HIV

Treatment Issues

-Adherence to medication regimen -Drug Resistance -Side effects -Cost -Requires lifetime commitment to taking meds as prescribed. -Every missed dose increases the chance of the virus developing resistance to the drugs -Drugs are expensive -Limited access to drugs and HIV providers -Side effects -If do not adhere to routine may develop resistance to drugs and must start new drugs

Transmission of HIV: Modes

-Blood transfusion -Sexual contact -Injection drug use -Perinatal (vertical transmission): Mother-to-child- has been drastically reduced due to testing mother -Occupational exposure Six common transmission categories are: -male-to-male sexual contact, -injection drug use, -heterosexual contact, -mother-to-child (perinatal) transmission, -and other (includes blood transfusions and unknown cause).

Commonly Used Laboratory Tests

-HIV viral load (PCR) - The amount of HIV RNA in a blood sample. Reported as number of HIV RNA copies per mL of blood. Treatment goal: < 50 copies/mL -CD4 cell - also known as helper T cell. A type of white blood cell that fights infection and coordinates the cell mediate immune response. It is the target cell for HIV. -CD4 Cell percentage/count - a measurement of the percentage of lymphocytes that are CD4 cells. ---CD4% < 20 correlates with immunosuppression ---CD4% < 14 meets criteria for AIDS Viral load: used as measure of antiretroviral effectiveness CD4 lymphocyte percentage CD4% < 20 correlates with immunosuppression CD4%< 14 meets criteria for AIDS

Side Effects of Antiretroviral Drugs

-Nausea, vomiting or diarrhea -Abnormal heartbeats -Shortness of breath -Liver damage -Elevated blood sugar levels -Skin rash -Weakened bones -Bone death, particularly in the hip joints

PEP: Postexposure Prophylaxis

-Risk assessment -Treatment: Goal is to begin treatment within 2 hours*** -Follow-up Optimal PEP treatment when initiated within 2 hrs of exposure has been shown to reduce the incidence of HIV seroconversion by up to 81% (CDC, 2001) **Health Care Worker Precaution if Stuck: 4 week treatment 2 pills start within the first 2 hours of exposure

Public Health Prevention Strategies

-Routine testing in all health care settings for pregnant women and persons between ages 13-64 years -Routine testing in substance use treatment and correctional facilities -Increase awareness of HIV -Provide needle exchange programs -Increase funding and access to HIV treatment -Male circumcision

Secondary Prevention for HIV Positive Pregnant Woman

-Should take HIV medications by the second trimester of pregnancy -HIV medications given during labor and delivery; continue after giving birth -Newborn should begin receiving HIV medication within 6-12 hours after delivery and continue taking for 6 weeks [ziduvine (ZDV)] -Vaginal delivery is safe for women who: ---take HIV medications treatment during pregnancy during labor and delivery, and immediately after giving birth, and ----mother's viral load is less than 1,000 copies/ml near time of delivery -Cesarean delivery is indicated for women who: ----have not received HIV medications during pregnancy; ----Have a viral load greater than 1,000 copies/ml or an unknown viral load near time of delivery. -HIV-positive mothers should not breastfeed their newborns

Primary Prevention of HIV

-abstinence -condoms -not sharing needles

HIV Disease Progression

1. Primary infection: cold like symptoms 2. Window period 3. Asymptomatic chronic HIV infection 4. Symptomatic HIV infection 5. Advanced HIV infection 6. AIDS 7-10 yrs. for progression

