When to Start Therapy? The Patient’s Viewpoint

1. When to Start Therapy?The Patient’s Viewpoint Gus Cairns NAM Publications Patient Rep, BHIVA Executive Committee EATG

2. Contents • Background – guidelines change • What do we tell patients? • Readiness • Swiss HIV Cohort study • Barriers to starting • EACS Algorithm • NAM Study • Quantitative Findings • Qualitative Findings • Themes and Conclusions

3. Post-SMART and other studies, guidelines on when to start therapy have swung back to starting at 350 CD4 cells/mm3 • BHIVA: “The initiation of therapy should be recommended in all patients with a CD4 count of <350 cells/mL” • CDC: “Antiretroviral therapy should be initiated in patients with a history of an AIDS-defining illness or with a CD4 T-cell count <350 cells/mm3.” • EACS: “CD4 201-350: treatment recommended” Background – guidelines change

4. BHIVA audit 2005*: • 1/3 of patients were diagnosed with CD4s <200 • 2/3 of patients started therapy with CD4s <200 • Swiss HIV Cohort†: • Only 30% of 1730 naive patients with CD4s ≥200 at 2nd cohort visit started ARVs with CD4s ≥200 Most patients start later *Sullivan AK et al. Newly diagnosed HIV infections: review in UK and Ireland. BMJ 330(7503):1301-2. 2005. †Wolbers M et al. Delayed diagnosis of HIV infection and late initiation of antiretroviral therapy in the Swiss HIV Cohort Study. HIV Medicine 9(6): 397-405. 2008.

5. Some of this is late diagnosis:CD4 count at diagnosis, UK

6. UK CHIC Cohort: relative risk of AIDS for people with CD4 count*: Over 650: 1.0 500-649: 1.55 350-499: 2.49 200-349: 4.91 Why have CD4 criteria at all? Why not just when patients ready? *The UK Collaborative HIV Cohort (UK CHIC) Study Steering Committee. Rate of AIDS disease or death in HIV-infected antiretroviral therapy-naïve individuals with high CD4 cell count. AIDS 21: 1717 – 1721, 2007.

7. All guidelines depend on concept of ‘readiness’ • BHIVA: with CD4s 200-250, “Treat as soon as possible when patient ready” • EACS: “Time should be taken to prepare the patient, in order to optimise compliance and adherence” • US (CDC): “The necessity for patient adherence...should be discussed in depth between the patient and clinician. Potential barriers...should be identified and addressed before therapy is initiated.” • How is this determined? • What is ‘ready’? • How much time to prepare the patient? • How do you establish that a barrier has been ‘addressed’? • Does this vary according to disease stage? • Are some patients never ready? • Are some ready before their doctor? • Presupposes a partnership between patient and doctor What is readiness?

8. “The readiness of HIV-infected individuals to start or change therapy has been poorly investigated so far.” Study took 75 patients eligible to start or change therapy (due to guideline criteria or patient wish) at 3 clinics 62 said they would start or change, 13 decided not to 54 eventually did: 21ended up not starting/changing (35% fewer than estimate) Swiss HIV Cohort readiness study* *Fehr J et al. Starting or changing therapy – a prospective study exploring antiretroviral decision-making. Infection 33:249-256. 2005.

9. Potential starters with depression very significantly less likely to start (p=<0.05 in a group of only 34) • Trends towards people with anxiety and lower QoL also being less likely to start • Patients who made decision ‘mainly by myself’ less likely to start/change. Decision to start/change mainly seen as shared decision • Both patients and doctors too optimistic about who would start. Out of those originally assessed for starting: • Doctors predicted 2 wouldn’t start and 5 not sure • 2 patients predicted they wouldn’t start and 6 not sure • In the end 13 didn’t start Swiss HIV Cohort study 2

10. Information is not the issue; 97% said they’d had enough info to make decision • Reasons not to start/change include: • I fear the side effects • I feel healthy • I need more time • I am about to travel • I will wait for better drugs • I know other HIV+ people who have had bad experiences • My partner advised me not to start/change Swiss HIV Cohort study 3

11. Result: EACS Starting Algorithm* * See http://www.eacs.eu/Guidelines_Livret/index.htm

12. Internet Questionnaire on www.aidsmap.com • English, Spanish, French, Portuguese • 12 September – 06 November 2008 • Asked (among other things:) • Whether respondent was in a country where treatment is accessible • Therapy status: naive/started/stopped • Sources of information/decision making • Disclosure • Knowledge of current guidelines • If naive: when would they start? • If started: side effects etc • Main concerns about starting/resuming treatment • Main concerns if on treatment • Open Qs: What helps with adherence + other comments NAM Studyof patient attitudes to treatment

13. 2189 respondents • 1547 (71%) in drop-down menu of countries with ‘open access’ i.e. Europe, N America, Australasia, Japan • Should we have differentiated between ‘limited-access’ and ‘open-access’ countries? • We only gathered demographic data on open-access countries • 55.5% of people in limited access countries were in fact on treatment • A number of people in ‘open access’ countries esp. USA pointed out they had no or limited treatment access • 70% of responses in English, 16% Spanish, 12% French, 2% Portuguese NAM Study

