Increase in human immunodeficiency virus 1 diversity and detection of various subtypes and recombinants in north-eastern Brazil

Lima, Kledoaldo; Leal, Élcio; Cavalcanti, Ana Maria Salustiano; Salustiano, Daniela Medeiros; Medeiros, Luzidalva Barbosa de; Silva, Sirleide Pereira da; Lacerda, Heloísa Ramos

doi:10.1099/jmm.0.000447

Cited by 11 publications

(11 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, as Brazil is a country of continental dimensions, there is variation in the HIV-1 genetic diversity in the same macroregion. Thus, in the Northeast, there are states with lower proportions of HIV-1 B, as Pernambuco, where the subtype is F common (31.4%) [5], and Bahia with a frequency of 18.6% for BF recombinants [3]. BF recombinants were detected in 9.5% of all sequences in our study.…”

Section: Discussionmentioning

confidence: 53%

“…However, some regions have a high proportion of other subtypes and/or recombinants. Some regions of Northeast Brazil have a high proportion of subtype F (~30%) [5] and recombinant BF (18%) [3], as well as circulation of recently identified recombinant circulating forms (CRFs) such as the CRF70 and 71BF [8]. In the southern region, HIV-1 subtype C and its recombinant forms, mainly CRF31_BC, are predominant [9].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Characterization of HIV-1 genetic diversity and antiretroviral resistance in the state of Maranhão, Northeast Brazil

et al. 2020

Self Cite

View full text Add to dashboard Cite

The HIV-1 epidemic in Brazil has been growing in northeast and north regions, particularly an increase in AIDS cases among the younger male population has been observed. This study aims to characterize the HIV-1 genetic diversity and to evaluate its antiretroviral resistance profile among individuals presenting virological failure in the state of Maranhão-Brazil. HIV-1 pol gene sequences from 633 patients on antiretroviral therapy were obtained from the Department of Surveillance, Prevention and Control of Sexually Transmitted Infections, HIV/AIDS and Viral Hepatitis of the Brazilian Ministry of Health. Phylogenetic and recombination analyses were performed to characterize viral genetic diversity. The presence of antiretroviral resistance mutations was assessed using the HIV Drug Resistance Database online platform of Stanford University. A predominance of subtype B (84.5%) was observed, followed by recombinant BF (9.5%), where more than half of the sequences were dispersed in 3 clusters. Antiretroviral resistance was detected in 74.1% of the sequences, and it was significantly higher for nucleoside analogue reverse-transcriptase inhibitors (NRTIs) than for non-nucleoside analogue reverse-transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs). Inference of putative transmissions clusters identified 11 clusters with 22 query sequences (22/633, 3.5%). Thus, we conclude that continuous monitoring of the molecular epidemiology of HIV-1 is essential for prevention strategies, epidemic control, and treatment adequacy.

show abstract

Section: Discussionmentioning

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Characterization of HIV-1 genetic diversity and antiretroviral resistance in the state of Maranhão, Northeast Brazil

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…4B). For this analysis we assumed an exponential (Malthusian) relationship based on the nature of HIV growth and diversity in acute infection (66, 67).…”

Section: Resultsmentioning

confidence: 99%

Impact of suboptimal APOBEC3G neutralization on the emergence of HIV drug resistance in humanized mice

