HIV Update: Epidemiology and Pathophysiology MATEC Michigan AIDS Research and Education Center Wayne State University School of Medicine (313) 962-2000 matecmichigan.org 1
Epidemiology of the Epidemic: World People living with HIV/AIDS 33.4 million Adults living with HIV/AIDS 31.3 million Women: 15.7 million Children living with HIV/AIDS 2.1 million More than 25 million persons have died of AIDS since 1981. 2
Epidemiology of the Epidemic: United States People living with HIV/AIDS 1.4 million Number of new infections per year 56, 000 Affected populations, risk factors MSM (53% of all infections) Heterosexual (31% of all infections; 83% of infections in women) Drug use (12%) Affected populations, race African Americans (45%) Whites (35%) Latinos (17%) 3
Epidemiology of the Epidemic: Michigan People living with HIV/AIDS Approximately 20,000 The majority are diagnosed in the Detroit Metropolitan Area Outstate cases account for around 30% of the total Males constitute about 60% of HIV cases in Michigan 40% are exclusively MSM 22% have both male and female partners Nearly ¾ of HIV-positive women are infected by their male partners 2/3 are diagnosed between the ages of 20 and 40 years Minorities are disproportionately affected by HIV/AIDS 4
Pathophysiology of HIV/AIDS A retrovirus unknown until early 1980s: 1. Cannot replicate outside of living host cells 2. Contains only RNA, no DNA 3. Destroys the body s ability to fight infections and certain cancers 4. Infects CD4 cells, an important part of the body s immune system Patients infected with HIV are at risk for illness and death from: 1. Opportunistic infections 2. Neoplastic complications 5
Types of HIV: HIV-1 and HIV-2 HIV-1 and HIV-2 appear to lead to clinically indistinguishable AIDS HIV-2 may be less virulent and have a longer latency period EIA tests can detect either one or both types of HIV Worldwide, the predominant virus is HIV-1 The relatively uncommon HIV-2 type is concentrated in West Africa Both types can be transmitted: by sexual contact through blood and body fluids from mother to child during the perinatal period 6
Phases of the HIV Life Cycle Establishing infection in a host cell Attachment, fusion and entry Transcription Integration Cellular latency Active production Assembly Budding 7
CD4 Count in HIV Infection The CD4 cell signals other parts of the immune system to respond to an infection. Normal CD4 counts range from 500 to 1500 Initially in HIV infection there is a sharp drop in the CD4 count and then the count levels off to around 500-600 cells/mm 3. CD4 count is a marker of likely disease progression. CD4 percentage tends to decline as HIV disease progresses. CD4 counts can also be used to predict the risks for particular conditions such as: Pneumocystis carinii pneumonia CMV disease MAC disease. Treatment decisions are often based on: Viral Load CD4 count. 8
Natural History of Untreated HIV Infection 9
Opportunistic Infections 10
Manifestations of HIV Infection Primary Infection Clinical Latency Advanced Disease Often asymptomatic or overlooked Symptoms 1-6 weeks after infection Viral-like syndrome: sore throat, fever, lymphadenopathy, rash Differential includes EBV, CMV, hepatitis, toxoplasmosis Antibody (ELISA, Western Blot) may not be detected Usually asymptomatic Lymph nodes site of ongoing viral latency Massive viral production Destruction of CD4 cells Decrease in lean body mass without apparent total body weight change Vitamin B12 deficiency Increased susceptibility to food and water-borne pathogens. Symptomatic Plasma viremia begins to rise CD4 cell count falls further A decline in nutrient status or body composition Opportunistic infections develop: fever, weight loss, lymphadenopathy, thrush, diarrhea, malignancies, wasting syndrome, neurologic syndrome including dementia 11
AIDS/HIV Stage 3 Defined HIV positive with a CD4 cell count that is or has been less than 200 cells/mm 3 HIV positive with a CD4 percent below 14%. HIV positive and with an AIDS defining illness such as PCP, toxoplasmosis, MAC, Kaposi s Sarcoma, etc. regardless of CD4 cell count 12
