HIV-1 Diversity in Brazil: Genetic, Biologic, and Immunologic Characterization of HIV-1 Strains in Three Potential HIV Vaccine Evaluation Sites

Bongertz,; Bou-Habib, Dumith Chequer; Brigido, LF; Caseiro, Marcos Montani; Pj, Chequer; Couto-Fernandez, José Carlos; Pc, Ferreira; Galvão–Castro, Bernardo; Greco, Donato; Ml, Guimarães; Mi, Linhares; Masucci, Maria G.; Ca, Oliveira; Osmanov, Saladin; Ca, Ramos; Rossini, Marika; Sabino, Ester C.; Tanuri, Amílcar

doi:10.1097/00126334-200002010-00011

Cited by 55 publications

(31 citation statements)

References 36 publications

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“…HIV-1 diversity in this city is distinct from that observed in the major metropolitan areas (São Paulo and Rio de Janeiro), where clade B predominates and, apart from clade F, other subtypes are rarely identified (Bongertz et al 2000, Barreto et al 2006. The same is true in other regions of the country (Gadelha et al 2003, Cerqueira et al 2004, Stefani et al 2007) and elsewhere in South America (Hemellar et al 2004, Montano et al 2005, with the exception of Argentina, where BF recombinants predominate.…”

Section: Discussionmentioning

confidence: 73%

“…A study performed in Santos has reported the highest drug resistance rates in the country, with 37% among recent infections and 25% among chronic cases (Sucupira et al 2007). The predominant clade in Brazil is HIV-1 B, except in some areas in the south of the country, where clade C predominates (Bongertz et al 2000, Brindeiro et al 2003, Gadelha et al 2003, Cerqueira et al 2004 The use of the BED assay to estimate HIV incidence provides further insights into the understanding of HIV epidemic dynamics (Hall et al 2008). Along with a relatively well organised public health infrastructure, this epidemiological setting may represent an interesting environment to monitor the potential of clade C expansion in the epidemic and to study the impact of clades B and C on treatment and disease outcome.…”

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confidence: 99%

“…A study performed in Santos has reported the highest drug resistance rates in the country, with 37% among recent infections and 25% among chronic cases (Sucupira et al 2007). The predominant clade in Brazil is HIV-1 B, except in some areas in the south of the country, where clade C predominates (Bongertz et al 2000, Brindeiro et al 2003, Gadelha et al 2003, Cerqueira et al 2004, Barreto et al 2006, Rodrigues et al 2006, Stefani et al 2007). Moreover, different recombinant forms have been described in Brazil, including a BC mosaic, CRF31_BC (Santos et al 2006).…”

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confidence: 99%

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Molecular characterisation of newly identified HIV-1 infections in Curitiba, Brazil: preponderance of clade C among males with recent infections

Ferreira

Thomaz

Rodrigues

et al. 2008

Mem. Inst. Oswaldo Cruz

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The Research Capacity ProgramAs in many areas of Brazil, the AIDS epidemic in Curitiba is relatively stable, but surveillance is important to support public policy. The molecular characteristics of HIV may be instrumental for monitoring epidemic trends. We evaluated plasma HIV-1 RNA (n = 37) from 38 cases presenting with positive serology, who were among 820 consenting volunteers visiting the downtown counselling and serology testing centre. Seroprevalence was 4.6% 3) and the estimated HIV incidence, as defined by the BED assay, was 2.86 persons/years ). An additional set of contemporaneous, anonymous samples from a local laboratory was also analysed (n = 20) . Regions of the HIV-1 polymerase (n = 57) and envelope (n = 34) were evaluated for subtyping, determination of mosaic structure, primary drug resistance mutations (pDRM), envelope V3 loop motifs and amino acid signatures related to viral tropism. HIV-1 clade B was observed in 53% of cases; HIV-1C in 30% and BC mosaics in 14%, with one F genome and one CF mosaic. Clade C infection was associated with recent infections among males (p < 0.03). Stanford surveillance pDRM was observed in 8.8% of sequences, with 7% showing high level resistance to at least one antiretroviral drug. Tropism for CXCR4 co-receptor was predicted in 18% of envelope sequences, which were exclusively among clade B genomes and cases with serological reactivity to chronic infection.Key words: epidemiology -antiretroviral resistance -genetic diversity -HIV-1 -tropism -BrazilUnderstanding the local HIV-1 epidemic will not only support the regional response, but it may also provide information to nationwide efforts in the fight against AIDS. The variability of HIV-1 has been an obstacle to treatment and to the development of prevention innovations such as vaccines. HIV-1 clusters phylogenetically into distinct clades (subtypes), a fact that has helped to unravel the molecular characteristics of the epidemic. In some regions, differential distribution of HIV-1 clades has been documented (Van Harmelen et al. 1997, Tovanabutra 2001, Rios et al. 2005, Ryan et al. 2007) and phylogeny may indicate the source(s) of incoming variants (Sarker 2008). Worldwide, clade C is responsible for about half of the epidemic, whereas clade B is the major variant in industrialised nations (Hemelaar et al. 2006). HIV variability may influence the performance of laboratory tools for diagnostic, monitoring and surveillance (Koch et al. 2001 (Baeten et al. 2007, Kaleebu 2007 and transmission potential (Yang et al. 2003, John-Stewart et al. 2005 have been associated to distinct HIV clades, but the actual impact of genetic diversity in HIV disease still remains uncertain (Stebbing & Moyle 2003, Hemelaar et al. 2006, Tebit et al. 2007). However, some characteristics of HIV, such as tropism to either CCR5 or CXCR4 coreceptors, seem to be associated with a distinct pattern of disease progression (Shepherd et al. 2008). Another relevant issue is the identification of primary drug resistance mutations (pDRM) among untreate...

