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Keywords:

  • antiretroviral therapy;
  • treatment failure;
  • second-line therapy;
  • immunologic and virologic screening;
  • capacity building
  • thérapie antirétrovirale;
  • échec du traitement;
  • traitement de seconde ligne;
  • dépistage immunologique et virologique;
  • renforcement des capacités
  • terapia antirretroviral;
  • fallo en el tratamiento;
  • segunda línea de tratamiento;
  • pruebas inmunológicas y virológicas;
  • formación

Summary

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References
  9. Supporting Information

Objectives  Evaluating treatment failure is critical when deciding to modify antiretroviral therapy (ART). Virologic Assessment Forms (VAFs) were implemented in July 2008 as a prerequisite for ordering viral load. The form requires assessment of clinical and immunologic status.

Methods  Using the Electronic Medical Record (EMR), we retrospectively evaluated patients who met 2006 WHO guidelines for immunologic failure (≥15 years old; on ART ≥6 months; CD4 count <baseline OR CD4 count >50% drop from peak OR CD4 persistently <100 cells) at the Lighthouse Trust clinic from December 2007 to December 2009. We compared virologic screening, VAF implementation and ART modification during the same period using Fisher’s exact tests and unpaired t-tests as appropriate.

Results  Of 7000 enrolled ART patients ≥15 years old with at least two CD4 counts, 10% had immunologic failure with a median follow-up time on ART of 1.4 years (IQR: 0.8–2.3). Forty (6%) viral loads were ordered: 14 (35%) were detectable (>400 HIV RNA copies/mL) and one (7%) patient was switched to second-line therapy. Overall, 259 VAFs were completed: 67% for immunologic failure and 33% for WHO Stage 4 condition. Before VAF implementation, 1% of patients had viral loads drawn during routine care, whereas afterwards, 8% did (P < 0.0001; 95% CI: 0.03–0.08).

Conclusions  Clinicians did not identify a large proportion of immunologic failure patients for screening. Implementation of VAFs produced little improvement in virologic screening during routine care. Better training and monitoring systems are needed.

Contexte:  Evaluer l’échec du traitement est cruciale lorsqu’il s’agit de décider de modifier un traitement antirétroviral (ART). Des formulaires d’évaluation virologique (FEV) ont été introduits en juillet 2008 comme préalable à la demande d’un test de la charge virale. Le formulaire exige une évaluation de l’état clinique et immunologique.

Méthodes:  En utilisant le dossier médical électronique, nous avons rétrospectivement évalué les patients répondant aux directives 2006 de l’OMS pour l’échec immunologique (≥ 15 ans; sous ART ≥ 6 mois; taux des CD4 < valeur initiale ou taux des CD4 > 50% de la chute de la valeur pic ou taux des CD4 constamment <100 cellules), à la clinique du Lighthouse Trust, de décembre 2007 à décembre 2009. Nous avons comparé le dépistage virologique, l’implémentation des FEV et la modification de l’ART durant la même période en utilisant les tests exacts de Fisher et le cas échéant, les tests t non appariés.

Résultats:  Sur 7000 patients recrutés ≥ 15 ans et sous ART avec au moins deux mesures des taux de CD4, 10% avaient un échec immunologique avec une durée de suivi médian de 1,4 ans sous ART (IIQ: 0,8 à 2,3). Des mesures de la charge virale ont été demandées pour 40 (6%) patients: 14 (35%) avaient des taux détectables (> 400 copies de l’ARN du VIH/ml) et 1 (7%) des patients a été mis sous traitement de seconde ligne. En tout, 259 FEV ont été remplis: 67% pour l’échec immunologique et 33% pour la condition de stade 4 de l’OMS. Avant l’implémentation des FEV, 1% des patients avaient une charge virale mesurée au cours des soins de routine, mais après, ce taux est passéà 8% (p <0,0001; IC95%: 0,03 à 0,08).

