GUM & HIV - An Update

1. GUM & HIV - An Update Dr.S.Uthayakumar Consultant Physician GUM & HIV Lister Hospital 23 November 2017

2. Sexually Transmitted Infections * Chlamydia Gonorrhoea Trichomanas vaginalis (TV) Bacterial vaginosis Syphilis

3. Sexually Transmitted Viral Infections Human Immunodeficiency Virus (HIV) Hepatitis B & C Herpes Simples Virus (HSV) Human Papilloma Virus (HPV)

4. What's different about a sexual history? • Emotional issues • Emotive issues • Embarrassment • Involves other people • Attendance as a contact • Moral/legal issues

5. TV / BV & Candida • TV- Commonest STI- worldwide • 6 % in pregnancy • BV- Asymptomatic infection- common • 15-20% pregnancy • Chorio-amnionitis/ pre-term labour • Candida- • incidence increases during pregnancy, greatly reduces after post-partum • 36% - pregnant, 16% non-pregnant • Baby- 2-6 weeks • Diabetes, Broad spectrum antibiotics

6. Vaginal discharge Bacterial Vaginosis (BV) Trichomonas Vaginalis(TV) & Candida BV TV Candida Asymptomatic 50% 10-50% 10-20% Discharge thin/grey thin/frothy Thick/white Smell Fishy Fishy Not offensive Other symptoms none itchy/sore itch/sore Rx Metronidazole tablets or gel Clotrimazole

7. Clinical presentation of Chlamydia Symptoms *Asymptomatic up to 80% in women 50% in men *Post coital/inter-menstrual bleeding *Vaginal discharge - purulent *Urinary symptoms -frequency/dysuria *Lower abdominal pain (Can cause proctitis) Signs Normal /* Cervicitis/ mucopurulent discharge/ urethral discharge *Cervical contact bleeding *Local complications- PID/bartholinitis Doxycyline 100 mg bd x 7/7 or Rx-Azithromycin 1G oral stat or Erythromycin 500 mg bd x 14/7 ( no Doxycycline in preg)

8. Gonorrhoea Gonorrhoea • Caused by Neisseria Gonorrhoea. • The second most common bacterial STI in the UK. • Majority of reported cases are in men. • A third of infections in men were in men who have sex with men (MSM). • Most common in individuals 15 to 29 year old. • Often occurs as a co-infection with chlamydia. • Can affect the cervix, urethra, rectum, throat, and occasionally the eyes. • Rx • Ceftriaxone injection 500 mg IM + • Azithromycin 1 G oral stat • Need Test of cure and treatment of all sexual contacts

9. Syphilis • Syphilis infections had been relatively rare in the UK since WWII but numbers began to increase sharply during the late 1990s until 2005 and then started to decline very slowly. • The rates were highest in 35 to 44 years men age group (19/100,000) and in the 20 to 24 years women age group (4/100,000). • Nearly 60% per cent of diagnoses in men were known to be in MSM.

10. Syphilis- Treponema pallidum screening for syphilis- Ante-natal & GU clinics EIA- Enzyme Immuno assay- (antigen/antibody) if positive or high degree of suspicion VDRL – Venereal Disease Reference Laboratory or RPR TPHA- Treponema Pallidum Haemagglutination Assay Transmission to baby- always from the infected mother Does not occur before 4/12, usually occur after 6/12 Urgent referral to the local GUM clinic- Rx Benzathine Penicillin 2.4MU Deep IM x1 Regular follow-up-

11. Genital herpes • Genital herpes simplex virus (HSV) infection is the most common ulcerative sexually transmitted disease in the UK • There are two distinct subtypes of HSV. Type 2 is almost exclusively associated with genital infection. Type 1 causes oral herpes (or cold sores) but has increasingly been implicated in genital infections • Efficiency of sexual transmission is greater from men to women than from women to men

12. Primary infection • Incubation period <7days • Painful multiple genital ulcers (site, No. of ulcers) (erythema  vesicle  ulcer  healing) • Healing time upto 3/52 • Most cases have tender inguinal lymphadenopathy. • 1/3rd has constitutional symptoms • fever • malaise • headache • Photophobia, etc. • Retention of urine - rare complication. • pain • virus affecting sacral autonomic nerves • cervicitis 70% - 90% of women • Can affect the • urethra • pharynx • rectum

