Posts filed under ‘Antirretrovirales’

EDITOR’S CHOICE – Practical Review of Recognition and Management of Obesity and Lipohypertrophy in Human Immunodeficiency Virus Infection.

Clin Inf Dis May 15, 2017 V.64 N.10

Jordan E. Lake; Takara L. Stanley; Caroline M. Apovian; Shalendar Bhasin; Todd T. Brown …

Obesity and lipohypertrophy are common disease states in treated HIV infection that may have overlapping pathophysiologies and/or synergistic metabolic consequences. This is a consensus opinion on the epidemiology, diagnosis, and treatment of excess adiposity in adults with treated HIV infection.

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/cid/64/10/10.1093_cid_cix178/2/cix178.pdf?Expires=1494189161&Signature=Z86YQmq8fpG3rQeDTAgf-6dxeGAza3rir8VbdzT6~Y8BIIegZ9YFhVmvfCuuioUe6flXY~hkwOyW7VuLWzgwbl7oy15P8wEYUEyQ2~C6byqQrWFGAUGBe8sNOThSWkwuZhd-XSRlqUHu6mJlvYckWuaPcXk~BQ3NPGQNOgYlyfTs-ZiwqMg5SQThms7YEmJz2WzX8t3bXBFqazRAFCyGRixH~xhOTwmUm-Rmb1yBBo1Cvo0a0RmSK4juCMpxjC8U2b~LA2taJsD77csu3AsNFu4yG2r2X8vWA-QankHJZyzkO~aRfQNNx8913ZMbOUOsmf7nUemdLsBx-kXkO4LCHw__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

May 6, 2017 at 3:50 pm

Correspondence: Multidrug-resistant HIV-1 infection despite preexposure prophylaxis.

N Engl J Med 2017 Feb 2; 376:501

Knox DC et al.

To the Editor:

Preexposure prophylaxis with emtricitabine (FTC)–tenofovir disoproxil fumarate (TDF) has been shown to be efficacious in preventing human immunodeficiency virus type 1 (HIV-1) infection in men who have sex with men and in whom adherence to treatment is high, as measured by levels of tenofovir diphosphate (TFV-DP) in dried blood spots.1 We describe a case of HIV-1 infection despite FTC-TDF–based preexposure prophylaxis.2

A 43-year-old man in Toronto who reported having sex with men began to receive oral daily FTC-TDF in April 2013 and had seven nonreactive fourth-generation HIV screening tests over the next 21 months. Pharmacy dispensation records provided support for his report of “perfect” adherence to preexposure prophylaxis over 24 months……

PDF

http://www.nejm.org/doi/pdf/10.1056/NEJMc1611639

March 14, 2017 at 7:35 am

Brief Report: Enhanced Normalization of CD4/CD8 Ratio With Earlier Antiretroviral Therapy at Primary HIV Infection.

J Acquir Immune Defic Syndr. 2016 Sep 1;73(1):69-73.

Thornhill J1, Inshaw J, Kaleebu P, Cooper D, Ramjee G, Schechter M, Tambussi G, Fox J, Samuel M, Miro JM, Weber J, Porter K, Fidler S.

1 *Department of Medicine, Imperial College, London, United Kingdom; †Medical Research Council Clinical Trials Unit, University College London, London, United Kingdom; ‡Medical Research Council/Uganda Virus Research Institute Research Unit on AIDS, Entebbe, Uganda; §Kirby Institute University of New South Wales and Centre for Applied Medical Research, St Vincent’s Hospital, Sydney, Australia; ‖HIV Prevention Unit, Medical Research Council, Durban, South Africa; ¶Projeto Praça Onze, Hospital Escola Sao Francisco de Assis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; #Division of Infectious Diseases, Ospedale San Raffaele, Milan, Italy; **Department of HIV, Faculty of Medicine, Guys and St Thomas’ NHS Trust/Kings College London, United Kingdom; and ††Hospital Clinic – IDIBAPS, University of Barcelona, Barcelona, Spain.

Abstract

BACKGROUND:

Total CD4 T-cell counts predict HIV disease progression but do not necessarily reflect normalization of immune function. CD4/CD8 ratio is a marker of immune dysfunction, a prognostic indicator for non-AIDS mortality, and reflects viral reservoir size. Despite antiretroviral therapy (ART), recovery of CD4/CD8 ratio in chronic HIV infection is incomplete; we hypothesize enhanced CD4/CD8 ratio recovery with earlier treatment initiation in recently infected individuals.

METHODS:

CD4 count and CD4/CD8 ratio were analyzed using data from 2 cohorts: SPARTAC trial and the UK HIV Seroconverters Cohort where primary HIV infection (PHI) was defined as within 6 months from estimated date of infection. Using time-to-event methods and Cox proportional hazard models, we examined the effect of CD4/CD8 ratio at seroconversion on disease progression (CD4 <350 cells per cubic millimeter/ART initiation) and factors associated with time from ART initiation to CD4/CD8 normalization (ratio >1.0).

