BDS10034 Viral Infections HIV_Dr Noha.pdf

BDS10034 Viral infections: HIV disease Viral infections - HIV disease Aims: The aim of this lecture is to detail the orofacial manifestations of HIV disease Objectives: On completion of this lecture, the student should be able to: •Understand the oral manifestations of HIV disease •Have awareness...

BDS10034 Viral infections: HIV disease Viral infections - HIV disease Aims: The aim of this lecture is to detail the orofacial manifestations of HIV disease Objectives: On completion of this lecture, the student should be able to: •Understand the oral manifestations of HIV disease •Have awareness of the significance of such oral manifestations in the monitoring of affected individuals Human immunodeficiency virus (HIV) • Origins in Africa. • Spread as a consequence of politics, societal behavior, migration. • HIV 1: Chimpanzee subspecies Pan troglodytes troglodytes to apes to man • HIV 2: Sooty mangabeys to humans • Species jump probably via bites or injury then: - Spread in humans via effects of European colonialism and urbanisation Spread to US via Hiati (migration from Congo) Spread within Africa and across the globe starting in the 1960s Oral aspects described in 1981 First 25 years of AIDS People living with HIV Million 50 1 First cases of unusual immune deficiency are identified among gay men in USA, and a new deadly disease noticed 45 2 Acquired Immune Deficiency Syndrome (AIDS) is defined for the first time 40 15 3 The Human Immune Deficiency Virus (HIV) is identified as the cause of AIDS 4 In Africa, a heterosexual AIDS epidemic is revealed 35 25 20 8 The first therapy for AIDS – zidovudine, or AZT -- is approved for use in the USA 15 10 10 Highly Active Antiretroviral Treatment launched 11 Scientists develop the first treatment regimen to reduce mother-to-child transmission of HIV 13 11 10 9 12 Children orphaned by AIDS in subSaharan Africa 1 2 3 4 5 12 UNAIDS is created 13 Brazil becomes the first developing country to provide antiretroviral therapy through its public health system 14 The UN General Assembly Special Session on HIV/AIDS. Global Fund to fight AIDS, Tuberculosis and Malaria launched 15 WHO and UNAIDS launch the "3 x 5" initiative with the goal of reaching 3 million people in developing world with ART by 2005 7 8 5 16 In 1991-1993, HIV prevalence in young pregnant women in Uganda and in young men in Thailand begins to decrease, the first major downturns in the epidemic in developing countries 14 5 The first HIV antibody test becomes available 6 Global Network of People living with HIV/AIDS (GNP+) (then International Steering Committee of People Living with HIV/AIDS) founded 7 The World Health Organisation launches the Global Programme on AIDS 30 9 6 16 Global Coalition on Women and AIDS launched 0 1980 1985 1990 1995 2000 2005 Current therapeutic strategies for HIV disease 1) SPECIFIC inhibition of HIV replication (ART) • NRTIs • NNRTIs • PIs Generally not available in developing world Drug resistance still possible Notable side effects • EIs 2) PREVENTION and MANAGEMENT • Opportunistic infections • Malignancies Not always available in the developing world New low-cost therapies in development ART: antiretroviral therapy HIV Epidemiology recent worldwide trends • Worldwide: 1.8-1.9 million new infections in adults (decline in both genders; decline is greatest in Southern Africa) • Europe: Rise in new infections in Eastern Europe and Central Asia • Eastern Europe: Rise in new infections • Asia and Pacific: Fall in most areas other than central Asia • South America: No change in last few years. • HIV adversely affects: health, employment, education, economies • 1. 2. 3. HIV related deaths: 48% fall in deaths between 2005 and 2016; reflects access to ART Deaths in women are less than men – reflecting ART compliance BUT HIV related deaths is still the most common cause of death worldwide in women of reproductive age See: http://www.unaids.org/sites/default/files/media_asset/20170720_Data_book_2017_en.pdf Trends in oral consequences of HIV disease • Continue to arise. • Reflect immune status. • May be influenced by risk activity and geography. • Reduced with ART. • Can be drug-associated. • As the life span of HIV-infected individuals increases so they are at risk of common oral disease. • Classification system for HIV oral manifestations is outdated but it provides a marker of what oral disease can arise if therapy is not given or patients are unaware of their HIV infection. Common oral consequences of HIV include: I. Infections (fungal, viral, bacterial, others). II. Malignancy (typically viral-related). III. Salivary gland