Thirty years of the human immunodeficiency virus epidemic and beyond. Int J Oral Science 2013;5:191-9

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原文題目(出處): Thirty years of the human immunodeficiency virus epidemic and beyond. Int J Oral Science 2013;5:191-9

原文作者姓名: Younai FS

通訊作者學校: Division of Oral Biology and Medicine, School of Dentistry, University of California, Los Angeles, USA

報告者姓名(組別): 黃齡瑤 (R2)

報告日期: 103/1/14

內文:

一、 INTRODUCTION

1 .After more than 30 years of battling a global epidemic human

immunodeficiency virus (HIV) as the most challenging infectious disease.

2 discoveries about the virus, including its pathogenesis, transmission patterns and clinical course, have led to the development of potent antiretroviral drugs that offer great hopes in HIV treatment and prevention

3 Timely initiation of antiretroviral drugs, appropriate therapeutic regimens, pre and post-exposure prophylaxis contexts, treatment of comorbid

conditions and addressing social and psychological factors involved in the care of individuals continue to be important considerations.

二、 THE ORIGIN OF HIV

1. it is now widely accepted that HIV originated from cross species transmission of simian immunodeficiency viruses from the primates to human

2. Urbanization, spread of sexually transmitted diseases, poor infection control methods, development of a perfect environment for HIV and spread among many African nations many years before its original reports in the USA and Western Europe.

三、 GLOBAL EPIDEMIOLOGY

1. People living with the HIV or AIDS diagnoses is 34 million worldwide 2. 2.7 million new HIV infections in 2010, including 390 000 children,

numbers that were 21% below the number of new infections at the peak of the epidemic in 1997

3. Coupled with the wider availability of antiretroviral (ARV or ART) therapies and intervention programs that have especially targeted maternal-child transmission, reduce new HIV infections, especially in Sub-Saharan Africa, South and South-East Asia, and in India.

4. the predominant HIV transmission mode is heterosexual

(1) generalized epidemic pattern seen in many Sub-Saharan African countries

(2) The at-risk populations include men who have sex with men, injecting drug users and sex workers and their sexual partners in the rest of the world

. HIV STRUCTURE AND LIFE CYCLE 1. HIV structure

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(http://www.helpcure.com/hiv/hiv-virus.htm)

2. The HIV genome consists of three structural and at least six regulatory genes

(1) Env( viral envelope proteins gp 120 and gp 41)

(2) Gag (matrix and core proteins p17 and p24)

(3) Pol ( protease, reverse transciptase and integrase)

(4) The regulatory genes include Tat, Rev, Nef, Vif, Vpr, Vpx and Vpu.

3. HIV entry and life cycle

(1) R5 strain : CCR5 receptor,the predominant type of HIV in mucosal Transmissions

(2) X4 strain : CXCR4 coreceptor ,blood-borne transmissions

(3) genetically variable region of the gp120 (V3 region) plays an important role

(4) HIV may remain dormant for a long time inside the cell or begin its replication process by penetrating the host cell nucleus

五. HIV INFECTION AND HOST FACTORS

1. A small subset of ARV-untreated HIV-infected individuals (about3%-5%) can maintain normal CD4 cell counts for many years (long-term non-progressors), and an even smaller subset (1%) can maintain suppressed viral loads for years (elite controllers) without ART

2. Genetic variability : mutation in 32-base pair deletion in CCR5 receptor (CCR5-∆32 allele) without the full coreceptor expression

3. viral strains, having protective HLA alleles (HLA -B27 and -B57), strong innate immune responses involving the natural killer cells and effective viral

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restriction factors

(1) ‘Apolipoprotein B or APOBEC 3G’, responsible for newly synthesized viral DNA that functions in interrupting HIV replication.

(2) ‘Tetherin”, a membrane protein (CD317) can block the envelope protein release

六. MECHANISMS AND REGIMENS OF ANTI-RETROVIRAL DRUGS 1. Primary aim of anti-HIV treatment is to provide durable suppression of HIV

replication to a level that is below the detection limits for plasma HIV quantification viral assays.

(1) fewer drug-resistant viral variants, (2) prevents HIV transmission

2. commercially available ARV drugs (table1)

(1) Nucleoside and nucleotide analog reverse transcriptase inhibitors (NRTI and NtRTI)

(2) non-nucleoside reverse transcriptase inhibitors (NNRTI) (3) protease inhibitors (PI)

(4) fusion inhibitors

(5) integrase inhibitors (INSTI or integrase strand transfer inhibitors) (6) entry inhibitors that currently consist of CCR5 antagonists

(7) combination agents.

