5 research outputs found
Analysis of the CCR5 gene coding region diversity in five South American populations reveals two new non-synonymous alleles in Amerindians and high CCR5*D32 frequency in Euro-Brazilians
The CC chemokine receptor 5 (CCR5) molecule is an important co-receptor for HIV. The effect of the CCR5*D32 allele in susceptibility to HIV infection and AIDS disease is well known. Other alleles than CCR5*D32 have not been analysed before, neither in Amerindians nor in the majority of the populations all over the world. We investigated the distribution of the CCR5 coding region alleles in South Brazil and noticed a high CCR5*D32 frequency in the Euro-Brazilian population of the Paraná State (9.3%), which is the highest thus far reported for Latin America. The D32 frequency is even higher among the Euro-Brazilian Mennonites (14.2%). This allele is uncommon in Afro-Brazilians (2.0%), rare in the Guarani Amerindians (0.4%) and absent in the Kaingang Amerindians and the Oriental-Brazilians. R223Q is common in the Oriental-Brazilians (7.7%) and R60S in the Afro-Brazilians (5.0%). A29S and L55Q present an impaired response to β-chemokines and occurred in Afro- and Euro-Brazilians with cumulative frequencies of 4.4% and 2.7%, respectively. Two new non-synonymous alleles were found in Amerindians: C323F (g.3729G > T) in Guarani (1.4%) and Y68C (g.2964A > G) in Kaingang (10.3%). The functional characteristics of these alleles should be defined and considered in epidemiological investigations about HIV-1 infection and AIDS incidence in Amerindian populations
Faster HIV-1 Disease Progression among Brazilian Individuals Recently Infected with CXCR4-Utilizing Strains
Introduction: Primary HIV infection is usually caused by R5 viruses, and there is an association between the emergence of CCXR4-utilizing strains and faster disease progression. We characterized HIV-1 from a cohort of recently infected individuals in Brazil, predicted the virus's co-receptor use based on the env genotype and attempted to correlate virus profiles with disease progression. Methods: A total of 72 recently infected HIV patients were recruited based on the Serologic Testing Algorithm for Recent HIV Seroconversion and were followed every three to four months for up to 78 weeks. The HIV-1 V3 region was characterized by sequencing nine to twelve weeks after enrollment. Disease progression was characterized by CD4+ T-cell count decline to levels consistently below 350 cells/mu L. Results: Twelve out of 72 individuals (17%) were predicted to harbor CXCR4-utilizing strains; a baseline CD4,350 was more frequent among these individuals (p = 0.03). Fifty-seven individuals that were predicted to have CCR5-utilizing viruses and 10 individuals having CXCR4-utilizing strains presented with baseline CD4.350; after 78 weeks, 33 individuals with CCR5 strains and one individual with CXCR4 strains had CD4.350 (p = 0.001). There was no association between CD4 decline and demographic characteristics or HIV-1 subtype. Conclusions: Our findings confirm the presence of strains with higher in vitro pathogenicity during early HIV infection, suggesting that even among recently infected individuals, rapid progression may be a consequence of the early emergence of CXCR4-utilizing strains. Characterizing the HIV-1 V3 region by sequencing may be useful in predicting disease progression and guiding treatment initiation decisions.Brazilian Program for STD and AIDSBrazilian Program for STD and AIDSMinistry of Health [914/BRA/3014-UNESCO/Kallas]Ministry of HealthSao Paulo City Health DepartmentSao Paulo City Health Department [2004-0.168.922-7/Kallas]Fundacao de Amparo a Pesquisa do Estado de Sao PauloFundacao de Amparo a Pesquisa do Estado de Sao Paulo [04/15856-9/Diaz]Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)Brazilian Ministry of EducationBrazilian Ministry of Educatio
Antiretroviral resistance in individuals presenting therapeutic failure and subtypes of the human immunodeficiency virus type 1 in the Northeast Region of Brazil
This study aimed to analyze human immunodeficiency virus (HIV) mutation
profiles related to antiretroviral resistance following therapeutic
failure, and the distribution of hiv subtypes in the Northeast Region
of Brazil. A total of 576 blood samples from AIDS patients presenting
therapeutic failure between 2002 and 2004 were analyzed. The genotyping
kit viroSeq® was used to perform viral amplification in order to
identify mutations related to hiv pol gene resistance. An index of
91.1% of the patients presented mutations for nucleoside reverse
transcriptase inhibitors (nrti), 58.7% for non-nucleoside reverse
transcriptase inhibitors (nnrti), and 94.8% for protease inhibitors
(pi). The most prevalent mutations were 184V and 215E for nrti, 103N
and 190A for nnrti. Most mutations associated with PIs were secondary,
but significant frequencies were observed in codons 90 (25.2%), 82
(21.1%), and 30 (16.2%). The resistance index to one class of
antiretrovirals was 14%, to two classes of antiretrovirals 61%, and to
three classes 18.9%. Subtype B was the most prevalent (82.4%) followed
by subtype F (11.8%). The prevalence of mutations related to nrti and
nnrti was the same in the two subtypes, but codon analysis related to
PI showed a higher frequency of mutations in codon 63 in subtype B and
in codon 36 in subtype F. The present study showed that there was a
high frequency of primary mutations, which offered resistance to nrti
and nnrti. Monitoring patients with treatment failure is an important
tool for aiding physicians in rescue therapy