FINDINGS:

Of 573 seroconverters, 482 (84%) had abnormal CD4/CD8 ratios at HIV seroconversion. Individuals with higher CD4/CD8 ratio at seroconversion were significantly less likely to reach the disease progression endpoint [adjusted hazard ratio (aHR) (95% CI) = 0.52 (0.32 to 0.82), P = 0.005]. The longer the interval between seroconversion and ART initiation [HR (95% CI) = 0.98 per month increase (0.97, 0.99), P < 0.001], the less likely the CD4/CD8 ratio normalization. ART initiation within 6 months from seroconversion was significantly more likely to normalize [HR (95% CI) = 2.47 (1.67 to 3.67), P < 0.001] than those initiating later.

INTERPRETATION:

Most individuals presenting in PHI have abnormal CD4/CD8 ratios. The sooner the ART is initiated in PHI, the greater the probability of achieving normal CD4/CD8 ratio.

PDF

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4981213/pdf/qai-73-069.pdf

March 11, 2017 at 6:39 pm

The Brief Case: A Reactive HIV Rapid Antibody Test in a Pregnant Woman

Journal of Clinical Microbiology April 2016 V.54 N.4 P.826-828

Melanie L. Yarbrough and Neil W. Anderson

A 32-year-old pregnant woman presented to her obstetrician for routine prenatal care during her 3rd month of pregnancy. She reported no major health concerns, with the exception of mild morning sickness that had been gradually improving. Upon physical examination, she appeared healthy and her vitals were stable and within normal limits.

Abdominal ultrasound revealed reassuring fetal heart tones, and her remaining physical exam was unremarkable.

She was counseled regarding the need for several routine prenatal laboratory tests, including testing for human immunodeficiency virus (HIV), to which she agreed.

A rapid HIV test performed in the obstetrician’s office was positive for antibodies against HIV.

The positive rapid antibody result was shared with the patient. She denied any risk factors for HIV infection, including intravenous drug use and sex with multiple partners.

The obstetrician stressed that the results were only preliminary and required confirmatory testing. Prior to sending the patient home, a blood sample was drawn for submission to the local clinical laboratory for additional testing. The obstetrician called the laboratory asking how long it would take for the Western blot confirmatory test to be performed.

A representative from the testing laboratory informed him that they now used the fourth-generation algorithm and therefore no longer performed confirmatory testing by Western blot assay….

PDF

http://jcm.asm.org/content/54/4/826.full.pdf

February 23, 2017 at 7:54 am

CD4 Decline Is Associated With Increased Risk of Cardiovascular Disease, Cancer, and Death in Virally Suppressed Patients With HIV

Clinical Infectious Diseases July 15, 2013 V.57 N.2 P.314-321

Marie Helleberg, Gitte Kronborg, Carsten S. Larsen, Gitte Pedersen, Court Pedersen, Niels Obel, and Jan Gerstoft

1Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet

2Department of Infectious Diseases, Copenhagen University Hospital, Hvidovre

3Department. of Infectious Diseases, Aarhus University Hospital, Skejby

4Department of Infectious Diseases, Aalborg University Hospital

5Deptartment of Infectious Diseases, Odense University Hospital, Denmark

Background

The clinical implications of a considerable CD4 decline despite antiretroviral treatment and viral suppression are unknown. We aimed to test the hypothesis that a major CD4 decline could be a marker of cardiovascular disease or undiagnosed cancer.

Methods

Patients with human immunodeficiency virus (HIV) were followed in the Danish nationwide, population-based cohort study in the period 1995–2010 with quarterly CD4 measurements. Associations between a CD4 decline of ≥30% and cardiovascular disease, cancer, and death were analyzed using Poisson regression with date of CD4 decline as a time-updated variable.

Results

We followed 2584 virally suppressed HIV patients for 13 369 person-years (PY; median observation time, 4.7 years). Fifty-six patients developed CD4 decline (incidence rate, 4.2/1000 PY [95% confidence interval {CI}, 3.2–5.4]). CD4 counts dropped from a median of 492 cells/µL to 240 cells/µL. CD8, CD3, and total lymphocyte counts dropped concomitantly. No HIV-related factors, apart from treatment with didanosine, were associated with CD4 decline. The risk of cardiovascular disease, cancer, and death increased markedly ≤6 months after CD4 decline (incidence rate ratio, 11.7 [95% CI, 3.6–37.4] and 13.7 [95% CI, 4.3–43.6], respectively, and mortality rate ratio 4.3 [95% CI, 1.1–17.6]).

Conclusion

A major decline in CD4 count is associated with a marked increased risk of cardiovascular disease, cancer, and death among virally suppressed HIV patients. We studied the clinical implications of CD4 decline among virally suppressed human immunodeficiency virus patients and found that the risk of cardiovascular disease, cancer, and death was substantially increased within 6 months after a major CD4 decline and moderately increased thereafter.

PDF

http://cid.oxfordjournals.org/content/57/2/314.full.pdf

February 20, 2017 at 3:23 pm

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

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