Posts filed under ‘HIV/SIDA HAART’

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

4HIV i-Base

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.

PDF

http://jid.oxfordjournals.org/content/214/9/1302.full.pdf+html

 

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 [3], the signature mutation conferring resistance to TDF [4].

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 [13].

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 …

PDF

http://jid.oxfordjournals.org/content/214/9/1289.full.pdf+html

December 22, 2016 at 8:17 am

Impact of Cigarette Smoking and Smoking Cessation on Life Expectancy Among People With HIV: A US-Based Modeling Study

Journal of Infectious Diseases December 1, 2016 V.214 N.11 P.1672-1681

Krishna P. Reddy, Robert A. Parker, Elena Losina, Travis P. Baggett, A. David Paltiel, Nancy A. Rigotti, Milton C. Weinstein, Kenneth A. Freedberg, and Rochelle P. Walensky

1Medical Practice Evaluation Center

2Division of Pulmonary and Critical Care Medicine

3Division of General Internal Medicine

4Biostatistics Center

5Tobacco Research and Treatment Center

6Mongan Institute for Health Policy

7Division of Infectious Diseases, Massachusetts General Hospital

8Harvard Medical School

9Department of Orthopedic Surgery

10Division of Infectious Diseases, Brigham and Women’s Hospital

11Department of Biostatistics

12Department of Epidemiology, Boston University School of Public Health

13Boston Health Care for the Homeless Program

14Department of Health Policy and Management, Harvard T. H. Chan School of Public Health, Boston, Massachusetts

15Yale School of Public Health, New Haven, Connecticut

Background

In the United States, >40% of people infected with human immunodeficiency virus (HIV) smoke cigarettes.

Methods

We used a computer simulation of HIV disease and treatment to project the life expectancy of HIV-infected persons, based on smoking status. We used age- and sex-specific data on mortality, stratified by smoking status. The ratio of the non-AIDS-related mortality risk for current smokers versus that for never smokers was 2.8, and the ratio for former smokers versus never smokers was 1.0–1.8, depending on cessation age. Projected survival was based on smoking status, sex, and initial age. We also estimated the total potential life-years gained if a proportion of the approximately 248 000 HIV-infected US smokers quit smoking.

Results

Men and women entering HIV care at age 40 years (mean CD4+ T-cell count, 360 cells/µL) who continued to smoke lost 6.7 years and 6.3 years of life expectancy, respectively, compared with never smokers; those who quit smoking upon entering care regained 5.7 years and 4.6 years, respectively. Factors associated with greater benefits from smoking cessation included younger age, higher initial CD4+ T-cell count, and complete adherence to antiretroviral therapy. Smoking cessation by 10%–25% of HIV-infected smokers could save approximately 106 000–265 000 years of life.

Conclusions

HIV-infected US smokers aged 40 years lose >6 years of life expectancy from smoking, possibly outweighing the loss from HIV infection itself. Smoking cessation should become a priority in HIV treatment programs.

PDF

http://jid.oxfordjournals.org/content/214/11/1672.full.pdf+html

December 11, 2016 at 8:29 pm

Editorial – The Shifting Paradigm of Care for Adults Living With HIV – Smoking Cessation for Longer Life

Journal of Infectious Diseases December 1, 2016 V.214 N.11 P.1618-1620

Keri N. Althoff

Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland

There are few truths in medical science that are as agreed upon as this: smoking is bad for health. In persons with human immunodeficiency virus (HIV) infection, smoking is a scourge, with recent prevalence estimates of 42%, which Reddy et al, in this issue of The Journal of Infectious Diseases, translated to an estimated 247 586 smokers among those in HIV care in the United States [1, 2]. It is hypothesized that adults living with HIV start smoking at younger ages, smoke more heavily and for a longer duration, and have lower rates of cessation than the general population in the United States. However, population-based estimates are not available. The problem may seem insurmountable, particularly because a delay in the manifestations of harm from smoking creates a lack of urgency for cessation. Because the HIV infection paradigm has changed from an acutely terminal illness to a chronic infection with a life expectancy approaching that of uninfected adults, the paradigm of how we protect the health of people living with HIV has also evolved.