Conclusions:  Les cliniciens n’ont pas identifié une large proportion de patients avec un échec immunologique pour le dépistage. L’implémentation des FEV a apporté peu d’amélioration dans le dépistage virologique au cours des soins de routine. Une formation et des systèmes de surveillance meilleurs sont nécessaires.

Antecedentes:  Evaluar el fallo en el tratamiento es crítico a la hora de decidir modificar la terapia antirretroviral (TAR). Se implementaron los formularios de evaluación virológica (FEV) en Julio 2008 como un prerrequisito para pedir la carga viral. El formulario requiere la evaluación del estatus clínico e inmunológico.

Métodos:  En la clínica Lighthouse Trust, entre 12/2007-12/2009, y utilizando la Historia Clínica Electrónica (HCE), hemos evaluado de forma retrospectiva a los pacientes que alcanzaron la definición de fallo inmunológico según las guías de la OMS del 2006 (≥15 años; recibiendo TAR ≥ 6 meses; conteo de CD4 < el inicial O conteo CD4 >50% caida del pico máximo O CD4 persistentemente <100 células). Hemos comparado las pruebas virológicas, la implementación del FEV y la modificación del TAR durante el mismo periodo utilizando las pruebas exactas de Fisher y pruebas t no pareadas según conveniencia.

Resultados:  De los 7,000 pacientes en TAR, ≥15 años y con al menos dos conteos de CD4, un 10% tenían un fallo inmunológico con una mediana de tiempo de seguimiento en TAR de 1.4 años (IQR: 0.8–2.3). Se ordenaron cuarenta (6%) cargas virales: 14 (35%) eran detectables (>400 VIH copias/mL ARN) y a 1 (7%) paciente se le cambió a la segunda línea de tratamiento. En general, se completaron 259FEVs : un 67% por fallo inmunológico y 33% por estar en el Estadío 4 según la OMS. Antes de la implementación del FEV, un 1% de los pacientes tenían cargas virales tomadas durante cuidados rutinarios, mientras que después, lo tenía un 8% (p<0.0001; 95% IC 0.03-0.08).

Conclusiones:  Los clínicos no identificaron una gran proporción de pacientes con fallo inmunológico a ser incluidos en las pruebas. La implementación de los FEV produjo poca mejoría en la detección virológica durante los cuidados rutinarios. Se requiere una mejora en la formación y en los sistemas de monitorización.


Introduction

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References
  9. Supporting Information

As of December 2008, nearly 3 million adults and children in sub-Saharan Africa were receiving highly active antiretroviral therapy (HAART) and treatment programmes continue to expand (Joint United Nations Programme on HIV/AIDS). Still, it is estimated that only 44% of patients eligible for antiretroviral therapy (ART) are receiving it (WHO et al. 2010).

In Malawi, 198 846 patients were receiving ART in 277 public and private clinics nationwide at the end of 2009. Fewer than 1% of patients on ART have been switched to second-line therapy (Ministry of Health of Malawi 2009). Even in large cohorts with access to immunologic monitoring, the proportion of patients switched to second-line drugs only approaches 3%. As most treatment clinics in Malawi rely on clinical monitoring, the population of patients requiring second-line therapy is markedly underestimated. WHO criteria for clinical and immunologic failure have low sensitivity and specificity and lead to frequent misclassification of ART failure (Castelnuovo et al. 2009; Geng et al. 2009; McGuire et al. 2009; Mee et al. 2008; Moore et al. 2008; Reynolds et al. 2009; van Oosterhout et al. 2009). Late detection of failure can be associated with accumulation of resistance mutations and increased morbidity and mortality (Bositis et al. 2009; Hosseinipour et al. 2009; Kantor et al. 2004). As rapid expansion of first-line therapy continues, national treatment programmes in resource-limited settings (RLS) must now decide how to balance monitoring costs for treatment failure in patients already on therapy with a continuing demand to initiate ART in new patients (Hosseinipour & Schechter 2010).

