STARTING ART: YOUR KEY QUESTIONS ANSWERED

1. STARTING ART: YOUR KEY QUESTIONS ANSWERED

2. If I take ART will I have a normal life expectancy? • Life expectancy for PLWHA has improved since the introduction of effective ART in the mid’ 1990s[1] • People with a history of injection drug use, hepatitis C co-infection and those who smoke may be at risk of reduced life expectancy[2,3,4] • People who start ART and attain a CD4 cell count > 350 cells within one year have a normal life expectancy[5] [1] Harrison KM et al. J Acquir Immune DeficSyndr 2010;53:124-30 accessed January 2018 [2] Hogg R et al. The Lancet 2008;372(9635):293-299 accessed January 2018 [3] American Cancer Society: Cigarette Smoking. http://www.cancer.org/Cancer/CancerCauses/TobaccoCancer/CigaretteSmoking/cigarette-smoking-who-and- how-affects-health Accessed May 2011 accessed January 2018 [4] Center for Diseases Control and Prevention: https://www.cdc.gov/hiv/pdf/library/factsheets/hiv-viral-hepatitis.pdf accessed January 2018 [5] May et al AIDS 2014 May 15; 28(8): 1193–1202.

3. Life expectancy has continued to rise for people with HIV on ART Adapted from Helfland, The Body, Life Expectancy Continues to Rise for HIVers on Treatment. http://www.thebody.com/content/art52963.html. Accessed May 2011

4. Estimated life expectancy in UK 2000 - 2010 for HIV+ vs HIV- people May MT, Gompels M, Delpech V et al. Impact on life expectancy of HIV-1 positive individuals of CD4+ cell count and viral load response to antiretroviral therapy. AIDS 2014; 28: 1193–1202.

5. Why are PLWH still dying? D:A:D Study: Causes of Death Other unknown 15% Lactic Acidosis / Pancreatitis 1% AIDS-related 30% Bacterial Infection 7% Non-natural 9% Renal 1% CVD-related 12% Non-AIDS Cancers 11% Liver-related 14% • N = 33,308 patients • 2.482 deaths over 180176 PY (1.38 deaths per 1000 PY [95% CI: 13.2-14.3]) • “This study reiterates the importance of addressing traditional, non-HIV specific risk factors in order to further reduce death rates in HIV positive populations” D:A:D Study Group. AIDS 2010 24(10) 1537-48

6. How has ART become more simple over time? • The story of ART is one of evolution and revolution • Early protease inhibitor-based ART was taken three times a day becoming twice and then once daily[1] • Many drugs were re-formulated to reduce pill burden • Many drugs were co-formulated, and some twice daily drugs were relicensed for once-daily dosing [1] Gulick et al. Medscape: HIV Management: The New York Course, New York 2006; HIV Protease Inhibitors accessed January 2018

7. What ART circumstances require special consideration? • Pregnancy • AIDS-defining conditions, including HIV-associated dementia (HAD) and AIDS-associated malignancies (cancers) • Acute opportunistic infections • Lower CD4 counts (e.g., <200 cells/mm3) • HIV-associated nephropathy (HIVAN) [kidney disease] • Acute/early infection • HIV/hepatitis B virus co-infection • HIV/hepatitis C virus co-infection Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Department of Health and Human Services. October 2017 Available at https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv/10/initiation-of-antiretroviral-therapy accessed January 2018

8. How will I know ART is working? • During the first 2 months your HIV viral load should drop at least 90%; for example from 100,000 to 10,000 copies • By 6 months your HIV viral load should usually be undetectable • The higher your HIV viral load was when you started ART the longer it will take to become undetectable • Your CD4 count should rise Expert Opinion of Author Robert Fieldhouse

9. Will people notice if I am taking ART? • In the past, people worried about developing body fat changes fearing that this will be stigmatising and reveal their HIV status[1] • Evidence suggests newer ART is much less likely to cause body fat changes[2] • Today’s ART is easier to take privately (once daily dosing and many drugs have no food restrictions)[3,4] • In the past the risk of developing body fat loss was increased if people start ART with a CD4 count of 200 cells/mm3 [5] [1] Martinez E et al. Drug Safety 2001;24 (3):157-166 accessed January 2018 [2] Jemsek et al. Clinical Infectious Diseases 2006;42:273-280 accessed January 2018 [3] Stone, VE et al. JAIDS Journal of Acquired Immune Deficiency Syndromes 2004;36(3):808-816 accessed January 2018 [4] Johnston Roberts K and Mann T. AIDS Care 2000;12(4):377-386 accessed January 2018 [5] Lichtenstein K et al. JAIDS 2003;32:48-56 accessed January 2018

