 17 organizations met the threshold Figure 4. The total numbers of Links and TLS were 310 and 66,503, respectively. In terms of TLS, NIAID was in the lead with a 6,481, followed by Scripps Research Institute (TLS =5,462) and Harvard University (TLS =4,951).

Factors influencing citations analysis

Table 5 shows an analysis of factors that potentially determine the number of citations for the 100 top-cited articles on HIV/AIDS. We investigated potential relationships between citations and variables including the period of time since publication, the number of authors, the amount of organizations involved, the participating countries, and the journal impact factor. We found a positive correlation between the number of times articles were cited in WOS and the impact factor of the journal in which it was published. (r=0.283, P=0.004). Similarly, a positive correlation was observed between the number of authors per publication and the number of citations (r=0.258, P=0.010). No significant correlations were found between the number of citations and years since publication (r=0.093 P=0.358), the number of countries per publications (r=0.014 P=0.893), or institutions involved (r=0.094 P=0.351).

Table 5 Relationship between number of citations and number of years, authors, institution, and countries involved in HIV/AIDS research
Full table

Discussion

We used bibliometric methods to understand the state of main contributions towards HIV/AIDS research in the past decade. With this, we aimed to highlight and provide a historical perspective for future research directions. The analysis included the most cited articles among those published over the recent 10 years [2010–2020], however the results only cover the earlier eight years as the articles published after 2017 most probably have not yet had enough exposure in comparison to the older ones.

The citations for the top 100 were between 338 and 4,396, numbers close to those found in similar studies (21). A decrease in citation numbers was noted after 2013, suggesting that despite a non-significant association between the citation number and the time elapsed since publication, articles dating from earlier years were more cited than the recent ones. That may be wrongly perceived as a reduced interest in HIV research; however, a possible reason for that time factor is that older articles have had a long time to gain recognition and popularity among researchers in the field. Furthermore, studies have shown that it may take at least two to three years after publication for papers to accumulate enough citations for reliable bibliometric consideration (22,23).

Looking at the top 100 cited articles in the ten years prior to our study period, peaks in citation emerged in 2006, and 2008, which may lead to the assumption that influential publications precede or follow scientific breakthroughs in the field, since that period preceded the publication of a series of randomized controlled trials between 2005 and 2007 which shed the light on male circumcision as an effective intervention for HIV prevention. Following that, WHO and UNAIDS issued joint recommendations highlighting the potential efficacy of male circumcision for HIV prevention (24,25).

The peak in publication numbers for our study period was observed in 2011 (22%) and for the whole period between 2010 and 2013. This period concurs with several shifts in HIV control. First, following the introduction of highly active antiretroviral therapy (HAART) in 1996 and the presentation of preliminary results at the 2006 International AIDS Conference showing a decrease in the number of HIV diagnoses as HAART use increased (26), Montaner et al. [2010] provided strong evidence of HAART use as a method of reducing the number of new infections (27).

During the same time that treatment as a preventive measure for new infections was making a significant contribution to HIV control, patient disengagement remained a problem. Gardner et al. [2011] proposed a comprehensive model of ongoing patient care that included encouraging testing, treatment, and ensuring adherence with the goal of achieving undetectable viral load (28). This concept also known as “care cascade” is currently still at the heart of HIV control under the UNAIDS 90-90-90 strategy which aimed for 90 percent of people living with HIV to be diagnosed, 90 percent of those diagnosed to be on treatment, and 90 percent of those on treatment to have an undetectable viral load by 2020 (29). An undetectable viral load had previously been associated with a reduction in HIV transmission in the 2008 Swiss Statement (30), and despite initially facing controversy and being disputed as lacking tangible evidence, it was later supported by the famous HPTN 052 (17) and PARTNER (31) studies published in 2011 and 2015 respectively and showing evidence that ART significantly reduced risk of HIV transmission. According to our findings, Cohen et al. (17) publication of the HPTN 052 Study is the most cited in the last ten years. During the same time period, other studies focused on the potential benefits of early versus late ART start in different HIV patient groups (32,33). In 2015, the START study, led by Lundgren et al., concluded that starting ART in HIV-positive adults with a high CD4+ count provided significant benefits over starting such therapy in patients with a low cell count (34).

The complexity here is that, despite the fact that several publications have laid the groundwork for major shifts in HIV control and are expected to have greatly inspired and been cited by other researchers, the citations do not reflect such influence. As a result, it is prudent not to rely solely on the number of citations as a measure of a publication's influence and to interpret results with caution.

The most frequently covered topics in the top-cited articles in the last ten years have been those related to ART use in HIV-negative people, a concept known as pre-exposure prophylaxis (PrEP). This includes the CAPRISA004 trial, which used a vaginal gel containing Tenofovir (35) and the iPrEX study recommending the use of Truvada to reduce the risk of HIV among HIV-negative adults (36). The topics of vaccine and neutralizing antibodies also emerged as particularly frequent. Burton DR, Mascola JR, and Kwong PD were the most productive authors during our study period, with a common focus on HIV vaccine strategies research, particularly through antibody neutralisation; they worked together on several articles that are currently on the list of the most cited publications (37,38) and should be closely followed for HIV vaccine updates.

