The Medical Microbiology Laboratory has acquired state-of-the-art equipment to better detect mutations in the human immunodeficiency virus, or HIV. A first in Belgium.
According to UNAIDS, the United Nations agency in charge of combatting AIDS, in 2017, 36.9 million people worldwide were living with the HIV virus (19,000 in Belgium). About 75% of them knew it; the rest didn’t. The same year, 21.7 million patients had access to antiretroviral treatment, and 1.8 million people were newly infected (890 in Belgium). UNAIDS has a three-fold goal to reach by the end of 2020 via a treatment planned called ‘90-90-90’: 90% of infected people must know their status, 90% must be treated before the disease develops, 90% of those treated must have an undetectable viral load. ‘The last two goals are almost achieved in Belgium’, says Professor Benoît Kabamba-Mukadi, head of UCLouvain's AIDS Reference Laboratory. ‘But the first objective remains problematic: it’s estimated that 15% of infected people don’t know they’re infected. Although research has made enormous progress in 35 years, and even if there are effective treatments given that over 90% of treated patients have an undetectable viral load, the HIV pandemic remains a global public health problem. It shouldn’t be forgotten that AIDS hasn’t been cured: it’s not currently possible to completely eradicate the HIV virus in patients who have been infected.’
This brief summary of the situation highlights the three actors involved in the disease: the patient, the virus, the drugs. Each has its role and importance. The effectiveness of current drugs shouldn’t hide that some patients experience troublesome side effects or drug interactions, may have other pathologies, or require precautions, such as women who are pregnant or want to be. Treatment modification according to these parameters may be required, without loss of effectiveness. As for viruses, they don’t remain inactive: some mutate to become resistant to antivirals. Resistance can appear during either treatment or a new infection by an already mutated virus. Hence the resistance tests carried out at UCLouvain using a new high throughput sequencing platform.
Géraldine Dessilly, a doctor in biomedical sciences and head of analysis at the laboratory, explains, ‘This next-generation sequencing, or NGS, platform is the first of its kind in routine clinical use in Belgium and makes it possible to perform high throughput sequencing of the viral genome. That is, it reads the order of nucleotide sequence of the virus RNA. It’s this order that will determine whether the virus is mutated and will resist drugs.’ Obtaining the genome sequence of the virus is obviously not new, even to routine use. But the new platform has several advantages over the traditional method. In addition to its greater sensitivity, automation reduces manual errors. The technology also makes it possible to quantify resistance mutations, whereas previously it was only possible to ‘qualify’ them – detect their presence or absence. Now so-called minority variants, that is, small quantities within the viral population, can be quantified.
Quite rare mutations
This genotypic test of resistance is carried out in recently infected patients and in those whose treatment is failing; the UCLouvain laboratory performs approximately 15 tests every two weeks. In recently infected patients, tests show that about 10% carry a mutated, resistant virus, which has been a stable figure since the early 2000s. In patients with treatment failure (who represent only 4 to 5% of treated patients), fewer than half of them have a resistance problem. These are rather reassuring figures that tell Prof. Kabamba-Mukadi that current drugs cause much less resistance than those used when the epidemic began: ‘When we started to treat with AZT in 1987, resistances were described in the majority of patients treated as early as 1992. Today, thanks to new molecules, patients are treated for years without resistance problems. But the virus tries to persist by developing coping skills; so there’s a race between it and us.’ The test results are sent to the patient’s doctor, who determines the most optimal regimen.
‘Even if a patient responds correctly to treatment, there’s no more detectable viral load, that is, no more cell-free viruses in the blood, it doesn’t mean that all the viruses have disappeared: there are still some inside cells,’ Dr Dessilly. ‘We therefore obtained funds from the Louvain Foundation to sequence intracellular viruses as well.’ For what purpose? If a patient who has no viral load wants or needs to change treatment for whatever reason (comfort, pregnancy, interaction with a drug for another illness, etc.), the doctor must be able to tell if resistance will be encountered. There’s no doubt that the new tool at the disposal of researchers and clinicians will further refine AIDS treatment.
Published by ScienceToday on June 18th, 2019