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HIV and AIDS Diagnosis & Treatment. Dr. Waseem Hamoudi, M.D Internal Medicine Gastroenterology & Hepatology. Acquired Immune Deficiency Syndrome - AIDS-. AIDS is caused by the human immunodeficiency virus (HIV).
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HIV and AIDSDiagnosis & Treatment Dr. Waseem Hamoudi, M.D Internal Medicine Gastroenterology & Hepatology
Acquired Immune Deficiency Syndrome - AIDS- • AIDS is caused by the human immunodeficiency virus (HIV). • The primary mechanism is to infect a particular subset of T lymphocyte called CD4 cells. • Over the time HIV decreases the number of CD4 cells. • As a person’s CD4 count drops, they become at increasing risk of developing opportunistic infections. • HIV, by itself, does not harm the patient. • HIV harms by destroying cell-mediated immunity • The infections that develop are what harm patients.
Etiology • Intravenous drug use is one of the most common risk for the development of HIV. • Homosexuality is also a common risk factor. • There is often a 10 year lag between contracting HIV infection and developing the first symptoms. • This is because CD4 cells drop at a ate of 50-100/year without therapy. • It would take 5-10 years to drop from a normal level of around 700 to a CD4 count of 200.
Diagnosis • Detection of IgG antibodies to envelope of HIV by ELISA (anti HIV Ab). • HIV RNA by PCR (quantative). • Isolation of virus in special cultures.
Clinical features of HIV infection • In the United States, the definition of AIDS means individuals with CD4 counts below 200 and clinical pictures. • European definition means only clinical features.
There are multiple systems involved in this syndrome • Neurological disease: 1. AIDS dementia complex. 2. Distal sensory polyneuropathy. • Eye disease: 1. Cytomegalovirus retinitis. 2. Anterior uveitis. • Muco-membranous manifestations: 1. Skin: Pruritis, papular eruption and eosinophilic folliculitis. 2. Mouth: aphtous ulceration.
Hematological complications: Anemia, neutropenia and thrombocytopenia. • Gastrointestinal manifestations: weight loss, diarrhea (HIV enteropathy). • Kidney complications: HIV associated nephropathy.
Respiratory complications: repeated upper and lower respiratory infections. • Cardiological complications: cardiomiopathy and congestive cardiac failure. • Cancers: 1. Kaposi sarcoma: skin cancer. 2. Lymphoma: cancer in the lymphoid system. 3. Squamous cell carcinoma: of the anus and cervix.
Early symptoms • Many people will not have any symptoms when they first become infected with HIV. They may, however, have a flu-like illness within a month or two after exposure to the virus. This illness may include • Fever • Headache • Tiredness • Enlarged lymph nodes (glands of the immune system easily felt in the neck and groin) • These symptoms usually disappear within a week to a month and are often mistaken for those of another viral infection. During this period, people are very infectious, and HIV is present in large quantities in genital fluids.
Later symptoms • The immune system becomes more debilitated, a variety of complications start to take over. For many people, the first signs of infection are large lymph nodes, or swollen glands that may be enlarged for more than 3 months. Other symptoms often experienced months to years before the onset of AIDS include • Lack of energy • Weight loss • Frequent fevers and sweats • Persistent or frequent yeast infections (oral or vaginal) • Persistent skin rashes or flaky skin • Pelvic inflammatory disease in women that does not respond to treatment • Short-term memory loss
The 4 stages of AIDS clinical manifestations 1. Antibody negative asymptomatic carrier state: immediately after infection. 2. Primary HIV infection: within 2-4 weeks, after infection, this may be associated with fever, malaise, rash, arthralgia, lymphadenopathy and these remains from 1 to 3 months. 3. Antibody positive asymptomatic carriers: seropositive stage with low CD4 but with no symptoms. 4. AIDS related complex: chronic symptoms and signs manifested by HIV persons; generalized lymphadenopathy, weight loss, fatigue, chronic diarrhea, anemia, leucopenia, thrombopenia, candida and opportunistic infections and cancers.
