Clinical Manifestations & Management of HIV Dr.Shervin Shokouhi Infectious Disease Specialist & Associate Professor of Shaheed Beheshti University of Medical Sciences 1
CLINICAL MANIFESTATIONS OF HIV / AIDS SEXUAL, EXPOSURE BLOOD, VERTICAL Days to weeks(2-4w.) ACUTE HIV INFECTION (1-2W.) *<5%, 2y. 5-8% *20-25%, 6y. *50%, 10y. long term nonprogressors NEOPLASM, INFECTIONS AIDS 2
Natural history of human immunodeficiency virus (HIV) infection 3
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CLINICAL CATEGORIES Category A: Asymptomatic HIV infection -persistent generalised lymphadenopathy )PGL( - Acute (primary) HIV infection Category B : bacillary angiomatosis candidiasis (thrush) in the mouth candidiasis of the vagina and/or vulva cervical abnormalites of moderate or severe extent constitutional symptoms herpes zoster (shingles) involving at least one episodes or more than one dermatone (skin area( idiopathic thrombocytopenia purpura listeriosis oral hairy leukoplakia Category C : AID s Indicator Conditions 5
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Acute Retroviral Syndrome A mononucleosis-like like illness (1/2-2/3) 2/3) Onset 1-6w after exposure, peak at 3w. Fever,sweats,adenopathy,nonexudative adenopathy nonexudative pharyngitis, myalgia or arthralgia, nausea,diarrhea, rash:maculopapular,urticarial,roseaola-like.( like.(2/3) Headache, photophobia, meningismus, encephalitis, peripheral neuropathy, GBS Hepatosplenomegaly, oral aphthous ulceration, oral & esophageal candidiasis 8
Lymphadenopathy &Maculopapular lar rash 9
Laboratory evaluation ation Reduced total Lymphocyte count: (CD4 & CD8 with normal ratio, within several weeks CD4 & CD8 increase with CD4/CD /CD8 inverted). Elevated ESR Negative heterophile antibody Elevated transaminase & alkaline phosphatase levels HIV Vco core(p24 24) )a antigen tge in serum &CS CSF (75 75%) Plasma HIV RNA test (>10,000) the most sensitive marker Enzyme immunoassay HIV Ab remains negative 10 2-6 w
Differential Diagnosis Infectious mononucleosis Influenza Viral hepatitis i Measles Rubella Primary herpes simplex infection Secondary syphilis 11
Evaluation of patients with Acute Retroviral Rt ls Syndrome Careful history to elicit risks for HIV infection Laboratory tests to rule out Mononucleosis & Syphilis, HIV antibody, Plasma RNA test CBC & diff 12
Persistent Generalized Lymphadenopathy Presence of 2 or more extrainguinal sites of lymphadenopathy for min. 3-6 m, which no other explanation. 50-70% of HIV infected patients Cervical, submandibular, occipital, axillary Symmetric, mobile, rubbery L. N, 0.5-2cm, no pain, no tenderness Pathology: fullicular hyperplasia without specific pathogen 13
Differential Diagnosis HIV infection Sarcoidosis Secondary syphilis Hodgkin disease Mycobacterial infection KS Lymphoma Castleman disease 14
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Constitutional & Wasting Being easily fatigued, low grade fever, night sweats, intermittent diarrhea Severe wasting Anxiety y, depression 16
Wasting Syndrome Definition of wasting syndrome is the presence of unexplained constitutional disease for more than 1 month with a temperature greater than 38.3 C, diarrhea, and loss of more than 10% of baseline body weight. A thorough evaluation to identify specific pathogens that would explain the symptoms and that might be amenable to treatment is essential before wasting syndrome is diagnosed, and usually a specific cause can be implicated. 17
Oral Candidiasis Oral Diseases Oral Hairy Leukoplakia Gingivitis i i i & Periodontitis i i Oral ulcers KS NON-Hodgkin lymphoma Oral wart 18
Oral Candidiasis Types: Thrush (most common form ) Atrophic form of candidiasis Hypertrophic form Angular chelitis Diagnosis of candidiasis: Physical examination KOH preparation of scraped material from a plaque is diagnostic Cultures from Candida (rarely) Biopsy 19 Therapeutic trial of antifungal agents
Oral Candidiasis (thrush) 20
Angular cheilitis 21
Oral Hairy Leukoplakia Replication of EBV in epithelium of keratinaized cells on the surface of tongue & buccal mucosa. Raised white lesion of oral mucosa, usually on lateral margin of tongue Usually asymptomatic,large lesions impair taste, discomfort Diagnosis by : 1/ visual inspection 2/ failure to scrap off lesion with a tongue blade 3/ failure of lesion to respond to antifungal therapy 4/ biopsy material or scraping (EBV) Therapy: High dose acyclovir or gancyclovir, podophyllin, isotretinoin 22 only temporarily
Oral Hairy Leukoplakia 23
Human Papiloma Virus 24
Oral ulcers HSV 1 & 2 CMV & HPV* Aphthous stomatitis Kaposi Sarcoma* & N. H. Lymphoma* Drugs*(AZT, ddc, Dapson) 25