10. What side effects might I experience? • Side effects may be short-term or long-term[1] • They may occur in the first few weeks – nervous system effects including dizziness, rash, nausea, headaches and insomnia[2] • These early effects can be planned for and managed[3] • Some blood fat increases may show up in your blood results and can be managed by switching ART or taking additional medication[4] • Not all side effects will mean you have to switch ART[5] • There are many alternative medicines to switch to [1] Montessori et al. CMAJ 2004 170 (2):229-238 accessed January 2018 [2] Sustiva SPC accessed January 2018 [3] Expert Opinion of author Robert Fieldhouse as well as the BEST Advisory Board and Review Committee; agreed on 24th September 2009 [4] Calza L et al. AIDS 2005 19:1051-1058 accessed January 2018 [5] Expert opinión of Author Robert Fieldhouse

11. Do women respond as well as men to ART? • Some women achieve undetectable HIV viral load at a faster rate than men and have a more durable response[1,2] • Once established on ART, women respond at least as well as men[3] • If women experience higher drug levels due to body weight or hormone levels it is possible they may experience more side effects[4] [1] Moore AL et al. J Acquir Immune DeficSyndr 2001 ;26:159–63 accessed January 2018 [2] Patterson K et al. Conference on Retroviruses & Opportunistic Infections (CROI) 2005, Boston, MA; Abstract 596 accessed January 2018 [3] Moore AL et al. J Acquir Immune DeficSyndr2001 Feb 1;26(2):159-63 accessedJanuary 2018 [4] Clark RA, et al. Expert Rev Anti Infect Ther. Apr 2005;3(2):213-227. Accessed January 2018

12. Will taking ART protect my baby from acquiring HIV? • The risk of mother-to-child transmission if the mum has an undetectable viral load is 0.09%[1] • If a woman has an undetectable HIV viral load there is no added benefit to elective Caesarean section, making vaginal delivery possible[2] • There is a small increase in miscarriage among women living with HIV compared with HIV negative women[3,4] • Women living with HIV in the UK are advised to exclusively formula feed their babies[5] [1] Townsend CL et al. AIDS 2014; 28 (7): 1049-57. accessed January 2018 [2] Shapiro D et al. Conference on Retroviruses & Opportunistic Infections (CROI) 2010, San Francisco, CA; abstract 99 accessed January 2018 [3] Anderson J et al. BHIVA Conference, 2008, Belfast; abstract O14 accessed January 2018 [4] Ross, A et al. AIDS 2004;18:799-804 accessed January 2018 [5] Guidelines for the management of HIV infection in pregnant women 2018 British HIV Association accessed January 2018

13. Which ART is recommended for pregnant women? • The same as non-pregnant women • If on raltegravir, dolutegravir, rilpivirine or darunavir/r: can continue • Women on elvitegravir/cobisistat need to be informed that more monitoring of HIV viral load and drug levels may be necessary during pregnancy • Among PI/r, prefer atazanavir/r • Efavirenz is a suitable alternative for pregnant persons needing to start treatment. It can be continued if already started before pregnancy • Nevirapine not to be initiated, but continuation is possible if started before pregnancy • Limited experience with TAF and cobisistat in pregnancy: not recommended in initial regimen EACS Guidelines 9.0 September 2017 accessed January 2018

14. Why have some cancers risen in PLWH despite successful ART? • Since the introduction of ART there has been a sharp drop in AIDS-defining cancers but an increase in a range of other non-AIDS cancers[1] • Non–AIDS cancers are probably caused by immunodeficiency[1], leading to: • Reduced control of cancer-causing pathogens[2] • Damage due to infections and resulting in chronic inflammation[3] • Longer time spent with a low CD4 count and high HIV viral load before ART and time spent with low CD4 count on ART may place people at increased risk of developing cancers[4] • HIV increases the risk of lung cancer by nearly twofold but smoking increases it tenfold[5] • The most common cancers are anal, lung, and liver cancers, and Hodgkin lymphoma. This stems from co-infections such as human papillomavirus (HPV), hepatitis B and C viruses, and Epstein-Barr virus, as well as higher smoking rates in the HIV/AIDS population[6] [1] Deakin J et al Clinical Infectious Diseases Volume 55 Issue 9 November 2012 1228-1235 accessed January 2018 [2] Killebrew et al. Current HIV Research 2004;2:215-221 accessed January 2018 [3] Matsuzaki et al. Hepatology 2007;46(1):48-57 accessed January 2018 [4] Guiguet et al. Lancet, 2009;374(9696):1119-1212 accessed January 2018 [5] Sigel K et al. Conference on Retroviruses & Opportunistic Infections (CROI) 2010, San Francisco CA 2010;Abstract 30. accessed January 2018 [6] Shiels MS et al. J Natl Cancer Inst 2011;103:753-762 accessed January 2018

