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HIV/AIDS Overview

HIV/AIDS

HIV exists in two forms: HIV-1 (most common) and HIV-2. Type 2 is rare and impacts specifically in West Africa.2

The first identification of people with AIDS was in 1981 but the link between HIV and AIDS was not established until 1984.1

The transmission of HIV can occur through blood (e.g. transfusion, contaminated needles), sexual activity and from mother to infant.3 

For...

... 30 years AIDS has been a pandemic with a current global prevalence of about 33.3 million with 68% in Sub-Saharan Africa.4

 For the first time, the global incidence rate has stabilized. However, within 33 counties globally, 22 within Sub-Saharan Africa alone, the incidence rate has actually been reduced by 25% between 2001 and 2009.

As the therapeutic arsenal is constantly improving, the rate of AIDS-related deaths decreased 19% from 2004 to 2009.5 Currently, in low and middle-income countries, about 8 million people receive antiretroviral therapy, this number is 26 times bigger than in 2004.6

Retrovirus HIV enters the cells and after its RNA is converted to DNA, it integrates its genetic information in the cell DNA allowing viral reproduction. The cells targeted by HIV are ones that express the CD4 receptor and either coreceptor CCR5 (macrophages) or CXCR4 (T lymphocytes) at their surface.7 HIV needs to bind to the CD4 receptor and one of the coreceptors to enter the cell. Finally, the cells infected are destroyed so the HIV infection is characterized by a progressive loss of CD4+ T cells, weakening the immune system.7,3 Once the immune system is weakened enough, an opportunistic infection may develop and eventually kill the person infected.7,3  

The diagnosis of HIV infection is performed by a blood test and the diagnosis of AIDS is established when the number of CD4+ T cells (CD4+ T cell count) is equal to or below 200 per microlitre of blood (healthy people have 800-1300 per microlitre).3 The time between HIV infection and AIDS diagnosis is usually about 8-10 years.3

Two elements are measured in a patient with HIV: the CD4+ T cell count and the plasma HIV RNA (viral load).3,8
The CD4+ T cell count is used to evaluate immune function, to decide when to start an antiretroviral therapy and prophylaxis for opportunistic infections 3,8 and to monitor therapeutic response.8
The viral load assessment determines how contagious the patient is and evaluates the progression of the disease and the efficiency of the treatment. Treatment aims to control the viral load.3,8

Due to its modes of transmission, HIV infection is almost completely preventable. The different methods of prevention include using condoms, sexual abstinence or use of topical gels containing antiretroviral drugs, use of clean needles and the wearing of protection (e.g. glove, mask) for people in contact with contaminated body fluids. 3 Some studies have shown some efficiency of male circumcision for heterosexuals.9

Through HIV testing, along with the implementation of awareness campaigns and education programs, the number of people unaware of their seropositivity decreased,10 as a consequence increasing the number of individuals who can be treated quickly and reducing the spread of infection.

People who are possibly contaminated are given anti-retroviral drugs for four weeks to prevent the development of HIV infection.3
In spite of some interesting results, research of vaccines is not currently successful11 but some ways of pre-exposure prophylaxis have been shown to be efficient and safe in clinical trials, for example daily uptake of Truvada (Tenofovir Disoproxil Fumarate + emtricitabine).12

Since the 1990’s, the therapeutic arsenal has been dramatically increased. Currently there are more than 20 antiretroviral drugs divided into six classes: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), fusion inhibitors (FIs), CCR5 antagonists8, and integrase strand transfer inhibitors (INSTIs).8,13
The treatment typically consists of drug combinations depending on infection stage, patient and previous treatment.8

Drug resistance (virus can replicate despite use of antiretroviral drugs) has appeared. Two types of HIV drug resistance exist: acquired (mutation resistance) and transmitted (person is infected by resistant HIV). Transmitted HIV drug resistance, especially to non-nucleoside reverse transcriptase inhibitors, is increasing in low and middle-income countries.6 Fortunately, when first-line treatment is no longer efficient, second-line treatment combination seems effective in most cases.6