3. recent recommended combination regimens (table2)

(1) NNRTI-based regimen : NRTIs as the therapeutic backbone plus one NNRTI

(2) PI-based regimen : a boosted PI (3) INSTI-based regimen: INSTI.

4. Virological failure in a patient can occur because of poor patient drug adherence, drug intolerance/toxicity or pre-existing (transmitted) drug resistance; it is more likely with higher HIV RNA levels and/or lower CD4 T-cell counts at baseline

(1) HIV drug-resistance testing

(2) the regimen should be changed as soon as possible to avoid progressive accumulation of resistance mutations

七. HIV DISEASE MANAGEMENT

1. Timing for initiating ARV treatment is as early as possible in the course of HIV infection and definitely before patient’s CD4 count goes below 350 mm-3

2. CD4 count and plasma HIV RNA (viral load) should be measured at baseline and every 3–4 months)

(1). CD4 count values help guide ARV treatment initiation and prophylaxis for opportunistic infections

(2) viral load is the most important indicator of response to ART

八. HIV PREVENTION STRATEGIES 1. Perinatal HIV transmission

(1) Provision of lifelong ART for HIV-infected women who are in need of treatment (CD4 count <350 mm-3) in order to protect their own health and also to prevent transmission to their child

(2) Short-term combination ARV prophylaxis for HIV-infected women

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who are not in need of treatment (CD4 count>350mm-3) in order to prevent transmission of HIV to their child during pregnancy, delivery and breastfeeding

2. Male circumcision

Clinical trials in Kenya, South Africa and Uganda indicate that voluntary medical male circumcision reduces the risk of female-to-male sexual transmission by about 60%.

3. Treatment as prevention

ART not only averts AIDS-related complications and deaths by preventing HIV disease progression, also reduces the risk of HIV transmission by lowering individuals’ viral loads

4. Universal HIV screening

(1) It can help with early identification and treatment of those infected and also because the newly diagnosed are less likely to engage in unprotected sex and with multiple partners

(2) In Kenya showed only 16% of HIV-infected adults knew that they were infected, while in the United States, this percentage is currently about 20%

(3) Because fear of social stigma is still a key prohibitive factor for universal HIV screening, home HIV testing is identified as a significant HIV prevention strategy for the next decade 5. Non-occupational post-exposure prophylaxis and pre-exposure

prophylaxis

(1) Non-occupational post-exposure prophylaxis: 28-day course of ART as prophylaxis

(2) Pre-exposure prophylaxis: daily use of tenofovir/emtricitabine (Truvada)

九. NEW INTERVENTION STRATEGIES 1. Gene-based therapies

(1) Use of autologous transplantation of genetically modified CD4-positive T cells or even stem cells (CCR5-∆32 allele)

(2) siRNAs, to interference with HIV replication 2. HIV receptor, coreceptor inhibition

CCR5 antagonist maraviroc has entered clinical use for blocking HIV entry in individuals who are primarily infected with the R5 strain 3. Elimination of the HIV reservoirs and chronic immune activation

(1) Interruption of treatment results in a rapid viral rebound even after long-term ART use, due to latently reservoir cell

-- Activate the latent cells and making them more sensitive to host immune mechanisms have included the use of cytokines like IL-2 and IL-7, raltegravir and CCR5 antagonists, all in addition to the use of ART

(2) Chronic HIV infection not only leads to progressive loss of CD4 T cells and their depletion, but also promotes thrombosis and other aging-related diseases

-- Gut-associated lymphoid tissue is a prime target of HIV and remains a chronically infected tissue and a main reservoir for the dormant T cells

-- Cox-2 inhibitors and the lipid-lowering agent atorvastatin in conjunction with ART

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3. HIV vaccine

The extraordinary diversity of HIV-1, its capacity to evade host immune responses, a lack of broadly reactive antibody response in most

infections, rapid mutations, and the early establishment of latent viral reservoirs have been major obstacles for those in search of an effective HIV vaccine

十.Summary

1. A major challenge in HIV eradication is the presence of HIV reservoirs that persist, despite effective treatments and optimal medication adherence and require lifelong treatment for those infected.

2. The current trends in developing new HIV treatment and prevention approaches continue, the global target of zero new infections may soon be realized.

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題號 題目

1 下列關於 HIV 的傳染途徑何者為非?

(A) Sexual contact

(B) Parenteral exposure to blood (C) Mother to fetus

(D) salvia 答案

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出處:oral and maxillofacial pathology (2th edition)

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