13. Investigations & Management • PCR (Vs Viral culture) - Directly from the base of lesion Additional tests:- (Good sample) • Syphilis serology • STI screen • (HSV Serology not routinely done -limited value) Management Counselling Analgesia Rest (wash with Salt water) Rx- Aciclovir 400 mg three times daily x 5 days Suppressive Rx Discuss management plan Aciclovir 400 mg twice daily

14. Management of pregnant women • Primary herpes • 1st/2nd trimester acquisition • Usual Management • Last 4/52 suppressive aciclovir Rx to prevent recurrence and normal vaginal delivery • 3rd trimester acquisition Caesarean section should be considered (last 6/52) • If vaginal delivery is unavoidable • Rx –mother and baby Recurrent herpes: (new guidelines) If lesions at delivery - caesarean section is not indicated. Discuss with the senior team

15. External genital warts:background • Also termed condylomata acuminata • Benign epidermal growths caused by human papillomavirus (HPV) • Types 6 and 11 most commonly associated with external genital lesions (>90% of cases) • Some HPV types (16, 18, 31 & 33) are associated with genital intraepithelial neoplasm and cancers (oncogenic virus) • Prevention:- Vaccination

16. Human Papilloma Virus (HPV) Cytologically normal women 1.5 - 44.3% Sexually active younger women are more likely than older women to have HPV G.U attendees:Male 28 - 63 % Female 23 - 72% Rx- cryotheraphy (liquid nitrogen spray), Home Rx- Warticon solution (should not be used in pregnancy), Imiquimod cream(Aldara), Surgical excision Complication:- [Laryngeal papillomatosis (rare)] Abnormal smears Refer – to GUM clinic

17. Hepatitis B- Clinical Spectrum Asymptomatic Most children, 10-50% of adults Acute icteric hepatitis IP 40-160 days, lasts 2-24 weeks Chronic hepatitis 90% infants, 50% children, 5-10% adults often asymptomatic or mild Fulminant - 1%, high mortality

18. Chronic hepatitis B Defined as HBV sAg persisting >6/12 5-10% of those with acute hepatitis B will become chronically infected Rate is increased by HIV, renal failure and immunosuppresive drugs Most infants vertically infected become chronic carriers if not vaccinated 10-50% of people with chronic infection will develop cirrhosis Causes premature death in 50% 10% of cirrhotics develop liver cancer Hepatitis B can be monitored with liver function tests (6 monthly) and ultrasound Treatment (by hepatologists) aims to clear antigens, reduce HBV DNA, normalise liver function and delay disease progression Drugs available include lamivudine, adefovir and entecavir Prolonged monotherapy can lead to drug resistance (especially lamivudine) Stopping treatment can cause the hepatitis to flare up

19. Mother to Child Transmission 90% rate if mother HBeAg +ve 10% rate if mother anti-HBe +ve (HBeAg –ve). These transmissions occur when the mother is HBV-DNA +ve Mostly occurs during birth -a small number (?5%) before delivery No risk from breast feeding LSCS no benefit

20. Diagnosis Three types of test: Antigen (viral proteins): surface (HBsAg) and ‘e’ (HBeAg) antigens Antibody: anti-surface (anti-HBs), anti-’e’ (anti-HBe) and anti-core (anti-HBc). Also divided into early (IgM) and late (IgG) antibody responses Viral DNA : HBV-DNA

21. Hepatitis B tests Source: Center for Disease Control

22. Using Hepatitis blood tests Has my patient ever had hepatitis B? Do hepatitis B core antibody (HBV cAb) Is my patient a carrier of hepatitis B? Do hepatitis B surface antigen (HBV sAg) IF POSITIVE THEY ARE A CARRIER (IF >6/12 AFTER ACUTE INFECTION) LABORATORY SHOULD THEN TEST FOR HEPATITIS B ‘e’ ANTIGEN (HBV eAg) HBV sAg+ but eAg- LOW INFECTIVITY CARRIER HBV sAg+ AND eAg+ HIGH INFECTIVITY CARRIER

23. Using Hepatitis blood tests Has my patient ever had hepatitis B? Do hepatitis B core antibody (HBV cAb) Is my patient a carrier of hepatitis B? Do hepatitis B surface antigen (HBV sAg) Has my patient been vaccinated against hepatitis B? Do hepatitis B surface antibody (HBV sAb) CAN ALSO BE POSITIVE IF PATENT HAS HAD HEPATITIS IN THE PAST (SO WOULD BE HBV cAB+)

24. Who might benefit from hepatitis B vaccination? • MSM • IVDU who share needles • People at risk of occupational exposure • Sex workers • Babies born to women with acute or chronic infection • Close contacts (household/sexual) of hepatitis B carriers • Haemophiliacs • People on dialysis • People in prisons or institutions • People planning to live or work in a high prevalence country