HIV Life Cycle

2-10 Billion viral particles every 1-2 days 2 Billion new T cells every day, most destroyed by HIV -Primary event is entry of HIV into body's CD4 cells (also called T-helper cells or T4 cells) -T4 cells are white blood cells essential to immune system for fighting infection -Once inside a T4 cell the virus replicates & signals other cells that produce antibodies -Producing antibodies is essential immune system function -HIV infects & destroys T4 cells and damages their ability to signal for antibody production -Steadily deactivates immune system leading to dysfunction of various organ systems There are several steps in the HIV life cycle. (See Fact Sheet 400 for a diagram.) 1. Free virus circulates in the bloodstream. 2. HIV attaches to a cell. 3. HIV empties its contents into the cell. 4. The HIV genetic code (RNA) is used by the reverse transcriptase enzyme to build HIV DNA. 5. The HIV DNA is inserted into the cell's DNA by the integrase enzyme. This establishes the HIV infection in the cell. 6. When the infected cell reproduces, it activates the HIV DNA, which makes the raw material for new HIV viruses. 7. Packets of material for a new virus come together. 8. The immature virus pushes out of the infected cell in a process called "budding." 9. The immature virus breaks free of the infected cell. 10. The new virus matures: raw materials are cut by the protease enzyme and assembled into a functioning virus. A virus consists of an outer envelope of protein, fat and sugar wrapped around a set of genes (in the case of HIV, genetic information is carried as RNA instead of DNA) and special enzymes.HIV has proteins on its envelope that are strongly attracted to the CD4+ surface receptor on the outside of the T4-cell. When HIV binds to a CD4+ surface receptor, it activates other proteins on the cell's surface, allowing the HIV envelope to fuse to the outside of the cell. Entry can be blocked by entry inhibitors. Step 2: HIV's genes are carried in two strands of RNA, while the genetic material of human cells is found in DNA. In order for the virus to infect the cell, a process called "reverse transcription" makes a DNA copy of the virus's RNA.After the binding process, the viral capsid (the inside of the virus which contains the RNA and important enzymes) is released into the host cell. A viral enzyme called reverse transcriptase makes a DNA copy of the RNA. This new DNA is called "proviral DNA."Reverse transcription can be blocked by: Nucleoside Reverse Transcriptase Inhibitors (NRTIs), and Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs). Step 3: Integration. The HIV DNA is then carried to the cell's nucleus (center), where the cell's DNA is kept. Then, another viral enzyme called integrase hides the proviral DNA into the cell's DNA. Then, when the cell tries to make new proteins, it can accidentally make new HIVs. Integration can be blocked by integrase inhibitors. Step 4: Transcription. Once HIV's genetic material is inside the cell's nucleus, it directs the cell to produce new HIV.T he strands of viral DNA in the nucleus separate, and special enzymes create a complementary strand of genetic material called messenger RNA or mRNA (instructions for making new HIV). Transcription can be blocked by antisense antivirals or transcription inhibitors (TIs), new classes of drugs that are in the earliest stage of research. Step 5: Translation. The mRNA carries instructions for making new viral proteins from the nucleus to a kind of workshop in the cell. Each section of the mRNA corresponds to a protein building block for making a part of HIV.As each mRNA strand is processed, a corresponding string of proteins is made. This process continues until the mRNA strand has been transformed or "translated" into new viral proteins needed to make a new virus. Step 6: The final step begins with the assembly of new virus. Long strings of proteins are cut up by a viral enzyme called protease into smaller proteins. These proteins serve a variety of functions; some become structural elements of new HIV, while others become enzymes, such as reverse transcriptase.Once the new viral particles are assembled, they bud off the host cell, and create a new virus. The virus then enters the maturation stage, which involves the processing of viral proteins. Maturation is the final step in the process and is required for the virus to become infectious.With viral assembly and maturation completed, the virus is able to infect new cells. Each infected cell can produce a lot of new viruses. Viral assembly can be blocked by Protease Inhibitors (PIs). Maturation, a new target of companies developing anti-HIV drugs, may be blocked using Maturation Inhibitors.To see a picture of HIV budding from a T-cell,

HIV Tests

A positive antibody test means you are infected with HIV. Your body is producing the antibodies to HIV

HIV Occupational Exposure

As of 2010, 57 documented transmissions and 143 possible transmissions had been reported in the United States. Health care workers who are exposed to HIV-infected blood at work have a 0.3% risk of becoming infected. In other words, 3 of every 1,000 such injuries, if untreated, will result in infection. Underreporting of cases to CDC is possible, however, because case reporting is voluntary. Occupational exposures should be considered urgent medical concerns, and PEP should be started within 72 hours—the sooner the better; every hour counts.

When to Start HIV Treatment

CD4 Cell Count: -less than 350: strongly recommended initiating therapy -350-500: Recommended initiating therapy -Greater than 500: consider initiating therapy Initiating Antiretroviral Therapy Regardless of CD4 Cell Count: -History of AIDS: defining illness -Pregnancy -HIV associated nephropathy -Hep B virus co-infection when treatment of HBV is indicated -You have severe symptoms -Your CD4 count is under 500 -You're pregnant -You have HIV-related kidney disease -You're being treated for hepatitis B

CD4 and Viral Load

Development of AIDS is like an impending train wreck where: -Viral Load: Speed of the train -CD4: Distance form site of doom

Common HIV/AIDs Related Complications

Diabetes Lipodystrophy Lactic acidosis

Types of HIV Tests

Enzyme immunoassay (EIA or ELISA): standard HIV antibody screening test Western Blot (WB): confirmatory HIV-antibody test Rapid HIV antibody screening tests (oral and blood): designed to detect HIV antibodies within 20 minutes HIV RNA Testing: directly detects genetic material, or RNA, of the virus. RNA from HIV virus can be detected as soon as 6 to 12 days after exposure and about 2 weeks before antibodies are made. Both standard and rapid tests have sensitivity and specificity < 99% Tests that detect HIV RNA are very sensitive, but more costly to perform, so are not typically used as screening As reported by the New York State Department of Health AIDS Institute, during the initial phase of HIV infection, the amount of HIV RNA present typically ranges from 100,000 to more than 10 million copies of RNA per milliliter of blood.

