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Biomedical subjects

Marcelo A Soares

Publications and source records attributed to Marcelo A Soares.

21 records · Page 2Linked to original sources

A specific subtype C of human immunodeficiency virus type 1 circulates in Brazil.

OBJECTIVE: To characterize the subtype C strains of HIV type 1 that circulate in Brazil, especially those originated from the southern part of the country. DESIGN AND METHODS: One hundred and twelve HIV-1-positive subjects had their plasma viral RNA extracted. Protease (PR) and reverse transcriptase (RT) genomic regions were polymerase chain reaction-amplified and sequenced for subtype determination. Subtype C strains were selected and compared to other strains of this subtype from the database, and specific amino acid signature patterns were searched. RESULTS: Brazilian subtype C viruses form a very strong monophyletic group when compared to subtype C viruses from other countries and presented specific signature amino acids. Recombinants between subtype C and B viruses have been documented in areas of co-circulation. The incidence of primary PR and RT inhibitor resistance mutations in drug-naïve subjects was observed. An increasing number of secondary resistance mutations was also seen, some of which are characteristic of subtype C-related sequences. CONCLUSIONS: Introduction of subtype C of HIV-1 in Brazil was likely a single event of one or a mixture of similarly related strains. Recombination between subtype C and B viruses is an ongoing process in the country. Primary and secondary drug resistance mutations were observed, although some of the secondary mutations could be associated with subtype C molecular signatures. Subtype-specific polymorphisms of PR and RT sequences found in this subtype C Brazilian variant might influence this emergence and have an impact on HIV treatment and on vaccine development in the country.

Adolescent↗

In vitro hypersusceptibility of human immunodeficiency virus type 1 subtype C protease to lopinavir.

In order to characterize the impact of genetic polymorphisms on the susceptibility of subtype C strains of human immunodeficiency virus type 1 to protease inhibitors (PIs), a subtype B protease that originated from an infectious clone was modified through site-directed mutagenesis to include the amino acid residue signatures of subtype C viruses (I15V, M36I, R41K, H69K, L89 M) with (clone C6) or without (clone C5) an I93L polymorphism present as a molecular signature of the worldwide subtype C protease. Their susceptibilities to commercially available PIs were measured by a recombinant virus phenotyping assay. We could not detect any differences in the 50% inhibitory concentration (IC(50)s) of amprenavir, indinavir, ritonavir, saquinavir, and nelfinavir for the clones analyzed. However, we did observe hypersusceptibility to lopinavir solely in clone C6, which includes the I93L substitution (a 2.6-fold decrease in the IC(50) compared to that for the subtype B reference strain). The same phenotypic behavior was observed for 11 Brazilian and South African clinical isolates tested, in which only subtype C isolates carrying the I93L mutation presented significant hypersusceptibility to lopinavir.

Amino Acid Sequence↗

Prevalence of protease and reverse transcriptase drug resistance mutations over time in drug-naïve human immunodeficiency virus type 1-positive individuals in Rio de Janeiro, Brazil.

The prevalence of mutations that confer resistance to protease inhibitors and to nucleoside and nonnucleoside reverse transcriptase inhibitors in 49 blood samples from drug-naïve human immunodeficiency virus type 1-infected blood donors living in Rio de Janeiro state, Brazil, in 1998 was evaluated genotypically and phenotypically.

Amino Acid Substitution↗