Adolescents living with HIV เรืองท้าทายในวัยร่นกับุ HIV

By Kulkanya Chokephaibulkit, MD Faculty of Medicine Siriraj Hospital , ,

กรมอนามัย มีค 16 Epidemiology: 2.1 million adolescents aged 10 - 19 years living with HIV globally

• There are two HIV-infected adolescent populations – Grow up with HIV: mostly are perinatally acquired: • Currently, 30-70% of perinatal pediatric cohort are adolescents • Globally (2014), 3.2 M children (<15 yo) are living with HIV: they will be adolescents in 5-10 years – Recently infected: mostly behaviorally acquired: • Of the 2 M newly infected cases in 2013, 60% were adolescents 15-24 year-old • Young women, young gay men and MSM the highest risk group Children with HIV are Living Longer: 30-70% of them became adolescents

Estimated Number and Age of Perinatally- The TREAT Asia Pediatric HIV Infected Youth Living with HIV in the US Observational Database (TApHOD), CDC HIV Surveillance Report 2011 (50 6 countries in Asia, Mar 2011 states) (Pediatric HIV clinics only)

Sohn AH et al. JIAS 2013 <13 yrs <12 yrs >=13 yrs >= 12 yrs

10,798 persons with perinatal HIV living in 4,045 children: 53% female the US

The Thai national pediatric HIVQUAL database, 2013 <=10 yrs (Pediatric HIV clinics only) 11-15 yrs

3,654 children: 54% female; 161 hospitals >15 yrs Approximately 1/3 (23-86%)of high risk populations to HIV are under 25 year-old Adolescents Grown-up With HIV VS Those Who Acquired HIV Recently

Adolescents grown-up with HIV Adolescents recently infected

• High proportion of orphanage, raised-up by • Healthier baseline non-parent caretakers • Mostly sexually acquired or IVDU

• Better cope with HIV and treatment • Poor/chaotic family background

• Good HIV knowledge • Higher risk behaviors, STI

• Long experience of ART • Not accept/not believe about HIV • • More complications from chronic HIV and Poor HIV knowledge, misconceptions long-term ART • Poor compliance

– Neurodevelopmental deficit

– Poor growth, delayed puberty

– Metabolic/ lipodystrophy

• Tired /bored of ART Adolescents Grown-up With HIV VS Those Who Acquired HIV Recently

Adolescents grown-up with HIV Adolescents recently infected

• High proportion of orphanage, raised-up by • Healthier baseline non-parent caretakers • Mostly sexually acquired or IVDU

• Better cope with HIV and treatment • Poor/chaotic family background

• Good HIV knowledge • Higher risk behaviors, STI

• Long experience of ART • Not accept/not believe about HIV • • More complications from chronic HIV and Poor HIV knowledge, misconceptions long-term ART • Poor compliance

– Neurodevelopmental deficit – Poor growth, delayed puberty Many similarly teens’ problems….. – Metabolic/ lipodystrophy Moods, emotion….. Peer pressure, self esteem… • Tired /bored of ART Sex..etc UNAIDS 90-90-90 ambitious treatment target to help end the AIDS epidemic To achieve this goal in adolescents, the care and supports provided must answer to their needs

By 2020 Worldwide, 36.9 million people are estimated to be living with HIV of whom 53% are diagnosed, 13.4 million people short of the 90% target. 41% are on treatment, 14.9 million people short of the target, and 32% are virally suppressed, 15.3 million people short of the target. Approximately 2 million people each year are becoming infected at current rates of transmission.

