Basic HIV & AIDS Education for Health Care Providers Patricia R Jennings DrPH, PA-C Professor University of Alabama at Birmingham Learning Objectives After completing this lecture the participant should be able to discuss the epidemiology and demographics of human immunodeficiency virus (HIV) After completing this lecture the participant should be able to discuss the evaluation and treatment of patients diagnosed with HIV disease. HIV Infection & AIDS Essentials of Diagnosis – Risk factors: sexual contact with an infected person, parenteral exposure to infected blood by transfusion or needle sharing, perinatal exposure. – Prominent systemic complaints such as sweats, diarrhea, weight loss, and wasting. – Opportunistic infections due to diminished cellular immunity – often life-threatening – Aggressive cancers, particularly Kaposi sarcoma and extranodal lymphoma. – Neurologic manifestations, including dementia, aseptic meningitis and neuropathy. CDC Recommendations for HIV testing Adults and Adolescents Routine, voluntary HIV screening for all persons 13-64 in health care settings, not based on risk Repeat HIV screening of persons with known risk at least annually Opt-out HIV screening with the opportunity to ask questions and the option to decline Include HIV consent with general consent for care; separate signed informed consent not recommended Prevention counseling in conjunction with HIV screening in health care settings is not required Recommendations for HIV testing Adults and Adolescents Intended for all health care settings Communicate test results in same manner as other diagnostic/screening tests Provide clinical HIV care or establish reliable referral to qualified providers CDC AIDS case definition for surveillance of adults and adolescents (1) Definitive AIDS diagnosis (with or without laboratory evidence of HIV infection) (2) Definitive AIDS diagnoses (with laboratory evidence of HIV infection) (3) Presumptive AIDS diagnoses (with laboratory evidence of HIV infection) Summary: Patients have AIDS when: They are HIV+ with a CD4 cell count that is or ever has been less than 200 cells/mm3 They are HIV+ and have or ever have had a CD4 percent below 14%. They are HIV+ and have an AIDS defining illness - regardless of CD4 cell count HIV Prevalence Estimate At the end of 2009, an estimated 1,148,200 persons aged 13 and older were living with HIV infection in the United States, including 207,600 (18.1%) persons whose infections had not been diagnosed.1 HIV Incidence Estimate CDC estimates that approximately 50,000 people in the United States are newly infected with HIV each year. That number has remained stable overall in recent years. Most (62%) were attributed to maleto-male sexual contact. Black/African American men and women were also strongly affected and were estimated to have an HIV incidence rate that was almost 8 times as high as the incidence rate among whites. 90 80 70 AIDS Deaths Prevalence 1993 definition implementation 450 400 Prevalence (in thousands) No. of cases and deaths (in thousands) Estimated Number of AIDS Cases, Deaths, and Persons Living with AIDS,1985-2004, United States 350 60 50 300 250 40 200 150 30 20 100 10 0 50 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 Year of diagnosis or death Note. Data adjusted for reporting delays. 0 Persons Living with AIDS (PLWA) diagnosis At the end of 2009, the estimated number of persons living with an AIDS diagnosis in the United States and 6 U.S. dependent areas was 487,968. In the 50 states and the District of Columbia, this included 476,186 adults and adolescents, and 546 children aged less than 13 years at the end of the year. Pathogenesis The hallmark of symptomatic HIV infection is immunodeficiency caused by continuing viral replication. The virus can infect all cells expressing the T4 (CD4) antigen, which HIV uses to attach to the cell. Chemokine coreceptors (CCR5 and CXCR4) are required for virus entry and individuals with deletions are less likely to become infected and, once infected, the disease is more likely to progress slowly. HIV Lifecycle Natural History of Untreated HIV Infection Untreated HIV Infection Stages Viral Transmission 2-3 weeks Acute retroviral syndrome 2-3 weeks Recovery and seroconversion 2-4 weeks Asymptomatic, chronic HIV infection – Average 8 – 10 years Symptomatic, HIV infection/AIDS – Average 1-3 years Death