Monitoring HIV Viral Load in Resource Limited Settings: Still a Matter of Debate?

Arnedo, Mireia; Alonso, Elena Riera; Eisenberg, Nell; Ibáñez, Laura; Ferreyra, Cecilia; Jaén, Àngels; Flévaud, Laurence; Khamadi, Samuel; Roddy, Paul; Gatell, José M.; Dalmau, David

doi:10.1371/journal.pone.0047391

Cited by 21 publications

(19 citation statements)

References 32 publications

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“…There is an urgent need to develop an affordable, simple, easy to use point-of-care (POC) diagnosis technology for HIV viral load testing in resource-constrained settings. 8-11 …”

Section: Introductionmentioning

confidence: 99%

Membrane-Based, Sedimentation-Assisted Plasma Separator for Point-of-Care Applications

et al. 2013

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Often, high sensitivity, point of care, clinical tests, such as HIV viral load, require large volumes of plasma. Although centrifuges are ubiquitously used in clinical laboratories to separate plasma from whole blood, centrifugation is generally inappropriate for on-site testing. Suitable alternatives are not readily available to separate the relatively large volumes of plasma from milliliters of blood that may be needed to meet stringent limit-of-detection specifications for low abundance target molecules. We report on a simple to use, low-cost, pump-free, membrane-based, sedimentation-assisted plasma separator capable of separating a relatively large volume of plasma from undiluted whole blood within minutes. This plasma separator consists of an asymmetric, porous, polysulfone membrane housed in a disposable chamber. The separation process takes advantage of both gravitational sedimentation of blood cells and size exclusion-based filtration. The plasma separator demonstrated a “blood in-plasma out” capability, consistently extracting 275 ±33.5 μL of plasma from 1.8 mL of undiluted whole blood in less than 7 min. The device was used to separate plasma laden with HIV viruses from HIV virus-spiked whole blood with recovery efficiencies of 95.5% ± 3.5%, 88.0% ± 9.5%, and 81.5% ± 12.1% for viral loads of 35,000, 3,500 and 350 copies/mL, respectively. The separation process is self-terminating to prevent excessive hemolysis. The HIV-laden plasma was then injected into our custom-made microfluidic chip for nucleic acid Testing And Was Successfully Subjected To Reverse Transcriptase Loop mediated isothermal amplification (RT-LAMP), demonstrating that the plasma is sufficiently pure to support high efficiency nucleic acid amplification.

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“…There is an urgent need to develop an affordable, simple, easy to use point-of-care (POC) diagnosis technology for HIV viral load testing in resource-constrained settings. 8-11 …”

Section: Introductionmentioning

confidence: 99%

Membrane-Based, Sedimentation-Assisted Plasma Separator for Point-of-Care Applications

et al. 2013

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“…Even if the timing of VL evaluation is still a matter of debate [8], performing VL testing at 6 months after initiating ART and every 12 months is now the preferred monitoring approach to diagnose and confirm ART failure [9]. Indeed, late diagnosis of treatment failure is associated with accumulated drug resistance mutations and high level cross resistance to subsequent regimens [10].…”

Section: Introductionmentioning

confidence: 99%

Virological Failure and HIV-1 Drug Resistance Mutations among Naive and Antiretroviral Pre-Treated Patients Entering the ESTHER Program of Calmette Hospital in Cambodia

et al. 2014

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IntroductionIn resource limited settings, patients entering an antiretroviral therapy (ART) program comprise ART naive and ART pre-treated patients who may show differential virological outcomes.MethodsThis retrospective study, conducted in 2010–2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia) assessed virological failure (VF) rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL) was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF) (>1,000 copies/ml) underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms.ResultsOn a total of 209 patients, 164 (78.4%) were naive and 45 (21.5%) were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30–194) and 279 cells/mm3 (IQR: 103–455) (p<0.001), respectively. Twenty seven patients (12.9%) exhibited VF (95% CI: 8.6–18.2%), including 10 naive (10/164, 6.0%) and 17 pre-treated (17/45, 37.8%) patients (p<0.001). Among these viremic patients, twenty-two (81.4%) were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3%) harbored ≥1 drug resistance mutations (DRMs) whereas 3 (all belonging to pre-treated patients) harbored wild-types viruses. The most frequent DRMs were M184V (86.3%), K103N (45.5%) and thymidine analog mutations (TAMs) (40.9%)Two (13.3%) pre-treated patients harbored viruses that showed a multi-nucleos(t)ide resistance including Q151M, K65R, E33A/D, E44A/D mutations.ConclusionIn Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for ART pre-treated patients infection should be considered as well.

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“…Additional benefits of routine VL testing include (i) earlier detection of adherence problems (2), (ii) avoidance of unnecessary switches to second-line antiretroviral drugs (3), (iii) prevention of acquired viral resistance to antiretroviral drugs (4,5), and (iv) use as a measure in program evaluation (6).…”

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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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Monitoring HIV Viral Load in Resource Limited Settings: Still a Matter of Debate?

Cited by 21 publications

References 32 publications

Membrane-Based, Sedimentation-Assisted Plasma Separator for Point-of-Care Applications

Membrane-Based, Sedimentation-Assisted Plasma Separator for Point-of-Care Applications

Virological Failure and HIV-1 Drug Resistance Mutations among Naive and Antiretroviral Pre-Treated Patients Entering the ESTHER Program of Calmette Hospital in Cambodia

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

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