Updates in HIV Medicine. Dr. Jacky Chan Associate Consultant Princess Margaret Hospital
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1 Updates in HIV Medicine Dr. Jacky Chan Associate Consultant Princess Margaret Hospital
2 What is HIV? HIV - Human immunodeficiency virus Retrovirus Human Immunodeficiency virus type-1 (HIV-1) Global AIDS pandemic Human Immunodeficiency virus type-2 (HIV-2) Limited primarily to West Africa
3 HIV virus
4 HIV genome An enveloped virus containing two copies of positive-stranded RNA Transmembrane (gp41) and extracellular (gp120) envelope glycoproteins
5 Immune invasion
6 CD4
7 Replication HIV enters CD4+ T lymphocytes through a complex interaction that involves the binding of glycoproteins to particular receptor Intracellularly, the reverse transcriptase enzyme transcribes the RNA genome to DNA Integration of HIV DNA into host genome HIV matures by proteases releasing the individual HIV protein
8
9 Natural history of HIV infection Three phases Acute infection Asymptomatic phase Symptomatic disease AIDS The median time from infection to significant illness (AIDS) being between 8-10 years
10 Case Presentation
11 Case 1 M/40 Lorry driver 1 week history of fever+ Myalgia+ Malaise+ Faint rash over trunk and limbs
12 Shotty cervical LN+ Maculopapular rash over trunk, limbs Non itchy
13 NPA x influenza A/B ve WCC 5.6, atypical lymphocytes+ Monospot test +ve Further history reviewed: hx of commerical sex in China+
14 Anti-HIV Ab: indeterminate PHLC: HIV RNA +ve Imp: Acute seroconversion of HIV
15 Acute HIV infection 10-60% patients with early HIV infection were asymptomatic Usual time from HIV exposure to symptoms development: 2-4 weeks Fever, lymphadenopathy, myalgia, headache, mucocutaneous ulcers Rash typically occurs hours after onset of fever Small, well circumscribed, oval or round, pink to deeply red colored macules or maculopapules
16 Acute HIV infection Mild anemia or thrombocytopenia Elevations of ALT Atypical lymphocytes+
17 Diagnosis of HIV infection Rapid HIV antibody tests HIV antigen (p24) HIV antibody Confirmatory tests: Western Blot assay Reaction between antibodies and specific viral proteins can be determined after addition of patient s serum HIV RNA PCR
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19 Typical western blot assay for diagnosing HIV infection
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21 Case 2 M/35 History of herpes zoster over right thigh at age of 28 Sales Complained of 1 month history of low grade fever and dry cough Decrease exercise tolerance SOB on exertion TOCC -ve
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23 WCC 2.1 Lymphocyte 0.3 Cr/ ALT normal CRP 9.8 Sputum c/st: Commensals Sputum AFB smear -ve
24 Given Augmentin + azithromycin Persistent fever+ Oxygen desaturation in room air Bronchoscopy done BAL: pneumocystis carinnii (jiroveci) present
25 Anti-HIV +ve Hx reviewed: multiple sexual partners CD4: 45 Started on septrin and prednisolone CXR cleared up
26 Case 3 M/58 Hx of HT, DM Live with wife Complained of 1 month history of difficulty in swallowing No vomiting Subjective weight loss
27 Hb 10.8 HCMC WCC 4.5 lymphocyte 0.5 Cr 127 CXR: clear
28 OGD done: presence of generalized whitish plaque-like lesions over esophagus
29 Esophageal biopsy: Presence of candida+
30 Oral exam: Presence of oral thrush (candidiasis)
31 Hx reviewed: episode of prostitute visits in Shenzhen ~10 years ago Anti-HIV +ve CD4: 85 Started on oral fluconazole
32 Case 4 M/36 Thai, came to HK for 4 years GPH Presented with generalized non itchy skin rash for 2 months Associated with fever, weight loss
33 P/E: Febrile Cervical and groin LNs+ Erythematous papules over 4 limbs and face, some being umbilicated Liver edge palpable+
34
35 Blood c/st: penicillium marneffei Further history reviewed: Ex-IVDA Hx of HIV dx in Bangkok 6 years ago Defaulted FU and no treatment was given
36 Anti-HIV +ve CD4 14 Given 2 weeks of amphotericin B, followed by oral itraconazole
37 What is AIDS? Acquired immunodeficiency syndrome Case definition: CD4 cell count <200 cells/mm 3 and/ or Presence of AIDS defining conditions, listed by Centres for Disease control and Prevention (CDC) Prior to anti-hiv therapy, the median survival from the time of AIDS diagnosis was estimated to be approximately 20 months