disease. IV. Periodontal diseases. V. Oral adverse effects of therapy VI. Other oral features Oral consequences of HIV disease I. Infection A. Fungal infection 1) Superficial (candidosis) • Can be initial feature of HIV disease. • Now more common in developing than developed world. • Usually manifests as pseudomembranous candidosis. • Affects adults & children. • Usually correlates with CD4+ T cell count & high viral load. • Usually C. albicans, but can be C. dubliniensis, glabrata, Krusei or tropicalis • Possibly increased virulence of C. albicans. • Genotype of C. albicans usually remains stable. • Drug resistance to azoles & polyenes in some areas (esp developed world). • Non-sexual transmission of resistant strains is uncommon. 2. Systemic (rare fungal infection) • Aspergillosis v. rare (oral ulceration). • Histoplasmosis v. rare (oral ulceration/pigmentation). • Blastomycosis rare (Americas mainly) – oral/labial ulceration. • Cryptococcosis oral/gingival ulceration, on decrease due to ART. • Paracoccidiodomucosis S. America (esp Brazil, orofacial ulceration). • Mucormycosis rare, in US & Europe (palatal ulceration). Oral consequences of HIV disease I. Infection B. Viral infection: 1) HSV-1 (usually): • More likely in children (24%), not common in adults. • Not a strong marker of HIV disease. • Acyclovir resistance avoided with cidofovir. 2) Varicella zoster virus • Shingles is not a strong marker of HIV. • Disagreement regarding association of shingles with low CD4+ T cell counts • Trigeminal shingles more common in HIV than non-HIV groups 3) Epstein bar virus (EBV): • Causes oral hairy Leukoplakia (OHL). • Variable prevalence (0.42-38%) • Alcohol lessens occurrence • No link with oral sex • Reflects activation of previous EBV • Multiple EBV genotypic infection • Unclear if infection arises from basal cells or tonsils. • No malignant potential • Low frequency with ART & reversed by ART. 4) Human papillomavirus (HPV) • Sub-clinical HPV oral carriage increased in HIV disease. • 9.2-25% vs <7.6%. • But clinical disease seems uncommon. 5) Human herpes virus -8 (HHV-8/ Kaposi’s sarcoma herpes virus) • Gives rise to Kaposi’s sarcoma. • Oral carriage in healthy contacts of HIV/KS patients possible in endemic regions. • Non-sexual (oral) transmission common. • Multiple HHV-8 oral infection possible. 6) Other viral infections • Cytomegalovirus – rare, oral ulceration. • Molluscum contagiosum – rare, oral swellings. Oral consequences of HIV disease I. Infection C. Bacterial infection: 1) Mycobacterial infection: • Mycobacterium tuberculosis 1. More likely in developed world. 2. Oral ulceration usually secondary MTB 3. Labial disease may be primary MTB • Mycobacteria other than tuberculosis (MOTT) (ulcers). • Addisonian pigmentation with MTB, MOTT, histoplasmosis & CMV. 2) Others • Actinomycosis israelii (ulceration) • Treponema pallidum (ulceration). • Bartonella henselae (pigmented swellings). • Escherichia coli (ulceration). • Leishmaniasis (ulceration). Oral consequences of HIV disease II. Malignancy A) Kaposi’s sarcoma: • Remains the most common oral malignancy of HIV disease • 3 fold+ rise in some African regions • Can affect 20%+ of African groups • Affects children & adults. • Most common in palate & gingiva. • It can be first manifestation of HIV disease. • Usually indicates multi-system involvement • Immune reconstitution (ART) has caused increased epiglottic kaposi sarcoma. Oral consequences of HIV disease II. Malignancy B) Non-Hodgkin’s lymphoma: • Second most common oral malignancy of HIV. • 50% are B cell related. • Manifests as palatal/pharyngeal or gingival disease. • Can also give rise to salivary gland swellings. • Plasmablastic lymphoma may be distinct to the mouth. C) Hodgkin’s disease: • Very rare in the mouth • But common in HIV disease D) Oral squamous cell carcinoma: • Unclear if there is a strong likelihood of risk of OSCC in untreated/treated HIV disease. Oral consequences of HIV disease III. Salivary gland disease 1. Salivary gland enlargement : • Due to diffuse lymphocytosis syndrome. 2. Xerostomia : • Due to diffuse lymphocytosis syndrome or Protease inhibitors. • Gives rise to increased risk of caries, candidal infection etc. • Management similar to Sjogren’s syndrome. 3. Rare manifestations: • Acute suppurative sialadenitis. • MTB or MOTT NHL or KS (primary or secondary). • Reactive lymphadenopathy. Oral consequences of HIV disease IV. Periodontal disease • Specific types suggested: 1. HIV gingivitis (linear gingivitis) (0.11.9%, 47% reported in India) 2. Necrotising ulcerative gingivitis 3. Necrotising ulcerative periodontitis 4. Necrotising stomatitis • Associations with CD4+ T cell count seem to be variable. • Previously considered to be frequent & aggressive but present evidence doesn’t suggest this. • Periodontal diseases in HIV patient might be due to: 1. Plaque control 2. Xerostomia (?) 