Levi J et al. Can the UNAIDS 90-90-90 target be achieved? Analysis of 12 national level HIV treatment cascades.Eighth International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention, Vancouver, abstract MOAD0102, 2015. Can we achieve 90-90-90? Perinatally infected adolescents in Asia in 2011 Data from 18 pediatric sites in TApHOD (N=1254): high retention (>90%) but low viral suppression (68%)

At Last visit Active F/U N=1061

Median age 14.7 (13.3-16.4) Single/double orphan 72.6% In school 93.2% HIV disclosed 62.2% VL<400 67.7% On Regimen NNRTI 70.6%

Chokephaibulkit K. PIDJ 2014;33:291-4. Can we achieve 90-90-90? The estimated adolescent (13-29 year-old) HIV cascade of care in the US: Understanding the situation

40% 62% 44% 54%

The cascade could be worse in less resource-settings

Zanoni BC. AIDS Patient Care STDS. 2014 Mar;28(3):128-35. Let’s get to know adolescents

We all were adolescents once. Developments of Adolescents General Rule of Teens

The unique stage of life with significant physical, emotional, and mental change

12-14 (early) 14-17 (mid) 17-21 (late)

- Stick with parents - Disagreement - Accept parents - Same sex peer - Peer is everything - Stable partner - Ambitious - Too confident, no fear - Moral, wiser - Poor temp control - Ready to take risk - Set goal, self control - Impatience - Sexual orientation - Rigid concept Peer pressure “What is right is what I want” Low tolerance of opposite The 5 important challenges to achieve 90-90-90 goal Behavioral Perinatal Acquired Acquired Early diagnosis

Treatment and retention Complications

Sexual health and STI Prevention (of transmission) Challenge 1. Early Diagnosis: The first step of success Most behaviorally acquired HIV-infected adolescents were not diagnosed until they were symptomatic or become pregnant

A survey data collected in sub-Saharan Africa indicated that only 10% of young men and 15% of young women (15–24 years) were aware of their HIV status

WHO, HIV and Adolescents: Guidance for HIV Testing and Counselling and Care for Adolescents Living with HIV, 2013. The reported patients with AIDS (symptomatic) in Thailand: majority were contracted during adolescence (for >10 yrs) but never been diagnosed

How many cases were infected from these young people for 10 years without treatment?

They were contracted at 15-24 yo. Number

Male Female

BATS, Thai MOPH How can we draw adolescents to get HIV testing? The currently available services are not youth friendly

No Confidentiality

stigma Fragmented

Unfriendly Reimbursement environment Ad/ Demand promotion

Derived from series of FGDs in various locations and youth backgrounds. We need Youth Friendly Clinics to draw the teens Important characteristics • No stigma (not sign of STD/HIV/RH) • Easily accessible • Convenient location • One-stop services of HTC, HIV-STI treatment, contraception, immunization, PEP, PrEP • Integrated services of medical health, mental health, reproductive health • Minimal charge (or free) • Youth friendly staff: respect their sexual orientation • Match with teen lifestyle: off-hour service time, Online, Line, Facebook, Instagram YFS Model Social Enterprise Clinic

• Comprehensive sexual health service – Counselling on HIV/STI testing, prevention/treatment – Contraception – Mental health – Immunization – Lifestyle counseling: nutritional, hormone/Trans care, anal care, etc. • Gender responsive: MSM/TG/women/men • Integrated with online clinic and social medias • Great location: Red light district of BKK • Confidential and stigma-free: with beauty/acne treatment, acupuncture, etc. Need to be available at the clinic at low (no) cost iUSE –lovecare Station • Online youth clinic utilizing various social medias and application • Collaborative effort: • Path2Health Foundation • Siriraj Hospital • Queen Hospital • Thai US Collaboration -Of >190,000 users, • Sponsor: UNICEF 79% were <24 Y (peak 12-17Y) -FAQ are: unplanned pregnancy, sexual health, emergency pill, menstruation Unlocking Parental Consent For The Under 18: To help Adolescents

The 16 yo boy • Parental consent is a barrier to engaged known HIV testing in adolescents risk. He went for • The Thai Medical council issued blood donation in the new guidelines 2015 order to get the test – No need for written consent done free. – If the client is ready and able to understand, the test can be done regardless of age – The report of the test results to anyone are based on the best interest of the client. UNAIDS: Countries must consider lowering the age of independent consent so that more adolescents can access testing Opt-out Testing Normalize/destigmatize HIV testing • CDC recommendation since September 2006: – Routine HIV testing for everyone between the ages of 13-64 and all pregnant women, and at least yearly for high risk individuals – Use opt-out screening for HIV—meaning that HIV tests will be done routinely unless a patient explicitly refuses to take an HIV test – Eliminate the requirements for informed consent • The benefit of opt-out testing: – Earlier access to care and prevention of transmission with less stigmatization Challenge 2: Treatment and retention Treatment As Prevention (HPTN052) Early treatment can stop the epidemic!