15. Will it ever be safe for me to stop ART? • The SMART study found people taking episodic therapy had twice the risk of disease progression (the development of AIDS or death)[1] • Most doctors do not recommend taking breaks from ART but advice will be tailored to each individual situation[2] • For most people, HIV therapy will be for life[2] • Most people stick with ART once they have started[2] • A small trial suggested that it may be safe for some to interrupt ART but only if your CD4 count stays above 350 cells/mm3[3] • But remember, you are more likely to transmit HIV if you have a detectable viral load[4] [1] The Strategies for Management of Antiretroviral Therapy (SMART) Study Group N Engl J Med 2006; 355:2283-2296November 30, 2006 accessed January 2018 [2] Expert opinion of author Robert Fieldhouse as well as the BEST Advisory Board and Review Committee; agreed on 24th September 2009 [3] Maggiolo F et al. AIDS 2009 23:799-807 accessed January 2018 [4] Rodger A et al. 21st International AIDS Conference, Durban, abstract TUAC0206, 2016. accessed January 2018

16. Should I start ART if I have recently acquired HIV? • Treatment of PHI is recommended for all HIV positive persons • Several circumstances indicate immediate treatment initiation: • Acute infection • Severe or prolonged symptoms • Neurological disease • Age ≥ 50 years • CD4 count < 350 cells/µL EACS Guidelines 9.0 September 2017 accessed January 2018

17. Can I become re-infected with HIV? • Superinfection occurs when a PLWH is infected with a strain of HIV they do not already have • Superinfection may occur with wild-type or resistant virus but, based on data in serodifferent couples, is not a concern if both members of the couple are on suppressive ART[1,2] • For serosame couples attempting to conceive through unprotected intercourse, there are no conclusive data on the overall risk of superinfection • Small cohort studies of men who have sex with men failed to show any evidence of superinfection although there is one report of an MSM on fully suppressive ART who was superinfected with a multi-resistant strain of HIV[3] [1] Chakraborty B et al. AntivirTher 7: S47, 2002. accessed January 2018 [2] Shafer RW et al. AntivirTher 7: S149, 2002. accessed January 2018 [3] Buskin SE et al.. J Acquir Immune DeficSyndr 49: 205-212, accessed January 2018

18. What tips do you have for good ART adherence? • Get a pill box and fill it at the beginning of each week • Take your medicine at the same time each day. (Use a watch with an alarm or get a beeper) • Get a medication "diary" or notebook. In it, you can write the names of your drugs, and then check off each dose as you take it • Plan ahead for changes in your normal routine (for example, if you will be out all day, or if you're going on holiday) • Make sure you always have enough medicine! • Call your doctor or pharmacist if you are running low • Link taking your medicines to another established daily routine such as brushing your teeth Expert opinion of author Robert Fieldhouse

19. Are there interactions with ART and alcohol or recreational drugs? • There is no direct interaction between alcohol and ART but heavy drinking has been associated with lower adherence to ART • Controlled interaction studies with recreational drugs and ART are often not available • Interactions have been shown with protease inhibitors and GHB, MDMA, LSD, ketamine, opiates, methadone, amphetamines [1] Cook R et al. Journal of General Internal Medicine vol 16 issue 2 83-86, 2007 accessed January 2018 [2] Antoniou T et al. Ann Pharmacother. 2002 Oct;36(10):1598-613. accessed January 2018

20. HIV Cure: Where are we now? • Only one man- the “Berlin Patient” is believed to have been cured of HIV with a stem cell transplant from a donor with genetic protection against HIV[1] • Functional Cure: low level virus in absence of ARVs • Therapeutic Vaccine: University of Oxford[2] • Block and Lock Approach (reactivation of the virus within cells is prevented and HIV in the patient enters a latent state, doing no harm to the body)[3] • Hundreds of potential strategies are currently being explored but a cure for HIV is likely a long way off [1] Allers K et al. Blood 2011;117(10):2791-2799 accessed January 2018 [2] Mothe B et al Abstract 119LB CROI February 13-16 2017, Seatte, Washington. Accessed January 2018 [3] Kessing C et al Cell Reports Volume 21, Issue 3, p600–611, 17 October 2017 accessed January 2018