Herpes simplex 26
Aphthous ulcer 27
Kaposi Sarcoma 28
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Herpes zoster in dermatomal distribution tion 30
Molluscum Contagiosum 31
Kaposi s Sarcoma 32
Seborrheic Dermatitis 33
Eosinophilic dermatitis 34
Cryptococcosis 35
Norwegian scabies (in a patient t with wasting syndrome) 36
Onychomycosis 37
Bacillary Angiomatosis 38
Musculoskeletal Complications Polymyositis Pyomyositis ii Other rheumatologic findings in patients with HIV disease are not unusual. Avascular necrosis of bone 39
Renal Disease HIV-related nephropathy other causes: IVDU, hepatitis B and C infection, hypertension, fluid and electrolyte disorders, and concomitant opportunistic infections and malignancies are all associated with renal dysfunction. In addition, many drugs used to treat HIV infection and its associated opportunistic infections are nephrotoxic. Pentamidine, foscarnet, and the aminoglycosides id can cause ATN, and indinavir, sulfadiazine, and intravenous acyclovir can cause intratubular obstruction by crystal formation. Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome has been reported in HIV-infected persons. Immune complex mediated mediated glomerular diseases, such as those associated with immunoglobulin A nephropathy have also been reported. 40
CD4 Cell Count Ranges for Selected HIV-Related and Non-HIV HIV-Related Respiratory Illnesses CD4 cell count <500 cells/fl Bacterial pneumonia (recurrent) Pulmonary mycobacterial pneumonia (Tuberculous) CD4 cell count <200 cells/fl Pneumocystis jirovecii pne. Cryptococcus neoformans pne. Bacterial pneumonia (associated with bacteremia/sepsis) i Disseminated or extrapulmonary tuberculosis CD4 cell count <100 cells/fl Pulmonary Kaposi's Sarcoma Bacterial pneumonia (Gram- negative bacilli and Staphylococcus aureus increased) Toxoplasma pneumonitis CD4 cell count <50 cells/fl Disseminated Histoplasma capsulatum Disseminated Coccidioides immitis Cytomegalovirus pneumonitis Disseminated Mycobacterium avium complex Disseminated mycobacterium (non-tuberculous) Aspergillus pneumonia Candida pneumonia 41
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Screenings for specific diseases for patients presenting with HIV infection 43
Tests of questionable or no value in initial evaluation of patient presenting with HIV infection. 44
ANTIRETROVIRAL AGENTS Nucleoside and Nucleotide Analogue Reverse. Transcriptase Inhibitors. (NRTI / NdRTI) Non-nucleoside nucleoside Reverse Transcriptase Inhibitors. (NNRTI) Protease Inhibitors. (PI) Entry Inhibitors. CCR5 Antagonists Other Drugs 45
Approved Nucleoside Reverse Transcriptase Inhibitor (NRTI) 46
Approved Non-Nucleoside Nucleoside Reverse Transcriptase Inhibitor (NNRTI) 47
Approved Protease Inhibitor 48
Approved Entry Inhibitor 49
Estimated t Timeline for Availability of New Antiretrovirals MK-0518 Maraviroc GS-9137 Vicriviroc TNX-355 CXCR4 inhibitors Bevirimat Entry inhibitors (anti-gp120, CCR5) Maturation ti inhibitors Integrase inhibitors 2006 2007 2008 2009 2010 Etravirine TMC278 Brecanavir Apricitabine PIs NNRTI NRTI 50
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Indications to start HAART Therapy Acute HIV-1 Infection Postexposure Prophylaxis Symptomatic Stage Asymptomatic Stage: 1. CD4 Count < 350 2. CD4 Count > 350 3. CD4 Count < 200 52
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Recommended ARV Regimen for NRTI + NRTI + PI. Initial lt Treatment t NRTI + NRTI + NNRTI. NRTI + NRTI + NdRTI. Other Regimens. 56
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Assays for Monitoring Infection Baseline HIV-I I RNA levels: Two measurements separated by 1 to 4 week. After therapy is initiated or changed, it is prudent to check HIV-I RNA levels at least monthly until the nadir is reached, and then at least every 3 to 4 months. A consistent increase in viral load of more than 0.5 log suggests a failing antiretroviral regimen. HIV-I RNA levels in 4-8 w & 16-24 w. Baseline CD4+T-cell counts: Two measurements separated by 1 to 4 week. CD4+T-cell count should be measured periodically, at least every 3 to 4 months, to monitor immunologic i improvement. 59
Virologic & Immunologic failure Virologic failure :on treatment can be defined as a confirmed HIV RNA level >400 copies/ml after 24 weeks, >50 copies/ml after 48 weeks, or a repeated HIV RNA level >400 copies/ml after prior suppression of viremia i to <400 copies/ml. Immunologic Failure :can be defined as failure to increase the CD4 cell count by 25-50 cells/mm3 above the baseline count over the first year of therapy, or a decrease to 60 below the baseline CD4 cell count on therapy
Good Luck 61