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Immunologic Biomarkers, Morbidity, and Mortality in Treated HIV Infection

Rosuvastatin slows progression of subclinical atherosclerosis in patients with treated HIV infection

Antiretroviral therapy for the prevention of HIV-1 transmission

HIV Transmission Risk Persists During the First 6 Months of Antiretroviral Therapy

Review of the Efficacy, Safety, and Pharmacokinetics of Raltegravir in Pregnancy

Use of Abacavir and Risk of Cardiovascular Disease Among HIV-Infected Individuals

Rosuvastatin Is Effective to Decrease CD8 T-Cell Activation Only in HIV-Infected Patients With High Residual T-Cell Activation Under Antiretroviral Therapy

Botswana's progress toward achieving the 2020 UNAIDS 90-90-90 antiretroviral therapy and virological suppression goals: a population-based survey

Empirical tuberculosis therapy versus isoniazid in adult outpatients with advanced HIV initiating antiretroviral therapy (REMEMBER): a multicountry open-label randomised controlled trial

Feasibility and efficacy of early lung cancer diagnosis with chest computed tomography in HIV-infected smokers

Patterns of Cardiovascular Mortality for HIV-Infected Adults in the United States: 1999 to 2013

Adjunctive Dexamethasone in HIV-Associated Cryptococcal Meningitis

Outcomes of HIV-associated Hodgkin lymphoma in the era of antiretroviral therapy

CD4+ and CD8+ T-cell kinetics in aviremic HIV-infected patients developing Hodgkin or non-Hodgkin lymphoma

CD8 T-Cell Expansion and Inflammation Linked to CMV Coinfection in ART-treated HIV Infection

Human Immunodeficiency Virus Infection Does Not Worsen Prognosis of Liver Transplantation for Hepatocellular Carcinoma

Ongoing HIV Replication Replenishes Viral Reservoirs During Therapy

Incidence and progression of coronary artery calcium in HIV-infected and HIV-uninfected men

Transient elastography for the detection of hepatic fibrosis in HIV-monoinfected adults with elevated aminotransferases on antiretroviral therapy

Association of immune-activation and senescence markers with non-AIDS-defining comorbidities in HIV-suppressed patients

Effects of randomized rosuvastatin compared with placebo on bone and body composition among HIV-infected adults

Levels of intracellular HIV-DNA in patients with suppressive antiretroviral therapy

Cancer Risk and Use of Protease Inhibitor or Nonnucleoside Reverse Transcriptase Inhibitor–Based Combination Antiretroviral Therapy The D:A:D Study

Time trends for risk of severe age-related diseases in individuals with and without HIV infection in Denmark: a nationwide population-based cohort study

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The effect of cumulating exposure to abacavir on the risk of cardiovascular disease events in patients from the Swiss HIV Cohort Study

Course and Clinical Significance of CD8+ T-Cell Counts in a Large Cohort of HIV-Infected Individuals

Impact of low-level viremia on clinical and virological outcomes in treated HIV-1-infected patients

HIV-1 subtype B-infected MSM may have driven the spread of transmitted resistant strains in France in 2007-12: impact on susceptibility to first-line strategies

Influence of the Timing of Antiretroviral Therapy on the Potential for Normalization of Immune Status in Human Immunodeficiency Virus 1–Infected Individuals

Cross-sectional Comparison of the Prevalence of Age-Associated Comorbidities and Their Risk Factors Between HIV-Infected and Uninfected Individuals: The AGEhIV Cohort Study

CD4/CD8 ratio normalisation and non-AIDS-related events in individuals with HIV who achieve viral load suppression with antiretroviral therapy: an observational cohort study

Baseline HIV-1 resistance, virological outcomes, and emergent resistance in the SECOND-LINE trial: an exploratory analysis

Effects of statin therapy on coronary artery plaque volume and high-risk plaque morphology in HIV-infected patients with subclinical atherosclerosis: a randomised, double-blind, placebo-controlled trial

Low Bone Mineral Density in Patients With Well-Suppressed HIV Infection: Association With Body Weight, Smoking, and Prior Advanced HIV Disease

Early versus delayed initiation of highly active antiretroviral therapy for HIV-positive adults with newly diagnosed pulmonary tuberculosis (TB-HAART): a prospective, international, randomised, placebo-controlled trial

A chronic kidney disease risk score to determine tenofovir safety in a prospective cohort of HIV-positive male veterans

Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial

Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1

Baseline HIV-1 resistance, virological outcomes, and emergent resistance in the SECOND-LINE trial: an exploratory analysis
Published by Anton POZNAK

Updated: 15 April, 2015

Boyd MA et al. Lancet HIV 2015; 2: e42–51

The WHO-recommended second-line antiretroviral therapy of a pharmacologically enhanced protease inhibitor plus nucleoside or nucleotide reverse transcriptase inhibitors might be compromised by resistance. Results of the 96 week SECOND-LINE randomized trial showed that NtRTI-sparing antiretroviral therapy with LPV/r and RAL provided non-inferior efficacy to LPV/r and two or three NtRTIs in participants with virological failure of a first-line regimen of a NNRTI plus two NtRTIs. This exploratory analysis assessed the relation of baseline virological resistance with virological failure and emergent resistant on study. In the SECOND-LINE trial, selection of NtRTI as part of the second-line antiretroviral therapy was made by either genotype at local laboratory or algorithm. Genotypic resistance for the entire cohort at baseline was assessed on stored samples at a central laboratory. Virological failure was defined as plasma viral load > 200 copies/mL. Baseline viral isolates were assigned genotypic sensitivity scores by use of the Stanford HIV database version 6.3.1: a global genotypic sensitivity scores (gGSS), defined as the combined GSS for the 7 NtRTIs and a specific genotypic sensitivity scores (sGSS) defined as the genotypic sensitivity scores for the ART regimen initiated by a specific participant. Emergent resistance was reported on samples with a viral load > 500 copies/mL. A multivariate logistic regression with backward elimination assessed predictors of virological failure and emergent resistance. Of the 271 patients included in the NtRTI group and 270 in the RAL group, 215 and 236, respectively, had available baseline sequence data, and 240 and 255, respectively, had viral load measurements at 96 weeks. Median (IQR) gGSS was 3.0 (1.3-4.3) in the NtRTI group and 3.0 (1.0-4.3) in the RAL group. The median sGSS in the NtRTI group was 1.0 (0.5-1.8). Multivariate analysis showed significant associations between virological failure and less than complete adherence at week 4 (odds ratio 2.18, 95% CI 1.07-4.47, p=0.03) and week 48 (2.49, 1.09-5.69, p=0.03), baseline plasma viral load > 100,000 copies/mL (3.43, 1.70-6.94, p=0.0006), baseline gGSS > 4.25 (4.73, 1.94-11.6, p=0.0007), and being Hispanic (3.13, 1.21-8.13, p=0.02) or African (3.49, 1.68-7.28, p=0.0008) rather than Asian. Emergence of resistance was associated with the RAL group (odds ratio 2.47, 95% CI 1.02-5.99, p=0.05), baseline viral load (1.83, 1.12-2.97, p=0.02), and absence of the K65R or K70E mutation at baseline (3.18, 1.12-9.02, p=0.03). Poor adherence was a major determinant of virological failure in participants on second-line antiretroviral therapy. In settings with limited resources, investment in optimisation of adherence rather than implementation of drug resistance testing might be advisable .