Link between HIV and other STIs Sexually transmitted infections are among the most common reportable infections in Michigan Because of high levels of infection in young women, sexual activity alone represents a significant risk for acquiring chlamydia and gonorrhea. The presence of another STD significantly increases the risk of HIV transmission and acquisition. Many STDs, including HIV, do not have symptoms Assessment for asymptomatic, as well as symptomatic, sexually transmitted infections should be a routine part of every patient encounter. Perinatal STD/HIV transmission can be prevented with early detection and prompt treatment 13
TREATMENT OF HIV/AIDS The goals of HIV treatment include: Increase or improve immune status Reduce viral load Improve quality of life Reduce complications from co-morbidities Reduce transmission 14
HIV: Antiretroviral Therapy HIV Nucleoside Analogues CCR5 Blockers Integrase Inhibitors Fusion Inhibitors RNA DNA Nucleus Non-Nucleosides FrAdapted from: Walker B. IDSA 1998 Host Cell Protease Inhibitors 15
Current Antiretroviral Medications NRTI/NtRTI Abacavir Didanosine Emtricitabine Lamivudine Stavudine Tenofovir Zidovudine NNRTI Delavirdine Efavirenz Etravirine Nevirapine Rilpivirine Integrase inhibitor Elvitegravir Raltegravir Dolutagravir ABC DDI FTC 3TC D4T TDF AZT, ZDV DLV EFV ETR NVP RPV ELV RAL DTG PI Atazanavir Darunavir Fos-amprenavir Indinavir Lopinavir Nelfinavir Ritonavir Saquinavir Tipranavir ATV DRV fapv IDV LPV NFV RTV SQV TPV Fusion Inhibitor Enfuvirtide T-20 CCR5 Receptor Blocker Maraviroc MVC Non ARV Booster Cobicistat 16 16
Antiretroviral Medications: Combination Pills Atripla Combivir Epzicom Trizivir Truvada Complera Stribild Triumeq 2 NRTIs and 1 NNRTI (Efavirenz + emtricitabine + tenofovir) 2 NRTIs (Zidovudine + lamivudine) 2 NRTIs (Epivir + Ziagen) 3 NRTIs (Zidovudine + lamivudine + abacavir) 2 NRTIs (Emtricitabine + tenofovir) 2NRTIs plus 1 NNRTI (Rilpivirine + emtricitabine + tenofovir) 2 NRTIs, 1 Integrase Inhibitor, 1 Booster (Emtricitabine + tenofovir + elvitegravir + cobicistat) 2 NRTIs, 1 Integrase Inhibitor (Dolutegravir + abacavir + lamivudine) 17
Potential Adverse Drug Effects Mitochondrial dysfunction Metabolic abnormalities Hematologic complications Allergic reactions Lactic acidosis Hepatic toxicity Pancreatitis Peripheral neuropathy Lipodystrophy Fat accumulation Lipoatrophy Hyperlipidemia/? Premature CAD Hyperglycemia Bone marrow suppression Hypersensitivity reactions Skin rashes Insulin resistance/dm Bone disorders: oesteoporosis and osteopenia 18
Common Patient Complaints Anorexia Sore/dry/painful mouth Swallowing difficulties Constipation/diarrhea Nausea/vomiting/altered taste Depression Tiredness, lethargy 19
Mutations and Resistance HIV is a highly variable virus which readily mutates during replication. HIV mutations may result in resistance to one or more anti-retroviral drugs. Resistance testing is recommended for All patients at entry to care All patients experiencing virologic failure Perform while patient is taking ART, or 4 weeks after discontinuing therapy. Interpret in combination with history of ARV exposure and ARV adherence. Adherence to prescribed ART regimen is vital in order to prevent resistance 20
Discussion: How do we test for resistance? 1. Genotype 2. Phenotype 3. Virtual Phenotype Consider: Treatment history Naive Treatment failure 21
Direct Effect of HIV on End Organ Systems HIV infection causes inflammation and immune activation, resulting in potentially irreversible immune system and end-organ damage Liver disease, cardiovascular disease, renal disease and cancer account for more morbidity and mortality than opportunistic diseases in patients with CD4 counts >200 22
The Case for Early Initiation of ART CD4 counts in healthy people range between 500 and 1500 Substantial numbers of people with HIV have a significant drop in CD4 cells shortly after infection 57% are below 500 within 2 years 70% are below 500 within 3 years Incomplete restoration of CD4 cells is more common among patients who start therapy at lower CD4 counts Early control of viral replication and viral diversity and a greater immunologic benefit contribute to improved survival rates among patients who initiate ART CD4 counts above 350 23
Public Health Benefits In Michigan: One out of four HIV-positive persons is not aware of their infection. Two out four HIV-positive persons know they are infected but are not receiving treatment It is critical to identify HIV-positive individuals and to link them to comprehensive HIV care. Helps decrease high risk behavior Reduces the likelihood of HIV transmission 24
