HIV Viral Load: A Concept Analysis and Critique

Research and Theory for Nursing Practice An International Journal Vol 28 No 3 2014

204 copy 2014 Springer Publishing Companyhttpdxdoiorg1018911541-6577283204

HIV Viral Load A Concept Analysis and Critique

Marilou Gagnon PhD RN ACRN

School of Nursing Faculty of Health Sciences University of Ottawa

Adrian Guta PhD MSW RSW

Faculty of Arts amp Social Sciences Carleton University

In this article we examine the concept of HIV viral load and how it has evolved over time (1995ndash2013) in the field of HIVAIDS Although the term viral load is used extensively in this field few efforts have been directed toward the conceptualization of HIV viral load which is often left unquestioned undertheorized and portrayed as a neutral and objective laboratory value that has remained relatively stable over timemdashwith the exception of progressive advancements in technology techniques and sensitivity The purpose of this article is to apply the evolutionary concept analy-sis method developed by Rodgers (1989 2000a) to the concept of HIV viral load To set the stage we establish the need for a concept analysis of HIV viral load and provide an overview of the evolutionary view Then drawing on the steps proposed by Rodgers (2000a) we outline the process of data collection management and analysis We then offer an in-depth discussion of the findings (attributes anteced-ents and consequences) informed by Wuestrsquos (2000) critical approach to concept analysis We conclude by highlighting the implications of this analysis for clinical practice research and theory

Keywords antiretroviral therapy concept analysis concept critique HIV viral load

HIV profoundly affects the immune system by impairing multiple immune cell functions and causing a decline in CD4 T-lymphocytes over time Throughout the HIV epidemic CD4 T-lymphocyte counts have been used

by clinicians and researchers to monitor the progression and define the stages of HIV infection to establish diagnostic criteria for AIDS to determine prognosis to develop treatment eligibility and initiation guidelines and to measure the relation-ships between immune status and variables such as mortality morbidity treatment outcomes and so forth Although CD4 T-lymphocyte counts received much of the

RTNP28-3_Final_A3_204-227indd 204RTNP28-3_Final_A3_204-227indd 204 9314 147 PM9314 147 PM

HIV Viral Load Concept Analysis 205

early attention in the clinical management of HIV infection they are now used in combination with HIV viral load Together CD4 T-lymphocyte counts and viral load provide a more comprehensive understanding of disease progression and viral (or HIV) activity

Measurements of HIV viral load have become a critical component of the clinical management of HIV infection since the introduction of antiretroviral treatment in 1996 The goal of treatment is to achieve (and maintain) viral suppression and to reach a threshold where copies of the virus are no longer ldquodetectablerdquo in the blood Viral load calculations are now used routinely in clinical practice to assess viral dynamics and its effects in the body to predict the progression of HIV infection to determine when to begin or change HIV medications and to monitor for treat-ment effectiveness or failure (Sax Cohen amp Kuritzkes 2012) More recently HIV viral load has increasingly been used as a tool to monitor treatment adherence to track viral replication within the body to reduce the risk of HIV transmission to inform epidemiological surveillance and to map the virus at a population level (also known as community viral load for a more detailed analysis see Gagnon amp Guta 2012)

In this article we examine the concept of HIV viral load and how it has evolved over time (1995ndash2013) in the field of HIVAIDS Although the term viral load is used extensively in this field few efforts have been directed toward the conceptu-alization of HIV viral load which is often left unquestioned undertheorized and portrayed as a neutral and objective laboratory value that has remained relatively stable over timemdashwith the exception of progressive advancements in technology techniques and sensitivity The purpose of this article is to apply the evolutionary concept analysis method developed by Rodgers (1989 2000a) to the concept of HIV viral load To set the stage we establish the need for a concept analysis of HIV viral load and provide an overview of the evolutionary view Then drawing on the steps proposed by Rodgers (2000a) we outline the process of data collection manage-ment and analysis We then offer an in-depth discussion of the findings (attributes antecedents and consequences) informed by Wuestrsquos (2000) critical approach to concept analysis We conclude by highlighting the implications of this analysis for clinical practice research and theory

BACKGROUND

The approach to concept analysis we use recognizes that ldquoconcepts once formu-lated and labeled tend to shape and guide what we see and they provide order to observations and experiencesrdquo (Meleis 2012 p 371) that produce shared under-standings of situations and events Before ldquoHIV viral loadrdquo (as a concept) came into use clinicians and researchers did not see define think and talk about HIV in relation to viral load even though viral activity in both plasma and other bodily fluids (eg breast milk semen preseminal fluid vaginal fluids and rectal mucous) had been identified The introduction of a concept labelled ldquoHIV viral loadrdquo in the 1990s gradually transformed the way people living with HIV (PLWH) understand


206 Gagnon and Guta

and assign meaning to their own personal experiences of health and illness the way clinicians practice and engage with PLWH and the way we respond to the HIVAIDS epidemic in resource-rich countries and more recently in resource-limited countries across the globe (Sigaloff et al 2011) Yet this concept has never been formally analyzed in nursing and other health disciplines

Our approach is also underpinned by the dispositional view of concepts and the cycle of concept development described by Rodgers (1989 2000a) According to Rodgers (1989) a concept becomes associated with particular sets of attributes through socialization and repeated use These attributes are subject to change over time rather than static are context-dependent rather than universal and are defined by analyzing the ways in which the concept is usedmdashWhen is the concept used and for what purposes What is the idea expressed by the concept and who is it relevant to Why is the concept significant and how is it being applied (Rodgers 2000a) As a concept becomes associated with a particular use it is transferred through social interactions and is applied to assist in the construction of meaning the description of phenomena and the resolution of problems thus expanding the range or scope of the concept (Rodgers 1989 2000a) The focus here is on the development and common use of the concept as a way to shed light on temporal variations critically analyze contextual influences and make space for concept critique (Rodgers 2000a Wuest 2000)

The evolutionary approach is well suited for the concept of HIV viral load because it offers a structured yet flexible process of analysis that focuses on inductive rea-soning and takes into account context (including disciplinary context) time and the role of the researcher in the interpretation of data (Rodgers 2000a) This approach also serves as a heuristic tool (Rodgers 2000a) to further inquiry and conceptual understandings in the field of HIVAIDS As such the objective is not to ldquoreveal what the concept is or is not or what is or is not an instance of the conceptrdquo (Rodgers 2000a p 84) Instead the objective is to elucidate the conceptrsquos uses meanings and the behaviors responses and experiences that are made possible through interactions between PLWH clinicians researchers decision makers public health officials and so forth (Rodgers 1989) Using this approach we will critically examine how and why this concept developed over time in the literature

METHOD

The six steps of the evolutionary concept analysis method (Rodgers 2000a) were used to guide the analysis (see Table 1) A computer search of the databases PubMedMEDLINE and CINAHL was conducted using the keywords ldquoviral loadrdquo (title) and ldquoHIVrdquo (total 944 articles) After deleting duplicates and removing articles that were solely focused on virology this search generated the following number of articles from the time frame 1995 to 2013 1995 to 1999 ( n 117 articles) 2000 to 2004 ( n 64 articles) 2005 to 2009 ( n 39 articles) and 2010 to 2013 ( n 25 articles) for a total of 245 articles For each time period all relevant articles were reviewed and numbered 1 through the size of the sample for example articles



published between 1995 and 1999 were numbered sequentially 1 through 117 Next random numbers were generated for each time period using a random generator (httpwwwrandomizerorg) Articles selected during this process were included in the final sample of 100 articles 25 per time period This sample size is consistent with the evolutionary approach which states that the sample size should represent 20 of the total number of references included (Rodgers 2000a) In this case the sample size represents 40 of the total number of refer-ences initially included

Each article was read once by members of the research team before the begin-ning of the core analysis phase Then each time period was closely examined and analyzed using the questions outlined by Tofthagen and Fagerstroslashm (2010)

Do other words say the same thing as the chosen concept Do other words have some-thing in common with the concept Which events or phenomena have been associated with the concept in the past What are the concepts characteristics What happens after or as a result of the concept (p 24)

Articles were clustered by time period and each of them was analyzed using a color-coded coding scheme During this process emerging codes were written on a separate piece of paper and themes were gradually identified using the classifica-tion (a) antecedents (b) attributes and (c) consequences (Rodgers 2000a) Analytic memos were carefully recorded by a research assistant throughout this process and verbatim passages were organized to support the findings Findings for each time period were then compared to look for similarities differences variations between contexts changes over time and contradictions within the data

TABLE 1 Six Steps of the Evolutionary Concept Analysis Method

Step 1 Identify the concept of interest and associated expressions (including surrogate terms)

Step 2 Identify and select an appropriate realm (setting and sample for data collection)

Step 3 Collect data relevant to identify

bull The attributes of the conceptbull The contextual basis of the concept including interdisciplinary

sociocultural and temporal (antecedents and consequential occurrences) variations