Linked Overall Number Follow-up Study Arm Number Infections (PY) Infections *

Immediate 4 1 1,585

Delayed 35 27 1,567

p value <0.0001 <0.001 Immediate treatment was 96% effective in preventing transmission compared to CD4 guided treatment initiation

Cohen MS. NEJM 2011;1-13. Challenges in adhering to ART

• Denial and fear of their HIV infection; • Misinformation, Distrust • Low self-esteem; • Unstructured and chaotic lifestyles; • Fear and lack of belief in the effectiveness of medications; • Mood disorders and other mental illness; • Lack of familial and social support; • Absence of or inconsistent access to care or health insurance • Risk of inadvertent parental disclosure of the youth’s HIV status Treatment outcomes in adolescents is poorer than in adults % 90 78 80

70 59 60 56

50 43 Adult N=46 40 Adolescent N=46

30 Virologic 20 13 11 Outcomes 10 and Clinical 0 Retention VL <400 at 6 m. VL Rebound LTFU

Ryscavage PA. JAIDS 2011 High attrition among youth (15-24 years of age) enrolled in HIV care: In 160 HIV clinics in Kenya, Mozambique, Tanzania, and Rwanda

1 Y after starting ART • Attrition was highest among youth • Male youth had higher attrition than female • Those attending clinic providing SH service and support group had lower attrition rate

Lamb MR. AIDS. 2013 Sep 26. Always need to work on psychosocial/environmental factors to solve adherence problems

The solutions could be: • Simplify the regimen, once daily, STR • Set-up DOT (with Facetime) • Arrange home/environment/agreement • Some tools (weekly (lovely) drug box, watches, incentives, etc.). Make it easy to carry out. Lower Pill Burden and Once-daily Dosing Antiretroviral Treatment May not result in Higher Virologic Success: A Meta-Analysis ยาวันละครังก็ยังไม่กิน

Once daily regimen may not be the answer

Forest plot of the effect of once-daily versus twice-daily antiretroviral regimens on the virologic suppression (plasma RNA HIV level <50 or <200 copies/mL)

Nachega JB. CID 2014 Jan 22. [Epub ahead of print] Adolescents get smarter after 18

Age Regimen CD4 CD4% VL 5Y6M Start 388 14 AZT+3TC+EFV 10Y “ 451 18 24,100

14Y9M “ 756 26 4,320

14Y11M Start AZT+TDF+LPV/r (BID) 15Y3M “ 601 24 788 16Y Start Truvada+ATV/r (OD) 17Y2M “ 379 19 23,000

18Y1M “ 610 19 <40 Adolescents get smarter after 18

Age Regimen CD4 CD4% VL 5Y6M Start 388 14 AZT+3TC+EFV 10Y “ 451 18 24,100 Confess: 14Y9M “ 756 26 4,320 “I never take ARV 14Y11M Start AZT+TDF+LPV/r (BID) regularly 15Y3M “ 601 24 788 ” 16Y Start Truvada+ATV/r (OD) 17Y2M “ 379 19 23,000

18Y1M “ 610 19 <40

Declare: “I am smart now, Doc! Now, I take my meds, happy with once daily and less pills” Example: A young gentleman with perinatal HIV

• Poor adherence in the past 2 years, smoking, drink, and marijuana sometimes. He quite school. Live with grandparents. • He just got a new girl friend, and has unprotected sex. The different intervention strategies: - If he is 15: Multidisciplinary approach with family, place rules and incentives, DOT, close observation - If he is 18: Personal discussion the risk and benefit. Encourage out-of-school education degree. Discuss life plan. Challenge 3: Complications Highly specific to adolescents with perinatal HIV Clinical Complications Among Perinatally HIV-Infected Adolescents • Cardiovascular diseases risk: Charakida M et al. Circulation 2005;112:103-9 – Bunuparadah T. Antiviral therapy 2013;18:591-8. Dyslipidemia in 20-30% Chanthong P. AIDS. 2014 Sep 10;28(14):2071-9 – Insulin resistance in 20% Miller RF. CID 2013;56:576-82 – Cardiomyopathy in 10% – Increased cIMT if get PI >6 m

