Accumulation of Drug Resistance and Loss of Therapeutic Options Precede Commonly Used Criteria for Treatment Failure in HIV-1 Subtype-C-Infected Patients

Barth, Roos E.; Aitken, Sue; Tempelman, Hugo; Geelen, Sibyl P. M.; Bussel, Erik M. van; Hoepelman, Andy I. M.; Schuurman, Rob; Wensing, Annemarie M. J.

doi:10.3851/imp2010

Cited by 55 publications

(45 citation statements)

References 27 publications

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“…Based on immunological criteria in this study, 30% of the patients would have been classified as not failing, and therefore not switched to second line. Failure to switch a failing regimen has been shown to result into accumulation of mutations that will limit future treatment options [9,11].…”

Section: Discussionmentioning

confidence: 99%

Accuracy of WHO immunological criteria in identifying virological failure among HIV-infected adults on First line antiretroviral therapy in Mwanza, North-western Tanzania

et al. 2017

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Background: Optimal HIV treatment monitoring remains a big challenge in resource limited settings. Guidelines recommend the use of clinical and immunological criteria in resource limited settings due to unavailability of viral load monitoring; however their utility is questionable. This study aimed at assessing the accuracy of immunological criteria in detecting treatment failure among HIV infected Tanzanian adults receiving first line ART. Methods:A clinic based cross sectional study was conducted between February and July 2011 at Bugando Medical centre (BMC) HIV care and treatment clinic (CTC) involving HIV infected patients aged 18 years and above, receiving first line ART; followed up for at least 1 year. Viral load was tested for every enrolled patient. Standard WHO criteria were used to define immunological failure. Virological failure was defined as one viral load measurement of >5000 copies/ml and was used as a gold standard. A 2 × 2 table was used to assess the accuracy of immunological criteria in detecting treatment failure. Results:A total of 274 HIV-infected adults were enrolled into the study. Out of these, 65.7% were females, the median age was 39 years , the median BMI 21.9 kg/m 2 . Out of the 274 study participants 156 (56.9%) had immunological failure. Only 60 of the study participants (21.9%) had viral load >5000. Only 42 patients (70%) were found to have both immunological failure and virological failure. The sensitivity of immunological criteria in detecting treatment failure was 70%, specificity 46.7%, positive predictive and negative predictive values of 26.9 and 84.7% respectively. Conclusion: WHO immunological criteria have low sensitivity and positive predictive value for detecting treatment failure. Relying on CD4 counts for treatment monitoring would therefore lead to misclassifications of treatment failure that could result into unnecessary or delayed switch to second line ART. Access to viral load monitoring is important to avoid these misclassifications.

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Section: Discussionmentioning

confidence: 99%

Accuracy of WHO immunological criteria in identifying virological failure among HIV-infected adults on First line antiretroviral therapy in Mwanza, North-western Tanzania

et al. 2017

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“…A systematic review of VL in patients in sub-Saharan African ART programs (6) found similar prevalences of virological failure (median, 14% at a 1,000-copies/ml cut point and 10% at a 5,000-copies/ml cut point) as those found in our study. It has been shown, however, that drug resistance can develop in patients with a sustained VL of Ͼ1,000 copies/ml (25). Although current WHO guidelines recommend using a threshold of 1,000 copies/ml to define virological failure, they recommend the use of a cut point of 5,000 copies/ml for programs testing VL in DBS samples (1).…”

Section: Discussionmentioning

confidence: 99%

Prospective Evaluation of Diagnostic Accuracy of Dried Blood Spots from Finger Prick Samples for Determination of HIV-1 Load with the NucliSENS Easy-Q HIV-1 Version 2.0 Assay in Malawi

et al. 2014

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) and a specificity of 97.8% (95% CI, 96.1 to 98.9%) using a 1,000-copies/ml cut point and a sensitivity of 83.0% (95% CI, 73.4 to 90.1%) and a specificity of 100% (95% CI, 99.3 to 100%) using a 5,000-copies/ml cut point. This study shows that FP-DBS is an acceptable alternative to plasma for measuring VL using the NucliSENS Easy-Q HIV-1 v2.0. We are conducting a second study to assess the proficiency of health workers at preparing FP-DBS in primary health care clinics.