Previously, we determined that up to 40% of those meeting immunologic failure definitions were not in virologic failure (van Oosterhout et al. 2009). To promote thorough evaluation of patients suspected of ART failure in the setting of recent task shifts to lower cadre staff, Lighthouse Trust implemented a ‘Virological Assessment Form (VAF)’ in July 2008 (see Appendix S1). The form was designed to guide the provider through clinical and immunologic criteria that define failure and prompt HIV-1 RNA testing.

We evaluated ART failure screening practices at the Lighthouse Trust, elucidating how the VAF was used and its impact on failure identification. Further, we sought reasons why certain guidelines or clinical protocols were not applied.

Methods

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References
  9. Supporting Information

Study setting and the Lighthouse Electronic Medical Record (EMR)

The Lighthouse Trust clinic in Lilongwe, Malawi, is one of the country’s largest public sector ART programmes, providing free treatment to over 10 000 adults and children, since July 2004 with routine CD4 monitoring available since inception. All individuals diagnosed as HIV positive, who report to the Lighthouse and Martin Preuss ART clinics, are registered in the Lighthouse Trust EMR and receive a unique patient identification number. During initial registration, patient demographic details and WHO staging criteria are entered into the EMR via a touch-screen computer system (Douglas et al. 2010). Patients initiate ART if they present with a WHO clinical stage III/IV condition or have a CD4 count <250 cells/μl.

The first-line ART regimen includes stavudine (d4T), lamivudine (3TC) and nevirapine (NVP). Efavirenz (EFV) or zidovudine (ZDV) can be substituted as an alternative regimen in cases of side effects or toxicity. ART dispensing visits are scheduled monthly for the first 6 months and every 2 months thereafter if the patient is stable and adherent to therapy. For patients on ART, a CD4 count is drawn every 6 months. Continuing education and counselling sessions are tailored for non-adherent patients. Visit dates, side effects, remaining tablets and drug dispensing are recorded in real-time by clinic staff. Nurses review all clients, and only those with complaints are referred to physicians or clinical officers (physician assistants) for assessment.

Initially, all CD4 counts were performed by the University of North Carolina (UNC) Project laboratory through a capacity-building grant. As local capacity developed, Kamuzu Central Hospital (KCH) assumed a larger proportion of the total number of CD4 samples until all samples were processed at KCH. The UNC laboratory served as a back-up in the event of machine breakdown and currently serves as quality assurance.

Plasma HIV RNA assays were introduced at Kamuzu Central Hospital laboratory in December 2007 for confirmatory testing in patients suspected of failing first-line therapy. Second-line drugs [lopinavir/ritonavir, tenofovir (TDF), zidovudine (AZT) and lamivudine (3TC)] are available for patients with confirmed treatment failure (>400 HIV RNA/ml). In an effort to improve ART failure screening practices at Lighthouse Trust, clinicians were trained and instructed to complete a VAF when ordering plasma HIV RNA starting in July 2008.

We extracted demographic and clinical data from the Lighthouse EMR into a customized Microsoft® Access 2007 database. These data included sex, date of birth, duration on ART, CD4 and plasma HIV RNA results, and dates on which blood samples were processed and results obtained. Patients who were transferred in or out of our clinic were included if they had at least one follow-up CD4 count drawn at Lighthouse Trust. The study focused only on patients screened during routine care: those who were previously screened for treatment failure using WHO immunologic criteria during earlier research protocols were excluded (van Oosterhout et al. 2009) (Figure 1).

image

Figure 1.  Enrollment and outcomes.

Download figure to PowerPoint

We evaluated patients who met the 2006 WHO guidelines for immunologic failure (≥15 years old; on ART ≥6 months; CD4 count <baseline OR CD4 count >50% drop from peak OR CD4 <100 cells) from December 2007 to December 2009 and retrospectively reviewed virologic screening, VAF implementation and ART modification during the same period. At least three CD4 counts were required to meet the ‘50% drop from peak’ criterion and at least two CD4 counts to meet the ‘less than baseline’ or ‘persistently <100’ criterion. Time intervals between identification of immunologic failure and plasma HIV RNA screening were calculated.