• Renal insufficiency: 2%/yr receiving TDF Riordan A. PIDJ 2009;28:204-9

• Neuro/psychiatric problems Scharko AM. AIDS Care 2006;18:441-5; Pao&Lyon,2000 – ADHD 24%, Anxiety 29%, Depression 25%, – Depressive 68%, Substance abuse 59%, Conduct29% • Fractures risk/osteopenia, vitamin D deficiency Arpadi SM. JAIDS 2002;29:450-4. Body fat abnormality in HIV-infected children and adolescents: The difference of regions

Study Population

Lipohypertrophy or combine 2.5%% Lipoatrophy 23%

No fat maldistribution 75%

Europe (N= 426, LD = 42% Receiving PI 60%, Thailand, N=202, LD = 25% Received d4T 10% Receiving PI 41%, Received d4T 60%

Alam NM. J Acquir Immune Defic Syndr. 2012 Sawawiboon N. International Journal of STD & AIDS March 1; 59(3): 314–324 2012; 23: 497–501 Frequency of abnormal lipid profile in Thai adolescents: Siriraj, Bangkok, 2013

HIV-infected Healthy P value N = 100 Total = 50 CHOL > 200 mg/dl 25 (25%) 12 (24%) 0.867 LDL > 130 mg/dl 16 (16%) 8 (16%) 0.733 HDL < 35 mg/dl 8 (8%) 0 (0) 0.017 TG > 150 mg/dl 37 (37%) 1 (2%) <0.001 49% receiving PI

Chanthong P. AIDS. 2014 Sep 10;28(14):2071-9 The cIMT in association with on PI >6 months in HIV-infected Thai adolescents

cIMT (mm) Receiving PI > 6 Receiving PI < 6 P value months (n=53) months or never(n=47)

Proximal CCA 0.393 (0.284-0.478) 0.369 (0.289-0.448) 0.019

Distal CCA 0.40 (0.273-0.475) 0.381 (0.311-0.441) 0.022

ICA 0.353 (0.283-0.514) 0.345 (0.26-0.431) 0.179

Overall cIMT 0.379 (0.284-0.451) 0.372 (0.287-0.423) 0.02

The values were presented in median (range)

Chanthong P. AIDS. 2014 Sep 10;28(14):2071-9 Prevalence of abnormal glucose metabolism and lipid metabolism in HIV-infected children receiving PIs-based ART at Siriraj Hospital (median age 16.7 yr and median duration of PIs 72.6 mo.)

50 45 % 40 35 30 25 20 15 10 5 0 Impaired Impaired IR DM HyperCH HyperTG Hyper LDL- Hypo HDL- MS FBS OGTT C C Surapong. Metabolic Complications Among HIV-Infected Thai Children Receiving Protease Inhibitors Many adolescents with HIV have lipodystrophy, metabolic syndrome, and stunt

Acanthosis negricans on bPI From d4T years ago

Stunt

From bPI Prevalence of low BMD measured by spine BMD (L2-L4) in Thai HIV-infected adolescents at Siriraj and

Adjusted for % Thai reference N=98 % e % ore percentag ore

Z-sc % BMD

Puthanakit P. J Acquir Immune Defic Syndr. 2012 Aug 22 No chance for HIV-infected adolescent with renal failure A 13 year-old girl died from renal failure

• At 5 yo, presented with nephrotic syndrome responded well to HAART and steroid • She has been virologic suppressed with normalized CD4 for more than 6 years • At 12 yo, presented with renal failure required renal replacement with CAPD • Experienced several peritonitis events and failed CAPD • She was refused for hemodialysis An episode of HSV stomatitis and renal transplantation Prevention of Osteoporosis in HIV-Infected Children

