HIV Type 1 Antiretroviral Resistance Mutations in Subtypes B, C, and F in the City of São Paulo, Brazil

The emergence of resistance-associated mutations to the antiretroviral agents and the genetic variability of HIV-1 impose challenges to therapeutic success. We report the results of genotype testing assays performed between 2002 and 2006 in 240 antiretroviral-experienced patients followed up in an HIV reference center in Brazil. Drug resistance mutations and viral subtypes were assessed through the algorithms from the Brazilian Genotyping Network (RENAGENO-Brazil) and from Stanford University. Mutation 184VI was the most prevalent (70%) and the thymidine analogue mutations that appeared most frequently were 215FY, 41L, 67N, and 210W, in this order. Among nonnucleoside reverse transcriptase inhibitor mutations, 103NS (32.5%) stood out. HIV subtype B was identified in 184 patients (76.7%). A significant increasing trend in the prevalence of non-B subtypes was observed during the study period (p=0.004). The main differences in prevalence of mutations among HIV-1 subtypes were related to viral protease, with 20MRI, 36I, and 89IMT more prevalent among non-B subtypes, and 84V, 10FR, 63P, 71LTV, and 77I more common in subtype B (p<0.05). Most mutations to etravirine had a prevalence lower than 10%, but at least one mutation to this drug was observed in 45% of the patients. In only 11 patients (4.6%) three mutations to etravirine were verified. Regional surveillance of the resistance profile and HIV-1 subtypes is crucial in the context of public health, to prevent the transmission of resistant strains and to guide the introduction of new drugs in a specific population.

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confidence: 50%

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confidence: 99%

Resistance-Associated Mutation Prevalence According to Subtypes B and Non-B of HIV Type 1 in Antiretroviral-Experienced Patients in Minas Gerais, Brazil

Westin

Biscione

Fonseca

et al. 2011

“…For example, HIV-1C acquires less resistance mutations than HIV-1B to PI and NRTI. 29 HIV-1 RT C-terminal domains may as well display differences in the context of non-B variants, a subject that requires investigation. 30 This study aims to characterize resistance-related mutations in the C-terminal portions of HIV-1 RT from patients under virological failure followed in southern Brazil, a region where HIV-1C prevails.…”

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confidence: 99%

Identification of Novel Resistance-Related Polymorphisms in HIV-1 Subtype C RT Connection and RNase H Domains from Patients Under Virological Failure in Brazil

Barral

Sousa

Santos

et al. 2017

Mutations in the connection and RNase H C-terminal reverse transcriptase (RT) domains of HIV-1 have been shown to impact drug resistance to RT inhibitors. However, their impact in the context of non-B subtypes has been poorly assessed. This study aimed to characterize resistance-related mutations in the C-terminal portions of RT in treatment-failing patients from southern Brazil, a region with endemic HIV-1 subtype C (HIV-1C). Viral RNA was isolated and reverse transcribed from 280 infected subjects, and genomic regions were analyzed by polymerase chain reaction, DNA sequencing, and phylogenetic analysis. Two novel mutations, M357R and E529D, were evidenced in Brazilian HIV-1C strains from treatment-failing patients. In global viral isolates of subjects on treatment, M357R was selected in HIV-1C and CRF01_AE and E529D was selected in HIV-1 subtype B (HIV-1B). While most C-terminal RT mutations described for HIV-1B also occur in HIV-1C, this work pinpointed novel mutations that display subtype-specific predominance or occurrence.

“…Among the cases at this institution, 2474 samples presented with virologic failure and 95% presented with primary mutations related to antiretroviral resistance, with 21%, 49%, and 34% resistant to one, two, or three classes of antiretroviral drugs, respectively. 12 According to current Brazilian guidelines for antiretroviral treatment, patients eligible to receive enfuvirtide are those presenting with one or two active antiretrovirals according to resistance tests (www.aids.gov.br), and as of November 2008, there were approximately 1600 Brazilian patients receiving enfuvirtide.…”

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confidence: 99%

Short Communication: High Polymorphism Rates in the HR1 and HR2 gp41 and Presence of Primary Resistance-Related Mutations in HIV Type 1 Circulating in Brazil: Possible Impact on Enfuvirtide Efficacy

Teixeira

Sa-Filho

Alkmim

et al. 2010

Self Cite

We analyzed the gp41 sequences of 80 HIV-infected enfuvirtide-naive individuals who were eligible to receive this antiretroviral according to Brazilian guidelines. We analyzed the genetic diversity of pol and the heptad repeat 1 and 2 (HR1 and HR2) regions of gp41, and compared the genetic profile of HR1 and HR2 found in PBMCs with the profile found in plasma. The similarity between sequences obtained from DNA and RNA in the HR1 and HR2 regions was, on average, 98.6% and 98.9%, respectively. We detected mutations related to enfuvirtide resistance (L44M or N43K) in HR1 DNA samples from three individuals (3.8%) and RNA samples from three individuals (4.6%). Other polymorphisms frequently detected were E137K (10% and 13.8%), L130I (8.8% and 9.2%), S129N (6.3% and 10.8%), L44M (2.5% and 4.6%), S138A (2.5% and 1.5%), and N43K (1.3% and 0%) in DNA and RNA, respectively. Subtype B was identified in 68.8% of the samples [protease (PR) B, reverse transcriptase (RT) B, gp41 B], subtype F in 5.0%, subtype C in 1.3%, and the remaining sequences presented with a mosaic profile. These results suggest that genotyping the gp41 region prior to introducing an expensive and complex approach, such as enfuvirtide, may be cost effective. Moreover, assessment of proviral DNA may be less expensive than RNA, as well as being sufficient for this purpose.