Browsing by Author "Dunstan, Sarah J"

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    High prevalence of PI resistance in patients failing second-line ART in Vietnam.
    (J Antimicrob Chemother, 2016-03) Thao, Vu Phuong; Quang, Vo Minh; Day, Jeremy N; Chinh, Nguyen Tran; Shikuma, Cecilia M; Farrar, Jeremy; Van Vinh Chau, Nguyen; Thwaites, Guy E; Dunstan, Sarah J; Le, Thuy
    BACKGROUND: There are limited data from resource-limited settings on antiretroviral resistance mutations that develop in patients failing second-line PI ART. METHODS: We performed a cross-sectional virological assessment of adults on second-line ART for ≥6 months between November 2006 and December 2011, followed by a prospective follow-up over 2 years of patients with virological failure (VF) at the Hospital for Tropical Diseases, Vietnam. VF was defined as HIV RNA concentrations ≥1000 copies/mL. Resistance mutations were identified by population sequencing of the pol gene and interpreted using the 2014 IAS-USA mutation list and the Stanford algorithm. Logistic regression modelling was performed to identify predictors of VF. RESULTS: Two hundred and thirty-one patients were enrolled in the study. The median age was 32 years; 81.0% were male, 95.7% were on a lopinavir/ritonavir-containing regimen and 22 (9.5%) patients had VF. Of the patients with VF, 14 (64%) carried at least one major protease mutation [median: 2 (IQR: 1-3)]; 13 (59%) had multiple protease mutations conferring intermediate- to high-level resistance to lopinavir/ritonavir. Mutations conferring cross-resistance to etravirine, rilpivirine, tipranavir and darunavir were identified in 55%, 55%, 45% and 27% of patients, respectively. Higher viral load, adherence <95% and previous indinavir use were independent predictors of VF. The 2 year outcomes of the patients maintained on lopinavir/ritonavir included: death, 7 (35%); worsening virological/immunological control, 6 (30%); and virological re-suppression, 5 (25%). Two patients were switched to raltegravir and darunavir/ritonavir with good HIV control. CONCLUSIONS: High-prevalence PI resistance was associated with previous indinavir exposure. Darunavir plus an integrase inhibitor and lamivudine might be a promising third-line regimen in Vietnam.
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    HIV-1 drug resistance in antiretroviral-naive individuals with HIV-1-associated tuberculous meningitis initiating antiretroviral therapy in Vietnam.
    (Antivir Ther, 2012) Thao, Vu P; Le, Thuy; Török, Estee M; Yen, Nguyen TB; Chau, Tran TH; Jurriaans, Suzanne; van Doorn, H Rogier; de Jong, Menno D; Farrar, Jeremy J; Dunstan, Sarah J
    BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.