As the Lighthouse EMR does not collect information on WHO clinical stage-defining conditions other than tuberculosis (TB) after the initial visit, clinical evaluations resulting in virologic screening were assumed to be based on history and physical exam. We performed chart review on a subset of 171 (27%) patients with available paper files that had CD4 counts <200 cells/μl, and received follow-up during the period after VAF implementation (July 2008–July 2009), but did not receive HIV RNA screening to elucidate reasons why screening did not occur.

Study findings were disseminated to Lighthouse Trust staff to elicit feedback during a facilitator-led focus group discussion in March 2010. All clinicians, nurses and support staff working at the Lighthouse were invited to participate. Most were on active duty throughout the implementation period, although employees who had departed were not included. We collected staff responses to the following discussion questions: (i) Why are patients that meet criteria for immunologic failure not being identified during clinic visits? (ii) Why are viral loads not being ordered for patients suspected of ART failure? (iii) What mechanisms can improve clinic performance in identifying patients with ART failure? Staff responses were organized according to theme.

Analysis

All statistical analyses were performed using Stata 11.0 (Stata Corporation, College Station, TX, USA). Descriptive statistics included means, medians and proportions as appropriate for evaluation of baseline characteristics of subjects. Fisher’s exact tests and unpaired t-tests were performed to compare clinical and laboratory characteristics according to viral load screening status.

Ethical review

The study proposal was approved by the UNC, Chapel Hill, USA Institutional Review Board (IRB) and National Health Sciences Research Council (NHSRC), Malawi.

Results

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References
  9. Supporting Information

Immunologic screening

Of 12 206 patients on ART at Lighthouse Trust, 7000 patients were eligible for the study (excluded: 1676 ≤ 15 years old; 2605 missing CD4 data; 893 not on ART ≥6 months; 32 recruited for other studies; Figure 1). Six hundred and seventy (10%) patients met a WHO immunologic failure definition with a median follow-up time on ART of 1.4 years (IQR: 0.8–2.3). There was a median of 3 CD4 counts per patient (range 2–9). Specifically, 478 (71%) had declined to below the baseline CD4 value, 335 (50%) had a 50% decline from the peak value and 41 (6%) had CD4 counts persistently <100 cells. One hundred and sixty-seven (25%) patients met more than one criteria and seven (1%) met all three.

Virologic screening

Of the 670 patients who fulfilled WHO criteria during routine care, 40 (6%) viral loads were ordered; 14 (35%) were detectable and one (7%) patient was switched to second-line therapy. Among patients receiving viral load testing, median follow-up time on ART was 1.7 years (IQR: 0.8–2.6). 10/40 (25%) met the ‘<100 cells’ criterion and 15/40 (38%) met ≥2 criterion (Table 1).

Table 1.   Characteristics of patients meeting WHO immunologic failure criteria with and without virologic screening
= 670 WHO CD4 failureAll patientsViral loadNo viral loadP-value
= 670= 40= 630
  1. ART, antiretroviral therapy.

Age (mean years)39.139.239.10.92
Women (% women)296 (44)21 (53)275 (44)0.33
Years on ART, median (IQR)1.4 (0.8–2.3)1.7 (0.8–2.6)1.4 (0.8–2.3)0.35
Met ‘<100 cells’ criterion (%)41 (6)10 (25)31 (5)0.0001
Met ≥2 criteria (%)167 (25)15 (38)152 (24)0.0875
CD4 at baseline (median)1781131800.55
CD4 at date of failure (median)861381880.0015
Percentage drop from baseline (mean)2630250.08

Among patients receiving viral load testing, the mean time from identification of immunologic failure to blood draw for virologic screening was 5.5 months (range, 0–20). There were no significant differences in age, sex or duration on ART between the virologically screened and not screened groups (Table 1). A greater proportion of patients meeting ‘persistently <100’ or ≥2 WHO criterion had viral loads drawn (25%vs. 5%, P = 0.0001 95% CI: 0.008–0.027 and 38%vs. 24%, P = 0.0875, respectively). Those screened tended to have a lower median CD4 at baseline (113 cells vs. 180; P < 0.55) and at the date of immunologic failure (138 cells vs. 188; P < 0.0015), as well as a greater percentage drop from baseline (30%vs. 25%; P < 0.08) (Table 1).