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Section: Discussionmentioning

confidence: 73%

mentioning

confidence: 99%

“…A study performed in Santos has reported the highest drug resistance rates in the country, with 37% among recent infections and 25% among chronic cases (Sucupira et al 2007). The predominant clade in Brazil is HIV-1 B, except in some areas in the south of the country, where clade C predominates (Bongertz et al 2000, Brindeiro et al 2003, Gadelha et al 2003, Cerqueira et al 2004, Barreto et al 2006, Rodrigues et al 2006, Stefani et al 2007). Moreover, different recombinant forms have been described in Brazil, including a BC mosaic, CRF31_BC (Santos et al 2006).…”

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confidence: 99%

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Molecular characterisation of newly identified HIV-1 infections in Curitiba, Brazil: preponderance of clade C among males with recent infections

Ferreira

Thomaz

Rodrigues

et al. 2008

Mem. Inst. Oswaldo Cruz

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“…For use in this study, viral stocks from two replication cycles in pre-activated normal human peripheral blood mononuclear cells (PHA-PBMC NHu, mixture of at least two donors) were pooled. First to third passage viral stocks of the primary HIV-1 isolates FT015 (subtype F, in this report called FT15), FT089 (subtype B, in this report called FT89), and third to fifth passage of 95BRRJ021 (subtype F, in this report called RJ21) and 95BRRJ020 (subtype B, in this report called RJ20) were also included (Bongertz et al 2000). At least three 3-fold plasma dilutions, using 1:10 as the first step, were used.…”

Section: Plasma Samplesmentioning

confidence: 99%

Anti-human immunodeficiency virus type 1 humoral immune response and highly active antiretroviral treatment

