Detection of human immunodeficiency virus Type 1 phylogenetic clusters with multidrug resistance mutations among 2011 to 2017 blood donors from the highly endemic Northern Brazilian Amazon

Abstract

BACKGROUND This study describes transmitted drug resistance (TDR) in blood donors diagnosed with human immunodeficiency virus Type 1 (HIV‐1) infection from 2011 to 2017 in three reference public blood centers from the Northern Brazilian Amazon. STUDY DESIGN AND METHODS This was a cross‐sectional study on HIV‐positive blood donors from HEMOAM, Manaus, Amazonas, AM (n = 198); HEMERON, Porto Velho, Rondônia, RO (n = 20); and HEMORAIMA, Boa Vista, Roraima, RR (n = 9). HIV‐1 pol sequences (protease, reverse transcriptase) were analyzed for drug resistance mutations (DRMs) using the Calibrated Population Resistance tool (Stanford). TDR/DRM clusters were investigated by phylogenetic analysis after removing positions associated with drug resistance of Subtype B sequences from untreated and treated subjects from Northern Brazil. RESULTS Transmitted drug resistance/DRM in blood donors was 11% (25 of 227), all of them from HEMOAM. Most blood donors with TDR/DRM had multiple and similar DRMs. Nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations predominated (10.1%), followed by nucleoside reverse transcriptase inhibitor (NRTI) mutations (5.3%) and protease inhibitor mutations (0.4%). Dual‐class NNRTI/NRTI mutations represented 4.8%. Three highly supported Subtype B monophyletic clades mostly composed by individuals from Amazonas with TDR/DRM mutations were identified. The largest transmission cluster contained 10 sequences, eight from HEMOAM and two sequences described previously (one from a treated subject from Amazonas and the other one from Roraima). This cluster was characterized by NRTI (D67N, T69D, T215S/F/L, K219Q) and NNRTI (K101H, K103 N, G190A) mutations. The other two transmission clades comprised only three and two sequences from HEMOAM sharing the E138A NNRTI mutation. CONCLUSIONS The identification of transmission clusters of multidrug‐resistant viruses in blood donors from Amazonas highlight the need of continued monitoring of TDR/DRM and the importance of pretreatment genotyping in the highly endemic Amazonas state.

Homogenous HIV-1 subtype B from the Brazilian Amazon with infrequent diverse BF1 recombinants, subtypes F1 and C among blood donors

“…A recent report by our group described 11% transmitted drug resistance/TDR rate (25 out of 227) in these donors: 10.1% non-nucleoside-reverse-transcriptase-inhibitor/NNRTI mutations, 5.3% nucleoside-reverse-transcriptase-inhibitor/NRTI mutations and 0.4% protease-inhibitor/PI mutations; NNRTI/NRTI mutations represented 4.8%. Also, three highly supported subtype B monophyletic clades mostly composed by individuals from Amazonas with TDR/drug resistance mutations were identified suggesting transmission clusters of multi-drug-resistant viruses in these blood donors [52].…”

Reconstructing the Dissemination Dynamics of the Major HIV-1 Subtype B Non-Pandemic Lineage Circulating in Brazil

“…Despite the fact that the B CAR-BR-I dataset used in the present work comprises a more geographically balanced dataset than previous studies and that it could be useful for the spatial reconstruction of the lineage’s root, it is feasible that quite a larger number of B CAR-BR-I sequences from Amazonas and Roraima states would be required for understanding the structure and dynamics of the B CAR-BR-I transmission networks in those Northern Brazilian states. Assuming that the B CAR-BR-I infections accounts for approximately 15 and 30% of HIV-1 subtype B infections in Amazonas and Roraima [6,7], respectively, our sampling density probably corresponds to approximately 2–5% of the B CAR-BR-I -infected individuals living in those Brazilian states. Such a sampling density is below the minimal level of 10% suggested by simulation studies for HIV-1 clusters analysis [33].…”

“…A total of 76 HIV-1 subtype B pol sequences from Brazil that covered the entire protease and partial reverse transcriptase (PR/RT) regions (nucleotides 2253–3260 relative to HXB2 clone) and were previously classified within the B CAR-BR-I clade [6,7] were used in the present study (Table 1) . HIV-1 Brazilian sequences were aligned with subtype B CAR pol sequences from Hispaniola ( n = 130), noted as the most probable epicenter of subtype B epidemic, and with B CAR pol sequences representative of the B CAR-TT ( n = 41) and B CAR-SA-I clades ( n = 69) circulating in Trinidad and Tobago, French Guiana, Guyana and Suriname, that were described as the non-Brazilian lineages most closely related to the B CAR-BR-I clade [3,5,6] (see Table S1 for details about GenBank accession number, geographic origin and sampling time of all HIV-1 B CAR sequences used in this study).…”

“…Multiple B CAR strains were introduced into Brazil, but only some of them established onward transmissions and local clades [5,6]. The major non-pandemic subtype B Brazilian clade previously identified, named B CAR-BR-I , is a tributary of the B CAR-SA-I clade [5] and accounts for an important fraction of HIV-1 subtype B infections in Roraima (~33%) and Amazonas (~15%) [6,7]. Previous analyses support that the B CAR-BR-I clade probably arose by the dissemination of a founder B CAR-SA-I strain from French Guiana into Roraima around the late 1970s [5,6].…”

“…The recent characterization of new subtype B non-pandemic sequences from Amazonas state [7] allowed us to compile a more comprehensive dataset of 76 HIV-1 B CAR-BR-I pol sequences from Amazonas ( n = 45), Roraima ( n = 29), Rondonia ( n = 1) and Sao Paulo ( n = 1), collected between 2007 and 2017. With this new dataset, we obtain a more accurate reconstruction of the spatiotemporal origin of the HIV-1 B CAR-BR-I clade in Northern Brazil and we also infer the demographic dynamics of this lineage for the first time.…”