VAF performance

Overall, 259 VAFs were completed: 173/259 (67%) for WHO immunologic failure and 86/259 (33%) for WHO stage 4 condition. 157/259 (61%) forms were completed by clinical officers, and 96/259 (37%) forms were completed by physicians. No forms were completed by nurses. Virologic screening rates improved during the period after VAF implementation (1%vs. 8%; P < 0.0001) (Table 2). Overall, 80/259 (31%) patients with VAFs had detectable viral loads: 60/173 (35%) met immunologic failure criterion and 20/86 (23%) were evaluated for WHO stage 4 condition.

Table 2.   Screening and treatment modification before and after VAF implementation (December 2007–December 2009)
= 670 CD4 failureTotalDecember 2007–July 2008July 2008–December 2009P-value
Before VAF%After VAF%
Patients with CD4 failure6702043046670 
Viral loads ordered40253895 
Percentage screened 180.0001
Detectable1421001232 
Switched therapy10018 

Notably, 536/795 (67%) viral loads drawn from 2007 to 2009 were not accompanied by VAFs, but were ordered based on clinical evaluation alone. Only 16/536 (3%) met any of the WHO immunologic criterion, but 294/536 (55%) had detectable viral loads.

Chart review

In 94/171 (55%) paper charts reviewed, clinicians did not document an explicit reason why a plasma HIV RNA was not ordered for patients fulfilling WHO immunologic failure criteria. Review of paper charts yielded additional reasons for failure to screen: non-adherence to therapy (9%), CD4 rebounded (18%), discrepancy between laboratory results (2%), transferred out (2%), died (1%) and lost to follow-up (<1%).

Qualitative feedback from focus group

Twenty members of the clinical staff provided feedback during the focus group discussion and elaborated reasons why patients did not receive viral load screening. Providers commented that CD4 counts were not routinely followed. While CD4 trends are readily accessible from the EDS, they are located on a separate computer module from the ART clinic visit and require navigation to a different page to be reviewed. Furthermore, nurses viewed CD4 trend assessment as a clinician’s responsibility and rarely reviewed the laboratory values.

Clinicians and nurses commented that our study’s chart review underestimates the number of patients who did not receive virologic screening because of suspected non-adherence. Physicians and clinical officers also reported frequent discrepancies between CD4 results from Kamuzu Central Hospital and UNC Project laboratories for patients who had follow-up CD4 counts processed in both laboratories. In the setting of laboratory discrepancy, clinicians favoured clinical presentation over the CD4 trends. Clinical staff also reported the perception that budgetary issues prevented more expanded use of HIV RNA testing.

Discussion

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References
  9. Supporting Information

Much debate has occurred regarding optimal methods to monitor ART failure in RLS with the most recent call to provide virologic monitoring where possible (Hammer et al. 2008; WHO 2009). However, in our large and busy ART clinic, skilled staff missed a large proportion of immunologic failures for HIV RNA screening. Suboptimal treatment failure identification occurred, despite access to an electronic data system outlining CD4 trends and attempts to standardize treatment failure screening procedures through a VAF. Yet, consistent with our previous work (van Oosterhout et al. 2009), and despite suboptimal screening procedures, we again report a large proportion (65%) of patients who met immunologic criteria but had undetectable viral loads. This reinforces the principle that immunologic monitoring requires confirmatory HIV RNA testing when available (van Oosterhout et al. 2009). The relative merits of monitoring strategies and how they balance with the realities of daily clinic and laboratory operations require discussion.

