First-Ever Next Generation Sequencing Test to Detect HIV Drug Resistance

Highlights

• A first-ever genetic sequencing test to detect HIV drug resistance
• Could aid in better treatment for HIV patients
• Assist in curbing resistance towards anti-retroviral therapy

Acquired Immunodeficiency Syndrome (AIDS) is a syndrome that is caused due to the infection of the Human Immunodeficiency Virus (HIV). HIV affects the body’s immune system and lowers the body’s ability to fight off infections. There are different strains of HIV that infect humans and they are broadly classified into HIV1 and HIV2. After the initial infection of HIV into the human body, it could take even up to 10 to 15 years before symptoms begin to develop.

Global Statistics on HIV Infection

• 36.9 million people across the world are currently infected with HIV
• The highest number of people infected with HIV is found to be in middle or lower income countries.
• 2.6 million children across the world are infected with HIV. Mother to child transmission is the leading cause of HIV among children.

A large number of global efforts focus on controlling the spread of disease, with the U.N fixing the year 2030 as the “End of AIDS”. However, the numbers continue to rise. “I don’t believe the slogan ‘The End of AIDS by 2030’ is realistic and it could be counterproductive. It could suggest that it’s fine, it’s all over and we can move to something else. No. AIDS is still one of the biggest killers in the world.” said Prof Peter Piot who was the first executive director of UNAIDS and director of the London School of Hygiene and Tropical Medicine.

The pessimism revolving around the control of HIV spread is largely due to inequality in the distribution of medication and the increasing scourge of drug resistance.

Drug Resistance In HIV

HIV has the ability to mutate and then reproduce with the mutation intact, leading to failure of anti-retroviral therapy. The limited treatment options available to treat HIV infection make drug resistance to anti-retroviral therapy catastrophic. The result is an increase in HIV incidence, morbidity and mortality.

Advantages of Drug Resistance Testing

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Drug resistance to HIV medications affects the number of HIV patients receiving effective treatment. It is important to have drug resistance testing carried out to facilitate

• More effective treatment for HIV infection
• To ascertain if the individual was infected with drug resistance strain at the onset of infection or during the course of treatment.
• To monitor progress of the treatment procedure.

Existing Sequencing Test for HIV Drug Resistance

Most of the genomic sequencing kits that are available are now outdated and are no longer in use. The only test still in existence has the following disadvantages

• It uses the Sanger’s method of sequencing which is now replaced by better methods.
• Drug resistance that occurs at a frequency below 15-20% cannot be detected.
• The results take a long time, about one to two weeks.

First Next Generation Sequencing Test for Drug Resistance In HIV

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Dr. Gerd Michel and colleagues from Vela Diagnostics in Singapore have created a next generation genome sequencing kit to detect HIV resistance. The new test ‘Sentosa SQ HIV-1 genotyping assay’ offers hope to a future of better drug resistance testing.

This new-age testing offers an integration between automatic sample processing as well as analysis of the data obtained using a software.

Comparison Between Sentosa SQ HIV-1 Genotyping Assay and TruGene HIV-1 Genotyping Kit

The efficiency of Sentosa SQ HIV-1 genotyping assay was compared with that of TruGene HIV-1 genotyping kit which is based on the Sanger’s method of genome sequencing. The viruses’ protease gene and the reverse transcriptase gene were analyzed from 111 blood sample of HIV-1 positive patients.

Dr. Michel added “To our knowledge, nobody else has developed an assay like this. Now we have the opportunity to do HIV drug resistance testing much faster, at a lower cost, and also to test for mutations that are not visible with Sanger sequencing. The impact of these mutations that have not been seen by Sanger is not known yet. But now we have the tools to detect them so that researchers can determine how relevant they are clinically and physicians can determine if there should be a change in treatment.”

Results of the Comparison Study

• Sentosa SQ HIV-1 test found 100% mutations in all virus protease genes when compared with 90.45% detected by TruGene HIV-1.
• Sentosa SQ HIV-1 test found 98.16% mutations in reverse transcriptase genes when compared with 74.48% detected by TruGene HIV-1.
• The Sentosa SQ HIV-1 test detected 130 drug resistance genes not detected by TruGene HIV-1
• TruGene HIV-1 found only 8 drug resistance gene mutations that Sentosa SQ HIV-1 test missed
• Sentosa SQ HIV-1 test detected drug resistance in the HIV Integrase gene that is not detected by TruGene. The HIV Integrase gene shows high incidence of developing drug resistance through mutations in the U.S population.
• Sentosa SQ HIV-1 test provides results withing two and a half days, which is a lot faster than TruGene test.

Vela Diagnostics plans to bring out this innovative test for drug resistance testing soon, raising hopes for better control and treatment of HIV.

References:

1. AIDS Statistics - (https://www.aids.gov/hiv-aids-basics/hiv-aids-101/global-statistics/)
2. Drug Resistance - (https://aidsinfo.nih.gov/education-materials/fact-sheets/21/56/drug-resistance)
3. HIV Drug Resistance - (http://www.who.int/hiv/topics/drugresistance/en/)
4. Resistance Testing - (https://aidsinfo.nih.gov/education-materials/glossary/630/resistance-testing)

Source-Medindia