Editor’s Choice: No Evidence That HIV-1 Subtype C Infection Compromises the Efficacy of Tenofovir-Containing Regimens: Cohort Study in the United Kingdom
Journal of Infectious Diseases November 1, 2016 V.214 N.9 P.1302-1308
Ellen White, Erasmus Smit, Duncan Churchill, Simon Collins, Clare Booth, Anna Tostevin, Caroline Sabin, Deenan Pillay, and David T. Dunn on behalf of the UK HIV Drug Resistance Database and UK Collaborative HIV Cohort Study
1MRC Clinical Trials Unit at UCL
2Department of Infection and Population Health
3Division of Infection and Immunity, University College London
5Health Service Laboratories, Royal Free Hospital, London
6Public Health England, Birmingham Heartlands Hospital
7Brighton and Sussex Hospitals NHS Trust, United Kingdom
8Africa Centre for Population Health, University of KwaZulu-Natal, Durban, South Africa
Concern has been expressed that tenofovir-containing regimens may have reduced effectiveness in the treatment of human immunodeficiency virus type 1 (HIV-1) subtype C infections because of a propensity for these viruses to develop a key tenofovir-associated resistance mutation.
We evaluated whether subtype influenced rates of virological failure in a cohort of 8746 patients from the United Kingdom who received a standard tenofovir-containing first-line regimen and were followed for a median of 3.3 years.
In unadjusted analyses, the rate of failure was approximately 2-fold higher among patients infected with subtype C virus as compared to those with subtype B virus (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.50–2.31; P < .001). However, the increased risk was greatly attenuated in analyses adjusting for demographic and clinical factors (adjusted HR, 1.14; 95% CI, .83–1.58; P = .41).
There were no differences between subtypes C and subtypes non-B and non-C in either univariate or multivariate analysis. These observations imply there is no intrinsic effect of viral subtype on the efficacy of tenofovir-containing regimens.
J Infect Dis. (2016) 214 (9): 1289-1291
Editor’s Choice: HIV-1 Subtype C, Tenofovir, and the Relationship With Treatment Failure and Drug Resistance
Huldrych F. Günthard and Alexandra U. Scherrer
Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich and Institute of Medical Virology, Switzerland
Tenofovir disoproxil fumarate (TDF) has emerged as a cornerstone of initial antiretroviral therapy (ART) [1, 2].
However, human immunodeficiency virus type 1 (HIV) subtype C, the most prevalent worldwide subtype, accounting for >50% of all HIV infections, harbors polymorphisms in reverse transcriptase codons 64, 65, and 66, which lead to more-rapid in vitro selection of the K65R mutation , the signature mutation conferring resistance to TDF .
Subtype C viruses may only require a single point mutation at position 65 to select for K65R.
Several clinical studies have suggested that this mechanism may contribute to higher treatment failure rates and higher rates of the emergence of the K65R mutations observed in HIV subtype C–infected, compared with subtype B–infected, individuals treated with TDF-containing regimens [5–9], although others could not confirm different response rates between subtype B and C [10–12].
In this issue of The Journal of Infectious Diseases, White et al report a comprehensive study on this issue .
They analyzed data from the UK Collaborative HIV Cohort (CHIC) Study (available at: http://www.ukchic.org.uk) and included 8746 patients who had initiated ART containing TDF, plus lamivudine or emtricitabine and either a nonnucleoside reverse transcriptase inhibitor (NNRTI; efavirenz or nevirapine) or a ritonavir-boosted protease inhibitor (lopinavir, atazanavir, or darunavir), and were followed for a median of 3.3 years.
Unadjusted analyses indicated an approximately 2-fold higher virological failure rate for subtype C–infected individuals as compared to subtype B–infected individuals. However, when they adjusted …
Infectious Diseases Society of America Guidelines for the Diagnosis and Treatment of Asymptomatic Bacteriuria in Adults Genomic Epidemiology of Gonococcal Resistance to Extended-Spectrum Cephalosporins, Macrolides, and Fluoroquinolones in the United States, 2000–2013