Step 4 Analyze data regarding the above characteristics of the concept

Step 5 Identify an exemplar of the concept

Step 6 Identify implications hypotheses and implications for further development of the concept

Note Rodgers B L (2000a) Concept analysis An evolutionary view In B L Rodgers amp K A Knalf (Eds) Concept development in nursing Foundations techniques and applications (pp 77ndash102) Philadelphia PA Saunders


208 Gagnon and Guta

FINDINGS

The findings of this evolutionary concept analysis are summarized in Figure 1 The next section will provide in-depth discussion of the conceptrsquos attributes followed by a description of antecedents and consequences Articles were carefully selected from the total sample ( N 100) and incorporated in each subsection to support our findings These articles are representative of the literature analyzed across the time periods

ATTRIBUTES

Attributes capture the characteristics of the concept based on the ways in which this concept is used in the literature the purposes for which it is used and when it is used (Rodgers 2000a) The attributes identified in this analysis make it possible to find situations phenomena experiences and practices that fall under the concept of viral load or that can be characterized appropriately using the concept of viral load (Rodgers 2000a) Based on our analysis of the literature published between 1995 and 2013 five major attributes were identified These attributes are described in the following texts

Conceptualization This attribute refers to the specific idea or image of HIV viral load and its ability to ldquoperform certain tasksrdquo (Rodgers 2000b p 25) at a concep-tual level Here it is important to reinforce that our analysis was not specifically focused on the concept as a ldquothingrdquo (as described in entity theories) but rather on the ldquoabstract ideardquo of HIV viral load (as described in dispositional theories) This abstract idea makes it possible for PLWH clinicians researchers policymakers and public health officials to share a common conceptual understanding of HIV and accom-plish certain activities that would not be possible otherwise The dispositional view does not necessarily require an exploration of the actual conceptualization process but rather an analysis of its ldquooutward manifestationsrdquo (Rodgers 2000b p 25)mdashin scholarly literature for example Important manifestations of this process include

Figure 1 Summary of findings

Individual amp population perspectives

Compartmentalization amp connectivity

Patterns fluctuations amp ambiguities

Antecedents

Attributes

Consequences

OperationalizationConceptualization



(a) descriptions of self and others as well as biomedical descriptions of individual bodies (b) interpretations of health illness behaviors infectiousness and treat-ment responses and (c) predictions of illness trajectories risks and outcomes These manifestations reveal the conceptual nature of HIV viral load and the range of intellectual tasks that can be achieved through the use of this concept

HIV viral load functions as a defining feature for PLWH and plays an important role in the presentation of self This became particularly evident when analyzing articles on viral load discussions and sexual decision making (eg see Horvath Smolenski Iantaffi Grey amp Rosser 2012) HIV viral load also functions as a tool for reading individual bodies as particular targets of biomedical and pharmaco-logical interventions The literature reviewed for this analysis draws attention to viral load as a particular way to think about HIV treatment and care By 1996 the International AIDS Society (IAS) had introduced ldquoviral loadndashdrivenrdquo treat-ment guidelines asserting that the primary goal of HIV treatment is to achieve ldquoprofound and durable suppression of viral loadrdquo (Rhone et al 1998 p 662) In the years that followed this approach to HIV treatment was supported by numer-ous researchers clinicians and organizations most notably the BC Centre for Excellence in HIVAIDS in Canada and reinforced by the IAS in its yearly updated guidelines The vast majority of the articles published between 2000 and 2013 support this approach

HIV viral load has been shown to play an important role in the interpretation of health illness behaviors infectiousness and treatment responses We identi-fied several articles that explored the relationships between ldquoperceived viral loadrdquo and interpretations of HIV illness (eg HIV illness not as severe) health (eg HIV infection under control) and infectiousness (eg being less infectious) These relationships were studied with the ultimate objective of understanding sexual practices of PLWH and most importantly risk-taking practices (eg see Stolte de Wit van Eeden Coutinho amp Dukers 2004) The articles reviewed for this analysis pointed to the use of HIV viral load as a tool to hypothesize and study ldquoriskyrdquo behaviors Interestingly however they were not successful in demonstrating that viral load was in fact related to sexual risk taking (eg see Vanable Ostrow amp McKirnan 2003)

Over the course of our analysis HIV viral load was also identified as a core concept in the interpretation of treatment responses Based on the idea of HIV viral load it is possible to define what constitutes ldquotreatment failurerdquo (also known as virologic failure ) or ldquotreatment successrdquo (also known as virologic success ) and describe a range of treatment-related phenomena such as viral load (virologic) response (viral load lower than a measurable thresholdmdasheg less than 50 copiesml [Vrijens et al 2005]) and viral load (virologic) breakthrough (transient rise of viral load above levels of detection [Raboud Rae Wood Harris amp Montaner 2002]) This was echoed in studies published in each of the four time periods

HIV viral load is inextricably linked to the predictions of illness trajectories risks and outcomes The frequent reference to viral load in articles published between 1995 and 1999 revealed a certain way of thinking about the course of HIV infection Studies conducted during this time period used HIV viral load to conceptualize the


210 Gagnon and Guta

illness trajectory as linear progressive and characterized by distinct steps (Churchill amp Weber 1999) The introduction of antiretroviral treatment in 1996 was identi-fied as a key contextual factor in the subsequent conceptualization of the illness trajectory as dynamic preventable and manageable in the studies published after 2000 (Smith amp Stein 2002) The predictive aspect of this concept regarding risks and outcomes has also undergone many transformations over the yearsmdashthese transformations will be detailed in the other sections

It is worth noting here that these findings are reflective of the articles selected for this analysis to the extent that the vast majority of these articles were based on research conducted in resource-rich countries The use of HIV viral load did not vary significantly in the articles located outside this context However the evolution of this concept told a very different story about access to health care infrastructures and resources HIV testing and viral load monitoring technologies HIV treatment and HIV primary care This may explain the chronological discon-nect between literature published in resource-rich and resource-limited countries In other words this may help us understand why earlier conceptualizations of HIV viral load were identified much later in the resource-limited countries Looking at literature published exclusively on vertical transmission for example we were able to identify the exact same manifestations of the concept of HIV viral load in a paper published by the European Collaborative Study in 1999 in a paper published 6 years later by researchers conducting research in Cote drsquoIvoire (Jamieson et al 2003) This disconnect was consistently identified across the literature published on HIV treatment care and follow-up

Operationalization This attribute refers to the operationalization of HIV viral load and more specifically how this concept is articulated in language and expressed quantitatively in the literature The articles examined revealed the importance of paying close attention to words patterns of words and figures of speechmdashmost of which make up our ldquocommon senserdquo in the field of HIVAIDS Most discussions of HIV viral load represented this concept in the form of binary oppositions high versus low detectable versus undetectable suppressed versus unsuppressed clinically significant versus insignificant clinically meaningful versus meaningless accept-able versus unacceptable satisfactory versus unsatisfactory and so forth Overall it was clear that these binary oppositions fulfilled an important function in conveying what is desirable (or not) and providing a system of meanings from which to draw from when conducting research on HIV viral load or studying specific behaviors such as treatment adherence and ldquounsaferdquo sex For example authors frequently indicated that ldquohaving a low or undetectable viral loadrdquo is positively correlated with the clinically meaningful outcomes of optimal treatment adherence and the full prevention benefits of achieving viral suppression (Wilson Law Grulich Cooper amp Kaldor 2008) However further analysis revealed that the meaning of having a low or undetectable viral load was significantly altered in articles published on unsafe sexmdashthus shifting the focus away from the prevention benefits of achieving the desirable state of ldquobeing fully suppressedrdquo to undesirable sexual behaviors such as unprotected sex (Seng et al 2011) Likewise the meaning of having a low of undetectable viral load was inverted in articles published on treatment adherence



as a way to shift the focus away from the complexities involved in taking HIV medi-cations and redirecting it to the individual objective of achieving viral suppression (Widdrington Payne Medhi Valappil amp Schmid 2011)

In light of the literature published on HIV viral load one could conclude that this system of meanings is natural necessary and true However as the concept of viral load becomes associated with a particular use this system of meanings is passed on through knowledge production education and socialization Over time efforts to apply this concept produce meanings that structure what we are permit-ted to say and how we are able to think about HIV (Rodgers 1989) This is part of what Rodgers (1989) describes as the cycle of concept development Concepts assist in the ability to characterize phenomena adequately acquire meaning with frequency and the extent of their use and become associated with a particular use through the process of application (or operationalization) As such the evolutionary method entails closer analysis of continuing efforts to apply concepts over time with particular emphasis on variations innovations and redefinitions For this article we would like to turn our attention to the way HIV viral load has been redefined and expressed quantitatively over a 17-year period in copies per milliliter of blood (copiesml) numbers and correlations The use of this concept throughout the years provided evidence of a progressively narrower application of HIV viral load in the literature Between 1995 and 1999 authors frequently used the concept to discuss viral activity in the blood and describe acceptable outcomes of HIV treat-mentmdashthese outcomes were often expressed in log decreases from baseline viral load and defined as anything less than 5000 copiesml (Saag et al 1996) Between 2000 and 2004 authors used this concept to define specific treatment goals and stress the importance of achieving a viral load below a specific thresholdmdashat the time this threshold was 500 copiesml (Grossberg Zhang amp Gross 2004) Between 2005 and 2009 there was a consensus in the articles reviewed that treatment (virologic) success was best defined using the threshold of 50 copiesml (Vrijens et al 2005) The more current application of the concept signals a move to more sensitive viral load assays lower thresholds (30ndash40 copiesml) and specific ways of defining treatment (virologic) successmdashas sustained very low and durable viral load suppression (Widdrington et al 2011)

