Seafarers and HIV infection Dr. Michaela Schuhwerk GUM Physician MRCP, DTMH, DipGUM, DFFP, MSc, CCST in GUM Medicine

Overview Objectives: I. History of epidemic To provide an overview over the following topics I. History of epidemic Epidemiology (worldwide and UK) Clinical features of HIV IV. Diagnosis V. Treatment VI. Relevance for occupational health physicians

I. History of the epidemic -1 1981 First cases of PCP pneumonia and Kaposi’s sarcoma described in USA 1983 Discovery of the virus. First cases of AIDS in the UK 1984 Development of first antibody test 1987 AZT becomes available to treat HIV 1996: Protease inhibitors available, change dramatically treatment of HIV 1998 routine antenatal HIV testing with opt out policy 2009: 33 Mio worldwide HIV infected individuals

I. History of the epidemic -2 2009: HIV is now a chronic treatable conditions with a near normal life expectancy This depends on timely diagnosis and access to antiretroviral therapy

II. HIV Epidemiology

Source: UNAIDS/WHO AIDS Epidemic Update: December 2007 Number of people living with HIV worldwide in 2007 Adults 31.0 million Women 15.5 million Children under 15 years 2.0 million Total 33 million People newly infected with HIV worldwide in 2007 2.7 million 370,000 3.07 million AIDS deaths worldwide in 2007 2 million 270,000

Global trends of HIV infection

UK epidemiology 2007 73 000 individuals HIV positive Prevalence UK: 0.12 % Proportion of risk groups infected 43% MSM 31% Heterosexual women 21% Heterosexual men 4% IVDU 61% of all cases in African born individuals unaware of diagnosis 29% of HIV cases undiagnosed (21600)

Estimated late diagnosis1 of HIV infection and AIDS at HIV diagnosis by prevention group, UK: 2006 1CD4 cell count less than 200 cells/mm3 within 30 days of diagnosis among adults (aged >14 years) HIV/AIDS diagnoses and death reports, and surveillance of CD4 cell counts in HIV-infected persons

III. Clinical features of HIV infection

III. Clinical Features 1. Seroconversion illness - seen in 10% of individuals a few weeks after exposure and coincides with seroconversion. Presents with an infectious mononucleosis like illness. 2. Incubation period - this is the period when the patient is completely asymptomatic and may vary from a few months to a more than 10 years. The median incubation period is 8-10 years. 3. AIDS-related complex or persistent generalized lymphadenopathy. 4. Full-blown AIDS.

IV. Opportunistic Infections Protozoal pneumocystis carinii (now thought to be a fungi), toxoplasmosis, crytosporidosis Fungal candidiasis, crytococcosis histoplasmosis, coccidiodomycosis Bacterial Mycobacterium avium complex, MTB atypical mycobacterial disease salmonella septicaemia multiple or recurrent pyogenic bacterial infection Viral CMV, HSV, VZV, JCV

Opportunistic Tumours The most frequent opportunistic tumour, Kaposi's sarcoma, is observed in 20% of patients with AIDS. KS is observed mostly in homosexuals and its relative incidence is declining. It is now associated with a human herpes virus 8 (HHV-8). Malignant lymphomas are also frequently seen in AIDS patients.

Kaposi’s Sarcoma

Oral hairy leukoplakia

Oral hairy leukoplakia

Other Manifestations It is now recognised that HIV-infected patients may develop a number of manifestations that are not explained by opportunistic infections or tumours. The most frequent neurological disorder is AIDS encephalopathy which is seen in two thirds of cases. Other manifestations include characteristic skin eruptions and persistent diarrhoea.

IV. Diagnosis 1. Clinical diagnosis because of suspicious features, high risk group or reported symptoms 2. Laboratory diagnosis

Laboratory Diagnosis Antibody tests only: window period up to 3 months Combination ag/ab tests: p24/antibody tests positive after 4 weeks In special circumstances pro viral DNA

VI. Treatment

HIV life cycle

VI. Antiretroviral Therapy (HAART) 1. Nucleoside RTIs Ziduvudine, Lamivudine, Stavudine, Didanosine, Abacavir, Emtricitabine, 2. Nucleotide RTIs Tenofovir, 3. NNRTIs (Efavirenz, Nevirapine, Etravirine) 4. Protease inhibitors Amprenavir, Atazanavir, Fosamprenavir, Indinavir, Lopinavir, Nelfinavir, Ritonavir, Saquinavir), Tipranavir 5. Fusion inhibitors Enfurvirtide (T 20), sc injections 6. CCR5 Inhibitors Maraviroc 7. Integrase inhibitors Raltegravir

