sammanchester September 2015 HIV/AIDS: Symptoms, Prevention and Treatment

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1 sammanchester September 2015 HIV/AIDS: Symptoms, Prevention and Treatment Dr Pippa Newton Consultant in Infectious Diseases Wythenshawe Hospital, Manchester

2 Stages of HIV infection CDC WHO Overview Acute HIV infection Symptoms of Chronic HIV infection Clinical indicator conditions for testing Prevention of HIV related symptoms Prompt diagnosis of infection Prophylaxis against opportunistic infections Antiretroviral therapy

3 Stages of HIV infection

4 Symptoms of HIV infection Asymptomatic Persistent Generalised Lymphadenopathy Symptomatic Acute HIV infection Symptomatic disease AIDS defining illnesses Several classifications of disease stage (CDC, WHO) - once been defined as having a particular stage of disease, even if improves still keeps original staging

5 CDC categories: Stages of HIV infection -1 3 stages A,B, C 3 subgroups for each stage dependant upon CD4 count ( 500, , < 200) A: Asymptomatic, Acute HIV infection, Persistent Generalised lymphadenopathy (PGL) B: Symptomatic C: AIDS defining

6 Stages of HIV infection -2 WHO categories (5 stages) Acute HIV infection (asymptomatic or symptomatic) Clinical stages 1 4 Stage 1: Asymptomatic, PGL Stage 2: Unexplained Wt loss < 10% body weight Recurrent chest infections Herpes zoster Angular chelitis Recurrent oral ulceration Papular pruritic eruptions Seborrhoeic dermatitis Fungal nail infections

7 Stages of HIV infection -3 WHO categories (5 stages) Clinical stage: Stage 3: Stage 4: Unexplained Wt loss > 10% body weight Unexplained chronic diarrhoea for > 1/12 Unexplained fever for > 1/12 Persistent oral candidiasis TB (not extra-pulmonary) Severe presumed bacterial infections Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis Unexplained anaemia, neutropenia, chronic thrombocytopenia AIDS defining illnesses

8 Diagnosis often missed Acute HIV infection -1 Patients often do not realise that have had a specific risk exposure for acquiring HIV Need a high index of suspicion Mean time from exposure to onset of symptoms is 2 4 weeks (range 5 to 29 days) However, some cases have presented up to 3 months later Time course may be prolonged if had Post Exposure Prophylaxis

9 Acute HIV infection -2 Up to 80% of individuals may have some symptoms Fever Flu-like symptoms Mononucleosis like syndrome pharyngitis, mouth ulcers, lymphadenopathy Rash Neurological symptoms may present several weeks after other symptoms have resolved Eg Meningitis / Meningio-encephalitis / Guillain Barre Syndrome

10 Symptoms of Acute HIV infection Hecht et al. AIDS 2002;16: Frequency of symptom (%) in symptomatic patients Fever 80% Pharyngitis 44% Fatigue 78% Oral ulcers 37% Arthralgias 54% Neckstiffness 34% Headaches 54% Weight loss (> 2.5kg) 32% Loss of appetite 54% Confusion 25% Rash 51% Photophobia 24% Night sweats 51% Vomiting 12% Myalgias 49% Gum infection 10% Nausea 49% Anal sores 5% Diarrhoea 46% Genital sores 2% Fever and Rash 46%

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12 Window of detection of Acute HIV infection based on diagnostic test HIV Viral load

13 Symptoms of Chronic HIV infection Include symptoms described in WHO stages Clinical stages 2 and 3 Other clinical indicator conditions that should alert the physician to consider HIV testing Symptoms related to AIDS defining illnesses Opportunistic infections Malignancies Other AIDS defining illnesses eg HIV Dementia and HIV wasting

14 Clinical Indicator Diseases for HIV testing Respiratory Neurology Dermatology OTHER CONDITIONS WHERE HIV TEST SHOULD BE OFFERED Bacterial pneumonia Aspergillosis Aseptic meningitis / encephalitis Cerebral abscess Space occupying lesion of unknown cause Guillian Barre Syndrome Transverse myelitis Peripheral neuropathy Dementia Leucoencephalopathy Severe seborrhoeic dermatitis Severe psoriasis Multidermatomal / recurrent herpes zoster AIDS DEFINING Tuberculosis Pneumocystis Cerebral Toxoplasmosis Primary Cerebral Lymphoma Cryptococcal meningitis Progressive multifocal leucoencephalopathy Kaposi s sarcoma

15 Gastroenterology Oncology Clinical Indicator Diseases for HIV testing OTHER CONDITIONS WHERE HIV TEST SHOULD BE OFFERED Chronic diarrhoea cause unknown Weight loss cause unknown Salmonella, Shigella, Campylobacter Hepatitis B and / or C infection Anal cancer or Anal Intraepithelial Dysplasia Lung cancer Seminoma Head and Neck cancer Hodgkin s lymphoma Castleman s disease AIDS DEFINING Persistent cryptosporidiosis Non-Hogkin s Lymphoma Gynaecology Vaginal intraepithelial neoplasia Cervical cancer Haematology Thrombocytopenia Any unexplained blood dyscrasias