Also significant in regard to the operationalization of HIV viral load is the use of sophisticated methods for translating this concept in numbers This analysis revealed various numerical expressions ranging from average viral load mean viral load and median viral load to logarithms quartiles distributions and mathematical models We became particularly interested in a measure called ldquoviral yearrdquo which was first introduced in 1999 (Arnaout et al 1999) ldquoto interpret the relative uniformity of the viral constant (using) the total amount of viremia experienced by a given patient from seroconversion until deathrdquo (p 11549) Using this measure explains Arnaout and colleagues (1999) it is possible to determine that ldquoa patient with an average viral load of 1 10 4 copies of HIV-1 RNAml who survived for 13 years would be said to have experienced 1300 viral yearsrdquo (pp 11549ndash11550) Although the trans-lation of HIV viral load in ldquoviral yearsrdquo may seem of little interest in the current era of rapid scale-up of treatment coverage and treatment access it raises several


212 Gagnon and Guta

interesting points to consider at this stage in the article The numerical expressions of HIV viral load found in the literature were not only time- and context-specific but they were also continually subject to change This finding is consistent with the cycle of concept development described by Rodgers (1989) The importance of time and context became apparent when reading about the measurements of median viral load in cohorts of treatment-naiumlve men who have sex with men (MSM) in the United States in 1999 (Ioannidis Goedert McQueen Enger amp Kaslow 1999) the mathematical modelling of viral load in vertically infected children in the United Kingdom in 2004 (Gray Cortina-Borja amp Newell 2004) the distributions of viral load and the risk of mortality among women of reproductive age in Gambia in 2005 (Hansmann et al 2005) and the use of mean viral load to guide treatment-for-prevention interventions globally in 2012 (Novitsky amp Essex 2012) The general consensus was that numerical expressions increase the explanatory power of HIV viral load and its ability to describe a range of phenomena

On examination of articles published in each of the time period we noted that HIV viral load was used extensively as a ldquomarkerrdquo and expressed through a wide range of statistical correlations HIV viral load has been described as the best marker of disease progression (Ariyoshi et al 2000 Churchill amp Weber 1999) and mortality (Brown et al 2009 Wood et al 2006) Viral load has also been largely studied as a predictive marker of treatment response (Smith et al 2004) treatment efficacy (McKinnon James John amp Mallal 2003) treatment failure (Alvarez-Uria Naik Pakam amp Midde 2012) clinical outcomes in both pediatric (PENTA 1998) and adult populations (Smith amp Stein 2002) opportunistic infections (Swindells et al 2002) HIV transmission (Kamara Melendez-Guerrero Arroyo Weiss amp Jolly 2005 Pedraza et al 1999) and unprotected sex (Stolte et al 2004 Vanable et al 2003) Finally viral load has been used as a surrogate marker for clinically mean-ingful endpoints such as treatment adherence (Inciardi amp Leeds 2005 Martin et al 2008) fidelity to health services (Ortega et al 2003) pharmaceutical care (Castillo et al 2004) infectiousness (Wilson et al 2008) quality of life (Smith amp Stein 2002) lipid profile (Alonso-Villaverde et al 2003) and other conditions such as growth impairment (Pollack et al 1997) hepatic damage (Mata-Mariacuten et al 2009) metabolic syndrome and cardiac complications (Squillace et al 2009) neurologi-cal complications (Gurbindo Resino Saacutenchez-Ramoacuten Leoacuten amp Muntildeoz-Fernaacutendez 1999 Sacktor et al 2003) prolonged QT interval (Qaqa et al 2010) endothelial dysfunction (Blum Hadas Burke Yust amp Kessler 2005) just to name a few

Individual and Population Perspectives Our analysis suggests that the pro-cesses (conceptualization and operationalization) described earlier are shaped by individual and population perspectives notions of compartmentalization and connectivity as well as interpretations of patterns fluctuations and ambiguities As such the next three attributes are best understood as critical components of these processesmdasheach one describing an intersecting characteristic of the concept that is presented separately for this article During the late 1990s the concept of HIV viral load grew out of research conducted from an individual perspective At the time it was mainly described as an innovative tool to produce ldquoimportant information for patient managementrdquo (Saag et al 1996 p 628) HIV viral load was used to ldquopicturerdquo



viral activity and its effects in the individual bodymdashwhich were closely linked to unfavorable clinical outcomes such as progression to AIDS or death (Klaus 1996) It was also used to predict the course of HIV infection and evaluate the individual risk of disease progression (Saag et al 1996) By 1998 this concept was gaining momentum This momentum was attributable to several factors including the availability of sensitive new techniques to quantify the concentrations of HIV RNA in plasma and the introduction of combination antiretroviral treatment (Yogev 1998) Several authors began to describe HIV viral load as having the potential to provide new insights into the pathogenesis of HIV infection and the progression of the disease to produce a more comprehensive picture of individual health status and needs and to guide decisions regarding HIV treatment and treatment responses (Churchill amp Weber 1999) In addition authors began to compare the explanatory power of viral load and CD4 cell count with respect to the individual benefits of HIV treatment (Drusano amp Stein 1998) Our analysis suggests that this was a pivotal moment in the evolution of the concept of HIV viral load in that moment the argu-ment was made that individual benefits of HIV treatment are first and foremost virological rather than immunological

During the late 1990s and early 2000s a relational approach to the concept of HIV viral load began to appear in the literature on vertical and sexual transmission of HIV This approach suggested that viral load was not strictly contained in individual bodies and that in fact it could be viewed as a connection between two individu-als At the time studies were published describing HIV viral load as a ldquoconnectiverdquo concept between a mother and her child Recommendations to use antiretroviral treatment during pregnancy labor and at the time of delivery arose from studies that showed a connection between maternal viral load and the risk of transmission (Dickover et al 1996 Thea et al 1997) Mentions of maternal HIV viral load as the strongest risk factor for in utero and intrapartum transmission also began to appear in the literature during this time period (Mock et al 1999) Several authors started to recommend the implementation of viral loadndashdriven treatment guidelines to reduce maternal viral load and in turn reduce the overall risk of transmission (Mock et al 1999 The European Collaborative Study 1999) A similar connection between maternal HIV viral load and the risk of transmission during breastfeeding was also reported in studies conducted in resource-limited countries (Jamieson et al 2003) Furthermore we were able to identify an article that looked specifically at viral load and disease progression in infants with perinatally acquired HIV infection (Lambert et al 1997) In keeping with the findings described earlier a relational approach to HIV viral load was also identified in the literature on sexual transmis-sion of HIV (Pedraza et al 1999 Tovanabutra et al 2002) The use of viral load to portray individual-to-individual phenomena clearly signalled a shift from locating HIV in individual bodies to thinking about HIV through various connections between bodiesmdashthis is quite evident in the articles published after 2010

Since 2010 the concept of HIV viral load has rapidly evolved to become a new way of thinking about connections between individual bodies and populations Increasingly this concept is used to measure and map HIV burden at a population level (Castel et al 2012) to monitor treatment coverage and engagement in care (Raboud et


214 Gagnon and Guta

al 2010) to support the implementation and assess the efficacy of ldquoTreatment as Preventionrdquo (TasP) interventions which rely on the premise that increased individual treatment will reduce HIV incidence (Henard et al 2012 Montaner et al 2010) Furthermore viral load is used to inform public health surveillance allocate fund-ing and resources and identify priorities and targets for HIV prevention (Das et al 2010) This growing trend stems from newly established connections between viral load (as a population or community-based marker) and overall HIV incidence (Castel et al 2012 Das et al 2010 Montaner et al 2010) Viral load is also closely linked to a growing interest in TasP interventions in resource-rich (Sayles et al 2012) and resource-limited countries (Novitsky amp Essex 2012) In short these interventions are designed to achieve a sustained very low and durable viral load suppression in large numbers of PLWH as a way to prevent onward transmission of the virus Through our search we were unable to locate an article that offered an actual overview of the concept of HIV viral load and its evolution over the years However we were able to identify three important factors that have shaped the evolution of HIV viral load from an individual to a population-based concept (a) the versatility of this conceptmdashor its ability to perform a wide range of tasks and move effectively from one time period to another (b) the close association between viral load and HIV treatmentmdashthat is clinicians who use this concept effectively can make various treatment decisions and implement treatment interventions initiate treatment (as treatment or as preven-tion) monitor treatment response detect treatment failure and so forth and (c) the relationship between this concept and new understandings of HIV transmission