25. What do you give, and how? • Very safe recombinant vaccine • Primary course is three doses Day 1, day 7, day 21, booster at 12/12 SUPERACCELERATED Day 1, 1/12, 3/12 booster at 12/12 ACCELERATED Day 1, 1/12, 6/12 STANDARD • Hepatitis B Immunoglobulin (HBIG) 500iu im may be given to a non-immune person who has been exposed to infection - most effective if given within 48hr

26. Which Schedule? Accelerated Rapid immunity, eg post sexual assault or exposure to hepatitis B carrier Better uptake Needs booster at 12/12 Standard 0/12, 1/12, 6/12 Better researched Better protection at 12/12 Poorer uptake • Check sAb 8-12 weeks after last dose • If greater than 10iu/ml – no need to boost • Likely lifelong immunity (at least 10 years) in immunocompetant • Missed doses – just give remaining doses if within 4 years of last dose. • Non-responders - repeat a standard course

27. HIV • HIV is an STI -therefore same risk factors for acquiring infection. • Presence of many STIs increase shedding of HIV virus in an infected individuals and therefore increase risk of transmitting HIV to sexual partners. • Continues to be one of the most important communicable diseases in the UK. • The infection is still frequently regarded as stigmatising and has a prolonged ‘silent’ period during which it often remains undiagnosed. • Highly active antiretroviral therapies (HAART) have resulted in substantial reductions in AIDS incidence and deaths in the UK.

28. HIV-Terminology Human Immunodeficiency Virus (retrovirus) HIV test (antibodies) 4 week “window” Viral load ( RNA copies/ml) CD4= T4= T helper=T cell (lymphocytes) AIDS (Acquired Immune Deficiency Syndrome ) 28

29. Natural history Over course of infection: CD4 count declines & HIV viral load increases Increasing risk of developing infections and tumours The severity of these illnesses is greater the lower the CD4 count Most AIDS diagnoses occur at CD4 count <200 29

30. Natural history Acute infection – seroconversion Asymptomatic HIV related illnesses AIDS defining illness Death 30

31. Symptoms and parameters over time Opportunistic Infections Symptomatic HIV Infection 31

32. Medical benefits of early HIV diagnosis Treatments available (ART/ARV) not cure, but prevent people becoming unwell Prophylaxis against opportunistic infections if appropriate Appropriate investigations if unwell Reduce perinatal transmission treatment for mother delivery method avoidance of breastfeeding (in UK) 32

33. Other benefits Minimise the risk of infecting others Partner notification Ability to inform important life decisions Relief of anxiety about knowing HIV status Access to help from social services, drug services etc Benefits vs Quality of Life vs Stigma in certain population groups. 33

34. Clinical Indicator Diseases 34

35. Clinical indicator diseases Clinical Indicator Diseases 35

36. Clinical Indicator Diseases 36

37. HIV in primary care- patient’s view Confidentiality (secret safe?) NHS IT Systems Medical skill (health safe?) Ambience/time/team input Why take a risk when secondary care so comprehensive and accessible ? 37

38. HIV management in Primary Care Chronic disease management Adherence Mental health aspects: depression, chronic fatigue, stigma, anxiety Treatment side-effects : lipodystrophy, cardiovascular, sexual dysfunction Communication with secondary care shared care is a two way process- (? write letters) 38

39. Drug therapy in HIV Antiretroviral (ART) therapy suppresses viral replication which permits immune recovery ART dramatically improves survival and reduces morbidity ART is for life Never advise a patient to stop ART without advice from HIV unit

40. Antiretroviral therapy 4 main groups of drugs acting on different stages in HIV life-cycle. HAART (highly active antiretroviral therapy),at least 3 drugs from 2 different groups. Adherence vital (>90%) or resistance. Resistance to one drug in a group often confers resistance to other drugs in that group. HAART can offer normal life BUT side effects. 40

41. Drugs available for HIV therapy NRTIs • Abacavir • Didanosine • Emtricitabine • Lamivudine • Stavudine • Tenofovir • Zidovudine NNRTIs • Delavirdine • Efavirenz • Nevirapine • Etravirine • Rilpivirine ProteaseInhibitors • Atazanavir • Darunavir • Fos-Amprenavir • Indinavir • Lopinavir • Nelfinavir • Ritonavir • Saquinavir • Tipranavir New Classes • Fusion Inhibitors • Enfuvirtide • CCR5 Inhibitors • Maraviroc • IntegraseInhibitors • Raltegravir

42. Influence of HAART on Primary risk factors for CHD Background risk HAART Age Background risk/ Testosterone/Androgens Hypertension Diabetesmellitus CHD Male gender HAART Cigarettesmoking Family history of CHD Background risk lipids ±Recreational drugs HAART Dyslipidemia/hyperlipidaemia LDL/HDL/Lpa Fibrinogen/PAI 1 Non-modifiable Modifiable Wood D et al. Eur Heart J 1998;19:14341503.

