This Could Happen to YOU! Robert R. Tight, MD FACP Bradley Kasson, DDS Roger Schobinger Dakota AIDS Education and Training Center

Human: Infecting human beings What is HIV? Human: Infecting human beings Immunodeficiency: Decrease or weakness in the body’s ability to fight off infections and illnesses Virus: A pathogen having the ability to replicate only inside a living cell HIV stands for Human Immunodeficiency Virus. It is the virus that causes AIDS.

Types of HIV Virus HIV 1 HIV 2 Most common in sub-Saharan Africa and throughout the world Groups M, N, and O Pandemic dominated by Group M Group M comprised of subtypes A - J HIV 2 Most often found in West Central Africa, parts of Europe and India Both produce the same patterns of illness. HIV2 causes a more slow progress of disease than those with HIV 1 It is important for tests to detect the HIV subtypes that are circulating in the region. Otherwise, testing may lead to false negative results.

Acquired: To come into possession of something new What is AIDS? Acquired: To come into possession of something new Immune Deficiency: Decrease or weakness in the body’s ability to fight off infections and illnesses Syndrome: A group of signs and symptoms that occur together and characterize a particular abnormality HIV infection leads to a weakened immune system. This makes a person with HIV vulnerable to a group of illness, e.g., opportunistic infections, that would not as easily affect a healthy person AIDS results when HIV infection progresses to an advanced stage, damaging the immune system to a point at which the body can no longer fight illness. AIDS is a syndrome because it is characterized by a group of illnesses Drugs are available which can treat HIV and AIDS. These drugs are called antiretrovirals (ARVs). They prevent the virus from replicating and slow the progress of the disease, but there is still no cure for AIDS or vaccine to prevent HIV transmission. AIDS is the final stage of the disease caused by infection with a type of virus called HIV.

HIV vs. AIDS HIV is the virus that causes AIDS Not everyone who is infected with HIV has AIDS Everyone with AIDS is infected with HIV AIDS is result of the progression of HIV Infection Anyone infected with HIV, although healthy, can still transmit the virus to another person

How is HIV Transmitted? Unprotected sexual contact with an infected partner Exposure of broken skin or wound to infected blood or body fluids Transfusion with HIV-infected blood Injection with contaminated objects Mother to child during pregnancy, birth or breastfeeding

Basic Terms Antigen: A substance which is recognized as foreign by the immune system. Antigens can be part of an organism or virus, e.g., envelope, core (p24) and triggers antibody production. Antibody: A protein (immunoglobulin) made by the body’s immune system to recognize and attack foreign substances

Testing for Viral Infection and Immune Response Viral Load p24 Antigen Immune response Antibody (IgG, IgM) Cellular response (CD4) Over a period of time, HIV infects and kills white blood cells called CD4 lymphocytes or (T cells), leaving the body unable to fight off certain kinds of infections Both T & B cells are types of white blood cells called lymphocytes Helper T-Cells (also called T4 or CD4+ cells) help other cells destroy infective organisms.  Suppressor T-Cells (also called T8 or CD8+ cells) suppress the activity of other lymphocytes so they don't destroy normal tissue.  Killer T-Cells (also called cytotoxic T lymphocytes, or CTLs, and are another kind of T8 or CD8+ cell) recognize and destroy abnormal or infected cells.

Window Period Time from initial infection with HIV until antibodies are detected by a single test Usually 3-8 weeks before antibodies are detected May test false-negative for HIV antibodies during this time period Can still pass the virus to others during this period Represents the stage when you have been infected with HIV, but your body hasn’t created antibodies. “Seroconversion” is a term used to describe the change when antibodies are produced and the blood is tested positive. Seroconversion occurs when your body first begins to produce antibodies to HIV. In other words, your blood may be negative to HIV antibodies during a time period after infection, but may convert to positive to HIV antibodies after a certain period. Generally 3-8 weeks after the initial infection.

Disease Progression Severity of illness is determined by amount of virus in the body (increasing viral load) and the degree of immune suppression (decreasing CD4+ counts) As the CD4 count declines, the immune function decreases. Define viral load as the amount of HIV virus circulating in the bloodstream. Immune suppression, measured by CD4+ cells and total lymphocyte counts, alerts us to the risk of opportunistic infections and the need for prophylactic treatment to prevent such infections from developing.

WHO HIV/AIDS Classification System Stage I Asymptomatic Stage II Minor Symptoms Stage III Moderate Symptoms Stage IV AIDS HIV infection has various stages from primary infection (or acute phase) to asymptomatic phase (or chronic phase) and late stage disease (or AIDS) The first weeks after primary infection, seroconversion occurs and is associated with a rapid increase in circulating viral titers and a significant drop in the number of CD4+ cells.