Compartmentalization and Connectivity The articles reviewed for this analysis suggest that HIV viral load has been applied consistently throughout the years to gain new understandings of HIV transmission However we noted that authors dif-fered in their ways of articulating this conceptmdashthat is we identified two separate approaches to viral load one based on the notion of compartmentalization and the other one based on the notion of connectivity For some authors HIV viral load is a concept that separates the body in distinct compartments and locates the virus in blood breast milk semen vaginal or anal secretions cerebrospinal fluid or in the genital tract the brain vaginal or rectal mucosa the lymph nodes and so on It is a concept that can be divided isolated and studied separatelymdashin cerebrospinal fluid (Gissleacuten Fuchs Svennerholm amp Hagberg 1999 Sacktor et al 2003) semen and vaginal secretions (Vandermaelen amp Englert 2010) or breast milk (Colebunders et al 2005) for example This approach to viral load relies on the premise that each body compartment exists independently from other compartments and is charac-terized by its own unique features (eg viral concentration inflammation tissues immunologic response etc [OrsquoByrne amp MacPherson 2008]) As such it allows for boundaries to be drawn between different compartments (eg blood and genital tract compartment or blood and breast milk) and questions to be raised with respect to the prevention benefits of HIV treatment (OrsquoByrne amp MacPherson 2008) During the analysis we identified several articles that alluded to some viral load variations between body compartments and explored the relevance of these variations for HIV prevention (eg see Guzman et al 2006) These articles revealed a tension between the ldquoperceivedrdquo prevention benefits and the ldquorealrdquo prevention benefits of



HIV treatment which may be significantly impacted by localized immune activa-tion and viral replication uneven distribution of HIV medications and HIV strains across compartments and differences between viral loads from one compartment to another (as summarized in OrsquoByrne amp MacPherson 2008)

For other authors HIV viral load is a concept that is primarily imagined through its potential to connect body compartments together and produce a whole It is mani-fested in statistical analyses of two (or more) interrelated and correlated measures that reflect changes in ldquosystemic viral loadrdquomdasha term used by Sacktor et al (2003) to describe viral load as a concept that pertains to the whole body This approach to viral load stems from a body of literature on the systemic effects of HIV treatment and more specifically on the effects of treatment as prevention (Montaner et al 2010) As such it is concerned with a process of viral load reduction that unfolds sequentially starting with viral load in blood and moving on to other bodily fluids and reservoirs (Montaner et al 2010) Since 2010 there has been a growing use of the concept of HIV viral load as an evidence of transmission probabilities as a whole (Seng et al 2011) However our analysis revealed that this particular use of the concept was initially met with a great deal of resistance which included argu-ments for a compartmentalized approach to viral load These arguments were easily identified in articles published right after the release of a statement by the Swiss Federal AIDS Commission in 2008mdashin short this statement argued that a person living with HIV who is (a) treated and adherent (b) consistently undetectable for more than 6 months and (c) not currently diagnosed with a sexually transmitted infection was unlikely to transmit the virus sexually (Vernazza Hirschel Bernasconi amp Flepp 2008) In response to what became known as the ldquoSwiss statementrdquo authors emphasized the importance of describing transmission probabilities under the conditions listed earlier as ldquovery low but not zerordquo (Vandermaelen amp Englert 2010 p 374) In fact it was believed that an approach that is solely based on viral load as a whole (eg plasma viral load less than 50 copiesml equals no risk of trans-mission) could lead to increase trends in unsafe sex and potentially increase rates of HIV transmission because of factors (eg sexually transmitted infections [STIs]) that can create viral load variations in the genital tract (OrsquoByrne amp MacPherson 2008) Unsurprisingly efforts to split HIV viral load in partsmdasheach part with its own patterns fluctuations and ambiguitiesmdashwere seen as the best way to prevent this from happening (Wilson et al 2008)

The repeated use of the notions of compartmentalization and connectivity over the years has contributed to the development of HIV viral load as a concept that can be used to think more effectively about HIV prevention Over the course of this analysis we identified many instances where HIV viral load was used to perform certain tasks such as (a) describing HIV transmission dynamics and probabilities (b) drawing attention to the benefits and limits of HIV treatment (c) communicating complex science to PLWH and (d) opening possibilities for new kinds of prevention messages For this article we will focus on two specific instances where HIV viral load performed these tasks In the literature on maternal and infant health for example variations in the tasks performed by viral load revealed two distinct approaches to HIV prevention one approach that favored the compartmentalization


216 Gagnon and Guta

of viral load to reinforce the risks of breastfeeding (Mock et al 1999) and another approach that favored the association between viral load in plasma and breast milk to reinforce the benefits of HIV treatment in contexts where ldquoexclusive replacement feeding is not acceptable feasible affordable safe or sustainablerdquo (Lunney et al 2010 p 762) Another example that was identified during the analysis has to do with literature specific to MSM Here we were able to find several articles in which viral load was compartmentalized to call into question the supposed positive effects of treatment on sexual transmission of HIV and reinforce the need for continued prevention efforts among MSM (Guzman et al 2006 Stolte et al 2004 Vanable et al 2003) In addition we were able to find articles in which viral load (as a whole) was put forward as a risk factor for unsafe sex and a concept that should be used more effectively to change attitudes perceptions and behaviors that impact sexual risk decisions (Muntildeoz-Laboy Castellanos amp Westacott 2005 Van de Ven et al 2005) In both of these instances the articles reviewed described HIV viral load as a central concept of HIV prevention

Patterns Fluctuations and Ambiguities In this section we draw on selected articles that describe HIV viral load as a dynamic conceptmdashone that is charac-terized by predictable patterns and responses unpredictable fluctuations and situations in which ambiguities can arise The patterns discussed here were com-monly found in the literature published between 1995 and 2005 This decade saw a tremendous growth in knowledge about the ldquonatural historyrdquo of HIV infection At the time patterns in viral load were commonly described using the predictable course of HIV infection during which concentrations of the virus are expected to rise abruptly during acute seroconversion decrease progressively plateau dur-ing clinical latency and increase progressively back to the levels documented at the initial stage of the infection during symptomatic and late-stage infection (Saag et al 1996) These patterns provided a clear picture of how viral replica-tion actually appears at every stage of HIV infection and what to expect for every person diagnosed with HIV They were often portrayed alongside CD4 cell count patterns in a graphic (see Saag et al 1996 p 625) that would provide clinicians with a predictable course of events on which to draw from when providing care to people diagnosed with HIV They were also used by researchers to study the progression of HIV infection (Smith amp Stein 2002) Near the end of the decade a new kind of patterns had emerged These patterns were said to be representative of predictable treatment and viral responses For example patterns known as ldquoreboundsrdquo are said to occur in situations of incomplete adherence or treatment interruptions that are characterized by a sudden rise in viral load above the limit of detection (Raboud et al 2002) Thus HIV viral load continues to be seen as a dynamic concept partly because of these patterns and the way they have con-tributed to understanding its functionsmdashas a concept that explains and predicts certain phenomena

The frequent reference to HIV viral load as characterized by fluctuations was identified throughout the literature However it was obvious that fluctuations served a different function than patterns in depicting the dynamic nature of this concept In contrast to patterns which were seen as predictable and common



to all persons living with HIV fluctuations were seen as unpredictable rises and falls in viral load that are influenced by viral factors (eg viral strain) host factors (eg strength of immune system) and individual factors such as age and gender (Hudgens Hoering amp Self 2003) Authors mentioned various types of fluctuations including but not limited to fluctuations over time fluctuations between individu-als and fluctuations triggered by isolated events such as infection or vaccination The articles reviewed seemed to suggest that viral load is naturally expected to rise and fall over time during untreated and treated HIV infection (Arnaout et al 1999 Dickover et al 1996 Korenromp Williams Schmid amp Dye 2009 Ortega et al 2003) Yet these changes were often described as somewhat unpredictable The unpredictable occurrence of these fluctuations is among the reasons why viral load is monitored on a regular basis (Churchill amp Weber 1999 Yogev 1998) why the reliability of viral load has been called into question (Combescure et al 2009) and why several authors have insisted that the risk of sexual transmission is never completely eliminated even when viral load is undetectable (Guzman et al 2006 Muntildeoz-Laboy et al 2005 Stolte et al 2004 Vanable et al 2003 Van de Ven et al 2005) Fluctuations between adults and children were also described in the literaturemdashfor example children have higher viral loads than adults (PENTA 1998 Shah 2006) Similar fluctuations were reported between men and womenmdashfor example women have lower viral loads than men (Ortega et al 2003) It was generally recognized that diversity in HIV viral load is determined by individual characteristics (including viral and host characteristics) but the extent to which these characteristics determine how diverse viral load actually is remain unknown (Ariyoshi et al 2000) It was clear however that some fluctuations had nothing to do with individual characteristics and were triggered by isolated events For example fluctuations known as ldquoblipsrdquo were said to occur when someone experi-ence a transient rise in viral load without adverse clinical outcomes following vac-cination an episode of infection or an activation of the immune system (Churchill amp Weber 1999 Garcia et al 1997)

