title: Pretreatment HIV-drug resistance in Mexico and its impact on the effectiveness of first-line antiretroviral therapy: a nationally representative 2015 WHO survey.
abstract: WHO has developed a global HIV-drug resistance surveillance strategy, including assessment of pretreatment HIV-drug resistance. We aimed to do a nationally representative survey of pretreatment HIV-drug resistance in Mexico using WHO-recommended methods.
  
  
  
  Among 161 Ministry of Health antiretroviral therapy (ART) clinics in Mexico, the largest, including 90% of ART initiators within the Ministry of Health (66 in total), were eligible for the survey. We used a probability-proportional-to-size design method to sample 25 clinics throughout the country. Consecutive ART-naive patients with HIV about to initiate treatment were invited to participate in the survey; individuals with previous exposure to ART were excluded. We assessed pretreatment HIV-drug resistance by Sanger sequencing and next-generation sequencing of viruses from plasma specimens from eligible participants with Stanford University HIV Drug Resistance Database methods. We obtained follow-up data for a median of 9·4 months (range 6-12) after enrolment. We investigated possible relations between demographic variables and pretreatment drug resistance with univariate and multivariate logistic regression.
  
  
  
  Between Feb 3 and July 30, 2015, we screened 288 patients in 25 clinics, from whom 264 provided successfully sequenced viruses with no evidence of current exposure to antiretroviral drugs. With the Sanger method, of these 264 participants, 41 (15·5%, 95% CI 11·4-20·5) had pretreatment resistance to any antiretroviral drug and 28 (10·6%, 7·2-15·0) had pretreatment resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs). At least low-level pretreatment resistance (Stanford penalty score ≥15) was noted in 13 (4 · 9%) of participants to efavirenz and in 23 (8·7%) to the combination tenofovir plus emtricitabine plus efavirenz. With next-generation sequencing, of 264 participants, 38 (14·4%, 95% CI 10·4-19·2) had pretreatment resistance to any antiretroviral drug and 26 (9·8%, 6·5-14·1) had pretreatment resistance to NNRTIs. After median follow-up of 8 months (IQR 6·5-9·4, range 5-11) after ART initiation, 97 (72%) of 135 NNRTI initiators achieved viral suppression (<50 copies per mL) compared with ten (40%) of 25 individuals who started with protease inhibitor-based regimens (p=0·0045). After multivariate regression considering pretreatment resistance and initial ART regimen as composite variables, people starting NNRTIs with pretreatment drug resistance achieved significantly lower viral suppression (odds ratio 0·24, 95% CI 0·07-0·74; p=0·014) than patients without NNRTI resistance.
  
  
  
  High levels of pretreatment drug resistance were noted in Mexico, and NNRTI pretreatment drug resistance significantly reduced the effectiveness of first-line ART regimens based on these drugs. Baseline HIV-drug resistance testing for initial ART follow-up and decision making should be considered.
  
  
  
  The Mexican Government and Consejo Nacional de Ciencia y Tecnología.
authors.affiliation: Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Calzada de Tlalpan 4502, Mexico City, Mexico.
authors.forename: Santiago
authors.initials: S
authors.lastname: Ávila-Ríos
authors.affiliation: Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Calzada de Tlalpan 4502, 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, Calzada de Tlalpan 4502, 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, Calzada de Tlalpan 4502, Mexico City, Mexico.
authors.forename: Karla A
authors.initials: KA
authors.lastname: Romero-Mora
authors.affiliation: Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Calzada de Tlalpan 4502, Mexico City, Mexico.
authors.forename: Daniela
authors.initials: D
authors.lastname: Tapia-Trejo
authors.affiliation: Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Calzada de Tlalpan 4502, Mexico City, Mexico.
authors.forename: Verónica S
authors.initials: VS
authors.lastname: Quiroz-Morales
authors.affiliation: Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Calzada de Tlalpan 4502, Mexico City, Mexico.
authors.forename: Helena
authors.initials: H
authors.lastname: Reyes-Gopar
authors.affiliation: National HIV and Retrovirology Laboratories at JC Wilt Infectious Diseases Research Center, Public Health Agency of Canada, Winnipeg, MB, Canada.
authors.forename: Hezhao
authors.initials: H
authors.lastname: Ji
authors.affiliation: National HIV and Retrovirology Laboratories at JC Wilt Infectious Diseases Research Center, Public Health Agency of Canada, Winnipeg, MB, Canada.
authors.forename: Paul
authors.initials: P
authors.lastname: Sandstrom
authors.affiliation: Condesa Specialised Clinic, General Benjamín Hill 24, Colonia Condesa, Mexico City, Mexico.
authors.forename: Jesús
authors.initials: J
authors.lastname: Casillas-Rodríguez
authors.affiliation: National Institute of Medical Sciences and Nutrition Salvador Zubirán, Colonia Sección XVI, Mexico City, Mexico.
authors.forename: Juan
authors.initials: J
authors.lastname: Sierra-Madero
authors.affiliation: National Centre for HIV/AIDS Prevention and Control, Colonia Anzures, Mexico City, Mexico.
authors.forename: Eddie A
authors.initials: EA
authors.lastname: León-Juárez
authors.affiliation: National Centre for HIV/AIDS Prevention and Control, Colonia Anzures, Mexico City, Mexico.
authors.forename: Marisol
authors.initials: M
authors.lastname: Valenzuela-Lara
authors.affiliation: National Centre for HIV/AIDS Prevention and Control, Colonia Anzures, Mexico City, Mexico.
authors.forename: Carlos
authors.initials: C
authors.lastname: Magis-Rodríguez
authors.affiliation: National Centre for HIV/AIDS Prevention and Control, Colonia Anzures, Mexico City, Mexico.
authors.forename: Patricia
authors.initials: P
authors.lastname: Uribe-Zuñiga
authors.affiliation: Centre for Research in Infectious Diseases, National Institute of Respiratory Diseases, Calzada de Tlalpan 4502, Mexico City, Mexico. Electronic address: gustavo.reyesteran@gmail.com.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Reyes-Terán
mesh_terms: D000328:Adult; D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D035082:Federal Government; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008800:Mexico / Q000453:epidemiology; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D011795:Surveys and Questionnaires; D019562:Viral Load; D014944:World Health Organization; D055815:Young Adult
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; C098320:efavirenz