16 Clinical Indicator Diseases for HIV testing Ophthalmology ENT Other OTHER CONDITIONS WHERE HIV TEST SHOULD BE OFFERED Infective retinal diseases including herpes viruses and toxoplasma Any unexplained retinopathy Lymphadenopathy of unknown cause Chronic parotitis Lymphoepithelial parotid cysts Mononucleosis-like syndrome Oral Candidiasis Oral hairy leucoplakia Any sexually transmitted infection AIDS DEFINING Cytomegalovirus retinitis

17 Prevention of HIV related symptoms -1 Prompt diagnosis of HIV infection Be aware of when universal testing is recommended In areas where HIV prevalence > 2 in 1000 in the population In certain clinical situations where a specific risk is identified Other situations relating to blood or organ donation or as a organ recipient Consider prophylaxis against opportunistic infections Does the patient need to start antiretroviral therapy?

18 Prompt diagnosis of infection - National Standards for HIV testing

19 Prompt diagnosis of infection National Standards for HIV testing

20 HIV testing of acute medical admissions PHE 2014 report addressing late diagnosis through screening and testing

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23 Does the patient need prophylaxis against opportunistic infections? Pneumocystis jirovecii Persistent CD4 count < 200 or CD4% < 14% Or oral candidiasis Or previous AIDS defining illness Treatment: Co-tromoxazole or Dapsone or Pentamidine nebulisers or Atovaquone

24 Does the patient need prophylaxis against opportunistic infections? Toxoplasmosis If positive Toxoplasma serology and CD4 count < 200 Treatment: Co-tromoxazole or Dapsone and Trimethoprim Mycobacterium avium complex (MAC) Consider if CD4 count < 50 Treatment: Azithromycin 250 mg once a week

25 Impact of antiretroviral therapy on the incidence of opportunistic infections Adult and Adolescent Spectrum of HIV Disease (ASD) Project.

26 Timing of antiretroviral therapy Acute HIV infection Start within 12 weeks of acute infection in certain clinical situations Chronic HIV infections According to BHIVA criteria If patient has AIDS defining illness / severe infection and CD4 < 200 aim to start treatment within 2 weeks of commencing treatment for their presenting infection Can consider at higher CD4 counts following discussion with patient with the aim of reducing transmission to partners

27 Antiretroviral therapy Antiretroviral therapy Prior to commencing treatment Baseline investigations HIV resistance testing Surrogate markers (CD4 / viral load) Safety bloods (FBC, U+Es, LFTs) Any other co-infections to consider eg Hepatitis B infection Assessment of other co-morbidities (eg cardiac) Assess for evidence of an ongoing opportunistic infection Should be started on treatment by a HIV specialist

28 Antiretroviral therapy

29 Indications for treatment in Acute HIV Infection Neurological involvement Any AIDS defining illness Confirmed CD4 count 350 Also consider for patients presenting within 12 weeks of acute HIV infection if severe symptoms of seroconversion Such as rash, fever, weight loss, persistent lymphadenopathy, diarrhoea >4 days, malaise, headaches

30 Rationale for Antiretroviral therapy in Acute HIV infection Preservation of specific anti-hiv CD4 T lymphocytes that would otherwise be destroyed by uncontrolled viral replication, the presence of which is associated with survival in untreated individuals Reduction in morbidity associated with high viraemia and profound CD4 cell depletion during acute infection Reduction in the enhanced risk of onward transmission of HIV associated with PHI

31 Treatment duration in Acute HIV infection Start with a protease inhibitor containing regimen Duration of treatment 48 weeks? or indefinitely? USA: NYC / John Hopkins (September 2015): Recommended for all patients with PHI

32 Indications for HAART in chronic HIV infection When to start antiretroviral therapy in chronic infection CD4 count 350 AIDS defining illness irrespective of CD4 count HIV-related co-morbidity eg nephropathy, ITP, neurocognitive disorders Co-infection with Hepatitis B / C and CD4 500 If treating Hepatitis B infection would recommend HAART if CD4 > 500 Non AIDS defining malignancies requiring immunosuppressive treatment

33 Preferred HAART regimens in antiretroviral naïve patients with wild type virus PREFERRED ALTERNATIVE NRTI (2 drugs) Tenofovir and Emtricitabine TRUVADA Abacavir and Lamivudine KIVEXA 3 rd Agent Atazanavir / ritonavir Fosamprenavir / ritonavir Darunavir / ritonavir Efavirenz Raltegravir Lopinavir / ritonavir Nevirapine Rilpivirine Elvitegravir / cobicistat

34 Antiretroviral drug interactions -1 Drug Interaction Charts Many drugs are metabolised by Cytochrome p450 HIV ichart. A free app for mobile devices. Available for Apple (via itunes) and Android (via Google Play).

35 Antiretroviral drug interactions -2 Traffic light system Explains interactions Dose modification and monitoring advice

36 Summary HIV infection may present in many ways Asymptomatic Symptomatic acute HIV infection Symptoms of chronic infection AIDS defining illness National guidelines for testing Clinical indicators for HIV testing Prompt diagnosis - HIV testing on the acute medical unit Consider prophylaxis for opportunistic infections Antiretroviral therapy in acute and chronic infection