We would like to stress that patterns and fluctuations have contributed to the evolution of HIV viral load as an ambiguous conceptmdashone that is seen imagined and represented as stable and unstable predictable and unpredictable reliable and unreliable and so forth In fact the ambiguous nature of this concept has made it amenable to a broad range of applications over the years Our analysis revealed that patterns and fluctuations did not necessarily oppose but were often arranged in ways that (a) gave priority to certain arguments and interventions (b) assisted in the resolution of certain kinds of problems and (c) achieved specific goals In analyzing the literature we noted that patterns and fluctuations gave priority to certain arguments like the importance of monitoring viral load regularly and interventions such as the need to start treatment at a particular point in time in the natural course of HIV infection (as mentioned earlier) Furthermore we noted that HIV viral load was typically regarded with ambivalence by authors who were particularly interested in addressing the ldquoproblemsrdquo of treatment optimism compla-cency and risk taking It became clear that this particular use of HIV viral loadmdashas unpredictable and unreliablemdashwas concerned with changing the perceptions of


218 Gagnon and Guta

PLWH managing the risks of unsafe or ldquoriskierrdquo sex and reinforcing the need for more effective prevention interventions (Guzman et al 2006 Muntildeoz-Laboy et al 2005 Stolte et al 2004 Vanable et al 2003 Van de Ven et al 2005) HIV viral load was also presented as an ambiguous concept by authors who wanted to achieve specific goals with respect to treatment adherence In other words it was often presented as stable and unstable simultaneously stable to reinforce that taking HIV medications leads to predictable outcomes (most notably viral suppression) and unstable to substantiate the adverse clinical outcomes of incomplete adher-ence and treatment interruptions (Combescure et al 2009 Grossberg et al 2004 Martin et al 2008 Vrijens et al 2005)

ANTECEDENTS

According to Rodgers (2000a) antecedents are events or phenomena that precede the concept Or in other words what must happen before an instance of the concept occurs Three categories of antecedents were identified in this analysis (a) technol-ogy and infrastructures (b) laboratory values and parameters and (c) specimen col-lection frameworks Any instance of the concept presupposes access to technology (ie ultrasensitive viral load assays) and effective access to infrastructures for viral load analysis monitoring and reporting (Yogev 1998) Affordable access to tech-nology remains an important issue in most resource-limited countries due largely to costsmdasha single ultrasensitive viral load assay costs $75 (Smith et al 2009) In addition to high costs the difficult access to infrastructures for viral load analysis monitoring and reporting was identified as a barrier in the articles reviewed (Alabi et al 2003 Brown et al 2009 Jamieson et al 2003 Korenromp et al 2009 Wood et al 2006) In fact viral load was often described as optional rather than necessary in resource-limited countries (Calmy et al 2007) This is important to point out because it suggests that HIV viral load is predominantly a Westernized concept As such its evolution has been largely driven by the use of viral load in resource-rich settings and has little to do with the limited use of viral load in resource-limited settings Currently the World Health Organization recommends limiting the use of viral load in these settings to guide decisions to switch treatment regimens or to detect treatment failure (Alvarez-Uria et al 2012 Kanapathipillai et al 2011 Siberry et al 2012 Wilson et al 2009) The second antecedent identified in this analysis pointed to the importance of laboratory values and parameters as precursors to instances of the concept of HIV viral load Finally the last antecedent revealed that the concept of viral load was initiated by specimen collection frameworks that made it possible to collect and measure viral load in blood

CONSEQUENCES

The consequences of HIV viral load were difficult to separate from the attributes in this analysis This is not uncommon for researchers who use the evolutionary method because it requires a close analysis of the significance use and application of the concept (Rodgers 1989) In fact Cowles and Rodgers (2000) made a similar observation when they reported their findings of a concept analysis of grief For this



article we opted to focus on two major consequences namely the categorization of PLWH based on their viral load ldquostatusrdquo and the construction of several distinct types of risks

The categorization of patients based on their viral load ldquostatusrdquo was not specifi-cally discussed in the articles reviewed for this analysis Nevertheless this conse-quence of HIV viral load was clearly identified throughout the four time periods Authors would refer to patients using the following categories (a) progressors and nonprogressors (b) nonresponders partial responders and full responders (c) rebounders and nonrebounders (d) detectable (or persistently detectable) undetectable and unknown (e) adherent and nonadherent and (f) poor and good adherers These categories speak to the ability of HIV viral load to be used in such a way that patients can be labelled and separated into groups They also speak to the descriptive power of HIV viral load and its ability to assign particular mean-ings to individual responses (or lack of response) to treatment or to individual behaviors such as treatment adherence The use of this concept to categorize PLWH is indicative of a broader trend in the field of HIVAIDS which has not (to our knowledge) been addressed by researchers and clinicians This is particularly concerning because the categories listed earlier serve to reduce the bodies of PLWH to distinguish ldquogoodrdquo (the undetectable patients) from ldquobadrdquo patients (the detectable patients) sanction ldquoproblematicrdquo behaviors (the persistently detect-able patients) and identify patients in need of attention (the poor adherers) Furthermore these categories draw an incomplete portrait of the complexities involved in taking HIV medications and ignore the effect of other factors such as side effects complications specific requirements of HIV medications social and family support sociocultural context access (eg food housing pharmaceutical care health care support services) patient knowledge and resources on treat-ment adherence

The construction of several distinct types of risks was identified as a conse-quence of HIV viral load By this we mean that this concept provided the necessary conceptual framework to imagine new types of risks and intervene accordingly Between 1995 and 1999 HIV viral load was used to conceptualize the risk of disease progression the risk of AIDS and the risk of death It was also used to discuss the risk of HIVAIDSndashrelated complications and HIV transmission with a particular emphasis on vertical transmission Between 2000 and 2004 it was used to emphasize the risk of virologic failure including the risk of developing viral mutations and resistance and the risk of not achieving virologic success when taking HIV medications It was also used to increase preoccupation with risks of unprotected sex Between 2005 and 2009 it was used to discuss the potential risks of perceiving oneself as less contagious and less likely to transmit HIV when having an undetectable viral load It was also used to draw attention to increasing trends in sexual risks and risk-taking behaviors that could lead to HIV transmis-sion Between 2010 and the present HIV viral load has primarily been used to transform how we think about risk namely by using viral load (eg community viral load) as an indicator of risk at a population level In addition it has been found to play an important role in the perception of risk at the individual level


220 Gagnon and Guta

Findings of studies conducted with MSM showed that HIV viral load was an intri-cate part in the assessment of sexual risksmdashincluding the risks to self and others (Guzman et al 2006 Muntildeoz-Laboy et al 2005 Stolte et al 2004 Vanable et al 2003 Van de Ven et al 2005)

SURROGATE TERMS

According to Rodgers (2000a) surrogate terms express the same idea as the con-cept selected for the analysis but through different words or expressions The terms viral RNA concentration HIV-1 levels RNA load RNA viral load virus load (plasma) HIV-1 RNA levels HIV-1 viral load and plasma viral load were identified during data collection and analysis These terms were often used interchangeably in the litera-ture to refer to the concept of viral load The abbreviations VL (viral load) and pVL (plasma viral load) were also used by several authors The use of these surrogate terms reflected personal preferences variations across disciplines and contexts specificities of research methods (quantitative versus qualitative) and requirements of peer-reviewed journals

IMPLICATIONS FOR NURSING AND ALLIED HEALTH DISCIPLINES

The purpose of this article was to critically examine the literature on HIV viral load to identify the attributes antecedents and consequences of the concept The findings of this concept analysis have important implications for clinical practice research and theory These implications will be briefly discussed in the following section

CLINICAL IMPLICATIONS

The concept of HIV viral load is widely used in clinical practice Yet the contextual basis of this concept is rarely if ever called into question in nursing and allied health disciplines By this we mean that the situational relational temporal sociocultural and clinical contexts in which the concept is relevant effectively used and applied in various situations has not (to our knowledge) been critically examined by these disciplines So far attention to these contexts has come from other disciplines such as anthropology sociology psychology feminist and queer studies science and technology studies and cultural studies (eg see Mykhalovskiy McCoy amp Bresalier 2004 Persson amp Newman 2006 Race 2001 Rosengarten 2005 Wong amp Usher 2008) In light of our findings we argue that it is essential for nurses and allied health professionals to consider the ways in which HIV viral load informs their practice structures their interventions shapes the conceptualization of health and illness and assigns particular meanings to attitudes behaviors and relationships In addition we consider that the consequences of viral load such as categorizing patients and constructing risk should be further explored in nursing and allied health disciplines