• Exercise • Take enough calcium • Get adequate sun exposure (arm-leg exposure 5-30 min 10 am- 3 pm 2/wk) or take Vit D 400-1000 IU/day • Get ART started early to protect growth • Consider monitor Vitamin D level and DXA in cases with risk (low HAZ, fracture hx) • (Avoid PI and TDF when possible) Transitioning to adults Make our adolescents ready to live like adults

Transition is a multifaceted, active process that attends to the medical, psychosocial, and academic or vocational needs of adolescents as they move from the child-focused to the adult- focused health-care system. The Thai Happy Teen I/II Model

Goals: to help ALWH become a healthy, happy, coping, responsible adults Happy Teen Program Transfer perinatally infected youth from pediatric clinic to adult clinic

Introduce the adolescents to youth-friendly adult provider team Challenge 4: Sexual Health and STI This is to all adolescents Sexual Deviations: We need to be sensitive to all gender-specific needs Many youth were receiving street inappropriate hormone therapy that could induce AE (thromboembolism, hepatitis) Correlates of Sexual Activity and Sexually Transmitted Infections Among Human Immunodeficiency Virus-infected Youth in the LEGACY Cohort, United States, 2006.

Perinatal Behavioral %Sex active 34% (195-571) 89% (162/181) STI 10% 32%

Factors associated with sexual active: older, viremia, IVDU, have boyfriend/ girl friend

Setse RW. PIDJ 2011;30:967-73. 7th International workshop on HIV Pediatrics 2015, Vancouver The association of uncontrolled HIV infection and other sexually transmitted infections in metropolitan Atlanta youth

STIs contracted by controlled versus uncontrolled disease status.

Brownstein PS. PIDJ 2015;34:e119-24. Invasive cervical cancer risk among HIV-infected women: A North American multi-cohort collaboration prospective study

N=13,690 HIV+(66,249 py) Need Vaccination in HIV- infected adolescents 12,021 HIV-(70,812 py) Abraham AG. JAIDS 2012 Dec 18. 9 Risk of X 7.7 Invasive 8 cervical 7 cancer 6 (times higher 5 of HIV) 4 X3 3 X2.3 2 1 0 >350 200-350 <200 Immunogenicity and Safety of the Quadrivalent Human Papillomavirus Vaccine in HIV-1–Infected Women

% Seroconversion at week 28 (13-45 yo)

The quadrivalent HPV vaccine targeted at types 6, 11, 16, and 18 was safe and immunogenic in HIV-infected women aged 13–45 years. Women with HIV RNA load >10 000 copies/mL and/or CD4 count <200 cells/μL had lower rates of seroconversion rates. Kojic EM. CID 2014;59:127-135. No, Teens Did Not Create a Working Condom That Changes Colors if You Have an STI

http://rhrealitycheck.org/article/2015/06/30/teens-create- working-condom-changes-colors-sti-maybe-shouldnt/ Impact of HIV-1 infection and pregnancy on maternal health: perinatally vs behaviorally infected young women

Perinatally HIV-infected young women had poorer maternal outcomes than behaviorally infected women

Munjal I. Adolesc Health Med Ther. 2013 Feb 21;4:51-8

Challenge 5: Prevention of transmission

สิงทีต้องระวัง การตังครรภ์โดยไม่ตังใจ Teenage Pregnancy Condom use and HIV Counseling and testing coverage in youth 15-24 yo in Thailand

www.aidszeroportal.org Sexual Risk Behavior Among Youth With Perinatal HIV Infection in the United States

62% reported unprotected sex

Tassiopoulos K. CID 2013 Jan;56(2):283-290. Epub 2012 Nov 7. Prevalence of Drug Resistance Among Sexually Active Youth With Perinatal HIV Infection and VL>5,000 cp/ml: US

Proportion

• 42% had VL >5,000 after sex debut • 33% disclosed to partners • 84% resistance to drugs in >1 classes • 24% resistance to drugs in all 3 classes

Tassiopoulos K. CID 2013;56:283-90. Health Risk Behaviors among HIV-Infected Youth in Bangkok, Thailand

Male Female (n=29) (n=41) Having <95% adherence to treatment in the past 1 3 (33.3) 2 (10.5) month, n (% of those on treatment) Risk behaviors in the past 30 days Having sex, n (%) 19 (65.5) 26 (63.4) Consistent condom use, n (% of those who have had 11 (57.9) 14 (53.8) sex)