While immunologic definitions have been shown to be imperfect, they provide some guidance for those potentially at higher risk for treatment failure, particularly in the absence of virologic monitoring. When properly applied, immunologic monitoring and viral load monitoring can improve survival compared with clinical monitoring alone (Coutinho et al. 2008; DART Trial Team 2010). In recent studies, viral load monitoring has not demonstrated a significant advantage when compared to immunologic monitoring over 2–3 years of follow-up, although more patients were switched to second-line therapy in viral load monitoring arms (Coutinho et al. 2008; Jourdain et al. 2011; Kouanfack et al. 2011). Regardless, the current low rate of viral load screening observed in our clinic makes the realization of any survival benefit or second-line treatment modification advantage unlikely. Furthermore, in the absence of critically reviewing available CD4 trends, any potential cost-effectiveness of CD4 testing is compromised (DART Trial Team 2010).

Task-shifting to lower cadre staff has been a large component of service delivery in RLS to address shortages of skilled providers (Assefa et al. 2010). ART treatment outcomes can be similar between nurse- and physician-managed patients when using virologic monitoring (Sanne et al. 2010). However, task-shifting necessitates clear definitions of clinical responsibilities and adequate training. We noted a shortfall in our task-shifting operations, as providers perceived treatment failure assessment as a clinician’s responsibility rather than one to be adopted by all clinical staff. Nearly 80% of visits are handled only by nurses but no VAFs were completed by nurses. This likely explains the delay between identification of immunologic failure and blood draw for HIV RNA.

Our strategy to implement the VAF modestly improved virologic screening rates (1%vs. 8%). However, increasing awareness of treatment failure identification over time based on previous local research and practice may explain the improved screening rate.

We also noted limitations in the application of the VAF itself. While we conducted training on the form prior to implementation, understanding of its use was limited, and ongoing training with new staff was not adequate. Complex guidelines for immunologic failure may prove difficult to interpret, especially when compared to viral load, which can be simplified to a single, dichotomous variable: detectable or undetectable. While WHO immunologic criteria can be simplified by focusing on one criterion (e.g. CD4 < 250), this is also likely to be insensitive and misclassify treatment failure (Gilks et al. 2011).

This additional form, although simple in design, was potentially viewed as another administrative burden or as a performance indicator. Although this was not explicitly mentioned as a reason for lack of its application, if true, it may have discouraged clinicians from ordering plasma HIV RNA. As the majority of viral loads were ordered without a VAF (67%), it may be that clinicians did not like using the form.

We acknowledge certain limitations to our investigation. As a retrospective study, only patients with sufficient information recorded in the Lighthouse EMR could be evaluated. While the EMR centrally organizes demographic variables, CD4 values and viral loads, some patients may have been excluded because of missing electronic documentation (Makombe et al. 2008). As few patients meeting WHO immunologic criteria were screened with HIV RNA, sensitivity and specificity of the WHO CD4 criteria could not be calculated. Further, some questions regarding use of the VAF or limitations in screening practices relied in part on evaluating a subset of paper charts. Among these, lack of paper documentation often made it difficult to determine why a patient in immunologic failure was not screened with viral load. Discussions with clinical staff revealed some impressions that differed from EMR or paper chart review; for example, providers thought that a significant number of patients were not screened because of suspected non-adherence to medications, raising the possibility that the 9% reported is an underestimate. Clinicians also stated that discrepancies or lack of confidence in CD4 laboratory results was a major reason for not proceeding to virologic screening, although our chart review only identified this issue in 2% of cases. These discrepancies may also apply to other reasons for not screening.

While we noted marked deficiencies in treatment failure evaluation, our study provides important insights into our own clinic’s operations as well as how monitoring strategies may perform in other RLS as laboratory monitoring expands. Laboratory quality was noted to influence screening practices and underscores that any laboratory-based monitoring strategy requires that clinicians trust the results and allow them to inform clinical judgment. Initial and ongoing refresher training remains critical components of service delivery, particularly for more complex issues such as treatment failure.

