THE MOST COMPLETE WEBSITE ON CLINICAL TRIALS IN HIV INFECTION (FIRST-LINE, SWITCH, PHASE 2)

Breaking News

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

TEMPRANO

START

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

Successful Prevention of Transmission of Integrase Resistance in the Swiss HIV Cohort Study
Published by François RAFFI

Updated: 1 January, 2017

Scherrer AU et al. J Infect Dis. 2016 Aug 1;214(3):399-402

The prevalence of integrase strand transfer inhibitor (INSTI)–transmitted drug resistance (TDR) may increase with the increasing use of INSTIs.

We analyzed the prevalence of INSTI TDR in the Swiss HIV Cohort Study (2008–2014). 1316 patients had ≥1 genotypic drug resistance test performed for the integrase gene before the first exposure to an INSTI (earliest GRT per patient chosen). Samples retrieved before 2008 were summarized together as a group. We considered drug resistance mutations listed by the IAS–USA in 2015 and differentiated between minor mutations (T66AK, L74 M, E92G, T97A, E138AK, G140AS, and R263K) and major mutations (T66I, E92Q, F121Y, Y143CHR, S147G, Q148HKR, and N155H). To account for potential reversion of TDR mutations in the absence of drug pressure, we performed a subanalysis that included only GRTs from recently infected, treatment-naive patients.

We compared different aspects of the period after the introduction of INSTI (2008–2014) to the periods after introduction of NNRTIs (1998–2004), unboosted PIs (1996–2002), and PI/r (1999–2005).

Treatment failure was defined as ≥1 viral load of ≥ 500 HIV-1 RNA copies/mL (after 180 days of continuous treatment or previous viral suppression) followed by a treatment change or stop.

In 1 of 1316 drug-naive samples (0.1%), a major INSTI TDR mutation was detected (T66I, found in a sample retrieved in 2001). The most common minor mutations, most likely polymorphic, were L74M (17 of 1316 [1.3%]) and T97A (16 of 1316 [1.2%]). Minor mutations were more common in subtype non-B infections as compared to subtype B infections (24 of 466 [5.2%] vs 14 of 850 [1.6%]; P < .001, by the Fisher exact test). Prevalence of minor mutations was stable, although INSTIs were increasingly used. The results were similar when we restricted the analysis to recently infected patients (no major mutation in 303 samples). The low prevalence may be explained by the low number of patients who were potential transmitters of INSTI resistance (between 2008 and 2014, 85 patients experienced a treatment failure on ART including INSTIs in the entire SHCS database).

We showed that this is in contrast to the introduction of previous drug classes, in which more treatment failures with resistant strains occurred and TDR was observed more rapidly. In the 7 years after the introduction of unboosted PIs, PI/r, and NNRTIs, 18.2 times, 5.7 times, and 7.2 times more patients did not respond to the respective ART.

Conclusion : We demonstrated on a population-level that it is possible to avoid TDR to a new drug class for years.