References
  1. Gallo R. C. et al. The Discovery of HIV as the Cause of AIDS. N Engl J Med 2003; 349:2283-2285.
  2. Barroso H. et al. Evolutionary and Structural Features of the C2, V3 and C3 Envelope Regions Underlying the Differences in HIV-1 and HIV-2 Biology and Infection. PLoS One. 2011; 6(1): e14548.
  3. Beers M.H. et al. The Merck manual of medical information. Merck research laboratories. Second home edition. 2003, 1168-1184.
  4. World Health Organization. Global Health Sector Strategy on HIV/AIDS 2011-2015. Edition 2011.
  5. UNAIDS. Global Report: UNAIDS Report on the Global AIDS Epidemic 2010. Available at: http://www.unaids.org/globalreport/Global_report.htm, accessed the 1st of August 2012
  6. World Health Organization. HIV Drug Resistance Report 2012. Available at: http://apps.who.int/iris/bitstream/10665/75183/1/9789241503938_eng.pdf, accessed the 1st of August 2012
  7. Didiqu C. A. et al. Novel Approaches to Inhibit HIV Entry. Viruses. 2012 February; 4(2): 309–324.
  8. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Available at: http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf , accessed the 1st of August 2012
  9. Smith D. K. et al. Male Circumcision in the United States for the Prevention of HIV Infection and Other Adverse Health Outcomes: Report from a CDC Consultation. Public Health Rep. 2010; 125(Suppl 1): 72–82.
  10. Lasry A. et al. Allocating HIV Prevention Funds in the United States: Recommendations from an Optimization Model. PLoS One. 2012; 7(6): e37545.
  11. Reynell L. et al. HIV vaccines: an attainable goal? Swiss Med Wkly. 2012;142:w13535
  12. Heneine W. et al. HIV Prevention by Oral Preexposure Prophylaxis. Cold Spring Harb Perspect Med. 2012 March; 2(3): a007419.
  13. Quashie P. K. et al. Novel therapeutic strategies targeting HIV integrase. BMC Med. 2012; 10: 34.

Neuropathic Pain

The Neuropathic Pain Knowledge Centre is a unique resource containing a wealth of current information in this field of medicine.

The nervous system (central and peripheral) constantly receives and interprets information about the body's surroundings and the body's own functioning, responding by sending out messages to tissues and organs.

The Knowledge Centre addresses the two types of pain: nociceptive and clinical. Nocicpetive pain aims to protect individuals from harm. Clinical pain results from damage or inflammation of a part of the body and consists of both spontaneous pain that may arise with no apparent peripheral stimulus, and from hypersensitivity to peripheral stimuli1 due to peripheral and central sensitisations.

Neuropathic pain is often described as a shooting, stabbing or burning sensation. Estimates suggest that neuropathic pain may affect as much as 3% of the population.

Different types of neuropathic pain exist depending on their origin, details of which can be found in the Knowledge Centre: Painful Diabetic Neuropathy, Herpes Zoster and Post-Herpetic Neuralgia (PHN), HIV Associated-Neuropathy (HIV-AN), Cancer-related Neuropathic Pain, Post-surgical/Post-traumatic Neuropathic Pain.

In the clinic, the diagnosis of neuropathic pain relies on an accurate history and examination and some pain evaluation tools are used.

As Neuropathic pain doesn’t respond to conventional therapy with analgesics, the different treatment regimens are antidepressants, anticonvulsants, opioids, topical agents and combination treatment.

To help physicians in the pharmacological management of this condition, recent guidelines are available.

Enter the Neuropathic Pain Knowledge Centre


References:

1. Ji R-R, et al. Central sensitization and LTP: Do pain and memory share similar mechanisms? Trends in Neuroscience 2003;26(12):696–705


Date of preparation: August 2012 PAIN/12/0003/EUd

Hepatitis

Neuropathic Pain

Hepatitis can be caused by many different things including viral infections, parasites, bacteria, chemicals, autoimmunity, drugs or alcohol. Of these, viral infection is the most common cause of chronic (long-term) hepatitis, which can lead to severe liver damage including cirrhosis and liver cancer.

Hepatitis B and C viruses (HBV and HCV) are among the world’s most common infectious pathogens. It is estimated that 500 million people – 1 in 12 of the global population – are chronically infected with one or both of these viruses.1,2  The majority of these people live in the developing world and many of them are unaware that they are infected. Chronically infected patients are at increased risk of developing cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC), which together account for more than 1 million deaths annually.3

The hepatitis B virus is a resilient virus present in all bodily fluids of infected individuals. It is resistant to breakdown and able to survive outside the body. It can be transmitted effectively through contact with infected bodily fluids in the same way as HIV. However, HBV is 50–100 times more infectious than HIV.

Screening for HBV and HCV infection is crucial, not only to detect patients who may require treatment to reduce the risk of progression to severe sequelae, but also to reduce transmission rates.

The primary objective of therapy for chronic HBV is to achieve control of viral replication and halt disease progression/improve liver histology. This will decrease pathogenicity and infectivity and thereby stop or reduce hepatic necroinflammation.

Chronic hepatitis C infection may result in severe liver damage leading to liver failure, HCC and death. As a consequence, therapeutic intervention can arrest, and perhaps even reverse, the disease before irreversible liver damage occurs. 

