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Researchers may have caught HIV becoming more virulent
Gus Cairns, 2015-02-19 09:40:00
A study from Cuba has generated wide media interest because researchers have identified a particular variety of the virus which is associated with rapid post-diagnosis falls in CD4 count and progression to AIDS. In the study, every member of the still relatively small minority of people who had this viral variant had progressed to clinically-defined AIDS within three years of infection. It also seems to be becoming more common in Cuba and may partly explain what appears to be an increase in the proportion of people who progress rapidly to AIDS. However it is not a drug-resistant strain and antiretroviral therapy (ART) works just as well against it does against any other strain of HIV.
This viral strain, dubbed CRF19_cpx, is a recombinant: this means that its genetic code is a patchwork of gene fragments that come from other varieties of HIV. In this case the genes of CRF19_cpx come from subtypes A, D and G, which are mainly found in Africa. There, subtype D is associated with faster progression, and A/D recombinants even more so.
The researchers believe that the ultimate cause of CRF19_cpx's unusual virulence is that its protease gene, which comes from HIV subtype D, produces an unusually potent protease enzyme that generates exceptional numbers of viral copies and rapidly alters the arms race between HIV and the immune response against it in favour of the virus.
So-called 'circulating recombinant forms' (CRFs) are not uncommon. In some countries they may even predominate, such as Thailand, where CRF01_AE is so common it is often just called 'subtype E' (and has been associated with faster progression). CRF19_cpx has been found in Africa, but it is only in Cuba that it has been noted to be spreading.
It has also been noted that there appeared to be a trend towards faster progression to AIDS among people in Cuba diagnosed since 2007, with an estimated 13-16% being true ‘fast progressors’ (i.e. with a CD4 count below 200 cells/mm3 within three years of infection).This is higher than the 5-10% reported internationally, but is not unprecedented: a study published in December found in Europe the time between infection and a CD4 count below 200 cells/mm3 has halved in the last two decades. This may be driven by evolutionary pressure; because of antiretroviral therapy, HIV now has less time to jump between individuals and so only the fittest, fastest-replicating viruses will survive.
Conversely, pressures in some parts of Africa may be driving HIV towards lower virulence in that region.
The Cuban researchers only found that nine out of a minority of 52 people who had progressed to AIDS rapidly after diagnosis had CRF19_cpx, so this virus is not the cause of all cases; but it is striking that there was no-one in this small study with CRF19_cpx who was not a fast progressor. This is the first time a specific viral variant has so unambiguously been shown to be associated with rapid progression to AIDS.
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