NEW YORK (GenomeWeb) — ATCC has partnered with the US Centers for Disease Control and Prevention and Thermo Fisher Scientific's Life Technologies, among other organizations, to manufacture and distribute a rapid, cost-effective genotyping kit to monitor HIV-1 drug resistance in resource-limited countries, ATCC said this week.
Under the agreement, ATCC will use its expertise in cold-chain distribution and biological materials handling to distribute the assay to be performed in World Health Organization-designated and CDC-supported centralized genotyping laboratories established through the US President's Emergency Plan for AIDS Relief (PEPFAR). The assay also uses PCR and sequencing reagents from Life Tech and primers and probes from Biosearch Technologies.
And although the initial distribution network will focus on the African continent, the partners are already considering expanding distribution to other resource-poor areas of the world such as parts of Southeast Asia.
Should the assay, called the ATCC HIV-1 Drug Resistance Genotyping Kit, prove successful in helping to track HIV-1 drug resistance and inform regional therapeutic administration, ATCC may seek to rework the agreement to enable it to distribute the kit even more widely, Ted Mullins, program manager for ATCC Biological Services, told PCR Insider this week.
"Currently this kit is not available to the world; it's available to those WHO-designated and PEPFAR-funded laboratories," Mullins said. "If we choose to expand this, and make it available to anyone worldwide, then we will just have to adapt our license agreement, which we are perfectly ready to do. But we thought we would aim this at laboratories where it is exactly needed now, and then eventually expand this to the rest of the world."
Surveillance of HIV drug resistance by molecular genotyping has proven useful in ensuring antiretroviral therapies in resource-limited countries. However, existing commercial genotyping assays, manufactured by Abbott and Siemens, are expensive and detect HIV-1 group M subtype B viruses, strains most often found in more industrialized parts of the world, Mullins said.
"These kits just weren't aimed for … the type of drug resistance that is [seen] in Africa," Mullins said. "That's not a slam on those other kits. However, there was a very strong need to have something that was a little broader in its specificity."
To address this, researchers at the CDC over the past several years developed and optimized an HIV-1 pan group M drug-resistance genotyping assay, and described the test in a 2011 PLOS One paper.
The test comprises three primers for one-step reverse transcriptase and PCR, and two for nested PCR, to detect both the RT and protease regions from the HIV-1 pol gene; as well as an additional four primers specifically for sequencing.
In the PLOS One study, when compared with commercial HIV-1 group M subtype B genotyping assays, the CDC assay detected more mixture bases with minimal background noise.
Furthermore, the new kit is validated for use with both plasma and dried blood spots, whereas the two commercially available kits are validated for detection only in plasma. "As you can imagine, in a country [in Africa] with a very poor cold chain, having the ability to work with DBS is definitely advantageous," Mullins said.
After developing and successfully vetting the new kit, the CDC sought commercialization partners to help implement it in the developing world.
"Life Technologies worked very closely with this [CDC] HIV laboratory, and when this need arose, it was actually Life Tech that recommended us to the CDC group," Mullins said.
"We also have a very large influenza contract with CDC, and much of what they're talking about doing here, we're already doing under a government contract with CDC for influenza," he added. "We were contacted by them … and we signed a license agreement to manufacture the kit for CDC."
Mullins said that the majority of the components in the kit are sourced from Life Tech, except the primers and probes, which Biosearch supplies.
"Part of the agreement that we have … with this association is that we get premium pricing for these components … and we work very closely with these [partners]," Mullins said. "And because these are resource-limited countries, we worked very hard with Life Tech to make sure we could offer these kits at a price that would be amenable to these labs."
The kit consists of two "modules," one for RT-PCR and one for sequencing, but both modules aren't necessarily needed for every sample. Mullins said that it costs about $66.50 to run a sample through both RT-PCR and sequencing, and half that price if only one module is needed. This, he added, is about half the cost of current commercially available assays.
A key aspect of the partnership is the network of WHO-designated and PEPFAR-funded laboratories that will be performing the assay. According to the WHO website, there are currently nine such accredited labs in Africa, and a couple dozen additional labs on other continents.
"These were already mostly set up by the CDC and WHO, so they already have the networks designed to share data," Mullins said. "So we initially start with laboratories that are trained by the CDC staff, [who] make sure the labs can run these and the data can be trusted."
ATCC underscored the fact that the ATCC HIV-1 Drug Resistance Genotyping Kit is not intended to be used as a screening test for HIV or as a diagnostic assay to confirm the presence of HIV infection.
"A patient would have already been diagnosed with HIV before their samples are run on this kit," Mullins said. "It truly is not for diagnostic purposes. That relieves a lot of regulatory issues in the manufacture and distribution of the kit."
However, the information gleaned from the assay is expected to be highly valuable in the global fight against HIV-1, particularly in monitoring the efficacy of ARVs. According to ATCC, once genotyping information is generated for a given strain, the resulting final consensus sequences will be submitted to the Stanford HIV database to create a drug-resistance profile. This open access, public database assimilates this information and provides a wide range of tools to help understand ARV resistance.
The partnership is also an important step for ATCC in its quest to increase its distribution of molecular tests.
"We're known more for our repository and distribution; however, we are also the world's largest biorepository of biological reagents," Mullins said. "We are moving more into these types of … commercial contracts where we are able to produce these kits. This is kind of the future for us."