RESEARCH IMPLICATIONS

The findings of this concept analysis point to the importance of conducting research on the experience of PLWH with respect to HIV viral load Is this concept relevant and meaningful in everyday life If so why and in what ways How does this concept come into play in decisions about health treatment disclosure sexual-ity and so forth When is this concept used in day-to-day activities and for what purposes How does it affect interactions with health care professionals service providers sexual partners and others How does it affect perceptions (of self and others) interpretations (of health illness risks obligations etc) and meanings assigned to HIV (as a virus and an illness) and the experience of living with HIV Exploration of these questions using qualitative approaches such as phenomenol-ogy narrative inquiry discourse analysis and grounded theory is thus warranted Qualitative approaches such as situational analysis and ethnography are also needed to locate the concept of viral load at the intersection of bodies treatments discourses knowledge practices and apparatuses (public health law medicine etc [Rosengarten 2005]) The attributes and consequences identified through this analysis provide direction for additional research in this area

THEORETICAL IMPLICATIONS

The findings of this analysis reinforce the importance of drawing on theory to fur-ther our understanding of HIV viral load as a key concept in the field of HIVAIDS Attention should be focused on theories that can assist in analyzing the impact of HIV viral load on certain thought processes and behaviors (eg psychological and social theories of health behaviors) the use of HIV viral load in the construction and amplification of risk (eg social and cultural theories of risk and health governance) the incorporation of HIV viral load in public health legal and medical discourses (eg poststructuralist theories) the bodily experiences of HIV viral load (eg theories of embodiment) and the viral load test as technology (eg social theories focused on technology such as actor-network theory and assemblage theory) Finally we would like to point out the importance of applying these theories in nursing and allied health disciplines to question taken-for-granted assumptions in the field of HIVAIDS to critically reflect on the impact of our practices and to be potentially more creative at examining important clinical sociocultural political historical and legal aspects of the HIV response

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Alabi A S Jaffar S Ariyoshi K Blanchard T Schim van der Loeff M Awasana A A Whittle H (2003) Plasma viral load CD4 cell percentage HLA and survival of HIV-1 HIV-2 and dually infected Gambian patients AIDS 17 1513ndash1520

Alonso-Villaverde C Segues T Coll-Crespo B Peacuterez-Bernalte R Rabassa A Gomila M Masana L (2003) High-density lipoprotein concentrations relate to the clinical course of HIV viral load in patients undergoing antiretroviral therapy AIDS 17 1173ndash1178


222 Gagnon and Guta

Alvarez-Uria G Naik P K Pakam R amp Midde M (2012) Early HIV viral load determina-tion after initiating first-line antiretroviral therapy for identifying patients with high risk of developing virological failure Data from a cohort study in a resource-limited setting Tropical Medicine amp International Health 17 1152ndash1155

Ariyoshi K Jaffar S Alabi A S Berry N Schim van der Loeff M Sabally S Whittle H (2000) Plasma RNA viral load predicts the rate of CD4 T cell decline and death in HIV-2-infected patients in West Africa AIDS 14 339ndash344

Arnaout R A Lloyd A L OrsquoBrien T R Goedert J J Leonard J M amp Nowak M A (1999) A simple relationship between viral load and survival time in HIV-1 infection Proceedings of the National Academy of Sciences of the United States of America 96 11549ndash11553

Blum A Hadas V Burke M Yust I amp Kessler A (2005) Viral load of the human immuno-deficiency virus could be an independent risk factor for endothelial dysfunction Clinical Cardiology 28 149ndash153

Brown E R Otieno P Mbori-Ngacha D Farquhar C Obimbo E M Nduati R John-Stewart G (2009) Comparison of CD4 cell count viral load and other markers for the prediction of mortality among HIV-1-infected Kenyan pregnant women Journal of Infectious Diseases 199 1292ndash1300

Calmy A Ford N Hirschel B Reynolds S J Lynen L Goemaere E Rodriguez W (2007) HIV viral load monitoring in resource-limited regions Optional or necessary Clinical Infectious Diseases 44 128ndash134

Castel A D Befus M Willis S Griffin A West T Hader S amp Greenberg A E (2012) Use of the community viral load as a population-based biomarker of HIV burden AIDS 26 345ndash353

Castillo E Palepu A Beardsell A Akagi L Yip B Montaner J S amp Hogg R S (2004) Outpatient pharmacy care and HIV viral load response among patients on HAART AIDS Care 16 446ndash457

Churchill D amp Weber J (1999) Measurement of plasma HIV viral loadmdashClinical applications The Journal of Infection 38 147ndash150

Colebunders R Hodossy B Burger D Daems T Roelens K Coppens M Fransen K (2005) The effect of highly active antiretroviral treatment on viral load and antiretroviral drug levels in breast milk AIDS 19 1912ndash1915

Combescure C Vallier N Ledergerber B Cavassini M Furrer H Rauch A Hirschel B (2009) How reliable is an undetectable viral load HIV Medicine 10 470ndash476

Cowles K V amp Rodgers B L (2000) The concept of grief an evolutionary perspective In B L Rodgers amp K A Knalf (Eds) Concept development in nursing Foundations techniques and applications (pp 103ndash117) Philadelphia PA Saunders

Das M Chu P L Santos G M Scheer S Vittinghoff E McFarland W amp Colfax G N (2010) Decreases in community viral load are accompanied by reductions in new HIV infections in San Francisco PloS One 5 e11068

Dickover R E Garratty E M Herman S A Sim M S Plaeger S Boyer P J Bryson Y J (1996) Identification of levels of maternal HIV-1 RNA associated with risk of perinatal transmission Effect of maternal zidovudine treatment on viral load The Journal of the American Medical Association 275 599ndash605

Drusano G L amp Stein D S (1998) Mathematical modeling of the interrelationship of CD4 lymphocyte count and viral load changes induced by the protease inhibitor indinavir Antimicrobial Agents and Chemotherapy 42 358ndash361

Gagnon M amp Guta A (2012) Mapping community viral loads Space power and the gov-ernment of bodies Critical Public Health 22 471ndash483

Garcia F Vidal C Gatell J M Miro J M Soriano A amp Pumarola T (1997) Viral load in asymptomatic patients with CD4 lymphocyte counts above 500 10(6)l AIDS 11 53ndash57



Gissleacuten M Fuchs D Svennerholm B amp Hagberg L (1999) Cerebrospinal fluid viral load intrathecal immunoactivation and cerebrospinal fluid monocytic cell count in HIV-1 infection Journal of Acquired Immune Deficiency Syndromes 21 271ndash276

Gray L Cortina-Borja M amp Newell M L (2004) Modelling HIV-RNA viral load in vertically infected children Statistics in Medicine 23 769ndash781

Grossberg R Zhang Y amp Gross R (2004) A time-to-prescription-refill measure of anti-retroviral adherence predicted changes in viral load in HIV Journal of Clinical Epidemiology 57 1107ndash1110

Gurbindo D Resino S Saacutenchez-Ramoacuten S Leoacuten J A amp Muntildeoz-Fernaacutendez M A (1999)Correlation of viral load and CD8 T-lymphocytes with development of neurological manifestations in vertically HIV-1-infected infants A prospective longitudinal study Neuropediatrics 30 197ndash204

Guzman R Buchbinder S Mansergh G Vittinghoff E Marks G Wheeler S amp Colfax G N (2006) Communication of HIV viral load to guide sexual risk decisions with sero-discordant partners among San Francisco men who have sex with men AIDS Care 18 983ndash989

Hansmann A Schim van der Loeff M F Kaye S Awasana A A Sarge-Njie R OrsquoDonovan D Whittle H C (2005) Baseline plasma viral load and CD4 cell percentage predict survival in HIV-1- and HIV-2-infected women in a community-based cohort in the Gambia Journal of Acquired Immune Deficiency Syndromes 38 335ndash341

Henard S Jeanmaire E Nguyen Y Yazdanpanah Y Cheret A Hoen B Rabaud C (2012) Is total community viral load a robust predictive marker of the efficacy of the TasP strategy Journal of Acquired Immune Deficiency Syndromes 61 400ndash402

Horvath K J Smolenski D Iantaffi A Grey J A amp Rosser B R (2012) Discussions of viral load in negotiating sexual episodes with primary and casual partners among men who have sex with men AIDS Care 24 1052ndash1055

Hudgens M G Hoering A amp Self S G (2003) On the analysis of viral load endpoints in HIV vaccine trials Statistics in Medicine 22 2281ndash2298

Inciardi J F amp Leeds A L (2005) Assessing the utility of a community pharmacy refill record as a measure of adherence and viral load response in patients infected with human immunodeficiency virus Pharmacotherapy 25 790ndash796

