Pretreatment HIV Drug Resistance and Virologic Outcomes to First-Line Antiretroviral Therapy in Peru

Access to nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line antiretroviral therapy (ART) for HIV has been increasing in Peru since a national ART program was initiated in 2004. Between 2007 and 2009, we found a 1% prevalence of pr...

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Autores principales: Jaime Soria, Raquel Mugruza, Molly Levine, Segundo R. León, Jorge Arévalo, Eduardo Ticona, Ingrid A. Beck, Lisa M. Frenkel
Formato: Artículo
Lenguaje:inglés
Publicado: 2018
Materias:
Resistance mutation
Virology
Reverse transcriptase
Medicine
Reverse-transcriptase inhibitor
Drug resistance
Nucleoside Reverse Transcriptase Inhibitor
Cohort
Viral load
Zidovudine
HIV drug resistance
Stavudine
Dolutegravir
Viral quasispecies
Antiretroviral therapy
Internal medicine
Human immunodeficiency virus (HIV)
Biology
Virus
Polymerase chain reaction
Viral disease
Genetics
Hepatitis C virus
Gene
Adolescent
Adult
Female
Genes, Viral
Genotype
Humans
Male
Middle Aged
Mutation
Peru
Risk Factors
HIV-1 drug effects
HIV-1 genetics
HIV Infections blood
HIV Infections drug therapy
HIV Infections virology
Treatment Outcome
Anti-HIV Agents therapeutic use
Viral Load
Drug Resistance, Viral
Anti-Retroviral Agents
Young Adult
Health Sciences Medicine Infectious Diseases HIV/AIDS drug development and treatment
Life Sciences Immunology and Microbiology Virology HIV Research and Treatment
Health Sciences Medicine Infectious Diseases HIV/AIDS Research and Interventions
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Sumario:Access to nucleoside reverse transcriptase inhibitor (NRTI) and non-nucleoside reverse transcriptase inhibitor (NNRTI) first-line antiretroviral therapy (ART) for HIV has been increasing in Peru since a national ART program was initiated in 2004. Between 2007 and 2009, we found a 1% prevalence of pre-ART HIV drug resistance (PDR) among antiretroviral (ARV)-naive Peruvians. Given that PDR has been associated with virologic failure (VF) of ART, in 2014-2015 we enrolled a follow-up cohort at the same institution to determine whether the rate of transmitted resistance had increased and compared virologic outcomes of those with and without PDR. Blood specimens from ARV-naive individuals were assessed for PDR to NNRTI-based ART by an oligonucleotide ligation assay (OLA) sensitive to 2% mutant within an individual's HIV quasispecies at reverse transcriptase codons M41L, K65R, K103N, Y181C, M184V, and G190A, and by Sanger consensus sequencing (CS). Rates of VF (plasma HIV RNA >200 copies/mL) were compared between those with and without PDR. Among 122 ARV-naive adults, PDR was detected by OLA in 17 (13.9%) adults. Compared with the 2007-2009 cohort, the proportion with PDR at OLA codons was significantly increased (p < .001). A total of 11 of 19 OLA mutations conferring high-level drug resistance were also detected by CS, and 8 additional participants had mutations encoding low-level resistance detected by CS for a total of 25 participants (20.5%). VF at month 6 of NNRTI-ART appeared greater in participants with versus without PDR [4/18 (22.2%) vs. 3/71 (4.2%); p = .03]. An increasing prevalence of PDR was detected among ARV-naive Peruvians. Studies are needed to determine risks of specific PDR mutations.

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