Extensive variation in drug-resistance mutational profile of Brazilian patients failing antiretroviral therapy in five large Brazilian cities

Brites, Carlos; Pinto-Neto, Lauro; Medeiros, Melissa Soares; Nunes, Estêvão Portela; Sprinz, Eduardo; Carvalho, Mariana

doi:10.1016/j.bjid.2016.03.010

Cited by 8 publications

(11 citation statements)

References 28 publications

(30 reference statements)

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“…Genotypic and immunovirologic data from patients following the first virologic failure are scarce in Brazil, and they are limited to certain regions of the country. A recent study from the city of São Paulo 10 on patients who failed first-line therapy between 2013 and 2015 found a higher prevalence of the M184 V/I mutation (74.3%) and K103 codon (56.7%), similar to that found in other Brazilian states [ 11 ]. Among the 205 subjects who started the second-line therapy with NRTI(t)s combined with protease inhibitor/ritonavir (PI/r), 76.6% experienced virologic suppression (< 200 copies/ml), despite the extensive resistance of the virus to NRTI(t)s [ 10 ].…”

Section: Introductionsupporting

confidence: 70%

Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure

et al. 2018

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BackgroundIncomplete virologic suppression results in mutations associated with resistance and is a major obstacle to disease control. We analyzed the genotypic profiles of HIV-1 patients at the time of the first virologic failure and the response to a salvage regimen after 48 weeks.MethodsThis work was a cross-sectional, retrospective, analytical study based on data collected from medical records and genotyping tests between 2006 and 2016. The sample consisted of data on individuals living with HIV (PLWH) from three major reference centers.ResultsA total of 184 patients were included in the data analysis. Viral subtype B was the most common (81.3%) as well as M184 V/I (85.3%) and K103 codon mutations (65.8%). Forty-eight weeks after switching to a salvage regimen, 67.3% of patients achieved an undetectable viral load.DiscussionThe number of mutations associated with nucleos(t)ide reverse transcriptase inhibitors (NRTI(t)s) did not affect virologic suppression (9.3% for zero NRTI(t)-associated mutations vs 48.6% for 1–2 NRTI(t)-associated mutations vs 42.1% for ≥3 NRTI(t)-associated mutations, p = 0.179). An ARV time (the beginning of the first ARV regimen up to genotyping) of > 36 months was a protective factor for detectable viral load (PR = 0.60, 95% CI = 0.39–0.92, p = 0.020) and a risk factor for developing ≥3 NRTI(t)-associated mutations (PR = 2.43, 95% CI 1.38–4.28, p = 0.002).ConclusionsWe found that extensive resistance to NRTI(t)s at the time of the first virologic failure did not impact virologic suppression at 48 weeks after switching to a second-line therapy based on NRTI(t)s plus protease inhibitors.

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Section: Introductionsupporting

confidence: 70%

Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure

et al. 2018

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“…Brites et al (2016) defined the mutational profile associated with ARV resistance in infected individuals from five different cities in Brazil, and concluded that DRV and TPV are the most susceptible drugs in the PI group in Salvador city, which was confirmed in the present study. We also verified that there was lower susceptibility to 3TC in the NRTI group, and to NVP and EFV in the NRTI group (Brites et al 2016), with 3TC and EFV in combination with TDF used as the first line of treatment (IST-AIDS Hepatites Virais 2013). Clinical relevance was also demonstrated for the individuals BAS065, BAS069, BAS087, and BAS111 (Table IV), who had high and intermediate levels of resistance to all drug classes (PI, NRTI and NNRTI) while under treatment.…”

Section: Discussionsupporting

confidence: 83%

“…Clinical relevance was also demonstrated for the individuals BAS065, BAS069, BAS087, and BAS111 (Table IV), who had high and intermediate levels of resistance to all drug classes (PI, NRTI and NNRTI) while under treatment. These observations reinforce the idea that ARV treatment may lead to eventual drug failure, once exposure drives high selective pressure to the acquisition of resistance (Brites et al 2016). …”

Section: Discussionsupporting

confidence: 83%

An overview of the molecular and epidemiological features of HIV-1 infection in two major cities of Bahia state, Brazil

Amaral

Oliveira

Carneiro

et al. 2017

Mem. Inst. Oswaldo Cruz

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BACKGROUND The high mutation rate of the human immunodeficiency virus (HIV) has created a public health challenge because the use of antiretroviral drugs can generate selective pressure that drives resistance in these viruses.OBJECTIVE The aim of this work was to characterise the molecular and epidemiological profile of HIV in Bahia, Brazil.METHODS DNA sequences from regions of HIV gag, pol, and env genes were obtained from previous studies performed in this area between 2002 and 2012. Their genotype and drug-resistance mutations were identified using bioinformatics tools. Clinical and epidemiological data were analysed.FINDINGS Among 263 individuals (46.4% male), 97.5% were asymptomatic and 49.1% were receiving treatment. Most of the individuals were 31 to 40 years old (36.9%) and infected through heterosexual contact (40.7%). The predominant genotype was B (68.1%) followed by BF recombinants (18.6%). Among the individuals infected with either F or BF genotypes, 68.4% were women and 76.8% were infected through heterosexual transmission. The prevalence of associated mutations conferring antiretroviral resistance was 14.2%, with 3.8% of all mutations conferring resistance to protease inhibitors, 9.43% to nucleoside reverse transcriptase inhibitors, and 8.5% to non-nucleoside reverse transcriptase inhibitors. Drug resistance was higher in individuals receiving treatment (26.1%) than in the drug-naïve (4.3%) individuals.MAIN CONCLUSIONS This study will contribute to the understanding and monitoring of HIV epidemic in this Brazilian region.

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“…Only mutations for NRTIs and NNRTIs resistance were detected, demonstrating the low circulation of primary mutations to PIs in untreated patients. On the other hand, a study evaluating patients with therapeutic failure in large cities in Brazil, including the Northeast region, also indicated a higher level of resistance to NRTIs and NNRTIs, but with a lower frequency of mutations for PIs resistance in both naive and treated individuals [27]. Among NNRTIs, higher resistances were observed against Efavirenz and Nevirapine, which was largely used NNRTIs in Brazil as the recommended first-line regimen, being replaced, in 2017, by the integrase inhibitor dolutegravir.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2020

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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.

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Extensive variation in drug-resistance mutational profile of Brazilian patients failing antiretroviral therapy in five large Brazilian cities

Cited by 8 publications

References 28 publications

Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure

Virologic suppression in response to antiretroviral therapy despite extensive resistance within HIV-1 reverse transcriptase after the first virologic failure

An overview of the molecular and epidemiological features of HIV-1 infection in two major cities of Bahia state, Brazil

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

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