Posts filed under ‘HIV/SIDA’

Humoral and Innate Antiviral Immunity as Tools to Clear Persistent HIV Infection

Journal of Infectious Diseases March 2017 V.215 Suppl.3

Guido Ferrari; Justin Pollara; Georgia D. Tomaras; Barton F. Haynes

Human immunodeficiency virus (HIV) type 1 uses the CD4 molecule as its principal receptor to infect T cells. HIV-1 integrates its viral genome into the host cell, leading to persistent infection wherein HIV-1 can remain transcriptionally silent in latently infected CD4+ T cells.

On reactivation of replication-competent provirus, HIV-1 envelope glycoproteins (Env) are expressed and accumulate on the cell surface, allowing infected cells to be detected and targeted by endogenous immune responses or immune interventions.

HIV-1 Env-specific antibodies have the potential to bind HIV-1 cell surface Env and promote elimination of infected CD4+ T cells by recruiting cytotoxic effector cells, such as natural killer cells, monocytes, and polymorphonuclear cells.

Harnessing humoral and innate cellular responses has become one focus of research to develop innovative strategies to recruit and redirect cytotoxic effector cells to eliminate the HIV-1 latently infected CD4+ T-cell reservoir.

PDF

https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/jid/215/suppl_3/10.1093_infdis_jiw555/4/jiw555.pdf?Expires=1494420570&Signature=APpu07eiH~tbHqo6oB8~aBS75k1vuk2IAzN40RgtpuYUcIYvcmJ7Jb2WGpeMc-ZGFZwiX94~q~yqoO-c0MF6l4PoYVWspX3IyR213MixKtL5fJ-vADhNj9IF8SCplgXx~h2mq-rKXpFN0BvfKR9bfZuzHIzd7WVRSWZ2GrX1hgkYf0LUY5azWRny6FKmxfwzbaJFap0ZaXqB9PX1T85CQLLfxiBHUQF6YNlZL~Hv~ykl0MJKmiBxYVAxofGLcXnPrvmdfCKjfAy0GpTb3oVza533Q7vTKa5R5oIaFiqUqEQNBI7h4jVtRl2m7w5q8PM-Gss0YDn0S9w21Ew93y7oSw__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q

May 9, 2017 at 8:20 am

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

HIV Whole-Genome Sequencing Now: Answering Still-Open Questions

Journal of Clinical Microbiology April 2016 V.54 N.4 P.834-835

Karin J. Metzner

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; Institute of Medical Virology, University of Zurich, Zurich, Switzerland

Diversity, evolution, and epidemiology of HIV are directly relevant to HIV transmission and pathogenesis; hence, they play a key role in antiretroviral treatment and vaccine design. Global HIV whole-genome sequencing would provide a treasure chest of data to answer many questions still open in these fields. An article by Berg et al. in this issue of the Journal of Clinical Microbiology describes a universal strategy to amplify and sequence heterogeneous HIV whole genomes

PDF

http://jcm.asm.org/content/54/4/834.full.pdf

March 9, 2017 at 3:28 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

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