Pooled Nucleic Acid Testing to Detect Antiretroviral Treatment Failure in HIV-Infected Patients in Mozambique

Abstract

Background In resource-limited settings, viral load monitoring of HIV-infected patients receiving antiretroviral therapy (ART) is not readily available due to high costs. Here, we compared the accuracy and costs of quantitative and qualitative pooled methods to 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 (i.e. standard viral loads) and qualitatively (one and two 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 vast majority of the patients (93%) with viral loads >1,500 copies/ml 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 to quantitative testing of each sample individually. Pooled qualitative screening and deconvolution testing had a higher cost savings of $30,147 for one PCR round and $25,535 for two PCR rounds compared to quantitative testing each sample individually. Both pooled qualitative PCR methods had positive and negative predictive values ≥90%, but the pooled one-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 to 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.

Group Testing: An Information Theory Perspective

“…References [35,179,185] were early works showing that group testing offers an efficient way to estimate the proportion of defectives, particularly when defectivity is rare. This testing paradigm continues to be used in recent medical research, where pooling can provide significant reductions in the cost of DNA testing -see for example [121], [187].…”

Occult HBV infection in HIV‐infected adults and evaluation of pooled NAT for HBV

“…If found to be positive, individual samples will be tested. The performance of different pooling strategy has been widely studied for HIV . An important advantage with this strategy is that, pooling PCR is cost‐effective and efficient for prevalence up to 30% for any infection tested.…”

Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure

“…However, the importance of this therapy to global health has been threatened by an increased prevalence of resistance to antiretrovirals (ARVs), which has increased from 11 to 29% since 2001 [ 4 ]. Of the individuals under ARV treatment, 20% will have to switch ARVs due to virologic failure [ 5 , 6 ]. Thus, drug resistance is a real obstacle to viral suppression and disease control [ 1 ].…”