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Genetics

Tolerance to the cocktail

One third of those infected with HIV in São Paulo show some resistance to the anti-Aids drugs

Preliminary data from a study on four hundred and sixty people in the state of São Paulo infected with the HIV virus, which causes AIDS, indicates that 37% of these patients are showing total or partial resistance to the action of at least one of the medicines of the chemical cocktail used to fight the disease. It is a rate a little higher than that found in other surveys in the state or in the country, but, to a certain extent, was expected. Since the middle of the 90s, Brazil has adopted a policy of free distribution of the medicines used against Aids for those people infected with HIV. The problem is that the continual use of medicines against the illness, over a long period of time, decreases the effectiveness of certain drugs in some people. When this happens, one or more of the medicines in the cocktail is changed, the composition in general being made up of three anti-retroviruses: a nucleoside reverse transcriptase inhibitor (NRTI), a non-nucleoside reverse transcriptase inhibitor (NNRTI) and a protease inhibitor (PI).

The researchers believe that, in the majority of cases, the decrease in the effects of the drugs is come from the prolonged exposure to chemical treatment. The idea makes sense: among the patients with loss of effect of some anti-retroviral, 92% had been using or had already used anti-HIV drugs. “The remaining 8% had never before taken any medicine against the disease”, comments the virologist Paolo Zanotto, from the Biomedical Sciences Institute of the University of São Paulo (ICB/USP), one of the study’s coordinators, carried out under the umbrella of the Genetic Virus Diversity Network (VGDN), a program funded by FAPESP. From 1980 until the end of 2004, Brazil had counted up around 360,000 notified cases of Aids, of which almost 40% had been detected among the São Paulo population.

The individuals of the study’s initial sample, in more or less equal numbers from the four cities in the state: São Paulo, Ribeirão Preto, São Vicente and Araçatuba (shortly, more data from these four cities and a further six hundred (600) patients from four other localities in the state will be added to the study). “We didn’t select a particular profile of the patient to enter into the survey”, says the medical doctor Leda Jamal, from the Reference and Sexually Transmitted Diseases/Aids Training Center, linked to the state’s Secretary of Health, which coordinated part of the field study.

“Everyone was chosen at random.” We arranged the sample of those infected with the virus, with or without the illness’s symptoms, and if they had or had not started to take the cocktail of medicines, from those who had sought out the CRT/Aids units installed in the four cities. For the clinical analysis, which determined the presence of resistance towards the medicine cocktail through the form and number of viruses circulating in the organism, the study patients gave 10 ml of blood. From this material, the researchers in the area of molecular biology made copies of the virus found in the patients and sequenced regions of the genome of the pathogen that permitted a determination of its subtype and to find mutations that create resistance to the medicines of the cocktail.

According to the results, 83.3% of the patients analyzed carried within their organism the Aids virus of subtype B, the most common in the Western World and in Brazil. Only 2.6% had subtype F, which is relatively rare, and 1.5% that of C, the most common in East Africa, India and Nepal. A little over 12% presented recombinant strains of HIV, hybrid forms, composed of parts of two or more subtypes of the virus. The most common of these was the recombinant BF, present in 9.2% of the study’s participants. Next came the recombinant strains of BD (3.3%) and BA (0.2%).

More than 70% of those carrying the hybrid BD showed resistance to some medication within the anti-Aids cocktail, by far the highest percentage amongst all of the identified subtypes in the study. “Subtypes BF and BD are commonly found in port zones, where a large diversity of circulating virus types exist”, explains Zanotto. Such a particularity explains the flagrant discrepancy between the data on the patients from São Vicente, next to the Santos port, where there are multiple forms of the virus circulating, and those of the other three cities. In the city, 28% of the samples contained recombinant subtypes of HIV. In the interior city of Araçatuba, this index was less than 4%; in the capital, São Paulo, around 7%; and in Ribeirão Preto, a little more than 11%.

Aids in prison
The VGDN researchers also verified the existence of a large variety of subtypes of HIV among the one hundred and sixty-seven male inmates with Aids who are treated at the State Penitentiary Hospital, in the city of São Paulo. “In prison, the virus diversity was very high, comparable to that of Sao Vicente”, says the epidemiologist Eduardo Massad, from USP’s Medical School, who heads up the study with the prisoners. Since they gather together people from various regions of the state and the country, prisons are the depositories of the most diverse forms of HIV and of other viruses.

If the myriad of the HIV subtypes present amongst the prisoners is a worrying piece of data, the verification that the prevalence of Aids has diminished in the state’s male prison population serves as a positive counterbalance. In 2001 the USP epidemiologist carried out examinations on 1,022 detainees at the recently demolished Carandiru prison and concluded that only 4.9% of the individuals examined had HIV. In 2003 they had carried out a similar study, with 1,023 prisoners at the Provisional Detention Center of Osasco, in Greater São Paulo. The result had been even lower: 2.1% had the Aid’s virus.

According to Massad, today fewer prisoners are infected than during the period 1980/1990, when some studies pointed to the prevalence of up to 15% HIV infection among the detainees. The fall in the number of infected cases is probably due to the fact that inmates quit a habit that was the main vector of the epidemic amongst the prison population: the sharing of syringes for drug injections.  “Now crack is the drug most widely used by the prisoners”, says Massad. Since it is smoked, crack does not transmit Aids. Among the female prisoners, nevertheless, the levels of HIV infection continue high. The work of an USP team has registered the prevalence of 14% of the virus amongst two hundred and sixty seven (267) detainees from the women’s State Penitentiary in the State of São Paulo. “They contract the disease through their partners, on having unprotected sex, and not through the use of injected drugs”, says Massad.

The Project
Viral Genetic Diversity Network (VGDN); Modality Special programs;
Coordinators Eduardo Massad – Medical Faculty of USP – and Edison Durigon and Paolo Zanotto – ICB of USP; Investment R$ 6,687,937.23 and US$ 1,674,373.74 (FAPESP)

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