Reddy et al estimate a gain in life expectancy of 5.7 years among men and 4.6 years among women who quit smoking upon entering into HIV care [2]. The authors predict that if a quarter of HIV-infected adults quit smoking, 265 000 years of life could be regained at the population level. It is reasonable to assume that there is also an increased quality of life, not only quantity of life, given the strong associations of smoking with a poorer immunologic response to antiretroviral therapy (ART) and the development of cancer, cardiovascular disease, chronic obstructive pulmonary disease, and lower respiratory tract infections [3]. After accounting for nonadherence to …

PDF

http://jid.oxfordjournals.org/content/214/11/1618.full.pdf+html

December 11, 2016 at 8:28 pm

2016 BHIVA GUIDELINES for the routine investigation and monitoring of Adult HIV-1-positive individuals 72 pags

British HIV Association

Writing Group: Brian Angus (Chair), Gary    Brook (Vice-chair), Funmi Awosusi, Gary Barker, Marta Boffito, Satyajit Das, Lucy Dorrell, Esther Dixon-Williams, Charlotte Hall, Bridie Howe, Sebastian Kalwij, Nashaba Matin, Eleni Nastouli, Frank Post, Melinda Tenant-Flowers, Erasmus Smit, Dan Wheals

NHS Evidence has accredited the process used by the British HIV Association (BHIVA) to produce guidelines.

Accreditation is valid for five years from July 2012 and is applicable to guidance produced using the processes described in the British HIV Association (BHIVA) Guideline Development Manual. More information on accreditation can be viewed at www.nice.org.uk/accreditation

PDF

http://www.bhiva.org/documents/Guidelines/Monitoring/2016-BHIVA-Monitoring-Guidelines.pdf

December 3, 2016 at 9:35 am

2016 BHIVA GUIDELINES for the treatment of HIV-1-positive Adults with antiretroviral therapy

The British HIV Association

Writing Group

Laura Waters (Chair)

N Ahmed, B Angus, M Boffito, M Bower, D Churchill, D Dunn, S Edwards, C Emerson, S Fidler, †M Fisher, R Horne, S Khoo, C Leen, N Mackie, N Marshall, F Monteiro, M Nelson, C Orkin, A Palfreeman, S Pett, A Phillips, F Post, A Pozniak, I Reeves, C Sabin, R Trevelion, J Walsh, E Wilkins, I Williams, A Winston

†Professor Martin Fisher died in April 2015 – he made a significant contribution to these, many other guidelines and our speciality as a whole – he is greatly missed.

Introduction

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of adults with HIV infection on antiretroviral therapy (ART).

The scope includes: (i) guidance on the initiation of ART in those previously naïve to therapy; (ii) support of people living with HIV (PLWH) on treatment; (iii) management of individuals experiencing virological failure; and (iv) recommendations in specific populations where other factors need to be taken into consideration.

The guidelines are aimed at clinical professionals directly involved with and responsible for the care of adults with HIV infection, and at community advocates responsible for promoting the best interests and care of HIV-positive adults. They should be read in conjunction with other published BHIVA guidelines.

The 2016 interim update to the 2015 BHIVA antiretroviral guidelines has been published online to include tenofovir-alafenamide/emtricitabine as a preferred NRTI backbone for first-line therapy. Changes were based on new data and the consensus opinion of the writing committee. All changes to the guideline are highlighted and include updates to the chronic kidney disease and bone disease sections of special populations and some small changes to managing virological failure. The next formal update to the guidelines in anticipated in 2017.

