HIV2015

Human Immunodefeciency Virus InfectionProf. Sanaa M. Kamal

Epidemiology

Epidemiology

HIV infection is usually diagnosed through blood tests detecting the presence or absence of HIV antibodies. Preventable, manageable but not curable. .Effective treatment with antiretroviral drugs can control the virus so that people with HIV can enjoy healthy and productive lives. In 2012, more than 9.7 million people living with HIV

When the immune system becomes weakened by HIV, the illness progresses to AIDS Some blood tests, symptoms or certain infections indicate progression of HIV to AIDS

Microbiology of HIVHuman Immunodeficiency Virus (HIV) RetrovirusRNA viruses (RNA is their basic genetic material)Belongs to the lentivirus subgroupHIV-1 produces the acquired immunodeficiency syndrome (AIDS)HIV-2 produces a similar disease that is at present, largely restricted to West Africa.Has the enzyme reverse transcriptase that can make DNA from the RNA and allow them to integrate into the host cell genomeHIV virus targets the host immune systemInfects CD4+ T cells and macrophages.

HIV TransmissionHIV transmitted in bodily fluids semen, blood, vaginal fluid, breast milk. Enters via mucous membranes or into blood stream.

About 5-10% of new infections result from male-male sexual intercourse and about two thirds of all infections from male female intercourse.

Transmission by needle sharing accounts for about 10% of infections and about 5-10% of infections occur in health care settings (needle sticks, contaminated blood products)

About 11% of infections are of babies who acquire the virus during childbirth or from breastfeeding.

Public baths Handshakes Work or school contact Using telephones Sharing cups, glasses, plates, or other utensilsCoughing, sneezingInsect bitesTouching, huggingWater, foodKissing

*HIV makes contact with cells located within the genital mucosaVirus is carried to regional lymph nodes (1-2 Days)Exponential viral replicationWidespread systemic dissemination to the brain, spleen, distant lymph nodes, etc. (5-11 Days)

HIV ATTACKS T-CellsHIV binds to two protein receptors on cells surface : CD4 and a co-receptor, usually CCR5.Host cell membrane and viral coat fuse and virus contents enter cell.

I1. Infection: The moment the virus gets into the body2. Window period: The time between infection & enough antibodies for a positive HIV test3. Seroconversion: The body starts to make antibodies

IIAsymptomatic period:No illness

IIIHIV/AIDS-related illness: Less serious illnessesAIDS: Serious illnesses

*Duration of different phases of HIV/AIDS will vary in different people

It is not possible to predict the course of the disease in any one person

Factors affecting the course of HIV/AIDS include nutrition, emotional stress, and access to health care

People infected with HIV can infect others at any phase of the disease

*Progression of HIVAcute SeroconversionAsymptomatic HIV (Clinical latency)Symptomatic HIVAcquired Immune Deficiency Syndrome (AIDS)

*Patterns of HIV ProgressionTypical progressorsRapid progressorsSlow progressorsLong-term non-progressors

Lasts for an average of ten years This stage is free from symptomsThere may be lymphadenopathyThe level of HIV in the blood drops to low levels HIV antibodies are detectable in the blood

The immune system deteriorates Opportunistic infections and cancers start to appear.The immune system weakens too much as CD4 cells decrease in number.

HIV enzyme-linked immunosorbent assay (ELISA)Screening test for HIVSensitivity > 99.9%Western blotConfirmatory testSpecificity > 99.9% (when combined with ELIZA)HIV rapid antibody testScreening test for HIVSimple to performAbsolute CD4 lymphocyte countPredictor of HIV progressionRisk of opportunistic infections and AIDS when

If the source patient has unknown HIV status, two-drug PEP is indicated based on the source patients HIV risk factors. In such patients, rapid HIV testing also is indicated to aid in determining the need for PEP.When the source HIV status is unknown, PEP is indicated in settings where exposure to HIV-infected persons is likely.If PEP is indicated, it should be started as quickly as possible.

Nucleoside Reverse Transcriptase inhibitorsAZT (Zidovudine)Non-Nucleoside Transcriptase inhibitorsViramune (Nevirapine)Protease inhibitorsNorvir (Ritonavir)

Two nucleosides for low-risk exposuresTwo nucleosides plus a boosted protease inhibitor for high-risk exposures.

Examples of commonly used dual nucleoside regimens are Zidovudine plus Lamivudine (coformulated as Combivir) or Tenofovir plus Emtricitabine (coformulated as Truvada).

Current recommendations indicate that PEP should be continued for four weeks, with concurrent clinical and laboratory evaluation for drug toxicity.

