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virology

Subtle Change

Slowly, a subtype of the Aids virus, rather uncommon in the country, is spreading and altering the profile of the epidemic

MIGUEL BOYAYANThere is no longer any doubt. The epidemic caused by the Aids virus is undergoing a transformation in Brazil, where 140,000 persons are HIV carriers. Its former profile – called western, because of the predominance of a variety of the virus common in the Americas and in Western Europe, the HIV-1 of the subtype B – has been taking on, in the last few years, characteristics more and more similar to those to be seen in China, in India and in the African nations located to the south of the Sahara. In these countries, 83% of the 30 million carriers of the virus carry in their blood the subtype C, one of the nine varieties so far identified.

For some unknown reason, subtype C has come to dominate the epidemic as well in regions where, before, other variations of the HIV accounted for the majority of the cases of infection. The difference between one variety and another may lie in the ability of the virus to survive the medicines used against the infection. Almost everything that is known about the resistance of the HIV results from researches carried out with the B variety, and the effectiveness of the medicines against the other strains of the virus has still not been proved. For this reason, the change in the profile of the Brazilian epidemic may call for adjustments in the treatment and in the composition of the anti-HIV vaccines under development.

The first evidence of this changed appeared in the southern region, where in 1990 the first case caused by subtype C was recorded. Isolated studies pointed to a growing presence of this HIV variant in the region in the last five years. But the most forthright data arose last year, with the conclusion of the first nationwide survey of the resistance of the virus to medicines, carried out by the seven laboratories of the Ministry of Health’s Surveillance Network for HIV Resistance (Revire).

According to the results – published in Pesquisa Fapesp in August 2002 and published in June 2003 in the Aids magazine –, subtype C has overtaken the presence of B in the state of Rio Grande do Sul, appearing in 45% of the infections. In the rest of the country, subtype B is still the predominant strain, but it has been putting itself in a more discreet position. One third of HIV carriers in Paraná have in their blood the C variety of the virus. There are also indications that the presence of this strain is increasing in the southeast. Today, 6% of the carriers of the virus have HIV subtype C in Rio de Janeiro, while this strain contaminates 3% of the people with the virus in São Paulo.

These conclusions resulted from the research coordinated by Marcelo Soares and Amilcar Tanuri, both from the Molecular Virology Laboratory of the Federal University of Rio de Janeiro (UFRJ), one of the centers that make up Revire. In partnership with other teams from Rio, from São Paulo, and from the Ministry of Health, the researchers from UFRJ assessed the genetic material of the HIV that had contaminated 112 people from five states – Rio Grande do Sul, Paraná, São Paulo, Rio, and Mato Grosso do Sul.

The result, disclosed in January 2003 in the Aids magazine, showed that an average of one in three carriers of the virus in the southern and southeastern regions were now showing subtype C in their blood. Soares and Tanuri also saw that although the profile of the Brazilian epidemic is drawing closer to the profile to be seen in Africa and India, the HIV subtype C found in Brazil shows characteristics that are different from the African and Indian subtype C.

More recently, the researchers from UFRJ turned their attention to the capital of Rio Grande do Sul, to see how infection by HIV had evolved in the course of 18 years, looking for a probable indication of what may happen in the rest of the country. Soares and Tanuri collected blood samples from 77 HIV carriers attended to at the Porto Alegre Hospital and Clinics, the largest center for treating Aids in the state.

Following the analysis of the genetic material of the virus, they found that the proportion of the cases caused by subtype C went up from 20%, between 1986 and 1990, to 43%, between 2001 and 2002, as the researchers reported in the Journal of Acquired Immune Deficiency Syndromes of last December. According to Soares, this is a tendency that can be extrapolated for the whole of the state. In another study, carried out on 72 HIV carrier pregnant women from the city of Rio Grande in the state of Rio Grande do Sul, the virologist from Rio found that subtype C was responsible for 70% of the infections. “There is still no formal evidence that subtype C is disseminated more quickly than the others”, explains Soares, “but whenever this variety appears in a region, it ends up predominating over the others.”

The most immediate consequences of this alteration should appear in the treatment of the carriers of the virus. In another study, published in September last year in Antimicrobial Agents Chemotherapy, Soares’s team analyzed the genetic material of the B and C varieties, looking for alterations that might indicate resistance to the three classes of medicines used in highly active antiretroviral therapy (Haart), better known as the anti-HIV cocktail. The researchers noted that the C variety is more sensitive than B to lopinavir – a specific kind of protease inhibitor, a medicine that prevents new copies of the virus from maturing and infecting other defense cells.

With this data, it is becoming possible to outline new strategies for combating HIV. “Perhaps it may be more effective to include lopinavir in the treatment of the carriers of subtype C”, Soares ponders. It is an alternative to be considered, since the studies about the capacity for contaminating, the aggressiveness or resistance of the HIV to medicines are generally carried out in developed countries and only take subtype B into account.

As the distribution of medicine against the virus is free of charge – which makes the medicines available to all the carriers of HIV –, Rio Grande do Sul has become the state most indicated to assess the modifications observed in subtype C during the treatment, and also for testing vaccines of interest to poor or developing countries. In the next stage of the work, Soares intends to verify the effectiveness of lopinavir in people with the virus. In a study planned in partnership with the Porto Alegre City Hall, Soares is seeking to assess how carriers of subtypes B and C react to the treatment with lopinavir associated with two reverse transcriptase inhibitors. The study should begin this half year and last for two years.

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