43. Included in risk calculations • Age • Sex • BP • T-chol • LDL • Diabetic status • Smoker status • ECG LVH • History Not included in risk calculations • Insulin resistance (Impaired Glucose Phosphorylation in Skeletal Muscle) • Microvascular NO effects • Particle size • Endothelial dysfunction • Chronic inflammatory states Lipid abnormalities  HDL  LDL Cho  TG Insulin resistance Increased visceral fat Endothelial dysfunction Chronic inflammation HIV Infection and CV Risk

44. The risk of HIV transmission following an exposure from a known HIV positive individual Type of exposure Estimated risk of HIV transmission per exposure 5 Blood transfusion (one unit) 90 - 100% 6,7 Receptive anal intercourse 0.1 - 3.0% 7 - 12 Receptive vaginal intercourse 0.1% - 0.2% 10 Insertive vaginal intercourse 0.03% - 0.09% 13 Insertiv e anal intercourse 0.06% 13 Receptive oral sex (fellatio) 0 - 0.04% 14 - 16 Needle – stick injury 0.3% (95% CI 0.2% - 0.5%) 17 Sharing injecting equipment 0.67% 18 Mucous membrane exposure 0.09% (95% CI 0.006% - 0.5%) BASHH PEP guidelines – Truvada 1 tab od + Raltegravir 400 mg bd x 28 days

45. Basic principles-Window periods • Chlamydia – 2 weeks ( based on expert opinion, BASHH May 2008) • Syphilis and HIV serology – 4 weeks to 3 months • Hepatitis serology 3-6 months BASHH/EAGA statement on HIV window period, (November 2014) “A negative result on a fourth generation test performed at 4 weeks post-exposure is highly likely to exclude HIV infection. A further test at 8 weeks post-exposure need only be considered following an event assessed as carrying a high risk of infection.”

46. Can microbiological testing be combined with cervical cytology? Yes……. Suggested order: • Vulvo-vaginal swabs • Cervical examination and samples: • cytology • clean cervix • Gonorrhoea • Chlamydia

47. Diagnostic tests – Chlamydia NAAT (PCR, SDA) allows non-invasive testing and are the test of choice. Specimens that can be used: Pharyngeal and rectal specimens: Although not licensed from these sites, variable sensitivities. There is increasing evidence to support their use. Although manufacturers recommend 1-2 hour voiding interval prior to testing, a first catch urine 20 minutes post-micturation has been shown to be reliable.

48. Diagnostic tests - Gonorrhoea NAATs • High sensitivity (>96%) in both symptomatic and asymptomatic infection. They show equivalent sensitivity in urine and urethral swabs in men and in vaginal and endocervical swabs from women. • Sensitivity of NAATs for Gonorrhoea testing in female urine samples is very low, making it not an optimal specimen in women. • NAATs are more sensitive than culture at extra-genital sites and are the test of choice at these sites in MSM and other high risk individuals. Culture for Neisseria gonorrhoeae • Swab in transport medium (Amies or Stuart) • Urethra, cervix, throat, rectum • Sensitivity from urethra and cervical specimens – 85-95% • Essential for monitoring antimicrobial susceptibility Microscopy of Gram-stained smears

49. Diagnostic tests – vaginal infection • High vaginal swab in Amies or Stuart transport medium for: • Candida and Trichomonas (TV) – culture • Bacterial vaginosis (BV) – microscopy for Clue Cells etc. • Bedside test – vaginal pH (narrow range pH paper – if available). Normal – 3.5-4.5 BV (and TV) - >5.0 • NAAT test is best for TV (but not yet universally available) • Underlying cervical infection (chlamydia, gonorrhoea) should also be considered

50. Diagnostic tests – Mycoplasma genitalium • Mycoplasma genitalium is considered an STI • Responsible for 20% of NGU • Implicated in PID and likely proctitis • Tests currently not widely available in the UK • Helpful in the the management of NGU and PID • NAATs – Aptima and others