Opportunistic infections in AIDS Pneumocystis carinii (CD4<200) • Principle manifestation: Pneumonia: dyspnea on exertion, dry cough, fever, chest pain. • Principle diagnostic test: Bronchoscopy with bronchoalveolar lavage for direct identification of the organism. • Therapy and side effects; • Trimethoprim/sulfamethoxazole (TMP/SMZ) – rash • Pentamidine – Pancreatitis, hyper/hypo glicemia • Steroids if severe pneumonia (when Po2 <70)
Prophylaxis(in order of preference): • TMP/SMZ orally – this is the most effective. • Dapsone. • Atovaquone. • Aerosolized pentamidine • Prophylaxis of pneumonia may be discontinued if antiretrovirals raise the CD4 count above 200 for more than 6 months.
Cytomegalovirus (CD4<50) • Principle manifestations: • Retinitis: blurry vision, double vision, or any visual disturbances with low CD4. • Colitis: diarrhea (<20% of patients). • Principle diagnostic test: • Funduscopy for retinitis. • Colonoscopy with biopsy for diarrhea. • Therapy and side effects: • Ganciclovir – neutropenia • Intravitreal ganciclovir. • Cidofovir - renal • Prophylaxis: Oral ganciclovir
Mycobacterium avium complex (CD4<50) • Principle manifestation: fevers, bacterimia, wasting, anemia. • Principle diagnostic tests: • Blood culture. • Culture of bone marrow, liver or other body tissue or fluid. • Therapy: Clarithromycin and ethambutol • Prophylaxis: • Azithromycin orally once a week. • Clarithromycin twice a day • Stop prophylaxis if antiretrovirals raise the CD4 count above 100 for several months.
Toxoplasmosis (CD4 < 100) • Principle manifestation: Brain mass lesion; headache, confusion, seizures and focal neurologic deficits. • Principle diagnostic tests: • CT or MRI scan of the head (shows ring – contrast- enhancing lesion that shrink after 2 weeks of treatment) • Rare, brain biopsy. • Therapy: Pyrimethamine and sulfadiazine. Clarithromycin if sulfa allergic. • Prophylaxis: • TMP/SMZ. • Dapsone/pyrimethamine.
Cryptococcosis • Principle manifestation: Meningitis. • Principle diagnostic tests: - Lumbar puncture : with initial evaluation by India ink. - Specific crypococcal antigen testing. • Therapy: Amphotericin intravenously for 10 – 14 days at least, followed by fluconazole orally (lifelong). • Prophylaxis: Fluconazole. Vaccination: all HIV – positive persons should receive vaccinations for pneumococcus, influenza and hepatitis B.
Monitoring the immune System • CD4 count monitoring and viral load testing can be compared to the staging of cancer in terms of assessing prognosis for the patient. • CD4 cell count: is the most accurate method of determining what infections or other diseases the patient is at risk for. • Without treatment, the CD4 count drops 50-75 cells per year. • Also CD4 is useful for determining when to start prophylactic medications, and when to initiate antiretroviral medications and the adequacy of response to antiretroviral medications.
CD4 Count 700-1500: Normal 200-500: Oral thrush, Kaposi sarcoma, Tuberculosis, Zoster, Lymphoma. 100-200: Pneumocytosis carinii pneumonia, dementia. < 100: Toxoplasmosis, Cryptococcus, Cryptosporidiosis. < 50: Cytomegalovirus, Mycobacterium avium complex, Progressive Multifocal Leukoencephalopathy (PML)
Viral load monitoring • This test gives a numerical value to the quantity of HIV in the blood. • High viral loads are less desirable. • High viral loads indicate a greater risk of complications of the disease and a worse prognosis. • High viral load indicates that the level of CD4 cells is going to drop more rapidly. • Other uses for viral load testing are to determine when to initiate antiretroviral drugs and the adequacy of response to antiretroviral drugs.