HIV testing is important, but not sufficient. Linkage to and retention in care are key. 25
Patients with unrecognized, untreated, unmanaged HIV can present with a wide variety of symptoms, including: Fever Weight loss Swollen lymph nodes Rash Diarrhea, nausea, vomiting Sore throat Headache Muscle and joint pain Open sores or ulcers Dry cough Yeast infection of the mouth and/or esophagus 26
Primary care providers need to know: Potential risks of HIV infection in their patients and how to assess for them Signs and symptoms of undiagnosed HIV Michigan s HIV laws and guidelines 27
AIDS Institute: Clinical Guideline Recommendations Comprehensive quality dental care should be delivered using a multidisciplinary approach: Oral health should be integrated into the HIV care plan and coordinated between the oral health and medical teams An oral health practitioner should perform a welldocumented, hard and soft tissue examination that includes a complete head and neck examination at the initial and recall visits HIV primary care providers should document that all patients under care are referred annually to an oral health provider or that the patient is actively under the care of an oral health provider The medical team should encourage all patients to follow the recommendations of their oral health providers AIDS Institute: Oral Health Care for People With HIV Infection 28
Why? Oral manifestations may be the first sign of HIV disease Higher rates of oral manifestations have been documented in HIV-positive persons More than ninety percent of HIV-infected patients will have at least one HIV-related oral manifestation in the course of their disease Oral lesions may be the harbinger of a change in a person s HIV status Oral lesions have: Potential impact on systemic health care outcomes Potential impact on quality of life New York State Dept of Health AIDS Institute's Best Practices. Promoting oral health care for people with HIV infection. January 2004 29
Building a Team to Address Oral Health Issues Make medical staff aware of the importance of oral health in comprehensive HIV primary care Staff meetings and in-service conferences should be used to reinforce the importance of regular oral examinations for people living with HIV/AIDS All medical care providers should be made aware of oral health referral sources for patients under their care 30
Building a Team to Address Oral Health Issues Train all members of the primary health care team to perform an initial oral exam Dental staff can instruct the medical team to recognize early signs and symptoms associated with oral disease. Medical staff should be supplied with the necessary tools to conduct a proper oral examination Mouth mirror Gauze An appropriate light source 31
Building a Team to Address Oral Health Issues Utilize case managers to promote oral health care. These providers can: Serve as intermediaries between medical providers, dental providers and patients by interpreting care recommendations Remind patients of upcoming appointments Act as patient advocates for achieving improvements and expansion of oral health services in a broader range of settings 32
Building a Team to Address Oral Health Issues Encourage nurses and health educators to play important roles in reinforcing oral health messages Dentists can train other providers about oral health issues which they can then share with patients. Suggested topics include: The oral side effects of HIV medications, such as xerostomia, ulcerations, etc. The importance of preventive oral health care The relationships between oral health and systemic health 33
Building a Team to Address Oral Health Issues Consider including dental providers in HIV/AIDS patients care conferences The dental provider should function as a member of the HIV primary health care team The dental provider may become more aware of physical and psychosocial factors that are impacting the patient s response to oral care The dentist can provide additional insights to members of the HIV team on reasons, such as dental pain, that might contribute to patients nonadherence to drug therapy 34
Questions????? 35
References Conducting an Oral Health Examination. http://emedicine.medscape.com/article/1080850- overview#a1 Head and Neck Exams for Healthcare Providers, AETC Resource Center. https://www.youtube.com/watch?v=qwahbxy i2vw 36