Having sex with at least 1 HIV-negative partner, n (% 5 (26.3) 7 (26.9) of those who have had sex) HIV disclosure to partners, n (% of those who have 12 (63.2) 25 (96.2) had sex)

Rongkavilit C. The Lancet 2007;358:357.e2-358.e8. PrEP and PEP should be offered to HIV-infected adolescents’partners

• Recommendation: PrEP should be offered to adolescents at high risk for HIV – To date, no efficacy or safety studies have been published on the use of PrEP in younger than 18 year-old. However, CDC/IAS extended the use of TDF/FTC to include PrEP for adolescents at risk • Providers should carefully weigh the potential benefits and risks, before prescribing PrEP to a younger adolescent and should make clear that the efficacy of PrEP is highly dependent on strict adherence.

CDC. Preexposure Prophylaxis for HIV Prevention in the United States – 2014. Available at:http://www.cdc.gov/hiv/pdf/guidelines/PrEPguidelines2014.pdf Marrazzo JM, del Rio C, Holtgrave DR, et al. HIV prevention in clinical care settings: 2014 recommendations of the International Antiviral Society-USA Panel. JAMA 2014;312:390-409. PrEP Regimen

• TDF/FTC is recommended for PrEP for MSM, heterosexually active men and women, and IDU who meet recommended criteria. • TDF alone has been proven effective in trials with IDU and heterosexually active men and women, it can be considered as an alternative regimen for these specific populations. • As PrEP for MSM, TDF alone is not recommended because no trials have been done, so efficacy of TDF alone for MSM is unknown. Conclusion There are lots of challenges and unmet needs that we need to work on The problems and solutions we know but hardly achieve

Increasing incidence of HIV Declining HIV Teenage knowledge pregnancy

Youth Policy Substance Earlier abuse sexual debut Sex Youth Education leader

Low condom Rising STI Solution use

Social Parenting campaign

Friendly service We need staff team with expertise in adolescents in all genders DDC Poll ครังที 1 เรือง "การตีตราและกีดกันผ้ติดเชือู เอชไอวีและผ้ป่วยเอดส์ในสังคมไทย"ู 2,057 คน จาก 21 จังหวัดทัวทุกภาคของประเทศ ระหวางวันที่ 4-7 พฤศจิกายน 2556

• ร้อยละ 61.9 เห็นควรให้มีการบังคับตรวจหาเชือเอชไอวีก่อนสมัครเรียน • ร้อยละ 57.7 ก่อนการบวช • ร้อยละ 73.1 ก่อนสมัครเข้าทํางาน • ร้อยละ 63.1 จะไปตรวจเลือดเพือหาการติดเชือหากมีบริการตรวจฟรีในห้างสรรพสินค้า • ร้อยละ 50.6 ไม่ยินดีว่ายนําในสระเดียวกันกับผ้ติดเชือู • ร้อยละ 27.5 ไม่ยินดีอย่ร่วมบ้านกับคนในครอบครัวทีติดเชือู • ร้อยละ 30.6 ไม่ยินดีรับประทานอาหารกับคนในครอบครัวทีติดเชือ • ร้อยละ 27.4 ไม่ยินดีรับประทานอาหารร่วมกับเพือนสนิททีติดเชือ • ร้อยละ 33.3 ไม่ยินดี ให้ลูกเรียนร่วมชันกับเด็กทีติดเชือ • ร้อยละ 42.5 ไม่ยินดีให้ลูกเล่นกับเด็กทีมีเชือ • ร้อยละ 46.4 ไม่ยินดีใช้ห้องนําร่วมกับคนผ้ป่วยเอดส์ู • ร้อยละ 17.5 ไม่ยินดีดูแลคนในครอบครัวทีป่วยเอดส์ด้วย ตนเอง Thank you Acknowledgements: Dr. Wadchara Pumpradit Dr. Rangsima Lolekha and the happy teen team -Siriraj Pediatric team -Queen Sirikit Naitonal Institute of Child Health Thai-US CDC Collaboration