14. Countries

15. Ave age 35-40 • 10% female in English questionnaire, 24% in French and Spanish, 20% Portuguese • 8% with children in English questionnaire, 18% Spanish, 22% French, 15% Portuguese • 88% described themselves as white Demographics (open-access countries only)

16. Sexuality

17. Treatment status Including estimated nos. in limited-access countries Open-access countries only

18. In treatment naive people in developed countries: • Only 11% in English-language questionnaire had a CD4 count under 300 • Only 4% in Spanish questionnaire • None in French or Portuguese questionnaires CD4 count, treatment-naive

19. CD4 count guidelines All respondents were asked: “Did you know that the recommended time to start treatment is now when your CD4 count is around 350 cells/mm3?”

20. Drug-naive patients in developed countries were asked if they had a target CD4 count to start therapy. • 47% would start “when clinic advises”. Of the rest: • 12% said 400 • 25% said 350 • So at least 37% would wish to start at 350 or above • 8% said 300 • 3% said 250 • 4% said 200 • So at least 15% would wish to start at 300 or lower When would you start? (Treatment-naive)

21. Of developed-country respondents on ART: • 50% started treatment since 2004 • 31% in last two years • 17% in last year • 17% pre-1997 When did you start? (Treatment-experienced)

22. At what CD4 count?(Treatment-experienced)

23. CONCERNS 1 Proportion of all respondents who had “major or significant” concerns before starting or restarting therapy

24. CONCERNS 2

25. Concerns 3: Started, pre-treatmentNB Naive patients yet to start had virtually the same proportions of concerns

26. Concerns 4:started, post-treatment

27. Side effects: frequency

28. Side effects: severityPercentage reporting a “serious long term effect on my quality of life”

29. 355 replies out of 1424 respondents in English questionnaire (25%) • Terms frequently used: • ‘Alarm’ (48 mentions, 19%): most often, mobile phone alarm • ‘Pill box’ (32 mentions, 9.5%) • ‘Atripla’ (13 mentions) or ‘one pill once a day’ (12 mentions) (Together, 8%) • Support from ‘partner’ or ‘family’ (22 mentions) • Other mentions of ‘once a day’ (18 mentions) • ‘Routine’ (17 mentions) What helps with adherence?Answers to the question “please use this space to tell us about things that have helped you in taking HIV treatment”

30. Knowing that I live each day to see my children grow up Hope that one day a cure will be found and that this disfiguring, sickening and toxic treatment is only a bridge to keep me alive Most importantly, a consultant that worked with me over years to get the right combination with the fewest side effects Taking meds is my way of saying I want to live and not give up, even though my partner of 25 years has passed away Telling my daughter I have to take pills because of the menopause, which enables me to take them without disclosure Drinking less, having a job, having things to live for I have started and stopped my meds tooo many times and my doctor says they will run out of cocktails, so I have to get my act together A small plastic ‘bullet’ which holds my Atripla, it rattles with my body movement from time to time and reminds me if I haven’t taken the pill. I don’t want to die now my kids are so young. Who will look after them if I am not responsible enough to take my medication? What helps with adherence? Quotes

31. Topic cluster one: long term survivors • I started therapy in 1993 and many of the questions don’t apply to me, as you did what the doctors told you and hoped to stay alive • We took what was available, and there was no/little choice • I’ve had HIV 20-plus years, did not start meds till I had 26 cells, I now have 600. I have dedicated my life to health and freeing myself from stress. • I had to answer ‘no access to treatment’ when you asked why didn’t start because I was diagnosed in 1986. There are some of us still around you know! • When my CD4 counts fell below 200, there was only AZT available, and it was killing as many people as it was saving, so declined the offer • When I first became sick AZT was the only drug. That colored my decision to wait for other treatment. • I am 82 and have been HIV+ for 20 years • (Another respondent answered: “I was diagnosed today”) Other commentsAnswers to the question ‘Please use this space to make any comments about the topics raised in this survey” (365 answers)

32. I had an excellent consultant who knew everything about ne but she was in a temporary post and everyone in the clinic was shocked when she was not employed permanently. This made me lose confidence in my clinic Most women I know feel their doctors do not go into enough depth with them The nursing staff have been much more helpful and informative than the doctor. I do not understand what the doctor has said so ask the nurse after seeing the doctor I recently changed clinics. It was very stressful and felt like starting all over again I have a great working relationship with my doctor and his team. I’m in two clinical trials, the doctors talk to each other and I feel very well informed My ID doctor only wants to concentrate on HIV. I have high lipids, blood pressure, depression, unexplained back pain and he expects my GP to monitor them. Too many doctors, too many co-pays, too many things to track (US patient) I feel isolated. I was told my bloods would be done every month for the first 3 months, but they were only done once and the results were through the nurse rather than the doctor Other commentsCluster two: doctor and patient

