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.
HIV and AIDS
HIV (human immunodeficiency virus) is a virus that infects humans and is responsible for AIDS (Acquired Immunodeficiency Syndrome), a condition characterised by the weakening of the infected person’s immune system. It can therefore be fatal, if the disease is not treated with drugs that inhibit the replication of the virus, thus delaying the onset of AIDS. Current treatment, which is very effective, is generally based on a triple therapy: ingestion of three antiviral drugs belonging to different classes. Each class acts at different moments of virus multiplication in the target cells. There are several possible combinations that must be adapted to each patient.
When the treatment works (which is the case for more than nine out of ten patients), the patient has zero viral load (no cell-free virus is detected in the blood). This does not mean, however, that the virus has disappeared: it’s 'hidden' within cells and inactive, latent. The patient is not cured. Similarly, there is still no vaccine against AIDS.
Coup d’œil sur la bio de Benoît Kabaamba-Mukadi
Benoît Kabamba-Mukadi earned a master's degree in pharmaceutical sciences from UCLouvain in 1999, then specialised in clinical biology in 2002. He conducted research on the utility of proviral DNA of the type 1 human immunodeficiency virus in AIDS treatment decisions and earned his PhD in February 2013. Since 2014, he has been a professor at UCLouvain's Faculty of Medicine and Dentistry and at the Faculty of Pharmacy and Biomedical Sciences.
Essentially, he takes the general decision regarding diagnosis and validation of biomedical tests at Saint-Luc University Hospital. He heads the UCLouvain National Reference Centre for Borrelia (tick and lice-borne bacteria causing diseases such as Lyme disease). He co-partners with laboratories of the reference centres for viral hepatitis and bartonella (bacteria transmitted by cat scratches). He is also in charge of UCLouvain's AIDS Reference Laboratory and UCLouvain's ‘Pôle de Microbiologie Médicale’ (‘Medical Microbiology Centre’) research unit.
Coup d’œil sur la bio de Géraldine Dessilly
Géraldine Dessilly is the technical and scientific head of HIV testing at the AIDS Reference Laboratory and the UCLouvain National Reference Centre for Borrelia since the end of 2016. She earned her master's degree in biomedical sciences at UCLouvain in 2011. She has conducted PhD research in the context of ‘Télévie’ and obtained her PhD in August 2016. Dr Dessilly and her colleagues have developed (and used), for the first time in Belgium, a high-throughput sequencing platform for identifying resistance mutations in patients infected with HIV-1.