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Concentrated Risk

Nearly 60% of asymptomatic carriers of the Aids virus with resistance to drugs are in the city of São Paulo

cdcAnti-Aids drugs lose their efficacy if the HIV (in green) undergoes mutationscdc

A new nationwide survey has shown that the existence of HIV strains resistant to at least one of the drugs in the cocktail used to treat Aids is higher among asymptomatic virus carriers who live in the city of São Paulo than in other parts of the country. The survey analyzed the pathogen profile of a group of 387 patients from 13 cities- recently diagnosed patients or patients chronically infected by the virus – but who had not come into contact with the medications because they had not yet manifested symptoms of the disease – and found 22 individuals with the resistant HIV. Thirteen of these patients (59.1%) live in the capital city. “Statistically, this data on São Paulo is important,” says Marcelo Soares, from the Federal University of Rio de Janeiro/UFRJ, one of the coordinators of the study, published on the 18th of last month in the scientific journal AIDS Research and Human Retroviruses. The history of Aids in São Paulo is a long one. The first confirmed cases of the disease in Brazil, in the early 1980’s, were identified in São Paulo, and the city has the highest number of cases registered in the three decades since the outbreak of the epidemic: more than 71 thousand patients, not including thousands of asymptomatic carriers.

The other municipal regions did not report increased risks of infection by forms of HIV with genetic alterations that reduce the efficacy of the antiviral drugs, medications that hamper the multiplication of the virus in the organism. Strangely, the scientific study did not find any HIV strains resistant to the drugs in the cocktail in any of the 20 analyzed patients from the city of Santos. Ever since the outbreak of Aids in Brazil, this city on the São Paulo State coast is associated with an Aids epidemic and researchers had expected to detect a considerable number of resistant strains of the virus among asymptomatic carriers, in line with the results obtained from other surveys. “Perhaps the sample of patients that we focused on in the study is not entirely representative of the city of Santos,” says infectologist Eduardo Sprinz, from the Federal University of Rio Grande do Sul/UFRGS, the first author of the study.
The Brazilians who participated in this study – two-thirds of whom were men and one third were women, all over the age of 18, live in eight states and represent all of the country’s regions, with the exception of the North. Prepared by a national pool of researchers from 20 study centers, the study found that 5.7% of the group had resistant HIV, a proportion that is equal to the proportion verified in a similar survey reported in 2003. In North America and Europe, similar studies indicate that the percentage of individuals contaminated by the Aids virus with mutations associated with resistance to some drug in the cocktail is double or triple the percentage verified in Brazil.

Although they carry the virus in their blood, all the people who took part in this study are in good health and are not being medicated with the anti-Aids cocktail. Therefore, in the case of the 22 participants in the study who have strains of the virus with some level of resistance to the medication, it is possible to conclude that they may have been infected with forms of HIV already resistant to some drug in the cocktail. The resistance was not developed in their organisms. It was developed in the organisms of third parties, probably in contaminated patients with Aids symptoms undergoing anti-retroviral therapy, who had transmitted a mutated version of the virus to the referred participants.

Public health policy
Since the early 1990’s, Brazil’s Ministry of Health has maintained a policy of providing free treatment with anti-retroviral drugs only when HIV-positive patients manifest health problems related to the disease. Asymptomatic carriers do not get  free medication. This strategy has been praised internationally. Some developed countries have chosen to provide anti-retroviral medication to healthy HIV-positive individuals. The problem is that the prolonged use of anti-Aids medication can reduce the efficacy of certain drugs in some people, in addition to provoking side effects. In this case, one or two drugs that are part of the cocktail – usually a blend of drugs from three anti-retroviral classes – are prescribed in the following combination: two nucleoside inhibitors of reverse transcriptase and a non-nucleoside inhibitor of reverse transcriptase or a protease inhibitor. The reverse transcriptase and the protease are viral enzymes that are vital to the HIV’s replication process.

Nearly all the patients in the study with resistance to some drug of the cocktail (19 out of 22 cases) showed this resistance to drugs from only one anti-retroviral class (the reverse transcriptase inhibitors); two were resistant to drugs from two classes and only one individual was resistant to the drugs of all three classes. “We noticed an increase in the number of mutations that provoke the resistance to non nucleoside inhibitors of reverse transcriptase,” says Soares. “We know that, in this kind of medication, one or two mutations lead to this.” As only a few cases of resistance to multiple drugs have been reported and at present there are 19 kinds of medications available from the public health system to prepare the cocktail, it is usually possible to prescribe a personalized combined therapy by choosing the drugs to which the organism of each patient will respond accordingly.

Of the carriers of the virus with some kind of mutation, 91% (20 cases) had been contaminated with the subtype B of the HIV virus, the most common Aids virus in the country. Only 9% (2 cases) had been contaminated with the subtype C, which had come to Brazil more recently and is basically restricted to the South Region. Indirectly, data from the study also seems to confirm the suspicion voiced by some specialists: safe sex, with the use of condoms, is not the rule even in the case of HIV-positive couples.  Nearly half of the patients with HIV resistant to some antiretroviral drug admitted that his or her partner had Aids and was on medication. It is very likely that they acquired the mutated virus from their own partners.

Scientific article
SPRINZ, E. et al. Primary antiretroviral drug resistance among HIV Type 1-Infected Individuals in Brazil. AIDS Research and Human Retroviruses. Published on-line on August 18, 2009.