Sequence Diversity of the Reverse Transcriptase of Human Immunodeficiency Virus Type 1 from Untreated Brazilian Individuals

Brindeiro, Rodrigo M.; Vanderborght, Bart; Caride, Elena; Correa, Letícia; Oravec, Rejane Maria; Berro, O. J.; Stuyver, Lieven; Tanuri, Amílcar

doi:10.1128/aac.43.7.1674

Cited by 53 publications

(24 citation statements)

References 21 publications

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“…Although lower overall prevalence of antiretroviral resistance has been previously reported in Brazil, 88 we should delineate high-risk and low-risk areas in order to analyze each separately. It is also of note that HIV-1 B/F recombinant strains have been fixed and expanded in this population.…”

Section: Discussionmentioning

confidence: 99%

“…91 In at least one Brazilian-based cross-sectional study of untreated individuals, possibly natural polymorphisms were found in nonsubtype B viruses, potentially affecting the response to nucleoside analogues. 88 To date, however, no prospective investigation of subtype B versus non-subtype B treatment responses, measuring potential confounding factors such as disease stage and medication adherence, has been performed.…”

Section: Discussionmentioning

confidence: 99%

“…86 Theoretically, these natural polymorphisms may have an impact on the response to medications developed for subtype B virus. 5,[87][88][89] In fact, in a clinical study of indinavir, treatment-naïve individuals infected with subtype F presented poorer virologic responses than did individuals infected with subtype B. 77 Although multiple unmeasured confounding variables may have contributed to this differential response, the presence of different amino acids in the protease (e.g., L89M) may have contributed to a poorer response.…”

Section: Discussionmentioning

confidence: 99%

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High Levels of Primary Antiretroviral Resistance Genotypic Mutations And B/F Recombinants in Santos, Brazil

Sucupira

Caseiro

Alves

et al. 2007

AIDS Patient Care and STDs

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This study characterized HIV-1 among antiretroviral-naïve populations presenting recent infection (RI) or long-standing infection (LSI). Sera collected from January 1999 to December 2001 at an anonymous HIV testing site in Santos, Brazil, were submitted to serologic testing algorithm for recent HIV seroconversion (STARHS). The STARHS methodology uses a combination of a sensitive and a less sensitive version of an anti-HIV enzyme immunoassay (EIA), and specimens found to be positive on the sensitive EIA and negative on the less sensitive EIA are considered to represent RI. HIV-1 V3 and pol regions of those with RI and LSI were compared. Antiretroviral resistance was defined solely by genotypic analysis. Ninety samples were evaluated representing those taken from an original cohort of 345 individuals, for whom adequate samples were available. Of 90 HIV-positive individuals, 25 presented RI. Cumulatively, 36.8% of those with RI and 25% of those with LSI presented resistance to at least one antiretroviral class. In the pol and V3 regions, 47% and 53% of those with RI presented clade B viruses and B/F recombinant viruses, respectively, whereas 56.2%, 41.7%, and 2.1% of those with LSI harbored clades B, B/F, and clade C viruses, respectively. Primary resistance and the prevalence of B/F recombinants was high in this population. Monitoring HIV-1 genetic diversity is important for developing vaccines and treatment strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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High Levels of Primary Antiretroviral Resistance Genotypic Mutations And B/F Recombinants in Santos, Brazil

Sucupira

Caseiro

Alves

et al. 2007

AIDS Patient Care and STDs

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“…In the beginning of the HAART era (1996–8), two studies conducted in Brazil [34], [35] showed an overall prevalence rate for transmitted resistance that ranged from 0.0% to 0.9%; resistance was mostly to NRTIs [34]. In 2001, a large study assessing data from eight different Brazilian states found an overall prevalence of 6.6%, with an uniform distribution among different drug classes (2.4% for NRTIs, 2.0% for NNRTIs and 2.2% for PIs) [14].…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Diversity and Drug Resistance Mutations among People Seeking HIV Diagnosis in Voluntary Counseling and Testing Sites in Rio de Janeiro, Brazil