Enter the Hepatitis B and C Knowledge Centre


References

1. World Health Organization. World Health Organization Hepatitis B Fact Sheet. 1998.
2. World Hepatitis Alliance. www.aminumber12.org
3. Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet 2003;362:2089–94

Clinical Case Studies

Bloody Diarrhoea (E. coli O157)

Infection: Gastrointestinal Infection

Bloody Diarrhoea (E. coli O157)

Stephanie Dundas, Consultant in Infectious Diseases and General Medicine, Monklands General Hospital, NHS Lanarkshire, Airdrie, UK

Case History
A 67-year-old woman was admitted to the surgical ward with a 72-hour history of increasingly severe abdominal pain and bloody diarrhoea.

Complicated Urinary Tract Infection with ESBL-producing E. Coli

Infection: Genitourinary Infection

Complicated Urinary Tract Infection with ESBL-producing E. coli

Achyut Guleri, Consultant Medical Microbiologist, Rashmi Sharma, Consultant Medical Microbiologist, and Michael Przybylo , Registrar in Medical Microbiology, Blackpool Victoria Hospital, Blackpool, Fylde and Wyre Hospitals NHS Foundation Trust, UK

Case History
A 75-year-old male with a two-year history of vascular dementia was admitted with a three-day history of episodic confusion, agitation and urinary A 75-year-old male with a two-year history of vascular dementia was admitted with a three-day history of episodic confusion, agitation and urinary incontinence.

Drug News

FDA issues Complete Response Letters for elvitegravir and cobicistat (Gilead Sciences)

01-05-2013

Gilead Sciences, Inc. has announced that the company has received Complete Response Letters from the FDA for its New Drug Applications (NDAs) for elvitegravir and cobicistat for use as part of HIV...

CHMP recommends Stribild (Gilead Sciences) for the treatment of HIV

24-03-2013

Gilead Sciences, Inc. has announced that the Committee for Medicinal Products for Human Use (CHMP), has adopted a positive opinion on the company's Marketing Authorisation Application (MAA) for the...

Phase III SAILING study of dolutegravir(ViiV) success in HIV-1

11-03-2013

ViiV Healthcare has announced 24-week data from the Phase III SAILING (ING111762) study evaluating the investigational integrase inhibitor dolutegravir in patients with HIV-1 who are failing on...

HIV/AIDS Drug Data - A-Z

Possible searches include drugs or medicines (by brand, generic ingredient or drug class), diseases, conditions and more.

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Recent Drug Updates

ZIAGEN 300 mg Film Coated Tablets (HIV)

12-06-2013

Ziagen is indicated in antiretroviral combination therapy for the treatment of Human Immunodeficiency Virus (HIV) infection. The demonstration of the benefit of Ziagen is mainly based on results of...

REYATAZ

12-06-2013

REYATAZ is indicated for the treatment of HIV-1 infected adults in combination with other antiretroviral medicinal products. In antiretroviral treatment experienced patients, the demonstration of...

COMBIVIR Film Coated Tablets (HIV)

21-05-2013

Combivir is indicated in antiretroviral combination therapy for the treatment of Human Immunodeficiency Virus (HIV) infection...

Medical Images

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Buffalo hump and truncal obesity
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Sarcoma on gum
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Lemierre's Disease

Clinical Guidelines

British HIV Association guidelines for the management of HIV infection in pregnant women 2012

Apr 2012

The overall purpose of these guidelines is to provide guidance on best clinical practice in the..

... treatment and management of human immunodeficiency virus (HIV)-positive pregnant women in the UK. The scope includes guidance on the use of antiretroviral therapy (ART) both to prevent HIV mother-to-child transmission (MTCT) and for the welfare of the mother herself, guidance on mode of delivery and recommendations in specific patient populations where other factors need to be taken into consideration, such as co-infection with other agents. The guidelines are aimed at clinical professionals directly involved with, and responsible for, the care of pregnant women with HIV infection.

British HIV Association guidelines for the treatment of HIV-1-positive adults with antiretroviral therapy 2012

Apr 2012

The overall purpose of these guidelines is to provide guidance on best clinical practice in the..

... treatment and management of adults with HIV infection with antiretroviral therapy (ART). The scope includes guidance on the initiation of ART in those previously naïve to therapy, support of patients on treatment, management of patients experiencing virological failure and recommendations in specific patient 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

Online CME

FDA Approvals: First Antidiarrheal Drug for HIV/AIDS 

Apr 2013
... gastroenterologists, infectious disease specialists, and other specialists who care for patients who experience diarrhea while undergoing treatment of HIV/AIDS.