38 AIDS defining conditions Candidiasis of esophagus, trachea, bronchi, or lungs Cervical cancer, invasive Coccidioidomycosis Cryptococcosis, extrapulmonary Cytomegalovirus (CMV) of eye or any organ other than liver, spleen or lymph nodes Herpes simplex with chronic ulcer for >1 month; or bronchitis, pneumonitis, esophagitis Histoplasmosis, extrapulmonary HIV-associated dementia HIV-associated wasting (weight loss, chronic diarrhea, chronic weakness)
39 AIDS defining conditions Isosporiasis with diarrhea > 1 month Kaposi sarcoma Lymphoma (primary CNS, Burkitt s, immunoblastic) Mycobacterium avium complex (MAC) or M. kansasii infection (disseminated or extrapulmonary) M. Tuberculosis Pneumocystitis pneumonia (PCP) Recurrent bacterial pneumonia Progressive multifocal leukoencephalopathy (PML) Salmonella septicemia Toxoplasmosis of internal organ
40 Pneumocystitis pneumonia (PCP) Caused by pneumocystis jirovecii, classified as fungus but shared biologic characteristics with protozoa 90% cases occurred when CD4 counts drop below 200 cells/mm3 Chronic dry cough, SOB on exertion and fever
41 Diagnosis: Sputum induction, bronchoscopy, sent for histology staining CXR: diffuse, bilateral, symmetrical interstitial infiltrates from hila Treatment: High dose septrin +/- Steroid if severe cases
42 Mycobacterium tuberculosis infection Account for 13% cause of death with AIDS Latent TB CD4 >350: Limited to lungs, manifesting as upper lobe fibronodular infiltrates with or without cavitation CD4 <350 or more immunodeficient patients Less cavitations seen, atypical lung sites Extrapulmonary TB (lymphadenitis, pleuritis, pericarditis and meningitis)
43 Penicilliosis Caused by dimorphic fungus penicillum marneffei Endemic in Southeast Asia (especially Northern Thailand and Vietnam) and southern China Fever, anemia, weight loss, generalized skin papules with central umbilication resembling molluscum contagiosum
44 Penicilliosis Diagnosis by blood fungal culture, bone marrow culture Treatment: Intravenous anti-fungal (amphotericin B) for 2 weeks, followed by long term oral itraconazole
45 Local HIV/ AIDS situation
46
47 Local HIV/AIDs sit A total of 651 additional cases of HIV were reported in 2014, compared with 559 in 2013 Off the 651 newly reported cases, 378 via homosexual or bisexual exposure while 124 via heterosexual contact. 5 cases via drug injection and 1 case through blood transfusion outside Hong Kong. Remaining 143 cases had unknown route of transmission The most common AIDS-defining illness was pneumocystitis pneumonia
48
49
50
51 Management of HIV infection
52
53 What is HAART? HAART- Highly Active Antiretroviral Therapy Combination of antiretroviral drugs Six drug classes: Non-nucleoside reverse transcriptase inhibitors (NNRTIs) Nucleoside reverse transciptase inhibitors (NRTIs) Protease Inhibitors (PIs) Fusion inhibitors CCR5 antagonists (CCR5s) Integrase strand transfer inhibitors (INSTIs)
54 New drug 2014: dolutegravir
55 Goals of therapy Maximally suppress plasma HIV viral load Restore and preserve immunological function Reduce HIV-related morbidity and mortality Improve quality of life Prevent vertical transmission of HIV in women of childbearing potential
56
57 First line recommendation DHHS guideline 2015 Integrase strand transfer inhibitor-based regime Dolutegravir + truvada, Raltegravir + truvada, Stribild (single pill), Triumeq (single pill) Protease Inhibitor-based regime Darunavir boosted with ritonavir + truvada
58 When to start HAART? CD4 count <350 cells/mm3 ( by European society) Pregnancy (regardless of CD4 count) History of an AIDS-defining illness HIV-associated nephropathy HIV/ Hepatitis B coinfection Patients starting on ART should be willing to and able to commit to treatment and should understand the benefits and risks of therapy
59 HIV Prevention HIV is a very complex, highly changeable virus Difficult to eradicate In 2009, US Miliary HIV research Program (MHRP) published findings from a largescale HIV vaccine trial in Thailand called RV144
60 RV144, tested the primeboost combination of two vaccines: ALVAC HIV vaccine and the AIDSVAX B/E vaccine Safe and modestly effective in preventing HIV Lowered the rate of HIV infection by 31.2% compared to placebo Further secondary studies are necesary HIV vaccine trial
61 Summary Increasing HIV incidence in worldwide, including Hong Kong Early testing and diagnosis of HIV in high risk group of people Enhancement in number of pills for HIV treatment, resulting in better drug compliance No vaccination available and future studies and research are necessary
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