PDF

http://www.bhiva.org/documents/Guidelines/Treatment/2016/treatment-guidelines-2016-interim-update.pdf

December 3, 2016 at 9:33 am

Human Immunodeficiency Virus and Total Joint Arthroplasty: The Risk for Infection Is Reduced

Journal of Arthroplasty October 2016 V.31 N.10 P.2146–2151

Mohammad Ali Enayatollahi, Dermot Murphy, Mitchell G. Maltenfort, Javad Parvizi

Background

Highly active antiretroviral therapy (HAART) has changed the face of human immunodeficiency virus (HIV) and allowed patients to live for many decades. HIV and HAART are known risk factors for osteonecrosis of bone, osteopenia, and osteoporosis. Therefore, the demand for total joint arthroplasty (TJA) in HIV-infected patients is on the rise. We attempted to determine whether modern treatments for HIV have impacted the rate of periprosthetic joint infection (PJI).

Methods

Conducting a systematic review, 25 studies with a total of 722 TJAs were identified. We extracted data on rates of PJI after primary TJA in HIV-infected patients with and without hemophilia and data on administration of HAART at the time of arthroplasty.

Results

Three hundred eighty-one TJAs were performed in 293 patients with HIV infection without hemophilia. The follow-up ranged between 1.5 months and 11 years. Nine patients developed PJI. In patients with both HIV and hemophilia, 341 primary TJAs were performed. Forty-five received treatment for PJI. Follow-up ranged between 1 year and 26 years. Rates of PJI were 2.28% and 10.98% for HIV-only patients and patients with HIV and hemophilia, respectively. This difference was statistically significant (P < .0001) with a 5.28 odds ratio for hemophilia. HAART was associated with fewer infections overall (odds ratio, 0.12).

Conclusion

The rates of PJI after TJA in HIV-only patients are lower than those in patients with both HIV and hemophilia. Treatment of patients with HAART and optimization of underlying comorbidities appears to lower the rate of PJI in this patient population.

abstract

http://www.arthroplastyjournal.org/article/S0883-5403(16)00206-0/fulltext

PDF

http://www.arthroplastyjournal.org/article/S0883-5403(16)00206-0/pdf

November 2, 2016 at 12:48 pm

Virological efficacy of PI monotherapy for HIV-1 in clinical practice

Antimicrob. Chemother. November 2016 V.71 N.11 P. 3228-3234

Kate El Bouzidi, Dami Collier, Eleni Nastouli, Andrew J. Copas, Robert F. Miller, and Ravindra K. Gupta

1Research Department of Infection, Division of Infection and Immunity, University College London, London, UK

2Research Department of Infection and Population Health, University College London, London, UK

3Department of Clinical Virology, University College London Hospitals NHS Trust, London, UK

4NIHR University College London Hospitals Biomedical Research Centre, London, UK

5Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK

Background

Clinical trials of PI monotherapy indicate that most participants maintain viral suppression and emergent protease resistance is rare. However, outcomes among patients receiving PI monotherapy for clinical reasons, such as toxicity or adherence issues, are less well studied.

Methods

An observational study of patients attending an HIV treatment centre in London, UK, who had received PI monotherapy between 2004 and 2013, was conducted using prospectively collected clinical data and genotypic resistance reports. Survival analysis techniques were used to examine the times to virological failure and treatment discontinuation.

Results

Ninety-five patients had PI monotherapy treatment for a median duration of 126 weeks. Virological failure occurred during 64% of episodes and 8% of patients developed emergent protease mutations. We estimate failure occurs in half of episodes within 2 years following initiation. Where PI monotherapy was continued following virological failure, 68% of patients achieved viral re-suppression. Despite a high incidence of virological failure, many patients continued PI monotherapy and 79% of episodes were ongoing at the end of the study. The type of PI used, the presence of baseline protease mutations and the plasma HIV RNA at initiation did not have a significant impact on treatment outcomes.

Conclusions

There was a higher incidence of virological failure and emerging resistance in our UK clinical setting than described in PI monotherapy clinical trials and other European observational studies. Despite this, many patients continued PI monotherapy and regained viral suppression, indicating this strategy remains a viable option in certain individuals following careful clinical evaluation.

PDF

http://jac.oxfordjournals.org/content/71/11/3228.full.pdf+html

 

October 23, 2016 at 6:25 pm

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