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Virology

The tricks of HIV

Recombinant forms of the virus complicate the AIDS epidemic in Brazil

HÉLIO DE ALMEIDAThe computer screen shows an image with blue and green rectangles of different sizes: this is the reconstruction of the AIDS virus. After presenting the diagram, the virologist Ricardo Sobhie Diaz, a professor at the Federal University of Sao Paulo (UNIFESP), calls the attention to the two colors, used to identify parts – or better, genetic information – of two HIV subtypes. This mixture is a special characteristic of this colorful virus: one is dealing with a variety with epidemic potential, which was capable of overcoming  selection barriers and can be transmitted from one person to another. Called Circulating  Recombinant Form (CRF), this new variation of HIV was identified for the first time in Brazil and is already worrying specialists. “The AIDS epidemic is genetically becoming  much more complex” observes Diaz, one of the authors of a paper published in the magazine Aids Research and Human Retroviruses with these results. “We need to rethink some strategies of combating the illness and to become attentive to the sensitivity of diagnostic tests, the activity of the anti-retroviruses in the face of these genetically different lineages and to the choice of components that must be used in vaccine tests.”

Meeting of the virus
The identification of recombinant forms of the virus tends to make the control of the AIDS epidemic difficult. In Brazil, data from the Ministry of Health reveals that, from 1980 until June of 2005, around 372,000 cases of AIDS were  notified – more than 80% of them concentrated in the south and southeast regions. In the entire world, according to the UNAIDS, the United Nations Organization (UN) organ, in 2005 there were 40.3 million adults and children infected with HIV; of this total 4.9 million, around 10%, have become contaminated during the last year. The Sub-Saharan Africa houses 25.8 million victims with the disease – almost 65% of the total.

Variations of HIV have already been known for at least 15 years. Currently, as well as the two types (HIV 1 and 2), nine subtypes of the virus exist, identified as A, B, C, E, F, G, H, J and K. All act by destroying the immunological system of the infected person, and the symptoms and problems that they bring about, such as opportunistic infections, are also the same. The fundamental difference is that the variations are formed by sequences of distinct genes. For this reason, the subtypes can be more or less aggressive, can have greater or lesser resistance capacity to the anti-retrovirus medicines, can replicate quicker  or in a slower manner, as well as reaching social groups (drug users and heterosexuals, for example) and different regions (in the city of Santos, on the coast of the city of São Paulo, the most common are the B and F; in the south of the country that which appears most is the C, the most frequent in the worldwide epidemic). “These biological differences can offer advantages to some subgroups to the detriment of others” explains  Diaz.

When the genetic information of two subtypes mix themselves up, a microorganism that can be classed as a hybrid emerges, with gene sequences of two distinct origins. For this reason it is called recombinant. This genetic mix in general is born in the cells of people with risk behavior, with a double infection – in the maximum time of three weeks, after having been contaminated with the first virus, they end up contracting a second, from a different group. When they begin to reproduce and to multiply, the two types end up meeting each other.

However, not always does this variation have the potential of transmission. The scenario becomes graver when the recombinant expands itself into a population group and gains the status of circulating  – or epidemic. “This is one of the demands for classification. It must be found in at least three non-related individuals” says Luiz Mario Janini, also an author of the work. “For example, one can’t take into consideration sexual partners or mother and son.”Twenty seven subtypes of circulating recombinant had been described up until the start of this year throughout the world. Brazilians have identified two more, resulting from a mix of B and F subtypes, classified as CRF28_BF and CRF29_BF (the numbers indicate the order of discovery; the letters after the stroke are the subtypes that reunited). Although the two are very similar, the 29 has a sequence greater than the subgroup F.

More difficult treatment
The identification of the CRFs in Brazil has set off an alarm bell. Their possible consequences, although as yet placed in the plan of speculations, are not heartening. The Brazilian B and F subtype mixture was found in blood samples collected in the city of Santos, where other studies made by the UNIFESP team identified primary resistance – prior to the treatment with anti-retroviruses – of 36%, the highest index registered in the world. In studies published in 2000 and in 2005, the group have already demonstrated that, thanks to a mutation, the F subtype, the most frequent in the coastal city, has become more resistant to medicines.

“Based on a combination of factors, it’s possible to imagine that the medicines may have selected the virus of the F subtype, predominant in the municipality of Santos, which was able stand out and survive among the others” says Diaz. The B and F subtypes do not present the same responses to treatment and are resistant to different anti-retroviruses. In theory, the recombinant will put together these two advantages and will be free of the effects of a greater arsenal of medicines. This is one of the possibilities that Diaz intends to test in the laboratory, as well as evaluating if the recombinant can replicate itself more quickly and if the infections that it brings about will be more aggressive.

“The Brazilian epidemic has now at least five viruses that are in circulation, the B, C and F subtypes, long known, as well as the two new recombinants” reinforces Janini. The greater and greater genetic diversity represents a new profile of the illness and could be an impediment to current treatments and principally for the elaboration of a vaccine. Although the most precise impacts of this new scenario in Brazil are as yet unknown, it is possible to work with some analogues. At the start of the world epidemic, the main HIV subtype found in southeast Asia was the B subtype, which attacked, in the majority of cases, drug users.

In the middle of the 90s the circulating recombinant EA was detected in that region – the first in the world to be described – infecting homosexuals. Thanks to biological and adaptation advantages and for having already superceded the more rigorous processes of selection, the EA ended up sweeping away the B group, which currently is almost not found there. And, the recombinant AG, weaker, lost the dispute in Africa, to the C subtype. “The recombinants might not even prevail, but the fact that they appear with more and more frequency is frightening” insists Janine. “Involuntarily, we’re creating conditions for the HIV to amplify its genetic diversity.”

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