3. Malnutrition 4. Immunodeficiency (PMNL?) 5. Synergism of herpes viruses and gram-negative periodontal pathogens 6. HLA haplotype (overproduction of TNF and IL-1). Oral consequences of HIV disease: V. Oral adverse effects of therapy Erythema multiforme NRTIs Zidovudine Abacavir Didanosine Parotid lipomatosis Pis Indinavir Ritonavir Saquinavir Nelfinavir Amprenavir Cheilitis Perioral paraesthesia Pi Pis Indinavir Ritonavir Amprenavir Taste disturbances Pis Indinabir Ritonavir Facial oedema Pis Ritonavir Ulcers NRTIs Abacavir Zalcitabine Zalcitabine NNRTIs Efavirenz Delaviridine Nevirapine Saquinavir Hyperpigmentation Lipodystrophy NRTIs Zidovudine NRTIs Stavudine Pis Saquinavir Ritonavir Xerostomia NRTIs Lamivudine Didanosine Lip enlargement Pis Saquinavir Indinavir Nelfinavir Ritonavir EIs Nevirapine Enfuvirtide Oral consequences of HIV disease: VI. Other oral features HIV ulceration Disease observed in HIV infection • Usually with low CD4+ T cell count • Weak association of RAS with HIV • Thalidomide effective (usually) 1. 2. Trigeminal neuropathy Disease arising in some groups with HIV infection Uncommon, may reflect CNS disease Hypermelanotic pigmentation • Idiopathic, Reflect adrenocortical hypofunction • Adverse effect of ART 1. 2. 3. 4. Pemphigus vulgaris Chielitis glandularis Syphilis Malnutrition Recreational drug features HCV sialadenitis Transmission of HIV via oral fluids – highly unlikely •HIV RNA is present in up to 90% of whole saliva and 50% of Gingival crevicular fluid (GCF). •HIV RNA levels may be greater than those in plasma (in some studies). •HIV enters the mouth via CD4+T cells, Langerhans cells or via HIV trafficking via inter-epithelial cells •Oral transmission difficult to demonstrate, but little evidence of risk. •Suggested per-contact risk of 0.6% of receptive oral sex vs 0.8% for unprotected receptive anal intercourse. •Control study of gay men suggested an OR of 1.05 with oro-genital contact •Longitudinal study of HIV discordant heterosexuals – no HIV over 19,000 unprotected orogenital contacts. •No new infections in a cohort of MSM in San Francisco who only practiced orogenital sex (despite 1519 person-years exposure). •Mouth entry of HIV suggested via FIV, SIV, possible increased rate of HIV in first-born twins cf second-born. Factors influencing oral HIV load 1) Oral health status: • Gingival/periodontal inflammation. 2) Innate immunity: • • • • lysozyme Lactoferrins salivary agglutinin and mucins. Human Leukocyte proteinase inhibitor (SLPI) (serine protease inhibitor) – may prevent tranmucosal penetration of HIV via an inhibition of infection of monocytes. 3) Acquired immunity • IgA • Langerhans cells • Others BUT HIV salivary gland disease may reduce the functionality of several of these potential inhibitory factors. Risk of HIV acquisition during oral health care • Transmission of HIV during oral health care is VERY unlikely. • Factors affecting risk of HIV acquisition: 1. Volume of blood transferred (whether blood visible on the instrument). 2. Viral load of the patient. 3. Depth of injury. 4. Needle that has been in an vein or artery. Aspects of HIV disease relevant to dentistry in the 21st century Conclusions: • HIV here for many years to come. • Oral manifestations are unlikely if the patient is receiving ART. • Oral manifestations are likely if : 1. Patient does not know that they have HIV disease. 2. Therapy has stopped working (or patient is unable to take medication). 3. The virus has developed resistance. • Significant geographical/economic variation in oral presentation. • Oral health care workers are NOT at significant risk of nosocomial acquisition of HIV. Reading material Students are advised to review any relevant teaching provided in the earlier years. In addition they are advised to read relevant sections of the following texts: • Odell E.W. Cawson’s Essentials of Oral Pathology and Oral Medicine. 9th Edition. Elsevier, 2017 pp 235-241408-418 • Scully C. Oral and Maxillofacial Medicine Churchill Livingstone 2008 pp 305-324 Viral infections - HIV disease Aims: The aim of this lecture is to detail the orofacial manifestations of HIV disease Objectives: On completion of this lecture, the student should be able to: •Understand the oral manifestations of HIV disease •Have awareness of the significance of such oral manifestations in the monitoring of affected individuals Viral infections: HIV disease