Transmitted drug resistance in patients with acute/recent HIV infection in Brazil

Ferreira, Ana Teresa; Coelho, Lara E.; Grinsztejn, Eduarda; Jesus, Carlos Silva de; Guimarães, Monick Lindenmeyer; Veloso, Valdiléa G.; Grinsztejn, Beatriz; Cardoso, Sandra Wagner

doi:10.1016/j.bjid.2017.03.013

Cited by 21 publications

(21 citation statements)

References 41 publications

(48 reference statements)

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“…Azidothymidine (AZT), lamivudine (3TC), and tenofovir (TDF), as rst-line NRTI drugs in China, have meager rates of transmission resistance (0.3%, 0.15%, and 0%, respectively). However, unlike the ndings reported in other studies, [4,5,[36][37][38][39][40] NRTI resistance showed the most signi cant increase (from 0% to 5.17%) from 2009 to 2017 in this study. Although the prevalence of TDR to PIs (0.44%) was signi cantly lower than the prevalence of TDR to NNRTIs/NRTIs, the I54M mutation caused universal resistance to PI drugs.…”

Section: Discussioncontrasting

confidence: 99%

Increase in HIV-1 transmitted drug resistance among untreated 16~25-y-old youths in the China-Myanmar border areas during 2009~2017

Ding¹,

Chen²,

Wang³

et al. 2020

Preprint

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Background Transmitted drug resistance (TDR) can affect antiretroviral therapy (ART) efficacy. Surveillance drug resistance mutations in untreated youths newly reported with HIV-1 are highly representative of local TDR. We investigated HIV-1 TDR, TDR transmission based on molecular networks, and the effect of TDR mutations (TDRMs) on the CD4 count among youths in the China-Myanmar border area near the "Golden Triangle" to better understand TDR and guide ART.Methods From 2009 to 2017, 573 ART-naïve youths (16~25 y) newly reported with HIV-1 were enrolled. CD4 counts were obtained from whole blood. HIV pol gene sequences were amplified from RNA extracted from plasma. The Stanford REGA program and phylogenetic trees were used to determine genotypes. TDRMs were analyzed using the Stanford Calibrated Population Resistance tool. TDR transmission was evaluated from molecular networks of HIV-1 pol genes.Results The average prevalence of TDR was 6.3%, and the resistance to NNRTIs, NRTIs, and PIs was 3.49%, 2.62%, and 0.52%, respectively. TDR prevalence increased significantly during the period 2009~2017 (3.92%~9.48%, p<0.05). The mean CD4 count was significantly lower among individuals with TDRMs (373/mm3 vs. 496/mm3, p=0.013). The rate of network entry of youths harboring TDRMs (63.89%) was significantly higher than that of youths without TDRMs (44.9%).Conclusions The HIV-1 TDR increase and low CD4 count of patients with TDRMs in Dehong at the China-Myanmar border suggest the need for early ART and completion of resistance testing before initiating ART in HIV hotspots. Youths with TDRMs are likely to have links to others, necessitating intervention in onward transmission.

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Section: Discussioncontrasting

confidence: 99%

Increase in HIV-1 transmitted drug resistance among untreated 16~25-y-old youths in the China-Myanmar border areas during 2009~2017

Ding¹,

Chen²,

Wang³

et al. 2020

Preprint

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“…A cohort of Brazilian individuals presenting recent HIV-1 infection has been followed-up since August 2013 at the Instituto Nacional de Infectologia Evandro Chagas (INI-FIOCRUZ). These individuals initiated cART immediately after diagnosis and have been described elsewhere (Ferreira et al, 2017). For the present study, we selected only individuals, who started cART during the acute phase (Fiebig II–V) (Fiebig et al, 2003) of HIV-1 infection ( n = 10).…”