Innovation in screening protocols and technological advances in EMR hold promise for improving care (Were et al. 2010). The Lighthouse Trust EMR is versatile and can determine percentage adherence and missed pills, generate weight trends graphically as a component of the ART clinic visit, and create lists of patients who have missed treatment visits (Douglas et al. 2010; Keiser et al. 2010; Weigel et al. 2010). However, CD4 trends are not integrated into the ART clinic visit module and can only be accessed by navigating to a separate lab review module. Electronic systems should be modified to increase efficiency, deter errors, and alleviate the work burden on clinical staff. Two strategies for improving the EMR include integration of the CD4 trend review into the ART clinic visit module and providing automatic alerts within the module when a patient has met immunologic criteria for failure. While the paper version of the VAF was not effective, an electronic VAF could provide a mandatory prompt for clinical staff to complete a treatment failure evaluation during routine follow-up appointments.

A recent randomized trial from Kenya concluded that the use of mobile phone technology significantly improved adherence and virologic suppression in patients who received short messaging service reminders about their ART (Lester et al. 2010). Similarly, mobile phones can be used to track patients whose laboratory data suggests ART failure and prompt them to return to the clinic for further evaluation. Appropriate allocation of such technologies can result in a larger proportion of patients identified with WHO immunologic failure, screened with confirmatory HIV RNA testing, and appropriately switched to second-line therapy.

Importantly, despite continuing education on laboratory-based monitoring for treatment failure, Lighthouse clinicians relied heavily on clinical evaluation alone in identifying patients for treatment failure assessment. Similar outcomes have been shown among patients receiving clinical and laboratory-based monitoring, particularly during the first 2 years on ART (DART Trial Team 2010). Reliance on history and physical presentation is the crux of clinical training in Malawi and in many settings, is the only screening tool for treatment failure. We observed that more than half (55%) of patients screened with viral load based on clinical presentation alone had detectable plasma HIV RNA, outperforming those with WHO immunologic criteria for screening. In the absence of documentation of follow-up WHO clinical staging in the EMR or paper charts, we were unable to determine what specific aspects of a patient’s clinical presentation prompted clinicians to order a viral load. Future operational studies may better characterize clinician intuition for suspecting treatment failure as to optimize clinical monitoring strategies. Nonetheless, this trend suggests that annual viral load in adherent and immunologically stable patients may be more effective than interval CD4 blood draws in identifying treatment failure. Our findings demonstrate a value in using clinical assessment and viral load alone in diagnosing ART failure.

Where possible, it is worthwhile to investigate how annual or even less frequent viral load testing in immunologically stable patients – rather than serial CD4 monitoring – impacts ART failure detection and cost of therapy (Philips et al. 2008). Recent U.S. guidelines have reduced the CD4 monitoring frequency to every 6–12 months rather than every 3–6 months (Department of Health and Human Services 2011). Continuing operational studies of clinical and laboratory monitoring in adults and children is imperative to determining cost-effective practices for identifying ART failure that meet the logistical challenges of busy clinics (Bendavid et al. 2008; Lofgren et al. 2009; Meya et al. 2009).

Acknowledgments

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References
  9. Supporting Information

Parts of the data herein were presented at the 2010 International AIDS Conference in Vienna, Austria, on 21 July 2010. We are grateful for support from the University of North Carolina Center for AIDS Research (P30 AI50410), the International Union Against Tuberculosis and Lung Disease and the National Institutes of Health Office of the Director, Fogarty International Center, Office of AIDS Research, National Cancer Center, National Eye Institute, National Heart, Blood, and Lung Institute, National Institute of Dental & Craniofacial Research, National Institute On Drug Abuse, National Institute of Mental Health, National Institute of Allergy and Infectious Diseases, and NIH Office of Women’s Health and Research through the International Clinical Research Scholars and Fellows Programme at Vanderbilt University (R24 TW007988) and the American Relief and Recovery Act. CKV was a recipient of a NIH-Fogarty International Clinical Research Scholarship (2009–2010).

References

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References
  9. Supporting Information
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Supporting Information

  1. Top of page
  2. Summary
  3. Introduction
  4. Methods
  5. Results
  6. Discussion
  7. Acknowledgments
  8. References
  9. Supporting Information

Appendix S1. Virologic Assessment Form (VAF).

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TMI_2912_sm_AppendixS1.doc56KSupporting info item

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