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“…Informed therapy switching can prevent unnecessary treatment switching (4) to more expensive and less accessible second-line therapies. Moreover, early detection of VF using the VFA can prevent extended exposure to a failing regimen and possible accumulation of drug resistance mutations that may confer cross-resistance to other drugs or drug classes (8). Using the VFA for early detection of treatment failure could also prevent HIV-1 transmission (18).…”

Section: Discussionmentioning

confidence: 99%

“…Timely detection of VF by viral load (VL) testing, which is routine in industrialized countries (7), is necessary to prevent accumulation of HIV drug resistance (8) or to identify poor adherence to the treatment. However, in RLS, high costs and technical complexity limit VL monitoring, and treatment failure is determined primarily by clinical monitoring for stage three and four AIDS-defining illnesses and, if available, immunological monitoring using CD4 counts (6).…”

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confidence: 99%

Development and Evaluation of an Affordable Real-Time Qualitative Assay for Determining HIV-1 Virological Failure in Plasma and Dried Blood Spots

et al. 2013

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h Virological failure (VF) has been identified as the earliest, most predictive determinant of HIV-1 antiretroviral treatment (ART) failure. Due to the high cost and complexity of virological monitoring, VF assays are rarely performed in resource-limited settings (RLS). Rather, ART failure is determined by clinical monitoring and to a large extent immunological monitoring. This paper describes the development and evaluation of a low-cost, dried blood spot (DBS)-compatible qualitative assay to determine VF, in accordance with current WHO guideline recommendations for therapy switching in RLS. The assay described here is an internally controlled qualitative real-time PCR targeting the conserved long terminal repeat domain of HIV-1. This assay was applied to HIV-1 subtypes A to H and further evaluated on HIV-1 clinical plasma samples from South Africa (n ‫؍‬ 191) and Tanzania (n ‫؍‬ 42). Field evaluation was performed in Uganda using local clinical plasma samples (n ‫؍‬ 176). Furthermore, assay performance was evaluated for DBS. This assay is able to identify VF for all major HIV-1 group M subtypes with equal specificity and has a lower detection limit of 1.00E؉03 copies/ml for plasma samples and 5.00E؉03 copies/ml for DBS. Comparative testing yielded accurate VF determination for therapy switching in 89% to 96% of samples compared to gold standards. The assay is robust and flexible, allowing for "open platform" applications and producing results comparable to those of commercial assays. Assay design enables application in laboratories that can accommodate real-time PCR equipment, allowing decentralization of testing to some extent. Compatibility with DBS extends access of sampling and thus access to this test to remote settings.

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Accumulation of Drug Resistance and Loss of Therapeutic Options Precede Commonly Used Criteria for Treatment Failure in HIV-1 Subtype-C-Infected Patients

Abstract: Rapid accumulation of drug resistance occurred when ART was continued despite virological failure. Treatment options were lost, even when WHO-defined failure criteria were not met. This study calls for wider access to virological monitoring.

Cited by 55 publications

References 27 publications

Accuracy of WHO immunological criteria in identifying virological failure among HIV-infected adults on First line antiretroviral therapy in Mwanza, North-western Tanzania

Accuracy of WHO immunological criteria in identifying virological failure among HIV-infected adults on First line antiretroviral therapy in Mwanza, North-western Tanzania

Prospective Evaluation of Diagnostic Accuracy of Dried Blood Spots from Finger Prick Samples for Determination of HIV-1 Load with the NucliSENS Easy-Q HIV-1 Version 2.0 Assay in Malawi

Development and Evaluation of an Affordable Real-Time Qualitative Assay for Determining HIV-1 Virological Failure in Plasma and Dried Blood Spots

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