RESUMO
This paper describes genetic subtypes of HIV-1 found in blood samples from 31 HIV-1-infected people who visited the Counseling and Testing AIDS Center of Instituto de Medicina Tropical in Manaus, Brazil. Manaus, the main city in Brazil's Amazon Basin, is also the closest urban connection for more than 100,000 Indians living in the rain forests of this region. Although to date there is no evidence of increased incidence of HIV-1 infection among the indigenous population, our understanding of both the prevalence and nature of the epidemic in the region as a whole is limited. From the 31 samples analyzed by C2V3 sequencing, we found almost equal proportions of HIV-1 strains belonging to subtype B (n = 16; 51.6%) and subtype F (n = 15; 48.4%), a finding that differs from results from previous studies conducted in urban areas of southeastern Brazil. We also observed the presence of the GWGR amino-acid sequence in the critical tetra-peptide crown of the env V3 loop in the HIV-1 subtype B samples analyzed. Among these samples, we also found 14 mosaic genomes (45.16%) in which different combinations of subtypes B, C, and F were identified between the p24 gag, pro, and env regions. Our data support the hypothesis that the Amazonian HIV-1 infections linked to the urban epidemic in southeastern Brazil. The genetic diversity and the prevalence of mosaic genomes among the isolates in our study confirm an integral role of recombination in the complex Brazilian epidemic.
Assuntos
Surtos de Doenças , Infecções por HIV/epidemiologia , HIV-1/classificação , HIV-1/genética , Recombinação Genética , Adulto , Brasil/epidemiologia , DNA Viral/análise , Feminino , Produtos do Gene pol/genética , Proteína do Núcleo p24 do HIV/genética , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/virologia , Protease de HIV/genética , HIV-1/isolamento & purificação , Humanos , Indígenas Sul-Americanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Fragmentos de Peptídeos/genética , Filogenia , Reação em Cadeia da Polimerase , Análise de Sequência de DNARESUMO
We systematically evaluated multiple and recombinant infections in an HIV-infected population selected for vaccine trials. Seventy-nine HIV-1 infected persons in a clinical cohort study in Rio de Janeiro, Brazil, were evaluated for 1 year. A combination of molecular screening assays and DNA sequencing showed 3 dual infections (3.8%), 6 recombinant infections (7.6%), and 70 (88.6%) infections involving single viral subtypes. In the three dual infections, we identified HIV-1 subtypes F and B, F and D, and B and D; in contrast, the single and recombinant infections involved only HIV-1 subtypes B and F. The recombinants had five distinct B/F mosaic patterns: Bgag-p17/Bgag-p24/Fpol/Benv, Fgag-p17/Bgag-p24/Fpol/Fenv, Bgag-p17/B-Fgag-p24/Fpol/Fenv, Bgag-p17/B-Fgag-p24/Fpol/Benv, and Fgag-p17/B-Fgag-p24/Fpol/Fenv. No association was found between dual or recombinant infections and demographic or clinical variables. These findings indicate that dual and recombinant infections are emerging as an integral part of the HIV/AIDS epidemic in Brazil and emphasize the heterogenous character of epidemics emerging in countries where multiple viral subtypes coexist.
Assuntos
Infecções por HIV/virologia , HIV-1/genética , Recombinação Genética/genética , Adulto , Sequência de Bases , Brasil/epidemiologia , Clonagem Molecular , Estudos de Coortes , DNA Viral/análise , Surtos de Doenças , Feminino , Produtos do Gene env/genética , Produtos do Gene gag/genética , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Protease de HIV/genética , HIV-1/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Filogenia , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Estudos Prospectivos , Sensibilidade e Especificidade , Análise de Sequência de DNARESUMO
The genetic variation of the human immunodeficiency virus type 1 (HIV-1) protease gene (prt) permits the classification of HIV-1 strains into five distinct protease subtypes, which follow the gag subtyping patterns. The susceptibilities of non-B-subtype strains to protease inhibitors (PIs) and other antiretroviral drugs remain largely unknown. Subtype F is the main non-B strain contributing to the Brazilian epidemic, accounting for 15 to 20% of these infections. In this work, we report the findings on 81 isolates from PI-naive Brazilian patients collected between 1993 and 1997. In addition, the relevant PI resistance mutations and their phenotypes were determined in vitro for 15 of these patients (B = 9 and F = 6). Among these, the subtype F samples evidenced high sensitivities in vitro to ritonavir and indinavir, with MICs at which 50 and 90% of the isolates are inhibited similar to those of both the Brazilian and the U.S. subtype B isolates. Analysis of the 81 Brazilian prt sequences demonstrated that the subtype F consensus sequence differs from the U.S. and Brazilian subtype B consensus in eight positions (I15V, E35D, M36I, R41K, R57K, Q61N, L63P, and L89M). The frequency of critical PI resistance substitutions (amino acid changes D30N, V82A/F/T, I84V, N88D, and L90M) among Brazilian isolates is very low (mean, 2.5%), and the associated secondary substitutions (amino acid positions 10L, 20K, 36M, 46M, 48G, 54I, 63P, 71A, and 77A) are infrequent. These observations document the relative rarity of resistance to PIs in the treatment of patients infected with HIV-1 subtype F in South America.
Assuntos
Fármacos Anti-HIV/farmacologia , Variação Genética , Infecções por HIV/virologia , Inibidores da Protease de HIV/farmacologia , Protease de HIV/genética , HIV-1/efeitos dos fármacos , Indinavir/farmacologia , Saquinavir/farmacologia , Sequência de Aminoácidos , Brasil , DNA Viral/análise , Genótipo , Infecções por HIV/tratamento farmacológico , HIV-1/classificação , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Filogenia , Homologia de Sequência de AminoácidosRESUMO
This article describes a case of horizontal (heterosexual) and subsequent vertical (mother to infant) transmission of 2 human immunodeficiency viruses type 1 (HIV-1) subtypes. Dual infection in a husband, his wife, and their child was initially detected by use of a restriction fragment length polymorphism assay of the proviral protease in peripheral blood mononuclear cells. The simultaneous presence of highly similar sets of HIV-1 subtypes B and C infecting the 3 family members was confirmed by DNA sequence analysis of pol, gag, and env genes. These data, together with available epidemiologic information, may indicate that the husband's high-risk sexual behavior was the source of dual infections. Because his wife did not report such activities, it was likely that he passed HIV-1 strains to his spouse, who subsequently transmitted them to their child.