Ioannidis J P Goedert J J McQueen P G Enger C amp Kaslow R A (1999) Comparison of viral load and human leukocyte antigen statistical and neural network predictive models for the rate of HIV-1 disease progression across two cohorts of homosexual men Journal of Acquired Immune Deficiency Syndromes and Human Retrovirology 20 129ndash136

Jamieson D J Sibailly T S Sadek R Roels T H Ekpini E R Boni-Ouattara E Wiktor S Z (2003) HIV-1 viral load and other risk factors for mother-to-child transmis-sion of HIV-1 in a breast-feeding population in Cote drsquoIvoire Journal of Acquired Immune Deficiency Syndromes 34 430ndash436

Kamara P Melendez-Guerrero L Arroyo M Weiss H amp Jolly P (2005) Maternal plasma viral load and neutralizingenhancing antibodies in vertical transmission of HIV A non-randomized prospective study Virology Journal 2 15

Kanapathipillai R McGuire M Mogha R Szumilin E Heinzelmann A amp Pujades-Rodriacuteguez M (2011) Benefit of viral load testing for confirmation of immunological failure in HIV patients treated in rural Malawi Tropical Medicine amp International Health 16 1495ndash1500

Klaus B D (1996) Applying viral load measurements to HIV care The Nurse Practitioner 21 102ndash104

Korenromp E L Williams B G Schmid G P amp Dye C (2009) Clinical prognostic value of RNA viral load and CD4 cell counts during untreated HIV-1 infectionmdashA quantitative review PloS One 4 e5950


224 Gagnon and Guta

Lambert G Thea D M Pliner V Steketee R W Abrams E J Matheson P Kalish M L (1997) Effect of maternal CD4 cell count acquired immunodeficiency syndrome and viral load on disease progression in infants with perinatally acquired human immuno-deficiency virus type 1 infection New York City Perinatal HIV Transmission Collaborative Study Group The Journal of Pediatrics 130 890ndash897

Lunney K M Iliff P Mutasa K Ntozini R Magder L S Moulton L H amp Humphrey J H (2010) Associations between breast milk viral load mastitis exclusive breast-feeding and postnatal transmission of HIV Clinical Infectious Diseases 50 762ndash769

Martin M Del Cacho E Codina C Tuset M De Lazzari E Mallolas J Ribas J (2008) Relationship between adherence level type of the antiretroviral regimen and plasma HIV type 1 RNA viral load A prospective cohort study AIDS Research and Human Retroviruses 24 1263ndash1268

Mata-Mariacuten J A Gaytaacuten-Martiacutenez J Grados-Chavarriacutea B H Fuentes-Allen J L Arroyo-Anduiza C I amp Alfaro-Mejiacutea A (2009) Correlation between HIV viral load and aminotransferases as liver damage markers in HIV infected naive patients A concordance cross-sectional study Virology Journal 6 181

McKinnon E J James I R John M amp Mallal S A (2003) Viral load detectability profiles for HIV infection Statistics in Medicine 22 385ndash396

Meleis A I (2012) Theoretical nursing Development amp progress (5th ed) Philadelphia PA Lippincott Williams amp Wilkins

Mock P A Shaffer N Bhadrakom C Siriwasin W Chotpitayasunondh T Chearskul S Mastro T D (1999) Maternal viral load and timing of mother-to-child HIV trans-mission Bangkok Thailand Bangkok Collaborative Perinatal HIV Transmission Study Group AIDS 13 407ndash414

Montaner J S Lima V D Barrios R Yip B Wood E Kerr T Kendall P (2010) Association of highly active antiretroviral therapy coverage population viral load and yearly new HIV diagnoses in British Columbia Canada A population-based study Lancet 376 532ndash539

Muntildeoz-Laboy M Castellanos D amp Westacott R (2005) Sexual risk behaviour viral load and perceptions of HIV transmission among homosexually active Latino men An exploratory study AIDS Care 17 33ndash45

Mykhalovskiy E McCoy L amp Bresalier M (2004) Complianceadherence HIV and the critique of medical power Social Theory amp Health 2 315ndash340

Novitsky V amp Essex M (2012) Using HIV viral load to guide treatment-for-prevention inter-ventions Current Opinion in HIV and AIDS 7 117ndash124

OrsquoByrne P amp MacPherson P A (2008) Understanding HIV viral load Implications for coun-selling Canadian Journal of Public Health 99 189ndash191

Ortega M Eiros J M Labayru C Hernaacutendez B Bou G amp Ortiz de Lejarazu R (2003) Factors associated with the evolution of the viral load in individuals with HIV infection International Journal of Antimicrobial Agents 21 478ndash483

Paediatric European Network for Treatment of AIDS (PENTA) (1998) HIV-1 viral load and CD4 cell count in untreated children with vertically acquired asymptomatic or mild disease AIDS 12 F1ndashF8

Pedraza M A del Romero J Roldaacuten F Garciacutea S Ayerbe M C Noriega A R amp Alcami J (1999) Heterosexual transmission of HIV-1 is associated with high plasma viral load levels and a positive viral isolation in the infected partner Journal of Acquired Immune Deficiency Syndromes 21 120ndash125

Persson A amp Newman C (2006) Potency and vulnerability Troubled lsquoselvesrsquo in the context of antiretroviral theory Social Science amp Medicine 63 1586ndash1596

Pollack H Glasberg H Lee E Nirenberg A David R Krasinski K Oberfield S (1997) Impaired early growth of infants perinatally infected with human immunodeficiency virus Correlation with viral load The Journal of Pediatrics 130 915ndash922



Qaqa A Y Shaaban H DeBari V A Phung S Slim J Costeas C A Shamoon F E (2010) Viral load and CD4 cell count as risk factors for prolonged QT interval in HIV-infected subjects A cohort-nested case-control study in an outpatient population Cardiology 117 105ndash111

Raboud J M Loutfy M R Su D Bayoumi A M Klein M B Cooper C Hogg R S (2010) Regional differences in rates of HIV-1 viral load monitoring in Canada Insights and implications for antiretroviral care in high income countries BMC Infectious Diseases 10 40

Raboud J M Rae S Woods R Harris M amp Montaner J S (2002) Consecutive rebounds in plasma viral load are associated with virological failure at 52 weeks among HIV-infected patients AIDS 16 1627ndash1632

Race K (2001) The undetectable crisis Changing technologies of risk Sexualities 4 (2) 167ndash189 Rhone S A Hogg R S Yip B Sherlock C Conway B Schechter M T Montaner J S

(1998) Do dual nucleoside regimens have a role in an era of plasma viral load-driven antiretroviral therapy The Journal of Infectious Diseases 178 662ndash668

Rodgers B L (1989) Concepts analysis and the development of nursing knowledge The evolutionary cycle Journal of Advanced Nursing 14 330ndash335

Rodgers B L (2000a) Concept analysis An evolutionary view In B L Rodgers amp K A Knalf (Eds) Concept development in nursing Foundations techniques and applications (pp 77ndash102) Philadelphia PA Saunders

Rodgers B L (2000b) Philosophical foundations of concept development In B L Rodgers amp K A Knalf (Eds) Concept development in nursing Foundations techniques and applica-tions (pp7ndash37) Philadelphia PA Saunders

Rosengarten M (2005) The measure of HIV as a matter of bioethics In M Shildrick amp R Mykitiuk (Eds) Ethics of the body Postconventional challenges (pp71ndash90) Cambridge MA The MIT Press

Saag M S Holodniy M Kuritzkes D R OrsquoBrien W A Coombs R Poscher M E Volberding P A (1996) HIV viral load markers in clinical practice Nature Medicine 2 625ndash629

Sacktor N Skolasky R L Tarwater P M McArthur J C Selnes O A Becker J Miller E N (2003) Response to systemic HIV viral load suppression correlates with psychomo-tor speed performance Neurology 61 567ndash569

Sax P E Cohen C J amp Kuritzkes D R (2012) HIV essentials (5th ed) Burlington MA Jones amp Bartlett Learning

Sayles J N Rurangirwa J Kim M Kinsler J Oruga R amp Janson M (2012) Operationalizing treatment as prevention in Los Angeles County Antiretroviral therapy use and factors associated with unsuppressed viral load in the Ryan White system of care AIDS Patient Care and STDs 26 463ndash470

Seng R Rolland M Beck-Wirth G Souala F Deveau C Delfraissy J F Meyer L (2011) Trends in unsafe sex and influence of viral load among patients followed since primary HIV infection 2000ndash2009 AIDS 25 977ndash988

Shah I (2006) Correlation of CD4 count CD4 and HIV viral load with clinical manifestations of HIV in infected Indian children Annals of Tropical Paediatrics 26 115ndash119

Siberry G K Harris D R Oliveira R H Krauss M R Hofer C B Tiraboschi A A Hazra R (2012) Evaluation of viral load thresholds for predicting new world health orga-nization stage 3 and 4 events in HIV-infected children receiving highly active antiretroviral therapy Journal of Acquired Immune Deficiency Syndromes 60 214ndash218

