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Pooled nucleic acid testing to detect antiretroviral treatment failure in Mexico.

ABSTRACT: BACKGROUND:Similar to other resource-limited settings, cost restricts availability of viral load monitoring for most patients receiving antiretroviral therapy in Tijuana, Mexico. We evaluated if a pooling method could improve efficiency and reduce costs while maintaining accuracy. METHODS:We evaluated 700 patient blood plasma specimens at a reference laboratory in Tijuana for detectable viremia, individually and in 10 × 10 matrix pools. Thresholds for virologic failure were set at ?500, ?1000 and ?1500 HIV RNA copies per milliliter. Detectable pools were deconvoluted using pre-set algorithms. Accuracy and efficiency of the pooling method were compared with individual testing. Quality assurance (QA) measures were evaluated after 1 matrix demonstrated low efficiency relative to individual testing. RESULTS:Twenty-two percent of the cohort had detectable HIV RNA (?50 copies/mL). Pooling methods saved approximately one third of viral load assays over individual testing, while maintaining negative predictive values of >90% to detect samples with virologic failure (?50 copies/mL). One matrix with low relative efficiency would have been detected earlier using the developed QA measures, but its exclusion would have only increased relative efficiency from 39% to 42%. These methods would have saved between $13,223 and $14,308 for monitoring this cohort. CONCLUSIONS:Despite limited clinical data, high prevalence of detectable viral loads and a contaminated matrix, pooling greatly improved efficiency of virologic monitoring while maintaining accuracy. By improving cost-effectiveness, these methods could provide sustainability of virologic monitoring in resource-limited settings, and incorporation of developed QA measures will most likely maximize pooling efficiency in future uses.

SUBMITTER: Tilghman MW

PROVIDER: S-EPMC3039117 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Pooled nucleic acid testing to detect antiretroviral treatment failure in Mexico.

Tilghman Myres W MW Guerena Don Diego DD Licea Alexei A Pérez-Santiago Josué J Richman Douglas D DD May Susanne S Smith Davey M DM

Journal of acquired immune deficiency syndromes (1999) 20110301 3

<h4>Background</h4>Similar to other resource-limited settings, cost restricts availability of viral load monitoring for most patients receiving antiretroviral therapy in Tijuana, Mexico. We evaluated if a pooling method could improve efficiency and reduce costs while maintaining accuracy.<h4>Methods</h4>We evaluated 700 patient blood plasma specimens at a reference laboratory in Tijuana for detectable viremia, individually and in 10 × 10 matrix pools. Thresholds for virologic failure were set at ...[more]

PMID: 21124228

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Project description:BACKGROUND:In resource-limited settings, viral load monitoring of HIV-infected patients receiving antiretroviral therapy (ART) is not readily available because of high costs. Here, we compared the accuracy and costs of quantitative and qualitative pooled methods with standard viral load testing. METHODS:Blood was collected prospectively from 461 patients receiving first-line ART in Mozambique who had not been evaluated previously with viral load testing. Screening for virologic failure of ART was performed quantitatively (ie, standard viral loads) and qualitatively [one and 2 rounds of polymerase chain reaction (PCR)]. Individual samples and minipools of 5 samples were then analyzed using both methods. The relative efficiency, accuracy, and costs of each method were calculated based on viral load thresholds for ART failure. RESULTS:Standard viral load testing of individual samples revealed a high rate of ART failure (19%-23%) across all virologic failure thresholds, and the majority of the patients (93%) with viral loads >1500 copies per milliliter had genotypic resistance to drugs in their ART regimen. Pooled quantitative screening and deconvolution testing had positive and negative predictive values exceeding 95% with cost savings of $11,250 compared with quantitative testing of each sample individually. Pooled qualitative screening and deconvolution testing had a higher cost savings of $30,147 for 1 PCR round and $25,535 for 2 PCR rounds compared with quantitative testing each sample individually. Both pooled qualitative PCR methods had positive and negative predictive values ?90%, but the pooled 1-round PCR method had a sensitivity of 64%. CONCLUSIONS:Given the high rate of undiagnosed ART failure and drug resistance in this cohort, it is clear that virologic monitoring is urgently needed in this population. Here, we compared alternative methods of virologic monitoring with standard viral load testing of individual samples and found these methods to be cost saving and accurate. The test characteristics of each method will likely need to be considered for each local population before it is adopted.

Project description:ContextPresence of low-frequency, or minority, human immunodeficiency virus type 1 (HIV-1) drug resistance mutations may adversely affect response to antiretroviral treatment (ART), but evidence regarding the effects of such mutations on the effectiveness of first-line ART is conflicting.ObjectiveTo evaluate the association of preexisting drug-resistant HIV-1 minority variants with risk of first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral virologic failure.Data sourcesSystematic review of published and unpublished studies in PubMed (1966 through December 2010), EMBASE (1974 through December 2010), conference abstracts, and article references. Authors of all studies were contacted for detailed laboratory, ART, and adherence data.Study selection and data abstractionStudies involving ART-naive participants initiating NNRTI-based regimens were included. Participants were included if all drugs in their ART regimen were fully active by standard HIV drug resistance testing. Cox proportional hazard models using pooled patient-level data were used to estimate the risk of virologic failure based on a Prentice weighted case-cohort analysis stratified by study.Data synthesisIndividual data from 10 studies and 985 participants were available for the primary analysis. Low-frequency drug resistance mutations were detected in 187 participants, including 117 of 808 patients in the cohort studies. Low-frequency HIV-1 drug resistance mutations were associated with an increased risk of virologic failure (hazard ratio (HR], 2.3 [95% confidence interval {CI}, 1.7-3.3]; P < .001) after controlling for medication adherence, race/ethnicity, baseline CD4 cell count, and plasma HIV-1 RNA levels. Increased risk of virologic failure was most strongly associated with minority variants resistant to NNRTIs (HR, 2.6 [95% CI, 1.9-3.5]; P < .001). Among participants from the cohort studies, 35% of those with detectable minority variants experienced virologic failure compared with 15% of those without minority variants. The presence of minority variants was associated with 2.5 to 3 times the risk of virologic failure at either 95% or greater or less than 95% overall medication adherence. A dose-dependent increased risk of virologic failure was found in participants with a higher proportion or quantity of drug-resistant variants.ConclusionIn a pooled analysis, low-frequency HIV-1 drug resistance mutations, particularly involving NNRTI resistance, were significantly associated with a dose-dependent increased risk of virologic failure with first-line ART.

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Pooled nucleic acid testing to detect antiretroviral treatment failure in Mexico.

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Pooled nucleic acid testing to detect antiretroviral treatment failure in Mexico.

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