Continued advances in HIV treatment and diagnosis require shared resources

3rd March
By Astrid Gall

Cut-away model of HIV. Credit: John Wildgoose, Wellcome Images

Cut-away model of HIV. Credit: John Wildgoose, Wellcome Images

Treatment and diagnosis of Human Immunodeficiency Virus 1 (HIV-1) infection has improved tremendously since this global health threat was discovered in 1983. However, 35 million people worldwide are still infected with HIV-1 and, without therapy, most will go on to die between two and 20 years after infection from the acquired immunodeficiency syndrome (AIDS). Continued advances now depend on shared resources.

The first drug against HIV-1, azidothymidine (AZT, zidovudine), was approved by the US Food and Drug Administration in 1987 and highly active antiretroviral therapy, based on a combination of multiple drugs, was introduced in 1996. This was a major improvement for clinical management of HIV-1 infection.

Tests for diagnosis of HIV-1 infection have also improved. The first tests were based on serological techniques, which look for the virus antigen or the anti-HIV-1 antibodies an infected person generates. Nucleic acid tests detecting the genetic material of HIV-1, the viral RNA, became available shortly after the techniques were developed.

In 1986/87, Polymerase chain reaction (PCR) was introduced and, in 1995, quantitative TaqMan ® PCR, which allowed for the highly sensitive detection and quantification of HIV-1 RNA. This led to the introduction of viral-load testing in 1996, where the number of HIV-1 RNA molecules per ml of blood is measured, and routine drug resistance testing.

The variety of nucleic acid tests now available are only valuable if clinicians and researchers around the world can refer to the same material when they develop, validate and use their tests. To this end, the World Health Organization has established an International Standard for HIV-1 RNA.

In our recent study, we determined the complete genome sequence of the second International Standard for HIV-1 RNA by deep sequencing. The work is based on our universal primer set for HIV-1 described in my previous blog, but made use of newer sequencing (Illumina MiSeq) and computational technologies. The standard and its complete genome sequence will serve as important reference material.

We have produced this reference sequence and will continue to generate and share resources for more strains over the next five years. Complete genome sequences of historical, modern type and reference strains of 3,000 bacteria and 500 viruses will be generated and made publically available via an open access electronic resource and public databases. This is a joint effort of researchers at the Wellcome Trust Sanger Institute, led by Julian Parkhill and Paul Kellam, and Public Health England’s Culture Collections, led by Julie Russell. Public Health England holds the National Collection of Type Cultures (for bacteria) and National Collection of Pathogenic Viruses that will be used for this purpose.

Astrid Gall is a Staff Scientist in the Virus Genomics group at the Wellcome Trust Sanger Institute.