Laboratory Tests HIV infection is established by detecting antibodies to the virus, viral antigens, viral RNA/DNA or by culture. The standard test is serology for antibody detection. – The time delay from infection to positive EIA averages 10-14 days with newer test reagents. Some do not seroconvert for 3-4 weeks, but virtually all patients seroconvert within 6 months. Testing Methods Screening test: ELISA, high sensitivity Confirmatory test: Western Blot, high specificity NEVER suggest that a client/patient donate blood to determine their HIV Status CLIA Waived Rapid Tests Uni-Gold Recombigen OraQuick Advance Rapid Tests Persons tested must receive a “Subject Information Notice” provided with the test A negative test is definitive negative unless tested in the “window period” Positive tests are considered preliminary and should be confirmed with a Western blot or IFA Indeterminate tests should be repeated in 1 month Mass Screening The recommendation is to pool seronegative specimens for PCR testing, with PCR testing of individual samples from any batch that tests positive. In N.C., use of this method found that acute infections accounted for 4-10% of all newly detected HIV infections. Primary Infection – often asymptomatic or overlooked – symptoms 1-6 weeks after infection – viral like syndrome: sore throat, fever, lymphadenopathy, rash – differential includes EBV, CMV, hepatitis – antibody (ELISA, Western Blot, Rapid Tests) may not be detected – if diagnosed during this stage it is usually by Quantitative HIV by PCR Diagrammatic representation of the manifestations of HIV seroconversion. Clinical Latency – usually asymptomatic – lymph nodes site of ongoing viral latency – massive viral production – destruction of CD4 cells Advanced Disease Plasma viremia begins to rise CD4 cell count falls further Constitutional symptoms develop Opportunistic infections develop: – fever, weight loss, lymphadenopathy, thrush, diarrhea, malignancies, wasting syndrome, neurologic syndrome including dementia Modes of Transmission Blood Exposure Other Potentially Infectious Material (OPIM) – semen, vaginal fluid, any bloody fluid, CSF, and pus. Additionally, peritoneal, pleural, synovial, pericardial and amniotic fluid Sexual Exposure Congenital Exposure – antepartum, intrapartum, postpartum Occupational Exposure Initial Laboratory Testing Table Confirm HIV antibody status – ELISA and Western Blot CD4 count (baseline and every 3-4 months) viral load (baseline and every 3-4 months) Resistance testing (the prevalence of >1 major mutation in treatment naïve patients is 6-19% genotype if newly diagnosed pt – naïve patient with elevated viral load Initial Laboratory Tests CBC; G6-PD renal and liver function tests, cholesterol and triglyceride panel (fasting baseline) RPR, STD screening (including wet mount for trichomonas in women), hepatitis serologies toxoplasmosis IgG; CMV IgG; Varicella IgG (if negative history of chickenpox) PPD; +/- chest radiograph Pap smear (cervical, =/- anal) HIV Lifecycle Therapeutic Arsenal Fusion Inhibitors CCR5 inhibitors Nucleoside Reverse Transcriptase Inhibitors (NRTIs) Nucleotide Reverse Transcriptase Inhibitors Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs) Integrase Inhibitors Protease Inhibitors (PIs) Initiate Antiretroviral Therapy Treat all symptomatic patients – AIDS or severe symptoms Treat asymptomatic patients with CD4 < 200 Offer treatment to asymptomatic patients CD4 200 – 500 * Defer treatment to patients with CD4 > 500 unless VL> 100,000 * Goals of Therapy Clinical Goals: Virologic Goals: Immunologic Goals: Therapeutic Goals: Epidemiologic Goals: Health Maintenance Table Memorize table 31-3 Relationship of CD4 count to development of opportunistic infections (Figure 31-1) Bacterial infections, HSV, VZV, Vaginal candidiasis, KS, M Tuberculosis (PPD > 5mm induration) Pneumocystis jiroveci – CD4 < 200 Toxoplasmosis gondii, cryptococcosis – CD4 < 100 M avium complex, CMV retinitis, CNS lymphoma – CD4 < 50 Pulmonary Pneumocystis jiroveci pneumonia is the most common opportunistic infection associated with AIDS. – Hypoxemia may be severe with PO2 <60 – Cornerstone of diagnosis is chest x-ray (diffuse or perihilar infiltrates) – Definitive diagnosis can be obtained in 50-80% of cases by Wright-Giemsa stain or direct fluorescence antibody test of induced sputum. Other Infectious Pulmonary Diseases