Study indicates that HIV has genetic diversity in São Paulo

Brazilian research teams evaluated blood samples from 51 HIV+ children and adolescents and found an unexpected rate of recombinant subtypes of the virus that causes AIDS.

By Karina Toledo

Agência FAPESP – On analyzing blood samples from 51 HIV+ children and adolescents born between 1992 and 2009, researchers from Universidade de São Paulo (USP) and Universidade Federal de São Paulo (UNIFESP) observed greater genetic variability in the HIV virus than had been indicated by previous studies in adults.

According to scientists, the results of the investigation – detailed in the article Variability of HIV-1 Genomes among Children and Adolescents from São Paulo, Brazil – suggest that the profile of the epidemic in Brazil is changing, which could have implications for both the production of diagnostic tests and research focused on vaccine development.

“There are two types of the virus that cause AIDS, HIV-1 and HIV-2. Type 2 is essentially restricted to the African continent. Type 1, which is prevalent in the rest of the world, is split into several groups, with M, N, O and P as the main groups. The M group is causing the major epidemic, but it is also divided into different subtypes. There are also recombinant forms of the virus, which are a mixture of two subtypes,” explained Esper Kallás, professor at the Immunology and Allergy Clinics at USP Medical School and one of the authors of the FAPESP-funded study.

According to Kallás, previous studies showed that subtype B is the most prevalent in Brazil and throughout America and Europe. Indeed, in a 2011 article published by the same group in PLoS One, the researchers analyzed 113 samples from HIV+ men with an average age of 31. The analysis of the viral DNA showed that more than 80% of the patients were infected with subtype B.

However, in this recent study, conducted in patients aged 4 to 20 who were monitored at the Center for Pediatric Infection at UNIFESP, which was coordinated by Professor Regina Succi, only 52.4% of patients presented subtype B. Almost 40% of the youth were infected with subtype BF1 mosaic (a genetic mixture of the B and F1 subtypes), and another 9.5% presented the F1 subtype. All cases were the result of vertical transmission of the virus: i.e., infection during gestation, labor or breast-feeding.

“As these children typically contracted the virus more recently than the adults, roughly 11 years ago on average, our hypothesis is that the viruses circulating in Brazil are increasing in genetic diversity. This is a snapshot of the transmission that occurred more than a decade ago. Today, the variability could be even greater,” stated Kallás. According to Sabri Saeed Mohamed Ahmed Al Sanabani, a researcher at USP’s Tropical Medicine Institute and the first author of the article, previous studies have also indicated a high prevalence of the F1 subtype in Brazil; however, this subtype has since become much less common.

“Previous researchers sequenced only a segment of the virus, which could be pure [i.e., derived from a single subtype]. However, when we completely sequenced the viral genome, we found high recombination rates with subtype B. This is the situation in Brazil,” commented Sanabani, who also coordinates another FAPESP-funded study.

For Sanabani, this type of monitoring is important for understanding how HIV is evolving. “A change in the epidemic profile has been found in other countries. For example, subtype B was more prevalent in South Africa, but now subtype C is more prevalent. This knowledge is fundamental for adapting molecular diagnostic tests of the disease. If the virus is changing, the tests must be capable of also detecting these viral mixtures,” Sanabani affirmed.

Knowledge of the prevalent subtypes is essential for research focused on developing an AIDS vaccine. The bad news, according to Kallás, is that the increase in genetic variability of HIV-1 could make it even more difficult to create an effective immunogen.

Viral recombination

According to the researchers, the increase in HIV genetic variability can be explained by two main factors. The first is the constant battle with the immunological system of the host, which exerts pressure on the virus to mutate to escape attack.

The second factor is the occurrence of mixed infections. “In the same exposure, a person could, for example, contract subtypes B and F. But it is also common for a person infected by a viral subtype to have another exposure and contract a different subtype of the virus and for recombination to occur inside the patient,” explained Kallás.

Condom use between HIV+ partners is fundamental for preventing mixed infections and also for preventing the acquisition of a viral form that is more resistant to the medicines in use today, said the infectious diseases specialist.

The article Variability of HIV-1 Genomes among Children and Adolescents from São Paulo, Brazil (doi:10.1371/journal.pone.0062552) can be read at www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0062552.

The article Characterization of Partial and Near Full-Length Genomes of HIV-1 Strains Sampled from Recently Infected Individuals in São Paulo, Brazil (doi:10.1371/journal.pone.0025869) can be read at www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0025869&representation=PDF.