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First discovery of new strain HIV in 20 years

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The first discovery in nearly 20 years of a rare new strain of HIV is important, but it does not signify a new public health threat, writes Linda-Gail Bekker of the University of Cape Town in The Conversation.

The discovery of a rare new strain of HIV by a team of US researchers from Abbott – a US medical devices and health care company, led by Mary Rodgers – and co-authors at the University of Missouri, for the first time in nearly 20 years recently made headlines around the world.

The big question, writes Linda-Gail Bekker, professor of medicine and deputy director of the Desmond Tutu HIV Centre at the Institute of Infectious Disease and Molecular Medicine, University of Cape Town, in The Conversation, is what the discovery means for the overall response to the HIV epidemic.

The new subtype is the first strain to be identified since guidelines for classifying new HIV strains were first established in 2000.

HIV has a multitude of different subtypes and, like other viruses, it changes (mutates) over time. This new strain is an important discovery, but it does not signify a new public health threat. It occurs rarely and can be effectively treated with existing antiretrovirals. Because antiretrovirals target characteristics of HIV that are common across all different subtypes, this new finding will not affect treatment and antiretroviral agents will still be effective as long as drug resistant mutations have not occurred.

The essence of the discovery is that it enhances scientists’ understanding of the complexity of the human immunodeficiency virus and its evolution and adds detail to the already comprehensive viral picture. Having a thorough understanding of HIV is crucial in ensuring that HIV tests are effectively detecting the virus. Deeper insights could also have a bearing on vaccine development.

There are two main types of HIV. HIV-1 is the most common. HIV-2 is less common and accounts for fewer infections. The strains of HIV-1 can be classified into four groups – M, N, O and P. While N, O and P are quite uncommon, group M is responsible for most of the global HIV epidemic, accounting for roughly 95% of all infections worldwide. The newly discovered strain (also known as a clade) is part of group M and has been labelled as “subtype L”.

The prevalent strain found in South Africa is known as a subtype of clade C. One of the candidate HIV vaccine regimens currently under investigation in South Africa is designed to be effective against subtype C. It is not yet known whether, if found to be effective in this region, it will be as effective in a region with a different prevalent strain. For example, in the US the predominant strain is subtype B.

The process of confirming a new strain of any virus can be long. Three separate cases need to be identified before a new subtype can be announced. The first two cases of this new strain were found in the Democratic Republic of Congo in 1983 and 1990 and the third case in 2001. So, while the strain has been known to scientists for 18 years, the entire genome needed to be tested for confirmation. The technology to do this did not exist at the time.

The genome sequencing technology available today allows scientists and researchers to build entire genomes at a faster rate and lower cost than ever before. To use this next-generation technology successfully, the responsible scientists had to apply new techniques that focus on the virus portion of the collected sample in order to fully sequence the genome.

From a scientific point of view, the discovery helps us stay one step ahead of a virus. Furthermore, the role that new technology played in identifying the strain serves as an important reminder of how far we have come. The innovation and advancements in technology and molecular virology should be celebrated.

The fight against HIV has made some formidable gains in treatment and treatment outcomes with remarkable gains in longevity. UNAIDS estimates that new infections have decreased by 16% from 2.1m in 2010 to 1.7m in 2017. Undoubtedly one of the most promising achievements is the reduction in mother-to-child transmissions around the world. But the HIV response does not favour complacency.

The notion that HIV is no longer an emergent threat is one that jeopardises the work of scientists and communities who continue to drive prevention of HIV and fight against the pervading stigma. The HIV emergency is not over. The epidemic still needs vigilant attention, especially as reduction rates stall.

The ultimate solution is a working cure and preventative vaccine. The HVTN studies in South Africa are currently conducting HIV preventative vaccine trials in the hope that one day there will be an effective vaccine to prevent HIV. But until then, we need to refocus our energy on scaling up the effective treatment and prevention tools we have in hand to all those who need them.

Abstract
Background: The full spectrum of HIV-1 diversity can be found in central Africa, including two divergent HIV-1 strains collected in 1983 and 1990 in Democratic Republic of Congo (DRC) that were preliminarily classified as group M subtype L. However, a third epidemiologically distinct subtype L genome must be identified to designate L as a true subtype.
Methods: Specimen CG-0018a-01 was collected in 2001 in DRC as part of an HIV prevention of mother to child transmission (PMTCT) study. Prior sub-genomic HIV-1 sequences from this specimen branched closely with proposed subtype L references. Metagenomic (mNGS) and HIV-specific target enriched (HIV-xGen) libraries were combined for next generation sequencing (NGS) to extend genome coverage. mNGS reads were analyzed for the presence of other co-infections with the SURPI bioinformatics pipeline.

Results: A complete HIV-1 genome was generated with an average coverage depth of 47,783x. After bioinformatic analysis also identified Hepatitis B virus (HBV) reads, a complete HBV genotype A genome was assembled with an average coverage depth of 73,830x. The CG-0018a-01 HIV-1 genome branched basal to the two previous putative subtype L strains with strong bootstrap support of 100. With no evidence of recombination present, the strain was classified as subtype L.
Conclusions: The CG-0018a-01 HIV-1 genome establishes subtype L and confirms ongoing transmission in DRC as recently as 2001. Since CG-0018a-01 is more closely related to an ancestral strain than to isolates from 1983 or 1990, additional strains are likely circulating in DRC and possibly elsewhere.

Authors
Yamaguchi, Julie; McArthur, Carole; Vallari, Ana; Sthreshley, Larry P; Cloherty, Gavin A; Berg, Michael G; Rodgers, Mary A

Full report in The Conversation

Journal of Acquired Immune Deficiency Syndromes JAIDS abstract

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