HIV viral load < 400: Lower limit of detection and goal for therapy ( for sensitive tests <50) >55.000: Level above which drugs should be started 750.000: Upper limit of the test.
Antiretroviral therapy Nucleoside reverse transcriptase inhibitors • Zidovudine (ZDV or AZT)- leucopenia, anemia. • Didanosine (DDI)- pancreatitis, neuropathy. • Stavudine (D4T)- peripheral neuropathy. • Lamuvidine (3TC) • Abacavir – rash. Protease Inhibitors • Nelfinavir-gastrointestinal. • Indinavir- nephrolithiasis, hyperbilirubinemia • Ritonavir- gastrointestinal. Non-nucleoside reverse transcriptase inhibitors • Efavirenz- neurologic, psychatric
Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs )
When to start therapy? • When the CD4 count has dropped or the viral load has risen. • Both of these events imply a worse prognosis. • Antiretroviral therapy should raise the CD4 count and drop the viral load. Guidelines for starting: • CD4 < 350 or • Viral load (by PCR-RNA) > 55.000
What to start? • Use two nucleosides combined with protease inhibitor or • Use two nucleosides combined with efavirenz (Sustiva) or • Use two nucleosides combined with two protease inhibitors. • There is a general agreement that AZT/3TC/Nelfinavir is a good starting regimen • D4T (Stavudine) or didanoside can be used in combination instead of AZT.
What is considered adequate therapy? • Any regimen that increases the CD4 count and drops viral load to undetectable amounts or close to undetectable amounts is adequate. • When starting medication, a drop of at least 50% of viral load in the first month is expected to indicate adequate therapy.
Pregnant patients • Without treatment, approximately 25-39% of children born to HIV-positive mothers will truly be HIV positive. • All children at birth will carry he maternal antibody to the virus and will be positive by ELISA testing, but only 25-30% will remain truly infected. • Pregnant women with serious disease (low CD4 or high viral load) should be treated fully for their HIV infection. That is, they should get triple antiretroviral therapy as you would in a nonpregnant person.
C-section is only used routinely in those whose CD4 cont and viral load are not controlled with medication. • At least, Zidovudine (AZT) treatment indicated in all pregnant women. • AZT alone will decrease the transmission from 25 to 8%. • AZT should begin in pregnant women at 14 weeks of pregnancy if the patient is not already on therapy for their own disease. • The only adverse side effect is transient anemia. • The only known teratogen is efavirenz in animal studies.
Post exposure prophylaxis • All patients with serious exposure to blood body fluids oh HIV-positive patients should receive AZT + Lamivudine + nelfinavir or any other fully suppressive three drug combination for 4 weeks. • You can modify the regimen as needed to ensure compliance. • Zidovudine (AZT) alone will decrease the risk of transmission by 80% .
Post exposure prophylaxis (PEP) • Risk of contamination 0,1 -0,5%: • Skin injury: ex. Needle stick injury * Deep infection risk < 0,3% PEP * Superficial infection risk < 0,3% PEP 2. Mucous membrane/broken skin: * Large surface I. risk < 0,1% PEP * Small surface I. risk < 0,1% offer the option 3. Unbroken skin I. risk < 0,1% advice against PEP = Post Exposure Prophylaxis
What to do ? • Follow up examination for HIV infection ( at 1, 3, 6,12 months) • Give PEP for those with infection risk > 0,1% : IDV =Indinavir or nelfinavir. 3TC = Lamuvidine. ZDV = Zidovudine. - Early monotherapy with Zidovudine reduces HIV infection by 80%. • Start PEP within 6 hours of suspected exposure, do not wait results, stop treatment if results are negative. • Total course should take 4 weeks (28 days).
Follow up HIV at the start of treatment and after 1, 3, 6 and 12 months, if results still negative then no HIV infection has been taken place. • After 12 months take another HIV test to R/O delayed seroconversion.