V. Antiretroviral Therapy (HAART) Fixed dose combinations: Atripla (FTC/tenefovir/Efavirenz) Combivir 3TC/Zidovudine Truvada FCT/Tenofovir Kaletra Lopinavir/ritonavir Kivexa Abacavir/lamivudine Trizivir 3TC/Zidovudine/Abacavir

HAART Advantages: Hugh impact on mortality and morbidity Newer regimen fewer pill burden and less side effects Decrease in HIV transmission (vertical and horizontal)

HAART Disadvantages: Drug side-effects common (GI, rash, blood abnormalities) lipodystropy resistance Immune resconstitution Lactic acidosis hypersensitivity Cost Availability “Complacency”

Lipodystrophy

VI. Relevance for Seafarer’ occupational health physicians Important facts: HIV different disease in 2009

The HIV positive seafarer Fit or not?

HIV positive seafarer In all cases of confirmed HIV positive status the assessment and decision taking process should be informed by advice from the clinician responsible for the care of the individual. It is the clinician and not the Approved Doctor who is responsible for the determining the frequency of surveillance needed to guide clinical care, where it needs to take place and for treatment while the seafarer is at sea. However it is for the Approved Doctor to take the final decision and issue a fitness certificate in line with the guidance below.  

The HIV positive seafarer Routine pre employment HIV testing is not recommended. Yet: HIV testing is recommended and should strongly be suggested, if an individual, unknown to be HIV positive, exhibits physical signs during the medical examination, that rise suspicion of advanced HIV disease (and as such would be at greater risk to his/her health if undiagnosed than the implications of a positive HIV diagnosis to his/her employment otherwise.

Criteria for fitness decision CD4 count > 350 ? Clinically well/ asymptomatic? Any AIDS defining illnesses? If yes, which? On HAART? If yes, since when? Any side effects Compliance resistance

Clinical stage 1 Acute retroviral infection Asymptomatic Persistent generalized lymphadenopathy Performance scale 1: asymptomatic, normal activity

Clinical stage 2 Clinical Stage 2 Weight loss, < 10% of body mass Minor mucocutaneous manifestations Herpes Zoster in the last 5 years Recurrent upper respiratory tract infection Performance scale 2: Symptomatic, normal activity

Clinical Stage 3 Weight loss, >10% of body mass Unexplained chronic diarrhoea>1 month Unexplained prolonged fever> 1 month Oral candidiasis, Oral hairy leukoplakia Pulmonary tuberculosis, Severe Bacterial infections Performance scale 3: bed ridden < 50% of the day during the last month.

Clinical stage 4 AIDS complex HIV wasting syndrome: weight loss >10% body mass, plus unexplained chronic diarrhoea (>1 month) or chronic weakness and unexplained fever(>1 month) Performance Scale 4: bedridden for>50% day during the last month.

HIV seafarer and fitness categories Category 1 Fitness:(no restrictions) Stage 1 No complications CD4 count above 350 and never been on treatment Limit duration to time of next specialist appointment if start of HAART is anticipated.

HIV seafarer and fitness categories Category 2 Fitness:(fit with restrictions) Stage 2 CD4 count above 350 and seafarer on antiretroviral medication that needs regular monitoring; Restriction s apply to proof of regular treatment monitoring by specialist and locality: near coastal: until well established on antiretroviral regimen when specialist screening interval is only every 3-6 months

HIV seafarer and fitness categories Category 3 Fitness (temporarily unfit) Stage 3 (if symptoms impact significantly on performance status; e.g. oral candidiasis should not lead to being temporarily unfit) Initiation and change of antiretroviral therapy AIDS diagnosis: Most AIDS defining conditions that can be treated and in conjunction with antiretroviral therapy will significantly reduce the chance of relapse or further AIDS defining illnesses. The CD4 count should be as a minimum above 200 and the seafarer on antiretroviral medication.

HIV seafarer and fitness categories Category 4: (permanently unfit): No scope for improvement in condition (mainly limited to late diagnosis of HIV disease with CD4 counts often <=100, Lymphomas, Dementia, loss of vision with CMV retinitis etc). Resistant to all antiretroviral regimens with likelihood of CD4 count falling

Finally HIV very different disease in 2009 from 1983! Chronic treatable condition Survival very different only if HIV status known! Early diagnosis very important High level of suspicion in certain groups and with certain clinical signs Diagnosis prolongs life!!!

Thank you! Important Websites: www.bhiva.org.uk www.medfash.org.uk http://www.hiv-druginteractions.org M.schuhwerk@doctors.org.uk