Section: Methodsmentioning

confidence: 99%

Reduction of HIV-1 Reservoir Size and Diversity After 1 Year of cART Among Brazilian Individuals Starting Treatment During Early Stages of Acute Infection

et al. 2019

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The aim of early combined antiretroviral therapy (cART) of HIV is to limit the seeding of the viral reservoir during the initial phase of infection and, consequently, decrease intrahost viral diversity. Here, we assessed the effect of early cART on size and complexity of the proviral reservoir. Peripheral blood mononuclear cell (PBMC) and plasma samples were obtained from ten HIV-infected Brazilian individuals diagnosed at the acute phase of infection, before (PREART) and 12 months (M12ART) after suppressive cART. HIV proviral reservoir size was determined by quantitative real-time PCR; intrahost viral diversity of the env C2-V3 region was assessed by single genome amplification or next-generation sequencing in PBMC and plasma, respectively. Mean nucleotide diversity (π) and normalized Shannon entropy (HSN) were used to infer the complexity of the viral population. Compared to PREART, M12ART saw an immunological recovery with a gain of ∼200 CD4+ T cells (P = 0.008) and a normalization of the CD4/CD8 ratio [1.0 (IQR: 0.88–1.18), P = 0.016], as well as a significant decrease in HIV-1 RNA (∼4 log, P = 0.004) and DNA (∼1 log, P = 0.002) levels. The median time to achieve viral suppression was 3 months (IQR: 2.8–5.8 months). The high intermixing between sequences from both visits suggests that the HIV-1 DNA reservoir remained remarkably stable under cART. After 1 year of cART, there was a minor reduction in proviral π (PreART = 0.20 vs. M12ART = 0.10; P = 0.156) but a significant decrease in HSN (PreART = 0.41 vs. M12ART = 0.25; P = 0.019). We found no correlation between π or HSN at PreART and the rate of HIV DNA decay, T CD4+ counts, or CD4/CD8 ratio at M12ART. Based on a small cohort of Brazilian infected individuals under early cART and analyses of the env region, 1 year of follow-up suggested a reservoir size reduction, allowed a significant decrease of HIV-1 complexity, and achieved immunological restoration regardless of the initial HIV-1 plasma viral load, CD4+ T cell counts, or HIV-1 subtype. However, further studies in the Brazilian setting aiming a longer follow-up and larger cohort are required in this field.

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“…DRMs monitoring is an important tool for surveillance of drug-resistant variants, and genotyping test is very useful to define salvage therapy. 29 DRMs that may jeopardize the success of HIV treatment must be carefully tracked, as ARV drug therapy is still the only feasible treatment option to suppress the virus. 16,23,30 According to the 2018 report, the plan of action for the prevention and control of HIV and sexually transmitted infections 2016-2021 by WHO, surveillance of drug resistance continues to be fundamental to enable an effective drug monitoring of the currently available drugs and also of putative future drugs, and also to inform of policy changes in public health treatment.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of Antiretroviral Drug Resistance Mutations in HIV Seropositive Patients from an Outpatient Clinic of a Large University Hospital from São Paulo, Brazil

Constantinov

Brígido

Fonseca

et al. 2020

AIDS Research and Human Retroviruses

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Drug resistance mutations (DRMs) can affect the success of the therapy and compromise new prevention strategies. Increasing rates of resistance to antiretroviral (ARV) drugs have been reported in some areas. This study evaluated the DRMs prevalence among patients at Hospital das Clínicas (São Paulo). Among treatmentnaive patients, the prevalence of transmitted DRMs (Stanford Calibrated Population Resistance) was 8.4% (21/249), with 69% (75/109) of acquired resistance among treatment-experienced patients. Rates of transmitted DRM showed an increase (6.6% in 2002-2009 vs. 15.1% in 2010-2015, p = .05), from the first to the second decade, mainly due to mutations to the NNRTI (non-nucleoside reverse transcriptase inhibitor) class. Among treatment-experienced cases, a nonsignificant decrease overall, significant for the protease inhibitors (PIs) class, was documented. Subtype B predominated in both groups (78%), followed by subtype F, BF recombinants, and subtype C. Our results add to the growing evidence of an increase in transmitted DRM, document extensive DRM among experienced patients, and a decrease in resistance to PIs class that may reflect the increased use of boosted PIs and newer ARV classes in more recent years.

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Transmitted drug resistance in patients with acute/recent HIV infection in Brazil

Cited by 21 publications

References 41 publications

Increase in HIV-1 transmitted drug resistance among untreated 16~25-y-old youths in the China-Myanmar border areas during 2009~2017

Increase in HIV-1 transmitted drug resistance among untreated 16~25-y-old youths in the China-Myanmar border areas during 2009~2017

Reduction of HIV-1 Reservoir Size and Diversity After 1 Year of cART Among Brazilian Individuals Starting Treatment During Early Stages of Acute Infection

Prevalence of Antiretroviral Drug Resistance Mutations in HIV Seropositive Patients from an Outpatient Clinic of a Large University Hospital from São Paulo, Brazil

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