The most productive authors were affiliated to institutions based in USA with the Scripps Research Institute and NIAID at the top. The University of the Witwatersrand in South Africa and Chiang Mai University in Thailand were the only non-American institutions in the top ten with a significant contribution to HIV/AIDS research. This supports Falagas et al. recommendation’s that developing countries with a high burden of infectious and tropical diseases increase and strengthen their research capacity and collaboration networks within and outside the region in order to achieve better knowledge dissemination through international level publications (39).

Nearly one-third of the top-cited articles came from the United States of America, which is a common finding in studies on infectious diseases such as malaria (40) and tuberculosis (21) but also in other medical fields such as breast cancer research (41) and surgery (42). Despite the fact that the Sub-Saharan Africa region has the highest HIV/AIDS burden (43), it is clear that, with the exception of South Africa, the remaining countries in the region had minimal involvement and only collaborated with institutions located in developed countries. That can be explained not only by a critical lack of adequate research capacity and infrastructure but also by the lack of funds which are often required to publish in high-end journals with high impact factor, given the fact that in 2019, the 15 countries with the lowest gross domestic product (GDP), a tool commonly used for comparison of national economies on the international market, were located in Sub-Saharan Africa (44).

It has been argued that an impact factor for a journal does not always accurately represent the quality of the articles it publishes. However, it is already a widely used technique for determining a journal’s impact (45). In this study, we found a positive relationship between the citation times and the impact factor of the journal of publication. Nonetheless, the association with journal quartile, an alternative journal impact metric was non-significant although 94 percent of the publications in the 100 most cited were published in Q1 journals, and the vast majority of the top articles were published in well-known non-topic-specific medical journals with high impact factors such as The New England Journal of Medicine, Science, Nature, and Lancet, among others. There were no African journals on the list, raising the question of whether the findings and recommendations made in these top-performing studies are easily accessible to professionals in the countries where that knowledge is most needed.

Julien JP had the highest bibliographic coupling strength among the authors in our analysis. Using the same method, the NIAID ranked first among institutions and was one of the top three funding agencies, alongside the US Department of Health and Human Services and the National Institutes of Health (NIH). According to the bibliographic coupling, two South African institutions, the University of Witwatersrand and the University of Cape Town, were among the top ten.

Limitations

There are some weaknesses to the study that should be acknowledged. The first is the fact that the publications in this study were retrieved from the Web of Science database, which is the world's largest database, however, other well-known databases, such as Scopus or PubMed, were not explored this time, despite the fact that they could have enriched our findings. Moreover, because this study only included articles published after 2010, it excludes several other seminal articles published prior to 2010 that were more frequently cited and paved the way for those included in this study. Besides, because the time span for this study’s publications is recent, some relevant and prominent articles published more recently might have not made it to the top 100 most cited articles since they did not have enough time to accumulate the citations compared to older ones.

Finally, while the data analysis in this study aimed to be objective and comprehensive, the methods used were focused on the level of citations, which is not always a good indicator of quality; assessing scientific quality would necessitate taking into account more factors than the citation impact of publications. Citation frequency only reflects the overall attention paid to publications, which can be influenced and skewed by factors other than their quality. Self-citation, funder’s influence, citation of articles involving prolific or famous researchers, citation of previously highly cited articles, and so on are all common factors. As a result, all of the findings presented should be interpreted in light of these limitations.

Conclusions

The current study investigated the most recent trends in HIV/AIDS research worldwide by examining contributions in the 100 most cited articles over the last ten years. In terms of the number of publications, the United States played a major role. Mascola JR, Burton DR, and Julien JP as well as other researchers from institutions such as Scripps Research Institute and NIAID, Vaccine Research Center are great scientists to keep an eye on for future developments in antiretroviral therapy and vaccine research. Nature was the most prolific journal publishing HIV/AIDS research in recent years. We also found that the majority of influential articles were available in free full texts format and were mostly experimental studies such as clinical and randomised controlled trials investigating the timing of antiretroviral therapy, pre-exposure prophylaxis, and lab experiments on broadly neutralising antibodies in search of a vaccine. A positive correlation was found between the number of citations and the journal impact factor of the journal as well as the number of authors per publication.

Acknowledgments

The authors acknowledge the support of the Biomedical Research Institute, Darfur University College, Nyala, Sudan. The authors appreciate the research innovation of The Organization of African Academic Doctors (OAAD) for enhancing research collaboration and innovation in Africa and the Southeast University library for providing resources and metadata used for this research.

Funding: None.

Footnote

Peer Review File: Available at http://dx.doi.org/10.21037/aoi-20-17

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/aoi-20-17). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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