HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam

• Published in: Antiviral therapy 2012-01, Vol.17 (5), p.905-913
• Main Authors: Thao, Vu P, Le, Thuy, Török, Estee M, Yen, Nguyen T B, Chau, Tran T H, Jurriaans, Suzanne, van Doorn, H Rogier, van Doorn, Rogier H, de Jong, Menno D, Farrar, Jeremy J, Dunstan, Sarah J
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - pharmacology; Anti-HIV Agents - therapeutic use; Coinfection - drug therapy; Drug Resistance, Viral - genetics; Genotype; HIV Infections - complications; HIV Infections - drug therapy; HIV Infections - virology; HIV-1 - drug effects; HIV-1 - genetics; Humans; Mutation; Polymorphism, Genetic; Prevalence; Treatment Failure; Tuberculosis, Meningeal - complications; Vietnam - epidemiology
• ISSN: 1359-6535; 2040-2058
• DOI: 10.3851/IMP2098

Access to antiretroviral therapy (ART) for HIV-infected individuals in Vietnam is rapidly expanding, but there are limited data on HIV drug resistance (HIVDR) to guide ART strategies. We retrospectively conducted HIVDR testing in 220 ART-naive individuals recruited to a randomized controlled trial of immediate versus deferred ART in individuals with HIV-associated tuberculous meningitis in Ho Chi Minh City (HCMC) from 2005-2008. HIVDR mutations were identified by population sequencing of the HIV pol gene and were defined based on 2009 WHO surveillance drug resistance mutations (SDRMs). We successfully sequenced 219/220 plasma samples of subjects prior to ART; 218 were subtype CRF01_AE and 1 was subtype B. SDRMs were identified in 14/219 (6.4%) subjects; 8/14 were resistant to nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs; T69D, L74V, V75M, M184V/I and K219R), 5/14 to non-nucleoside reverse transcriptase inhibitors (NNRTIs; K103N, V106M, Y181C, Y188C and G190A), 1/14 to both NRTIs and NNRTIs (D67N and Y181C) and none to protease inhibitors. After 6 months of ART, eight subjects developed protocol-defined virological failure. HIVDR mutations were identified in 5/8 subjects. All five had mutations with high-level resistance to NNRTIs and three had mutations with high-level resistance to NRTIs. Due to a high early mortality rate (58%), the effect of pre-existing HIVDR mutations on treatment outcome could not be accurately assessed. The prevalence of WHO SDRMs in ART-naive individuals with HIV-associated tuberculous meningitis in HCMC from 2005-2008 is 6.4%. The SDRMs identified conferred resistance to NRTIs and/or NNRTIs, reflecting the standard first-line ART regimens in Vietnam.