title: HIV Drug Resistance in Antiretroviral Treatment-Naïve Individuals in the Largest Public Hospital in Nicaragua, 2011-2015.
abstract: BACKGROUND
  Increasing HIV pre-treatment drug resistance (PDR) levels have been observed in regions with increasing antiretroviral treatment (ART) coverage. However, data is lacking for several low/middle-income countries. We present the first PDR survey in Nicaragua since ART introduction in the country in 2003.
  
  
  METHODS
  HIV-infected, ART-naïve Nicaraguan individuals were enrolled at Roberto Calderón Hospital, the largest national HIV referral center, from 2011 to 2015. HIV pol sequences were obtained at a WHO-accredited laboratory in Mexico by Sanger and next generation sequencing (NGS). PDR was assessed using the WHO surveillance drug resistance mutation (SDRM) list and the Stanford HIVdb tool.
  
  
  RESULTS
  283 individuals were enrolled in the study. The overall PDR prevalence based on the list of SDRMs was 13.4%. Using the Stanford HIVdb tool, overall PDR reached 19.4%; with both nucleoside and non-nucleoside reverse transcriptase inhibitor (NRTI and NNRTI) PDR levels independently reaching moderate levels (6.7% and 11.3% respectively). Protease inhibitor PDR was low (2.8%). Using NGS with 2% threshold to detect SDRMs, PDR increased to 25.3%. K103N and M41L were the most frequent SDRMs and were present mostly in proportions >20% in each individual. A significant temporal increase in NNRTI PDR was observed (p = 0.0422), with no apparent trends for other drug classes. Importantly, PDR to zidovudine + lamivudine + efavirenz and tenofovir + emtricitabine + efavirenz, the most widely used first-line regimens in Nicaragua, reached 14.6% and 10.4% respectively in 2015. Of note, a higher proportion of females was observed among individuals with PDR compared to individuals without PDR (OR 14.2; 95% CI: 7.1-28.4; p<0.0001).
  
  
  CONCLUSIONS
  Overall PDR in the Nicaraguan cohort was high (19.4%), with a clear increasing temporal trend in NNRTI PDR. Current HIVDR to the most frequently used first-line ART regimens in Nicaragua reached levels >10%. These observations are worrisome and need to be evidenced to strengthen the national HIV program. Also, our observations warrant further nationally representative HIVDR surveillance studies and encourage other countries to perform national surveys. Cost-effectiveness studies are suggested to analyze the feasibility of implementation of baseline HIV genotyping as well as to review the choice of first-line ART regimens in Nicaragua.
authors.affiliation: Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico.
authors.forename: Santiago
authors.initials: S
authors.lastname: Avila-Ríos
authors.affiliation: Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico.
authors.forename: Claudia
authors.initials: C
authors.lastname: García-Morales
authors.affiliation: Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico.
authors.forename: Margarita
authors.initials: M
authors.lastname: Matías-Florentino
authors.affiliation: Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico.
authors.forename: Daniela
authors.initials: D
authors.lastname: Tapia-Trejo
authors.affiliation: Hospital Dr. Roberto Calderón Gutiérrez, Managua, Nicaragua.
authors.forename: Bismarck F
authors.initials: BF
authors.lastname: Hernández-Álvarez
authors.affiliation: Hospital Metropolitano Vivian Pellas, Managua, Nicaragua.
authors.forename: Sumaya E
authors.initials: SE
authors.lastname: Moreira-López
authors.affiliation: Hospital Dr. Roberto Calderón Gutiérrez, Managua, Nicaragua.|Hospital Metropolitano Vivian Pellas, Managua, Nicaragua.
authors.forename: Carlos J
authors.initials: CJ
authors.lastname: Quant-Durán
authors.affiliation: Hospital Metropolitano Vivian Pellas, Managua, Nicaragua.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Porras-Cortés
authors.affiliation: Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Mexico City, Mexico.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Reyes-Terán
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D005260:Female; D006678:HIV / Q000187:drug effects / Q000235:genetics*; D015658:HIV Infections / Q000821:virology*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D059645:Mutation Rate; D009527:Nicaragua; D017423:Sequence Analysis, RNA; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D019380:Anti-HIV Agents; D054302:pol Gene Products, Human Immunodeficiency Virus