Improving HIV Prevention: Communicating With Patients

Apr 2013
... specialists, primary care physicians, internal medicine physicians, pediatricians, emergency medicine providers, nurses and OB/GYN clinicians who are routinely engaging at-risk patients and all other clinicians who frequently care for patients with HIV.

Clinical Trials

THISTLE - The HIV-HCV Silibinin Trial

08-03-2013

Chronic hepatitis C virus (HCV) is a major cause of morbidity and mortality worldwide with an estimated number of 180 million infected patients. Until 2012 the current standard of care (SOC) treatment of patients with chronic hepatitis C was a 24 to 72 weeks therapy with pegylated interferon- and ribavirin (PR). In..

... 2012, the protease-inhibitors (PI's) telaprevir and boceprevir as first directly acting HCV drugs have been approved by the local Swiss authority for hepatitis C mono-infected and HCV-HIV-co-infected individuals. However, therapy success is strongly limited in null-responders (NR) to previous PR. Treatment of HCV-HIV co-infected individuals with the new PI's is accompanied by additional challenges (e.g. drug-drug interactions, toxicity, high pill burden). Patients with advanced fibrosis are at highest risk for decompensated liver disease and hepatocellular carcinoma (HCC) and prompt initiation of treatment is strongly recommended. Recently, data in mono-infected patients showed, that in prior non responders a 12 week course of a triple therapy (TT) with telaprevir and PR followed by another 24 weeks of PR resulted in an sustained virologic response (SVR) of only 29%. In HCV-HIV co-infected non-responders with unfavourable preconditions (e.g. HCV-genotype 1, interleukin 28 B non-CC genotype, advanced liver fibrosis, high baseline HCV viral load) SVR after TT is even expected to be lower. These patients urgently need additional therapeutic options with the goal to eradicate HCV in order to prevent further fibrosis progression and to reduce morbidity and mortality. A promising substance in the field of drugs targeting the HCV replication is silibinin. Silibinin is the main component of silymarin, an extract of the milk thistle Silybum marianum. Intravenous silibinin (iSIL) targets multiple steps in the virus life cycle and exhibits anti-oxidant, anti-inflammatory, anti-viral and immunomodulatory properties. iSIL inhibits the HCV NS5B polymerase activity directly or by interfering with the binding of RNA to this enzyme. In addition, iSIL appears to block virus entry, virus transmission and virus secretion.In 2008 Ferenci et al. for the first time reported the substantial clinical antiviral-effect of intravenous silibinin (iSIL) against HCV in PR non-responders. The administration of 20mg/kg iSIL in 20 patients led to a highly significant decrease in viral load. We intend to investigate the effect and tolerability of iSIL in HIV-HCV co-infected individuals with advanced liver fibrosis and previous non- or partial response to SOC. All included study-subjects will receive a lead-in therapy with iSIL in a dosage of 20mg/kg/day (expressed as silibinin concentration) once a day for 14 days. At the end of the THISTLE study, i.e. after the day of completion of the 14-day iSIL administration (day 15), the patients will be considered for eligibility to receive standard of care. We assume that the decline in HCV viral load would substantially improve the chances of SVR as the reduction of viral load should both increase the efficacy of PR and reduce the odds of drug resistance to HCV-specific protease inhibitor.

Study to Evaluate a HIV Drug for the Treatment of HIV Infection

01-03-2013

The primary purpose of this study is to study the safety and tolerability of a HIV drug and to evaluate a decrease of HIV-1 virus level in blood after treatments in HIV-1 infected patients

Medical Videos

An Animations Explaining the Mechanism by which the HIV Virus works
An Animations Explaining the Mechanism by which the HIV Virus works

Medical Journal Abstracts

Impact of baseline HIV-1 RNA levels on initial highly active antiretroviral therapy outcome: a meta-analysis of 12,370 patients in 21 clinical trials

HIV Medicine
Nov 2012

Background: Individual randomized trials of first-line antiretroviral treatment do not consistently show an association between higher baseline HIV-1 RNA and lower efficacy. Methods: A MEDLINE search identified 21 HIV clinical trials with published analyses of antiretroviral efficacy by baseline HIV-1 RNA, using a..

HIV-1 co-receptor expression and epithelial immune cells of the cervix in asymptomatic women attending a genitourinary medicine clinic

HIV Medicine
Nov 2012

Objectives: The aim of the study was to qualitatively and semiquantitatively characterize the expression of the principal HIV co-receptors chemokine (C-C motif) receptor 5 (CCR5) and chemokine (C-X-C motif) receptor 4 (CXCR4) on susceptible CD4 T-helper cell, monocyte/macrophage and Langerhans dendritic cell..

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