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High prevalence of PI resistance in patients failing second-line ART in Vietnam.

ABSTRACT: There are limited data from resource-limited settings on antiretroviral resistance mutations that develop in patients failing second-line PI ART.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.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.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.

SUBMITTER: Thao VP

PROVIDER: S-EPMC4743698 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature

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High prevalence of PI resistance in patients failing second-line ART in Vietnam.

Thao Vu Phuong VP Quang Vo Minh VM Day Jeremy N JN Chinh Nguyen Tran NT Shikuma Cecilia M CM Farrar Jeremy J Van Vinh Chau Nguyen N Thwaites Guy E GE Dunstan Sarah J SJ Le Thuy T

The Journal of antimicrobial chemotherapy 20151211 3

<h4>Background</h4>There are limited data from resource-limited settings on antiretroviral resistance mutations that develop in patients failing second-line PI ART.<h4>Methods</h4>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 ≥1 ...[more]

PMID: 26661398

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Project description:ObjectivesWe compared mortality between HIV-positive and HIV-negative South African adults with drug-resistant tuberculosis (DR-TB) and high incidence of acquired second-line drug resistance.MethodsWe performed a retrospective review of DR-TB patients with serial second-line TB drug susceptibility tests (2008-2015) who were hospitalized at a specialized TB hospital. We used Kaplan-Meier analysis and Cox models to examine associations with mortality.ResultsOf 245 patients, the median age was 33 years, 54% were male and 40% were HIV-positive, 96% of whom had ever received antiretroviral therapy (ART). At initial drug resistance detection, 99% of patients had resistance to at least rifampicin and isoniazid, and 18% had second-line drug resistance (fluoroquinolones and/or injectable drugs). At later testing, 88% of patients had acquired additional second-line drug resistance. Patient-initiated treatment interruptions (> 2 months) occurred in 47%. Mortality was 79%. Those with HIV had a shorter time to death (p = 0.02; log-rank): median survival time from DR-TB treatment initiation was 2.44 years [95% confidence interval (CI): 2.09-3.15] versus 3.99 years (95% CI: 3.12-4.75) for HIV-negative patients. HIV-positive patients who received ART within 6 months before DR-TB treatment had a higher mortality hazard than HIV-negative patients [adjusted hazard ratio (aHR) ratio = 1.82, 95% CI: 1.21-2.74]. By contrast, HIV-positive patients who did not receive ART within 6 months before DR-TB treatment did not have a significantly higher mortality hazard than HIV-negative patients (aHR = 1.09; 95% CI: 0.72-1.65), although those on ART had lower median CD4 counts than those not on ART (157 vs. 281 cells/μL, respectively; p = 0.02).ConclusionsA very high incidence of acquired second-line drug resistance and high overall mortality were observed, reinforcing the need to reduce the risk of acquired resistance and for more effective treatment.

Project description:IntroductionTuberculosis (TB) remains a significant cause of morbidity and mortality in Vietnam. The current TB burden is unknown as not all individuals with TB are diagnosed, recorded and notified. The second national TB prevalence survey was conducted in 2017-2018 to assess the current burden of TB disease in the country.MethodEighty-two clusters were selected using a multistage cluster sampling design. Adult (≥15 years of age) residents having lived for 2 weeks or more in the households of the selected clusters were invited to participate in the survey. The survey participants were screened for TB by a questionnaire and digital chest X-ray after providing written informed consent. Individuals with a positive symptom screen and/or chest X-ray suggestive of TB were asked to provide sputum samples to test for Mycobacterium tuberculosis by Ziehl-Neelsen direct light microscopy, Xpert MTB/RIF G4, BACTEC MGIT960 liquid culture and Löwenstein-Jensen solid culture. Bacteriologically confirmed TB cases were defined by an expert panel following a standard decision tree.ResultOf 87,207 eligible residents, 61,763 (70.8%) participated, and 4,738 (7.7%) screened positive for TB. Among these, 221 participants were defined as bacteriologically confirmed TB cases. The estimated prevalence of bacteriologically confirmed adult pulmonary TB was 322 (95% CI: 260-399) per 100,000, and the male-to-female ratio was 4.0 (2.8-5.8, p<0.001). In-depth interviews with the participants with TB disease showed that only 57.9% (95% CI: 51.3-64.3%) reported cough for 2 weeks or more and 32.1% (26.3-38.6%) did not report any symptom consistent with TB, while their chest X-ray results showed that 97.7% (95% CI: 94.6-99.1) had abnormal chest X-ray images suggesting TB.ConclusionWith highly sensitive diagnostics applied, this survey showed that the TB burden in Vietnam remains high. Half of the TB cases were not picked up by general symptom-based screening and were identified by chest X-ray only. Our results indicate that improving TB diagnostic capacity and access to care, along with reducing TB stigma, need to be top priorities for TB control and elimination in Vietnam.

Project description:IntroductionWhen protease inhibitor (PI)-based second-line ART fails, guidelines recommend drug resistance testing and individualized third-line treatment. However, PI-resistant viral strains are rare and drug resistance testing is costly. We investigated whether less costly PI-exposure testing can be used to select those patients who would benefit most from drug resistance testing.MethodsWe performed a retrospective analysis of South African adults living with HIV experiencing failure of ritonavir-boosted-lopinavir (LPV/r)-based second-line ART for whom drug resistance testing results were available. We included patients who received plasma-based drug resistance testing at a central South African reference laboratory in 2017 and patients who received dried blood spots (DBS)-based drug resistance testing at a rural South African clinic between 2009 and 2017. PI-exposure testing was performed on remnant plasma or DBS using liquid chromatography mass spectrometry (LCMS). Additionally, a low-cost immunoassay was used on plasma. Population genotypic drug resistance testing of the pol region was performed on plasma and DBS using standard clinical protocols.ResultsSamples from 544 patients (494 plasma samples and 50 DBS) were included. Median age was 41.0 years (IQR: 33.3 to 48.5) and 58.6% were women. Median HIV-RNA load was 4.9 log10 copies/mL (4.3 to 5.4). Prevalence of resistance to the NRTI-backbone was 70.6% (349/494) in plasma samples and 56.0% (28/50) in DBS. Major PI-resistance mutations conferring high-level resistance to LPV/r were observed in 26.7% (132/494) of plasma samples and 12% (6/50) of DBS. PI-exposure testing revealed undetectable LPV levels in 47.0% (232/494) of plasma samples and in 60.0% (30/50) of DBS. In pooled analysis of plasma and DBS samples, detectable LPV levels had a sensitivity of 90% (84% to 94%) and a negative predictive failure of 95% (91% to 97%) for the presence of major LPV/r resistance.ConclusionsPI-exposure testing revealed non-adherence in half of patients experiencing failure on second-line ART and accurately predicted the presence or absence of clinically relevant PI resistance. PI-exposure testing constitutes a novel screening strategy in patients with virological failure of ART that can differentiate between different underlying causes of therapy failure and may allow for more effective use of limited resources available for drug resistance testing.

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High prevalence of PI resistance in patients failing second-line ART in Vietnam.

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High prevalence of PI resistance in patients failing second-line ART in Vietnam.

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