Hernandez

Fahrny

Jayaprakash

et al. 2019

Preprint

View full text Add to dashboard Cite

HIV diversification facilitates immune escape and complicates antiretroviral therapy. In this study, we take advantage of a humanized mouse model to probe the contribution of APOBEC3 mutagenesis to viral evolution. Humanized mice were infected with isogenic HIV molecular clones (HIV-WT, HIV-45G, HIV-ΔSLQ) that differ only in their ability to counteract APOBEC3G (A3G). Infected mice remained naïve or were treated with the RT inhibitor lamivudine (3TC). Viremia, emergence of drug resistant variants and quasispecies diversification in the plasma compartment were determined throughout infection. While both HIV-WT and HIV-45G achieved robust infection, over time HIV-45G replication was significantly reduced compared to HIV-WT in the absence of 3TC treatment. In contrast, treatment response differed significantly between HIV-45G and HIV-WT infected mice. Antiretroviral treatment failed in 91% of HIV-45G infected mice while only 36% of HIV-WT infected mice displayed a similar negative outcome. Emergence of 3TC resistant variants and nucleotide diversity were determined by analyzing 155,462 single HIV reverse transcriptase (RT) and 6,985 vif sequences from 33 mice. Prior to treatment, variants with genotypic 3TC resistance (RT-M184I/V) were detected at low levels in over a third of all animals. Upon treatment, the composition of the plasma quasispecies rapidly changed leading to a majority of circulating viral variants encoding RT-184I. Interestingly, increased viral diversity prior to treatment initiation correlated with higher plasma viremia in HIV-45G but not in HIV-WT infected animals. Taken together, HIV variants with suboptimal anti-A3G activity were attenuated in the absence of selection but display a fitness advantage in the presence of antiretroviral treatment.IMPORTANCEBoth viral (e.g., reverse transcriptase, RT) and host factors (e.g., APOBEC3G (A3G)) can contribute to HIV sequence diversity. This study shows that suboptimal anti-A3G activity shapes viral fitness and drives viral evolution in the plasma compartment of humanized mice.

show abstract

“…4B). For this analysis, we assumed an exponential (Malthusian) relationship based on the nature of HIV growth and diversity in acute infection (58,59).…”

Section: Dynamics Of Genotypic 3tc Drug Resistancementioning

confidence: 99%

Impact of Suboptimal APOBEC3G Neutralization on the Emergence of HIV Drug Resistance in Humanized Mice

Hernandez

Fahrny

Jayaprakash

et al. 2020

J Virol

View full text Add to dashboard Cite

HIV diversification facilitates immune escape and complicates antiretroviral therapy. In this study, we take advantage of a humanized-mouse model to probe the contribution of APOBEC3 mutagenesis to viral evolution. Humanized mice were infected with isogenic HIV molecular clones (HIV-WT, HIV-45G, and HIV-ΔSLQ) that differ in their abilities to counteract APOBEC3G (A3G). Infected mice remained naive or were treated with the reverse transcriptase (RT) inhibitor lamivudine (3TC). Viremia, emergence of drug-resistant variants, and quasispecies diversification in the plasma compartment were determined throughout infection. While both HIV-WT and HIV-45G achieved robust infection, over time, HIV-45G replication was significantly reduced compared to that of HIV-WT in the absence of 3TC treatment. In contrast, treatment responses differed significantly between HIV-45G- and HIV-WT-infected mice. Antiretroviral treatment failed in 91% of HIV-45G-infected mice, while only 36% of HIV-WT-infected mice displayed a similar negative outcome. Emergence of 3TC-resistant variants and nucleotide diversity were determined by analyzing 155,462 single HIV reverse transcriptase gene (RT) and 6,985 vif sequences from 33 mice. Prior to treatment, variants with genotypic 3TC resistance (RT-M184I/V) were detected at low levels in over a third of all the animals. Upon treatment, the composition of the plasma quasispecies rapidly changed, leading to a majority of circulating viral variants encoding RT-184I. Interestingly, increased viral diversity prior to treatment initiation correlated with higher plasma viremia in HIV-45G-infected animals, but not in HIV-WT-infected animals. Taken together, HIV variants with suboptimal anti-A3G activity were attenuated in the absence of selection but displayed a fitness advantage in the presence of antiretroviral treatment. IMPORTANCE Both viral (e.g., RT) and host (e.g., A3G) factors can contribute to HIV sequence diversity. This study shows that suboptimal anti-A3G activity shapes viral fitness and drives viral evolution in the plasma compartment in humanized mice.

show abstract

Increase in human immunodeficiency virus 1 diversity and detection of various subtypes and recombinants in north-eastern Brazil

Abstract: HIV-1 shows high genetic diversity in the state of Pernambuco. Thus, additional molecular evaluations of circulating strains will provide a better understanding of the epidemic and may lead to more effective preventive strategies.

Cited by 11 publications

References 73 publications

Characterization of HIV-1 genetic diversity and antiretroviral resistance in the state of Maranhão, Northeast Brazil

Characterization of HIV-1 genetic diversity and antiretroviral resistance in the state of Maranhão, Northeast Brazil

Impact of suboptimal APOBEC3G neutralization on the emergence of HIV drug resistance in humanized mice

Impact of Suboptimal APOBEC3G Neutralization on the Emergence of HIV Drug Resistance in Humanized Mice

Contact Info

Product

Resources

About