Sigaloff K C Hamers R L Wallis C L Kityo C Siwale M Ive P de Wit T F (2011) Unnecessary antiretroviral treatment switches and accumulation of HIV resistance muta-tions two arguments for viral load monitoring in Africa Journal of Acquired Immune Deficiency Syndromes (1999) 58 23ndash31


226 Gagnon and Guta

Smith C J Staszewski S Sabin C A Nelson M Dauer B Gute P Gazzard B (2004) Use of viral load measured after 4 weeks of highly active antiretroviral therapy to predict virologic outcome at 24 weeks for HIV-1-positive individuals Journal of Acquired Immune Deficiency Syndromes 37 1155ndash1159

Smith C L amp Stein G E (2002) Viral load as a surrogate end point in HIV disease The Annals of Pharmacotherapy 36 280ndash287

Smith D M May S J Peacuterez-Santiago J Strain M C Ignacio C C Haubrich R H Little S J (2009) The use of pooled viral load testing to identify antiretroviral treatment failure AIDS 23 2151ndash2158

Squillace N Zona S Stentarelli C Orlando G Beghetto B Nardini G Guaraldi G (2009) Detectable HIV viral load is associated with metabolic syndrome Journal of Acquired Immune Deficiency Syndromes 52 459ndash464

Stolte I G de Wit J B van Eeden A Coutinho R A amp Dukers N H (2004) Perceived viral load but not actual HIV-1-RNA load is associated with sexual risk behaviour among HIV-infected homosexual men AIDS 18 1943ndash1949

Swindells S Evans S Zackin R Goldman M Haubrich R Filler S G Balfour H H Jr (2002) Predictive value of HIV-1 viral load on risk for opportunistic infection Journal of Acquired Immune Deficiency Syndromes 30 154ndash158

The European Collaborative Study (1999) Maternal viral load and vertical transmission of HIV-1 An important factor but not the only one AIDS 13 (11) 1377ndash1385

Thea D M Steketee R W Pliner V Bornschlegel K Brown T Orloff S Kalish M L (1997) The effect of maternal viral load on the risk of perinatal transmission of HIV-1 New York City Perinatal HIV Transmission Collaborative Study Group AIDS 11 437ndash444

Tofthagen R amp Fagerstroslashm L M (2010) Rodgersrsquo evolutionary concept analysismdashA valid method for developing knowledge in nursing sciences Journal of Caring Sciences 24 21ndash31

Tovanabutra S Robison V Wongtrakul J Sennum S Suriyanon V Kingkeow D Nelson K E (2002) Male viral load and heterosexual transmission of HIV-1 subtype E in northern Thailand Journal of Acquired Immune Deficiency Syndromes 29 275ndash283

Van de Ven P Mao L Fogarty A Rawstorne P Crawford J Prestage G Kippax S (2005) Undetectable viral load is associated with sexual risk taking in HIV serodiscordant gay couples in Sydney AIDS 19 179ndash184

Vanable P A Ostrow D G amp McKirnan D J (2003) Viral load and HIV treatment attitudes as correlates of sexual risk behavior among HIV-positive gay men Journal of Psychosomatic Research 54 263ndash269

Vandermaelen A amp Englert Y (2010) Human immunodeficiency virus serodiscordant couples on highly active antiretroviral therapies with undetectable viral load Conception by unprotected sexual intercourse or by assisted reproduction techniques Human Reproduction 25 374ndash379

Vernazza P Hirschel B Bernasconi E amp Flepp M (2008) Les personnes seacuteropositives ne souffrant drsquoaucune autre MTS et suivant un traitement antiretroviral efficace ne trans-mettent pas le VIH par voie sexuelle Bulletin des meacutedecins suisses 89 165ndash169

Vrijens B Goetghebeur E de Klerk E Rode R Mayer S amp Urquhart J (2005) Modelling the association between adherence and viral load in HIV-infected patients Statistics in Medicine 24 2719ndash2731

Widdrington J Payne B Medhi M Valappil M amp Schmid M L (2011) The significance of very low-level viraemia detected by sensitive viral load assays in HIV infected patients on HAART The Journal of Infection 62 87ndash92

Wilson D Keiluhu A K Kogrum S Reid T Seriratana N Ford N Taochalee N (2009) HIV-1 viral load monitoring An opportunity to reinforce treatment adherence in a resource-limited setting in Thailand Transactions of the Royal Society of Tropical Medicine and Hygiene 103 601ndash606



Wilson D P Law M G Grulich A E Cooper D A amp Kaldor J M (2008) Relation between HIV viral load and infectiousness A model-based analysis Lancet 372 314ndash320

Wood E Hogg R S Yip B Moore D Harrigan P R amp Montaner J S (2006) Impact of baseline viral load and adherence on survival of HIV-infected adults with baseline CD4 cell counts or 200 cellsmicrol AIDS 20 1117ndash1123

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Correspondence regarding this article should be directed to Marilou Gagnon PhD RN ACRN School of Nursing Faculty of Health Sciences University of Ottawa 451 Smyth Road Ottawa Ontario K1H 8M5 E-mail marilougagnonuottawaca



early attention in the clinical management of HIV infection they are now used in combination with HIV viral load Together CD4 T-lymphocyte counts and viral load provide a more comprehensive understanding of disease progression and viral (or HIV) activity

Measurements of HIV viral load have become a critical component of the clinical management of HIV infection since the introduction of antiretroviral treatment in 1996 The goal of treatment is to achieve (and maintain) viral suppression and to reach a threshold where copies of the virus are no longer ldquodetectablerdquo in the blood Viral load calculations are now used routinely in clinical practice to assess viral dynamics and its effects in the body to predict the progression of HIV infection to determine when to begin or change HIV medications and to monitor for treat-ment effectiveness or failure (Sax Cohen amp Kuritzkes 2012) More recently HIV viral load has increasingly been used as a tool to monitor treatment adherence to track viral replication within the body to reduce the risk of HIV transmission to inform epidemiological surveillance and to map the virus at a population level (also known as community viral load for a more detailed analysis see Gagnon amp Guta 2012)

In this article we examine the concept of HIV viral load and how it has evolved over time (1995ndash2013) in the field of HIVAIDS Although the term viral load is used extensively in this field few efforts have been directed toward the conceptu-alization of HIV viral load which is often left unquestioned undertheorized and portrayed as a neutral and objective laboratory value that has remained relatively stable over timemdashwith the exception of progressive advancements in technology techniques and sensitivity The purpose of this article is to apply the evolutionary concept analysis method developed by Rodgers (1989 2000a) to the concept of HIV viral load To set the stage we establish the need for a concept analysis of HIV viral load and provide an overview of the evolutionary view Then drawing on the steps proposed by Rodgers (2000a) we outline the process of data collection manage-ment and analysis We then offer an in-depth discussion of the findings (attributes antecedents and consequences) informed by Wuestrsquos (2000) critical approach to concept analysis We conclude by highlighting the implications of this analysis for clinical practice research and theory

BACKGROUND

The approach to concept analysis we use recognizes that ldquoconcepts once formu-lated and labeled tend to shape and guide what we see and they provide order to observations and experiencesrdquo (Meleis 2012 p 371) that produce shared under-standings of situations and events Before ldquoHIV viral loadrdquo (as a concept) came into use clinicians and researchers did not see define think and talk about HIV in relation to viral load even though viral activity in both plasma and other bodily fluids (eg breast milk semen preseminal fluid vaginal fluids and rectal mucous) had been identified The introduction of a concept labelled ldquoHIV viral loadrdquo in the 1990s gradually transformed the way people living with HIV (PLWH) understand


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METHOD



















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FINDINGS


ATTRIBUTES







Antecedents

Attributes

Consequences










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ANTECEDENTS


CONSEQUENCES








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SURROGATE TERMS












REFERENCES




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METHOD



















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FINDINGS


ATTRIBUTES







Antecedents

Attributes

Consequences










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ANTECEDENTS


CONSEQUENCES








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SURROGATE TERMS












REFERENCES




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FINDINGS


ATTRIBUTES







Antecedents

Attributes

Consequences










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ANTECEDENTS


CONSEQUENCES








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SURROGATE TERMS












REFERENCES




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ANTECEDENTS


CONSEQUENCES








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SURROGATE TERMS












REFERENCES




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ANTECEDENTS


CONSEQUENCES








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SURROGATE TERMS












REFERENCES




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ANTECEDENTS


CONSEQUENCES








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SURROGATE TERMS












REFERENCES




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ANTECEDENTS


CONSEQUENCES








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SURROGATE TERMS












REFERENCES




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ANTECEDENTS


CONSEQUENCES








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SURROGATE TERMS












REFERENCES




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SURROGATE TERMS












REFERENCES




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REFERENCES




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HIV Viral Load: A Concept Analysis and Critique

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Transcript of HIV Viral Load: A Concept Analysis and Critique