Can Disease Progression Be Delayed? Prevention and early treatment of opportunistic infections (OIs) Antiretroviral therapy Positive living YES

HCW HIV PEP Risk Stratification Highest risk: larger volume of blood (e.g., deep injury, large diameter hollow needle) and blood containing high titer of HIV (e.g., source patient with acute retroviral illness or end-stage AIDS) No increased risk (e.g., solid suture needle from asymptomatic source patient) No known risk (e.g., urine, saliva, tears) Source patient unknown or HIV status unknown: decide on case-by-case basis, in consultation

HCW HIV PEP Basic (2 drug) regimen Combivir® (ZDV/3TC) 1 tab bid or Truvada® (TDF/FTC) 1 tab daily Expanded regimen: Kaletra® (LPV/r)2 tabs bid Initiate promptly: 1-2hr/<72hr/?longer Duration: 4 wks BUAD:initial(3d), then 2 wksx2 initial supply packet 2 wks supply at a time start on basis of preliminary + stop if confirmatory test is negative 24 hours PEP line: 1-888-448-4911

dendritic cells, carried to lymph node Day 0-2 Exposure to HIV at mucosal surface (sex) Day 0 Virus collected by dendritic cells, carried to lymph node Day 0-2 HIV replicates in CD4 cells, released into blood Day 4-11 Day 11 on Virus spreads to other organs Kahn JO, Walker BD. N Engl J Med. 1998;339:33-39.

HCW HIV PEP Monitoring Anti-HIV: baseline, 6 and 12 wks, 6 (and 12 mo. if source + HCV/HIV) CBC, basic panel; UA: baseline, 2, 4 wks Baseline pregnancy test

This Could Happen to YOU! Robert R. Tight, MD FACP Bradley Kasson, DDS Roger Schobinger Dakota AIDS Education and Training Center Robert.tight@meritcare.com

Oral Manifestations of HIV Dakota AIDS Education and Training Center Bradley M Kasson, DDS Consultant for Infection Control Office of Dentistry, Washington DC Chief, Dental Service VA Medical Center, Fargo 18

Oral Manifestations of HIV No identified unique oral lesion specific to HIV Seldom manifest with CD4 >400 Some predict progression to AIDS Some meet criteria for AIDS diagnosis Casiglia JM, Mirowski GW, Oral Manifestations of Systemic Diseases. eMedicine. Oct 2006

Predictive Value CD4+ < 200 Major Aphthous Stomatitis 100% NUP 95.1% Intraoral Kaposi’s Sarcoma 93.6% HSV (long standing) 87.0% Oral Hairy Leukoplakia 70.3% Oral Candidiasis 69.9% Dental Management of the HIV-Infected Patient Supplement to JADA , December 1995

Candidiasis 90% of HIV patients* Pseudomembranous Erythematous Angular Cheilitis Hyperplastic *Casiglia JM, Mirowski GW, Oral Manifestations of Systemic Diseases. eMedicine. Oct 2006

Angular Cheilitis (Candida)

Pseudomembranous Candidiasis

Pseudomembranous Candidiasis

Pseudomembranous Candidiasis

Pseudomembranous Candidiasis: Wikipedia

Erythematous Candidiasis 33yo

Erythematous Candidiasis

Hyperplastic Candidiasis

HIV Oral Candidiasis Treatment Nystatin not first choice Increasing resistance to azoles Fluconazole Itraconazole Ketaconazole Clinical recovery precedes mycologic elimination Treat the removable denture Clean & disinfect daily Casiglia JM, Mirowski GW, Oral Manifestations of Systemic Diseases. eMedicine. Oct 2006

Necrotizing Ulcerative Periodontitis

Necrotizing Ulcerative Periodontitis

Necrotizing Ulcerative Gingivitis

Necrotizing Ulcerative Gingivitis post chlorhexidine therapy

NUG/NUP Treatment Debridement, usually with local anesthesia Oral hygiene instruction Chlorhexidine gluconate Apply with toothbrush, if possible Follow-up cleaning Regular dental cleanings

Oral Hairy Leukoplakia (OHL) Cardiac Transplant

Oral Hairy Leukoplakia (OHL) 33yo

Oral Hairy Leukoplakia (OHL) 21 yo

OHL Most specific oral manifestation of HIV* Usually no treatment indicated Usually responds to acyclovir High recurrence rate If symptomatic, usually indicates Candida superinfection* *Casiglia JM, Mirowski GW, Oral Manifestations of Systemic Diseases. eMedicine. Oct 2006

Aphthous Stomatitis

RAS Treatment Recommendations, Barron Topical is tx of 1st choice Amlexanox (Aphthasol) most extensively studied and most cost effective of topicals Inhibits inflammatory mediators Levamisole “…may prove to be the safest & most effective systemic agent for maintaining remission…” Normalize CD4/CD8 ratio Systemic corticosteroids Major RAS or esophageal/GI involvement Thalidomide Limited to patients with severe RAS as alternative to systemic corticosteroids for esophageal/GI involvement Significant adverse effects Normalize CD4/CD8 ratio, inhibit cytokines & TNF Barron RW. Treatment strategies for recurrent oral aphthous ulcers. Am J Health-Syst Phar 58(1):41-52,2001