Bongertz

Ouverney

Fernandez

et al. 2007

Mem. Inst. Oswaldo Cruz

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Highly active antiretroviral treatment (HAART) of human immunodeficiency type 1 (HIV-1) infection is very effective in controlling infection, but elimination of viral infection has not been achieved as yet, and upon treatment interruption an immediate rebound of viremia is observed. A combination of HAART with an immune stimulation might allow treatment interruption without this rebounding viremia, as the very low viremias observed with successful HAART may be insufficient to permit maintenance of a specific anti-HIV-1 immune response. The objective of this study was to compare the humoral immune response of individuals undergoing successful HAART (NF=no failure) with that of individuals with evidence of failure of therapy (FT) and to verify if the viremia peaks observed in individuals with therapy failure would act as a specific stimulus for the humoral anti-HIV-1 immune response. Antibodies binding to gp120 V3 genotype consensus peptides were more frequently observed for FT, mainly against peptides corresponding to sequences of genotypes prevalent in the Rio de Janeiro city area, B and F. HIV-1 neutralization of HIV-1 IIIB and of four primary isolates from Rio de Janeiro was less frequently observed for plasma from the NF than the FT group, but this difference was more expressive when plasma from individuals with detectable viremia were compared to that of individuals with undetectable viral loads in the year before sample collection. Although statistically significant differences were observed only in some specific comparisons, the study indicates that presence of detectable viremia may contribute to the maintenance of a specific anti-HIV-1 humoral immune response.Key words: antibodies -seroreactivity -neutralization -antiretroviral treatment -treatment failure Anti-HIV highly active antiretroviral treatment (HAART) reduces HIV in peripheral blood and reverts the characteristic immunodeficiency, and has benefited patients increasing individual survival at least 13-14 years (Vermund et al. 2006). However, no elimination of viral infection has been achieved, and the antiretroviral drugs will probably have to be taken throughout the life of the patient. Attempts to stimulate a potent specific anti-HIV-1 immune response to permit control of viral replication. After HAART has reduced viremia to undetectable levels, have so far been less than successful. During successful HAART, a decline in antibody response is generally observed (Fournier et al. 2002, Devito et al. 2006, with cases of seroreversion being described (Amor et al. 2006) and the extent of immune reconstitution in HAART treated individuals is controversial, apparently depending on the immune status of the individuals at the start of therapy (Cheonis et al. 2005). However, the benefits of HAART are evident even when treatment apparently fails, leading neither to a complete control of viremia nor to a complete reconstitution in CD4 T lymphocytes (Brígido et al. 2004, Kovacs et al. 2005).During successful anti-HIV therapy, a reduction in virus specific ce...

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“…However, 100% neutralization of the HIV-1 iso- late 95BRRJ021 was much more frequently observed for plasma from the S group (15/ 23, 65%) than for plasma from the IDU group (15/47, 32%; P = 0.0108) at 1:10 plasma dilution. The high susceptibility of the primary F genotype isolate 95BRRJ021 has been previously described, and motivated the choice of this isolate in the present study (13). This high susceptibility of the F genotype primary isolate agreed with the higher neutralizing ability of F plasma, both for plasma from the IDU group (8/35 B plasma vs 6/10 F plasma neutralized the 95BRRJ021 HIV-1 isolate, P = 0.0488) and the total F versus B genotype plasmas used for neutralization of this isolate (17/52 B vs 11/15 F, P = 0.0073).…”

Section: Neutralizationmentioning

confidence: 92%

HIV-1 binding and neutralizing antibodies of injecting drug users

Ouverney

Teixeira

Jesus

et al. 2005

Braz J Med Biol Res

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Previous studies have demonstrated a stronger seroreactivity against some synthetic peptides responsible for inducing neutralizing antibodies in injecting drug users (IDU) compared to that of individuals sexually infected with HIV-1 (S), but the effectiveness in terms of the neutralizing ability of these antibodies has not been evaluated. Our objective was to study the humoral immune response of IDU by determining the specificity of their antibodies and the presence of neutralizing antibodies. The neutralization capacity against the HIV-1 isolate MN (genotype B), the primary HIV-1 isolate 95BRRJ021 (genotype F), and the seroreactivity with peptides known to induce neutralizing antibodies, from the V2 and V3 loops of different HIV-1 subtypes, were analyzed. Seroreactivity indicates that IDU plasma are more likely to recognize a broader range of peptides than S plasma, with significantly higher titers, especially of V3 peptides. Similar neutralization frequencies of the MN isolate were observed in plasma of the IDU (16/47) and S (20/60) groups in the 1:10 dilution. The neutralization of the 95BRRJ021 isolate was more frequently observed for plasma from the S group (15/23) than from the IDU group (15/47, P = 0.0108). No correlation between neutralization and seroreactivity with the peptides tested was observed. These results suggest that an important factor responsible for the extensive and broad humoral immune response observed in IDU is their infection route. There was very little difference in neutralizing antibody response between the IDU and S groups despite their differences in seroreactivity and health status.

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HIV-1 Diversity in Brazil: Genetic, Biologic, and Immunologic Characterization of HIV-1 Strains in Three Potential HIV Vaccine Evaluation Sites

Cited by 55 publications

References 36 publications

Molecular characterisation of newly identified HIV-1 infections in Curitiba, Brazil: preponderance of clade C among males with recent infections

Molecular characterisation of newly identified HIV-1 infections in Curitiba, Brazil: preponderance of clade C among males with recent infections

Anti-human immunodeficiency virus type 1 humoral immune response and highly active antiretroviral treatment

HIV-1 binding and neutralizing antibodies of injecting drug users

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