1. HIV treatment as prevention Stephen Kegg

2. 2 Learning Outcomes Overview of HIV management HIV transmission risks Current prevention strategies Which new infections can we prevent? Evidence for treatment as prevention Contexts and clinical cases 2

3. HIV and STI Department, Health Protection Agency - Colindale HIV and AIDS Reporting System Annual new HIV and AIDS diagnoses and deaths: United Kingdom,1981-2010

4. HIV and STI Department, Health Protection Agency - Colindale HIV and AIDS Reporting System New HIV diagnoses by exposure group: United Kingdom, 2001 – 2010

5. HIV and STI Department, Health Protection Agency - Colindale HIV and AIDS Reporting System New HIV diagnoses by probable country of infection : 2001-2010

6. Benefits of early HIV diagnosis Treatments available (HAART) not cure, but prevent people becoming unwell Prevent disability late presentation Reduce transmission by promoting condom use Prophylaxis against opportunistic infections if appropriate Appropriate investigations if unwell Reduce perinatal transmission –treatment for mother –delivery method –avoidance of breastfeeding (in UK)

7. Benefits of early HIV diagnosis Treatments available (HAART) not cure, but prevent people becoming unwell Prevent disability late presentation Reduce transmission by promoting condom use Prophylaxis against opportunistic infections if appropriate Appropriate investigations if unwell Reduce perinatal transmission –treatment for mother –delivery method –avoidance of breastfeeding (in UK)

8. 8 When do we start treatment? Anyone with an HIV-related infection or cancer and started earlier now - except TB Anyone who has marked symptoms often non-specific Anyone with a CD4 count of 350 or less Other chronic infections - hepatitis B+C Patient choice To reduce mother to child transmission 4 >80% of patients are on ART

9. On treatment CD4 350 ART Treatment response Time Viral load Baseline 88 900 2/52 692 6/52 91 10/52 <50 SUCCESS

10. 10 Effects of treatment Plasma viral load is brought down to undetectable levels CD4 count recovers Immune activation is switched off Cause many HIV-related diseases to regress ART penetrates most compartments genital secretions CNS 6

11. 11 Why isn’t everyone on treatment? >95% of doses need to be taken to ensure efficacy and limit resistance Longer term toxicities of drugs Better drugs/treatments might emerge Benefit of treatment might be small Patient choice Treatment breaks are harmful and undesirable 7 c25% of HIV is undiagnosed

12. 12 Case 1 32 yr old man HIV+ diagnosed 2008 Good health CD4 540, viral load 31, 500 Partner is 34 yr old woman HIV-, last test Feb 2012 Duration of relationship 3 yr No pregnancies or children Wish for a child

13. 13 Case 2 22 yr old MSM HIV+ diagnosed 2010 CD4 650, viral load 89 000 in good health Uses crystal meth and MDMA twice per month Probably has unprotected sex with multiple partners syphilis, gonorrhoea (rectal and urethral) x3, warts Possibly doing some sex work 9

14. 14 HIV transmission risks

15. 15 HIV transmission risks per act, average viral load Unprotected receptive vaginal sex Unprotective insertive oral sex Unprotected insertive vaginal sex Unprotected receptive anal sex 11

16. 16 HIV transmission risks per act Unprotected receptive vaginal sex 1 in 800 Unprotective insertive oral sex Unprotected insertive vaginal sex Unprotected receptive anal sex 12

17. 17 HIV transmission risks per act Unprotected receptive vaginal sex Unprotective insertive oral sex Unprotected insertive vaginal sex Unprotected receptive anal sex 13

18. 18 HIV transmission risks per act Unprotected receptive vaginal sex Unprotective insertive oral sex very low Unprotected insertive vaginal sex Unprotected receptive anal sex 14

19. 19 HIV transmission risks per act Unprotected receptive vaginal sex Unprotective insertive oral sex Unprotected insertive vaginal sex Unprotected receptive anal sex 15

20. 20 HIV transmission risks per act Unprotected receptive vaginal sex Unprotective insertive oral sex Unprotected insertive vaginal sex 1 in 1500 Unprotected receptive anal sex 16

21. 21 HIV transmission risks per act Unprotected receptive vaginal sex Unprotective insertive oral sex Unprotected insertive vaginal sex Unprotected receptive anal sex 17

22. 22 HIV transmission risks per act Unprotected receptive vaginal sex Unprotective insertive oral sex Unprotected insertive vaginal sex Unprotected receptive anal sex 1 in 30 18

23. 23 Prevention - what works? Condoms/abstinence Post-exposure prophylaxis (PEPSE) c80% protection if taken on time, completed and patient not re- exposed Pre-exposure prophylaxis (PrEP) c45% reduction in acquisition of HIV in MSM, better results with better adherence Microbicides Topical preparations with anti-HIV activity Vaccines 20

24. Culture, religion, language Uncertain status in UK Unscheduled pregnancy Disclosure to partners Domestic violence Poverty Healthcare not a priority Poorer adherence Late presentation Mobility Stigma

25. 25 Treatment as prevention - a history Trial evidence for single-drug treatment reducing MTCT in 1990s c2001 “Undetectable doesn’t mean uninfectious” Increasing uptake of ART in San Francisco 2004-08 causes a drop in the “community viral load” and fewer new diagnoses Swiss Cohort Statement –In 2008 a group of Swiss scientists produced the first ever consensus statement that asserted that an HIV positive person who is taking effective antiretroviral therapy, who has an undetectable viral load and is free from STDs, has a negligible risk of infecting others with the virus. 25

26. 26 Evidence for TAsP Placebo-controlled RCT in heterosexual serodiscordant Africans –3381 heterosexual African couples –ART use by the HIV infected partner was associated with a 92% reduction in risk of HIV transmission to their partner HPTN 052 study of heterosexual serodiscordant couples –1,763 couple –Randomised to immediate treatment of HIV+ partner versus waiting until CD4 count approaches 250 –One person became infected from the early ARV group, versus 27 from the later ARV group, showing a 96 percent reduction in risk of transmission Study in a general population showed 38% fewer new diagnoses of HIV in areas with high (>30%) uptake of ART compared to areas with low (<10%) uptake 26 Large-scale “test-and-treat” strategy study in South Africa will deliver in 2015

27. 27 Case 1 32 yr old man HIV+ diagnosed 2008 Good health CD4 540, viral load 31, 500 Partner is 34 yr old woman HIV-, last test Feb 2012 Duration of relationship 3 yr No pregnancies or children Wish for a child

28. 28 Case 2 22 yr old MSM HIV+ diagnosed 2010 CD4 650, viral load 89 000 in good health Uses crystal meth and MDMA twice per month Probably has unprotected sex with multiple partners syphilis, gonorrhoea (rectal and urethral) x3, warts Possibly doing some sex work 26

29. 29 Limitations Cost UK HIV treatment costs c£7000 per year Continuous treatment eg if circumstances change Kenya study 2012 showed that 40% of HIV+ people were unwilling to consider early treatment in order to reduce risk to partner Would not prevent onward transmission by the undiagnosed or seroconverters Possibly would encourage non-disclosure to partners and increase risky sex 29

30. THANK YOU