et al. 2014

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The remarkable viral diversity remains a big challenge to the development of HIV vaccines and optimal therapy worldwide. In the latest years, as a consequence of the large expansion of highly active antiretroviral therapy (HAART) availability worldwide, an increase in transmitted drug resistance mutations (TDRM) has been observed, varying according the region. This study assessed HIV-1 diversity and TDRM profile over time among newly HIV-1 diagnosed individuals from Rio de Janeiro, Brazil. Blood samples were collected from individuals seeking HIV diagnosis in four voluntary counseling and testing (VCTs) sites located in the Rio de Janeiro Metropolitan Area, in 2005–2007. Recent (RS) and long-term (LTS) HIV-1 seroconverters were distinguished using BED-CEIA. Pol viral sequences were obtained for 102 LTS identified in 2005 and 144 RS from 2005–2007. HIV-1 subtype and pol recombinant genomes were determined using Rega HIV-1 Subtyping Tool and by phylogenetic inferences and bootscanning analyses. Surveillance of HIV-1 TDRM to protease and reverse transcriptase inhibitors were performed according to the Calibrated Population Resistance (CPR) Tool 6.0. Overall, subtype B remains the most prevalent in Rio de Janeiro in both LTS and RS HIV-1 infected individuals. An increased proportion of recombinant samples was detected over time, especially in RS heterosexual men, due to the emergence of CRF02_AG and URF samples bearing a subtype K fragment. The prevalence of HIV-1 samples carrying TDRM was high and similar between LTS and RS (15.7% vs 14.6%) or age (<25yo 17.9% vs >25yo 16.6%) along the study period. The high resistance levels detected in both populations are of concern, especially considering the dynamics of HIV-1 diversity over time. Our results suggest that the incorporation of resistance testing prior to HAART initiation should be highly considered, as well as permanent surveillance, aiming to carefully monitoring HIV-1 diversity, with focus on CRF/URF emergence and putative transmission.

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“…Similarly, it has been reported that some subtype G strains have decreased susceptibility to PIs [36], [37]. In HIV-1 CRF01_AE infection, the RT mutations T69N and V75M were seen more frequently than in HIV-1 subtype B [38].…”

Section: Introductionmentioning

confidence: 63%

HIV-1 pol Diversity among Female Bar and Hotel Workers in Northern Tanzania

et al. 2014

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A national ART program was launched in Tanzania in October 2004. Due to the existence of multiple HIV-1 subtypes and recombinant viruses co-circulating in Tanzania, it is important to monitor rates of drug resistance. The present study determined the prevalence of HIV-1 drug resistance mutations among ART-naive female bar and hotel workers, a high-risk population for HIV-1 infection in Moshi, Tanzania. A partial HIV-1 pol gene was analyzed by single-genome amplification and sequencing in 45 subjects (622 pol sequences total; median number of sequences per subject, 13; IQR 5–20) in samples collected in 2005. The prevalence of HIV-1 subtypes A1, C, and D, and inter-subtype recombinant viruses, was 36%, 29%, 9% and 27%, respectively. Thirteen different recombination patterns included D/A1/D, C/A1, A1/C/A1, A1/U/A1, C/U/A1, C/A1, U/D/U, D/A1/D, A1/C, A1/C, A2/C/A2, CRF10_CD/C/CRF10_CD and CRF35_AD/A1/CRF35_AD. CRF35_AD was identified in Tanzania for the first time. All recombinant viruses in this study were unique, suggesting ongoing recombination processes among circulating HIV-1 variants. The prevalence of multiple infections in this population was 16% (n = 7). Primary HIV-1 drug resistance mutations to RT inhibitors were identified in three (7%) subjects (K65R plus Y181C; N60D; and V106M). In some subjects, polymorphisms were observed at the RT positions 41, 69, 75, 98, 101, 179, 190, and 215. Secondary mutations associated with NNRTIs were observed at the RT positions 90 (7%) and 138 (6%). In the protease gene, three subjects (7%) had M46I/L mutations. All subjects in this study had HIV-1 subtype-specific natural polymorphisms at positions 36, 69, 89 and 93 that are associated with drug resistance in HIV-1 subtype B. These results suggested that HIV-1 drug resistance mutations and natural polymorphisms existed in this population before the initiation of the national ART program. With increasing use of ARV, these results highlight the importance of drug resistance monitoring in Tanzania.

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Sequence Diversity of the Reverse Transcriptase of Human Immunodeficiency Virus Type 1 from Untreated Brazilian Individuals

Cited by 53 publications

References 21 publications

High Levels of Primary Antiretroviral Resistance Genotypic Mutations And B/F Recombinants in Santos, Brazil

High Levels of Primary Antiretroviral Resistance Genotypic Mutations And B/F Recombinants in Santos, Brazil

HIV-1 Diversity and Drug Resistance Mutations among People Seeking HIV Diagnosis in Voluntary Counseling and Testing Sites in Rio de Janeiro, Brazil

HIV-1 pol Diversity among Female Bar and Hotel Workers in Northern Tanzania

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