title: Molecular diversity of HIV-1 and surveillance of transmitted drug resistance variants among treatment Naïve patients, 5 years after active introduction of HAART in Kuala Lumpur, Malaysia.
abstract: Expansion of antiretroviral treatment programs have led to the growing concern for the development of antiretroviral drug resistance. The aims were to assess the prevalence of drug resistant HIV-1 variants and to identify circulating subtypes among HAART-naïve patients. Plasma specimens from N = 100 HIV+ HAART-naïve adult were collected between March 2008 and August 2010 and viral RNA were extracted for nested PCR and sequenced. PR-RT sequences were protein aligned and checked for transmitted drug resistance mutations. Phylogenetic reconstruction and recombination analysis were performed to determine the genotypes. Based on the WHO consensus guidelines, none of the recruited patients had any transmitted drug resistance mutations. When analyzed against the Stanford guidelines, 35% of patients had at least one reported mutation that may reduce drug susceptibility to PI (24%), NRTI (5%), and NNRTI (14%). The commonly detected mutation that may affect current first line therapy was V179D (3%), which may lead to reduced susceptibility to NNRTI. The predominant circulating HIV-1 genotypes were CRF01_AE (51%) and CRF33_01B (17%). The prevalence of unique recombinant forms (URF) was 7%; five distinct recombinant structures involving CRF01_AE and subtype B' were observed, among them a cluster of three isolates that could form a novel circulating recombinant form (CRF) candidate. Transmitted drug resistance prevalence among HAART-naïve patients was low in this cohort of patients in Kuala Lumpur despite introduction of HAART 5 years ago. Owing to the high genetic diversity, continued molecular surveillance can identify the persistent emergence of HIV-1 URF and novel CRF with significant epidemiological impact.
authors.affiliation: Faculty of Medicine, Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Lai Yee
authors.initials: LY
authors.lastname: Ong
authors.forename: Siti Nur Humaira
authors.initials: SN
authors.lastname: Razak
authors.forename: Yeat Mei
authors.initials: YM
authors.lastname: Lee
authors.forename: Sasheela
authors.initials: S
authors.lastname: Sri La Sri Ponnampalavanar
authors.forename: Sharifah Faridah
authors.initials: SF
authors.lastname: Syed Omar
authors.forename: Raja Iskandar
authors.initials: RI
authors.lastname: Azwa
authors.forename: Kok Keng
authors.initials: KK
authors.lastname: Tee
authors.forename: Adeeba
authors.initials: A
authors.lastname: Kamarulzaman
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000453:epidemiology / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008296:Malaysia / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010949:Plasma / Q000821:virology; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents; D012367:RNA, Viral; D054303:HIV Reverse Transcriptase
keywords: HIV; antiretroviral therapy; phylogenetics; virus evolution/diversity