Nucleoside Reverse Transcriptase inhibitorsAZT (Zidovudine)Non-Nucleoside Transcriptase inhibitorsViramune (Nevirapine)Protease inhibitorsNorvir (Ritonavir)

Nucleoside Reverse Transcriptase inhibitorsAZT (Zidovudine)Non-Nucleoside Transcriptase inhibitorsViramune (Nevirapine)Protease inhibitorsNorvir (Ritonavir)

Two nucleosides for low-risk exposuresTwo nucleosides plus a boosted protease inhibitor for high-risk exposures.

Examples of commonly used dual nucleoside regimens are Zidovudine plus Lamivudine (coformulated as Combivir) or Tenofovir plus Emtricitabine (coformulated as Truvada).

Current recommendations indicate that PEP should be continued for four weeks, with concurrent clinical and laboratory evaluation for drug toxicity.

NY/NJ AETC Stuart Haber, MDVACCINE ISSUES IN HIV+ PatientsPotential exposure to pathogenPotential increase in side effects to vaccinePotential decreased efficacy of vaccine

VACCINES

VACCINESKilled (inactivated): Hepatitis A, Inactivated Polio (IPV), Rabies, Japanese encephalitis Live (attenuated): MMR, Yellow fever, oral TyphoidSubunit: Hepatitis BPolysaccharide: Pneumococcal, Meningococccal, Typhoid ViSplit antigen: Influenza

FOLLOW UP OF HIV INFECTED PATIENTSFor HIV-infected individuals with CD4 < 200 cells/mcL: Pneumocystis jiroveci1 prophylaxis For HIV-infected individuals with CD4 < 75 cells/mcL: Mycobacterium avium complex prophylaxis For HIV-infected individuals with CD4 < 50 cells/mcL: Consider CMV prophylaxis

****-Cant replicate outside of the cell because they use RNA as their genetic material.

-Acute Infection: Within 2-4 weeks after infection with HIV, you can experience an acute illness, which is often described as the worst flu ever. This is called acute retroviral syndrome (ARS) or primary HIV infection and its the bodys natural response to the HIV infection. (Not everyone develops ARS, howeverand it can take up to 3 months for it to appear in some people who do.)

-Clinical Latency: After the acute stage of HIV infection, the disease moves into a stage called clinical latency. This period is sometimes called asymptomatic HIV infection or chronic HIV infection. During this phase, HIV reproduces at very low levels, although it is still active. You may be able to maintain an undetectable viral load and a healthy CD4 cell count without the use of medication during the earlier years of this phase. You may not have symptoms or opportunistic infections. This period can last up to 8 years or longer.

AIDS: As the number of your CD4 cells begins to fall below 200 cells per cubic millimeter of blood (200 cells/mm3), you will be diagnosed as having AIDS. (Normal CD4 counts are between 500 and 1,600 cells/mm3.) This is the stage of infection that occurs when your immune system is badly damaged and you become vulnerable to opportunistic infections. Without treatment, people who are diagnosed with AIDS typically survive about 3 years. Once someone has a dangerous opportunistic infection, life-expectancy falls to about 1 year.*****

Trainers Notes:Use the image on the following slide to illustrate the steps involved in the pathogenesis of HIV infection. Ask participants to quickly name the modes of HIV transmission (refresher from Session 1).

Readers Notes:HIV transmitted through sexual activity enters the bloodstream via mucous membranes lining the vagina, rectum, and mouth. Macrophages and dendritic cells on the surface of mucous membranes bind virus and shuttle it into the lymph nodes, which contain high concentrations of Helper T cells (CD4+ T cells).Once HIV has entered the body, the immune system initiates anti-HIV antibody and cytotoxic T cell production. However, it can take one to six months for an individual exposed to HIV to produce measurable quantities of antibody. The immune response is weakened as memory T cells (CD4+ CCR5+) are destroyed.HIV enters the body and binds to dendritic cells (orange cells with projections) which carry the virus to CD4+ T cells in lymphoid tissue establishing the infection. Virus replication accelerates producing massive viremia and wide dissemination of virus throughout the body's lymphoid tissues. An immune response against virus causes some protection but a chronic persistent infection is established. The production of cytokines and cell divisions that regulate the immune response for protection also cause HIV replication. There is a rapid turnover of CD4+ T cells that ultimately leads to their destruction and to a change in lymphoid tissues that prevent immune responses.Source: GHTM Fellowship Programme, 2006 *****Readers Notes:Acute seroconversion:Fever, rash and adenopathyUsually 3-6 weeks after exposureAsymptomatic HIV (clinical latency):Patient often unaware of infection, antibodies detectable.Immune system able to control virus to limited extent and CD4 > 350/cu.mmAble to transmit HIV to othersSymptomatic HIV:Minor to moderately severe symptomsRecurrent symptomsAIDS:Severe immunosuppression associated with opportunistic infections or cancers

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