33. I am a nurse and expected to be able to handle a lot of my side effects but it scared me when the drugs made me feel out of control. No health professional said it would be that bad. I’m 65 and in the last 6 months have started to suffer from arthritis in the hands, no one can tell me if this is age or the AZT I’ve been on for the last 3 years You seemed to assume people would stop once. I have started and stopped 6-7 times due to side effects I suffer from lipodystrophy (LD) and fatigue – possibly side effects from a drug regime never disclosed till too late. I suffer from severe depression but accept this is maybe the lesser of two evils Despite the success of HAART the stigma of LD has a devastating effect. Appearance and its psychology could be better handled in the overall literature I am very scared of the side-effects especially this body-changing lipoatrophy (recent starter) We don’t easily get drugs of choice in the developed world. I got kidney problems, felt bloated, lost all my hair, terrible pain from ingrown toenails. When I moved from Africa to London my doctor took one look and took me off Crixivan. I immediately got better. After a bad reaction and change of meds (I was one of the unlucky ones with SJS) I got used to the routine and now it’s just part of life, far easier than I imagined. Other commentsCluster three: side effects

34. Taking meds feels like a rubber stamp on my diagnosis; once I say I am taking ARVs then I have disclosed my status With the drugs, people cannot see a difference between me and the general population. Lessens stigma and encourages people to get tested In Iceland where I am, all the patient’s personal data is included on the prescription. There is one person in the north, one in the west, everyone knows who they are There is no network or meeting place mediated by clinics where HIV+ can meet, socialise etc. Gaydar is a disaster – most people are just after sex I live in Granada, Spain. There’s not a special HIV hospital and I’m terrified of starting ARVs because the doctors here seem to decide on what ARVs to give according to what the hospital has & say they’re all the same I live in a rural town in Spain. Treatment is faultless but my consultant thinks there’s no such things as side effects and treats my efavirenz effects with a shrug I think there are long term issues of trust that have never gone away. I am extremely secretive of my diagnosis. Other commentsCluster four: disclosure, stigma, isolation

35. In the USA HIV robs many of living a life. I was a well paid professional but now if I were to work I would lose my social security disability and Medicare. The USA is so quick to help the rest of the world while many HIV+ US citizens lie on sidewalks. It was a waste of time going the prevention way in here in Africa. Since an HIV test was a death sentence PLWHAs started to wilfully infect others. I am one of the lucky ones but 400,000 people need ARVs in my country. This survey should bring to light the daily conditions in which people struggle to make a living, here in Malawi the centres are highly congested and there are long waiting lists for people to get started on therapy. Although a UK citizen I have always lived and worked abroad and don’t want to be forced to retire to the UK This survey only seems to be interested in the countries on the list. In my country you only get treatment if your CD4 count is under 200 – if you’re lucky. I wish the WHO could make it a law that people must be started at 350. I’m still not on treatment here in Africa having been diagnosed with HIV and TB for 13 years and seeking ARVs for ten. I recently lost my job and my Atripla copayment is over $300 a month. I am worried sick about this (US patient) Maybe you should get PEPFAR to conduct a similar survey in Africa! Other commentsCluster five: access and cost

36. You did not list depression as a reason for not staying on meds. I am now much more consistent in taking my meds since I started on anti-anxiety/depression meds One thing you didn’t mention that could delay treatment was fear. I waited almost 5 years to tell anyone or seek treatment: I had zero T-cells. Now I have over 700. There should be more psychological support for people with HIV, especially the newly diagnosed I am starting therapy next week and actually feel relieved as I have been thinking and talking about it for a long time. One of the stresses has been the constant readiness and then anticlimax of not starting. I rely on myself. Doctors’ primary concern is making sure your heart continues to beat and not your quality of life. I Have lost all trust in them No question allowed for the patient’s decision-making to be influenced by a lack of desire to live a longer life as HIV positive. This was my own reason for initially refusing treatment, even when my CD4 count was below 200. Other commentsCluster six: mental health

37. Rob Horne et al, 2002*: • Decision to start characterised by: • recognising personal need for HAART • anticipating benefits from taking HAART • having addressed concerns about taking HAART • believing personal circumstances to be conducive to starting treatment • being influenced by other people's experiences of HIV and HAART • being in accordance with medical recommendations to start. • Decision not to start characterised by: • doubting personal need for HAART • having concerns about taking HAART • having previous negative experience of HAART • holding negative beliefs about medicines in general • requiring autonomy in the treatment decision. What we already know helps * Cooper V, Horne R et al. Perceptions of highly active antiretroviral therapy (HAART) among HIV positive men who have been recommended treatment. Intl ads Conference, Barcelona, 2002. Abstract MoPeB3253.

38. Importance of assessing depression BEFORE starting ART Influence of previous experiences of ARVs in friends/partners Fear of side effects still extremely important, especially lipodystrophy The simplest things help most with adherence: alarms, pill boxes, once-a-day regimes Partnership with healthcare provider (of various types) as important than ever What these studies add

39. Keith Alcorn, NAM Jan Fehr, University Hospital, Basel David Haerry, EATG Ian Weller Thanks to...