Acute HIV Infection Signs and Symptoms

Fatigue Headache Pain Peripheral neuropathy Nausea/vomiting Wasting Diarrhea Skin rashes/itching Candidiasis Systemic: -Fever -Weight loss Central: -Malaise -Headache -Neuropathy Lymph Nodes: -Lymphadenopathy Skin: -Rash Gastric: -Nausea -Vomiting Liver and Spleen: -Enlargement Muscles: -Myalgia Esophagus: -Sores Pharyngitis Mouth: -Sores -Thrush

Acute Retroviral Syndrome: Signs and Symptom Primary Infection

Fever 96% Lymphadenopathy 74% Pharyngitis 70% Rash 70% Myalgia or arthalgia 54% Diarrhea 32% Person is highly infectious but has not seroconverted

Transmission of HIV: Sources

Fluids of Transmission: -Blood -Semem -Pre-Seminal Fluid (Pre-Cum) -Vaginal Fluid -Breast Milk

Blood Transfusion

Greatest risk for transmission

-Unprotected sex with an infected person -From Mother to Child in uterus; during childbirth or by breastfeeding -Sharing syringes, tattoo needles, or other devices exposed to blood

HIV is Transmitted by:

Types of Antiretroviral Drugs

Non-nucleoside reverse transcriptase inhibitors (NNRTIs). Disable a protein needed by HIV to make copies of itself. Nucleoside reverse transcriptase inhibitors (NRTIs). Faulty versions of building blocks that HIV needs to make copies of itself. Protease inhibitors (PIs). PIs disable protease, another protein that HIV needs to make copies of itself. Entry or fusion inhibitors. These drugs block HIV's entry into CD4 cells. Integrase inhibitors. Works by disabling integrase, a protein that HIV uses to insert its genetic material into CD4 cells. 1985 azt nrti Protease inhibitors 1996 potent ART DRUGS developed

Anitretoviral Drugs

Nucleoside Reverse Transcriptase Inhibitors (NRTIs): block reverse transcriptase, an enzyme HIV needs to make copies of itself. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs): bind to and later reverse transcriptase, an enzyme HIV needs to make copies of itself. Protease Inhibitors (PIs): block HIV protease, an enzyme HIV needs to make copies of itself. Fusion Inhibitor: inhibitors block HIV from entering the CD4 cells of the immune system Integrase Inhibitors: block HIV integrase, an enzyme HIV needs to make copies of itself. CCR5 Antagonists: entry inhibitors block CCR5, a protein on the CD4 cells that HIV needs to enter the cell. Combination Antiretrovirals: Fixed-dose combination tablets contain two or more anti-HIV medications from one or more drug classes. APPROVED ARV DRUGS Each type, or "class", of ARV drugs attacks HIV in a different way. The first class of anti-HIV drugs was the nucleoside reverse transcriptase inhibitors (also called NRTIs or "nukes".) These drugs block step 4, where the HIV genetic material is used to create DNA from RNA. The following drugs in this class are used: • Zidovudine (Retrovir, AZT) • Didanosine (Videx, Videx EC, ddI) • Stavudine (Zerit, d4T) • Lamivudine (Epivir, 3TC) • Abacavir (Ziagen, ABC) • Tenofovir, a nucleotide analog (Viread, TDF) • Combivir (combination of zidovudine and lamivudine) • Trizivir (combination of zidovudine, lamivudine and abacavir) • Emtricitabine (Emtriva, FTC) • Truvada (combination of emtricitabine and tenofovir) • Epzicom (combination of abacavir and lamivudine) Non-nucleoside reverse transcriptase inhibitors, also called non-nukes or NNRTIs, also block step 4 but in a different way. Five have been approved: • Nevirapine (Viramune, NVP) • Delavirdine (Rescriptor, DLV) • Efavirenz (Sustiva or Stocrin, EFV, also part of Atripla) • Etravirine (Intelence, ETR) • Rilpivirine (Edurant, RPV, also part of Complera or Epivlera). Protease inhibitors or PIs block Step 10, where the raw material for new HIV virus is cut into specific pieces. Ten protease inhibitors are approved: • Saquinavir (Invirase, SQV) • Indinavir (Crixivan, IDV) • Ritonavir (Norvir, RTV) • Nelfinavir (Viracept, NFV) • Amprenavir (Agenerase, APV) • Lopinavir/ritonavir (Kaletra or Aluvia, LPV/RTV) • Atazanavir (Reyataz, ATZ) • Fosamprenavir (Lexiva, Telzir, FPV) • Tipranavir (Aptivus, TPV) • Darunavir (Prezista, DRV)Entry inhibitors prevent HIV from entering a cell by blocking step 2 of the life cycle. Two drugs of this type have been approved: • Enfuvirtide (Fuzeon, ENF, T-20) • Maraviroc (Selzentry or Celsentri, MVC)HIV integrase inhibitors prevent HIV from inserting its genetic code into the human cell's code in step 5 of the life cycle. The two drugs of this type are: • Raltegravir (Isentress, RGV) • Elvitegravir (EVG, part of the combination Stribild)