Community-acquired pneumonia is the most common cause of pulmonary disease in HIV-infected persons. The incidence of Mycobacterium tuberculosis (TB) has markedly increased in metropolitan areas (TB occurs in an estimated 4% of persons in the US who have AIDS.) Noninfectious Pulmonary Diseases Kaposi sarcoma Non-Hodgkin’s lymphoma Interstitial pneumonitis Sinusitis Chronic sinusitis can be frustrating – Non-smoking patients: amoxicillin – Patients who smoke: amoxicillin-potassium with clavulanate – DURATION: most require 3 – 6 weeks CNS disease Toxoplasmosis is the most common spaceoccupying lesion in HIV-infected patients. – Headaches, focal neurologic deficits, seizures or altered mental status may be presenting symptoms. – Diagnosis is made presumptively based on the characteristic appearance of cerebral imaging studies in patients with + toxo IgG serology – “Multiple contrast-enhancing lesions” on CT scan Toxoplasmosis Other CNS infections Primary non-Hodgkin’s lymphoma is the second most common space-occupying lesion in HIV-infected persons (lymphoma tends to be more solitary) AIDS dementia complex: neuropsych testing Cryptococcal meningitis: + “CRAG” (1273) HIV myelopathy: leg weakness, incontinence Progressive Multifocal Leukoencephalopathy (PML): non-enhancing white matter lesions Peripheral Neuropathy Peripheral neuropathy is common among HIV-infected persons. Patients complain of numbness, tingling, and pain in the lower extremities. Treatment is aimed at symptomatic relief. Patients are initially treated with gabapentin. Retinitis CMV retinitis, characterized by perivascular hemorrhages and white fluffy exudates, is the most common retinal infection in AIDS patients. Oral Lesions The presence of oral candidiasis or hairy leukoplakia is suggestive of HIV infection in patients who do not know their HIV status. Hairy leukoplakia is caused by the EpsteinBarr virus. Angular cheilitis (fissures at the sides of the mouth), Aphthous ulcers, herpes stomatitis, gingivitis, Kaposi sarcoma, and warts (HPV) Gastrointestinal Manifestations Candidal esophagitis, Hepatic Disease, Billary Disease Malabsorption syndrome : (do not produce enough acid) can lead to inability to absorb drugs that require an acid medium. Endocrinologic Manifestations Endocrinologic manifestations: hypogonadism is probably the most common endocrinologic abnormality in HIV-infected men AIDS patients appear to have abnormalities of thyroid function tests different from those of patients with other chronic diseases. Skin manifestations Herpes simplex infections: occur more frequently, tend to be more severe and are more likely to disseminate in AIDS patients. Herpes zoster: common manifestation in HIV infection. Staphylococcus is the most common bacterial cause of skin disease in HIVinfected persons. Immune reconstitution syndromes or “IRIS” With initiation of HAART, some patients experience inflammatory reactions that appear to be associated with immune reconstitution as indicated by a rapid increase in CD4 count. These inflammatory reactions may present with generalized signs of fevers, sweats, and malaise with or without more localized manifestations that usually represent unusual presentation of opportunistic infections. Prevention Until vaccination is a reality, prevention of HIV infection will depend on effective precautions regarding sexual practices and injection drug use, use of perinatal HIV prophylaxis, screening of blood products and infection control practices in the health care setting. Primary care clinicians should routinely obtain a sexual history and provide risk factor assessment of their patients. Secondary Prevention S pneumoniae Hepatitis B Hepatitis A (some authorities recommend HAV for all susceptible patients as defined by negative HAV serology) Inactivated Influenza Daily multi-vitamin Do not consume raw eggs/meat Counseling for support of chronic illness Summary With improvements in therapy, patients are living longer after the diagnosis of AIDS. Sustaining lower mortality will require developing new treatments for patients in whom resistance to existing agents develops. Unfortunately, not all individuals have access to care. Contact Information Patricia R Jennings DrPH, PA_C Professor and Program Director Physician Assistant Program University of Alabama at Birmingham 1720 2nd Ave S., SHPB 482 Birmingham, AL 35294-1212 205-934-4432