Opportunistic Infections and Malignancies related to HIV

Pneumocystis Tuberculosis Cryptococcal meningitis Kaposi's sarcoma Opportunistic infections such as pneumocystis or malignancies such as Kaposi's sarcoma can signal the final stage of HIV infection, AIDS

Human Immunodeficiency Virus

Retrovirus Global pandemic driven by travel/migration, sex practices, drug use, war, economics ***Chronic infectious disease which can be controlled with effective treatment HIV is the viral cause of a syndrome characterized by a progressive, ongoing, and disabling deterioration of the human immune system n order for viruses to reproduce, they must infect a cell. Viruses are not technically alive: they are sort of like a brain with no body. In order to make new viruses, they must hi-jack a cell, and use it to make new viruses. Just as your body is constantly making new skin cells, or new blood cells, each cell often makes new proteins in order to stay alive and to reproduce itself. Viruses hide their own DNA in the DNA of the cell, and then, when the cell tries to make new proteins, it accidentally makes new viruses as well. HIV mostly infects cells in the immune system.****Infection: Several different kinds of cells have proteins on their surface that are called CD4 receptors. HIV searches for cells that have CD4 surface receptors, because this particular protein enables the virus to bind to the cell. Although HIV infects a variety of cells, its main target is the T4-lymphocyte (also called the "T-helper cell"), a kind of white blood cell that has lots of CD4 receptors. The T4-cell is responsible for warning your immune system that there are invaders in the system. Replication: Once HIV binds to a cell, it hides HIV DNA inside the cell's DNA: this turns the cell into a sort of HIV factory. A retrovirus is composed of RNA not DNA. They have an enzyme called reverse transcriptase that gives them the unique property of transcribing their RNA into DNA after entering a cell. The retroviral DNA can then integrate into the chromosal DNA of the host cell to be expressed there.

Secondary Prevention of HIV

Serodiscordant partners -Disclosure to sex partners -Always practice safe sex (condoms)

Treatment of HIV

Several different kinds of antiretroviral drugs are currently used to treat HIV infection.• These medicines do not cure HIV infection or AIDS• These medicines do not eliminate the risk of passing HIV to others• Treatment of HIV infection requires a combination of HIV medicines• Not all medicines are right for all people, and treatments may be different for each person; talk with your doctor or other health care provider if you have questions about your treatment

Viral Load

The higher the viral load, the faster the progression of HIV Range of viral load test is <50 to >10,000,000 copies Some HIV positive patients have a low or undetectable viral load off treatment, even after 10 years

Understanding HIV

There are a few things you need to know in order to understand HIV infection -DNA: DNA is like the "blueprint" for building living cells. -Enzymes: Enzymes are like the workers of a cell. They build new proteins, transport materials around the cell, and carry out other important cellular functions. -RNA: RNA is like the construction boss. Cells use RNA to tell enzymes how to build a specific part of a cell. To make a new protein, enzymes will copy a specific part of the DNA into a piece of RNA. This RNA is then used by other enzymes to build a new protein or enzyme. -Proteins: The building blocks that are used to make living things. -Nucleus: A small package inside the cell where the genetic material is kept.

T-Cell Count or Helper Cells

What your T Cells can tell you: -More than 500 cells, your immune system is NORMAL -200-500 cells, your immune sys me may be WEAKENED -Less than 200 cells, your immune system is VERY WEAK. You are at high risk for getting an opportunistic infection, an infection that develops only wen the immune system is weak -Normal count is 660-1550 -On average, a person loses 80-100 for each year of HIV infection -Count less than 200 is defined as AIDS -Opportunistic infections occur with lower counts -Do I have or will I get "full blown AIDS"?

20% of persons infected with HIV in U.S. do not know they have it 70% of new HIV transmissions are from persons who do not know they have it Persons who do not know they have it cannot benefit from effective treatment Persons who become aware of having HIV reduce their risk behaviors CDC recommends routine testing for all persons in U.S. between ages 13-64 years

Why HIV testing is important?

Window period for test

Window period: interval from primary infection to production of antibodies Seroconversion may take from 3-4 weeks Testing during window period may give false negative results