Hiv in children & adolescents and pmtct. Dr. P. Maes M. Willems K. De Winter: UZA Dr. I. Kint: ITG

Transcription

1 Hiv in children & adolescents and pmtct Dr. P. Maes M. Willems K. De Winter: UZA Dr. I. Kint: ITG

2 HIV

3 HIV PART 1: pmtct Epidemiology Risk factors of transmission PART 2: HIV in Children HIV in general: World report HIV in Belgium: HIV plan HIV in Children PART 3: Transition of adolescents PART 4: Local experience: CBSK

4 HIV PART 1: pmtct Epidemiology Risk factors of transmission PART 2: HIV in Children HIV in general: World report HIV in Belgium: HIV plan HIV in Children PART 3: Transition of adolescents PART 4: Local experience: CBSK

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6 Newborn Formula feeding AZT sirop during 6 weeks: 4 mg/kg/dosage every 12 hours, from 8-12 hours after birth until the age of 6 weeks; adapted dosages when prematurity But when the mother: Didn t have therapy Had a bad compliance Then combination therapy (Haart) is needed for the baby Controls at 1m (PCR), 3m (PCR), 6m (PCR), 12m (Sero) and if necessary also at 18m (Sero)

7 European collaborative study: Trends over time in mode of delivery elective Csection emergency Csection Vaginal delivery %

8 European collaborative study: Trends over time in vertical transmission rates % 16 13,7 13, , ,5 5,4 2,2 0, _14

9 HIV PART 1: pmtct Epidemiology Risk factors of transmission PART 2: HIV in Children HIV in general: World report HIV in Belgium: HIV plan HIV in Children PART 3: Transition of adolescents PART 4: Local experience: CBSK

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11 Websites British HIV Association: guidelines for the management of HIV infection in pregnant women enhiv_part_1.pdf also part 2 and part 3: very nice, focus on the US : A guide to the clinical care of women with HIV HIV/AIDS resource center for women: Treatment Guidelines: elines Scientific Institute of Public Health, Belgium: Breach:

12 Global summary of the AIDS epidemic Number of people Total living with HIV in 2015 Adults Women Children (<15 years) 36.7 million [34.0 million 39.8 million] 31.8 million [30.1 million 33.7 million] 16.0 million [15.2 million 16.9 million] 3.2 million [2.9 million 3.5 million] People newly infected Total with HIV in 2015 Adults Children (<15 years) 2.1 million [1.9 million 2.4 million] 1.9 million [1.7 million 2.1 million] [ ] AIDS deaths in 2015 Total Adults Children (<15 years) 1.1 million [ million] 1.0 million [1.2 million 1.5 million] [ ] Source: UNAIDS/WHO estimates.

13 Decline in HIV incidence and mortality over time People dying from AIDS-related causes globally People newly infected with HIV/AIDS globally Source: UNAIDS/WHO estimates.

14 Number of people newly infected with HIV Source: UNAIDS/WHO estimates. The red shading shows future targets.

15 Number of people dying from HIV Source: UNAIDS/WHO estimates. The red shading shows future targets.

16 HIV-plan EU-report on the AIDS epidemic

17 HIV-plan BE-report on the AIDS epidemic

18 New HIV Plan in Belgium: Official presentation on 15/10/13 Aims of the HIV plan: - First target: Prevention - Second target: Screening - Third target: Taking care of people with HIV - Fourth target: Daily living of people with HIV

19 New HIV Plan in Belgium:

20 New HIV Plan in Belgium:

21 New HIV Plan in Belgium:

22 New HIV Plan in Belgium:

23 New HIV Plan in Belgium:

24 Child with HIV or risc of infection with HIV: What to do?

25 First Diagnose! ELISA Western Blott PCR viral load

26 Then Start treatment? And when? And how?

27 HAART Highly Active Anti Retroviral Therapy Dramatic fall in child and adult mortality from HIV infection in Europe Very expensive major impact on the family Wide variation in prescribing practice across Europe: from 50% to 97% in different countries Problems of compliance/adherence

28 When to start a treatment with HAART?

29 When to start a treatment with HAART? - No randomised trial evidence is available in children - So decisions to start are based on: clinical disease stage? viral load? CD4%? cfr.: CDC 1994 Revised classification system for HIV infection in children less than 13 years of age. - AIDS stadium or not? - Age?

30 HAART guidelines for HIV+ children U.S.A.: 1993: Working Group on Antiretroviral Therapy and Medical Management of HIV-Infected Children: convened by the NPHRC, HRSA & NIH 1998: CDC: MMWR: April 17, 1998/Vol.47/No. RR-4 Europe: 09/99: Current evidence for the use of Pediatric Antiretroviral Therapy - A PENTA Analysis Belgium: National Pediatric Working group every 3 months with review of the guidelines once a year

31 Basic principles for HAART in HIV + children 1. Importance of clinical trials in children 2. Management of prescribing HAART is becoming increasingly complex and should wherever possible be directed in specialised centres by a multidisciplinary team 3. Regular monitoring (clinical/biochemical/psycho-social)

32 Basic principles for HAART in HIV + children 4. Factors to be considered before starting HAART: - availability, tolerability, efficacy, formulation, and side effect profile of currently available drugs, including dosage frequency, and impact on school, family, and social life - dosage in function of the farmaco-kinetic, complex differences in absorption, distribution and metabolism between neonates, infants, children, adolescents and adults

33 Personal conclusions HAART in HIV + children HAART, 95% compliance necessary 50% success is very good universal problem motivation if you try to get ideality, you get reality if you try to get reality, you get shit hit hard, hit early compliance - adherence -? Another way to look at it: living met HIV

34 Personal conclusions HAART in HIV + children Bad taste of the medication Difficult medicationscheme Food advise Quantity of pills, size of pills Adverse events Child Adaption of living to the medication scheme Environment is not aware of the diagnosis Therapy duration

35 Personal conclusions adherence in HIV + children daily confrontation with sickness daily struggle with the medication altered motivation when the child is going better Child is sometimes to young to understand the necessity of the medication QOL/Sleep/rest The weather / Seasons Fight with partner Relation doctor- patient Function of the multidisciplinary team Accesability of the hospital Influence of alternative medicines, healers, religious leaders, gossip in the community

36 Doctors should pay attention with the fact that patients often lie when they are telling that they ve taken their medication. Hippocrates ( BC)

37 Natural evolution of HIV infection?

38 And now Start treatment? when? and how?

39 Table 1: 1994 Revised HIV pediatric classification system: Immune categories based on Age-specific CD4+ T-cells count and percentage <12 months 1-5 years 6-12 years Immune category No./µL % No./µL % No./µL % Category 1- No suppression Category 2- Moderate suppression Category 3- Severe suppression % % % %-24% %-24% % < 750 < 15% > 500 < 15% < 200 < 15%

40 Table 2: 1994 Revised HIV pediatric classification system: Clinical categories Category N: Not symptomatic Children who have no signs or symptoms considered to be the result of HIV infection or who have only one of the conditions listed in Category A Category A: Mildly symptomatic Children with 2 or more of the following conditions but none of the conditions listed in categories B and C. - lymfadenopathy ( 0.5 cm at more than two sites; bilateral = 1 site) - hepatomegaly - splenomegaly - dermatitis - parotitis - recurrent of persistent upper respiratory infection, sinusitis or otitis media

41 Table 2: 1994 Revised HIV pediatric classification system: Clinical categories Category B: Moderately symptomatic Children who have symptomatic conditions, other than those listed for category A or category C, that are attributed to HIV infection. Examples of conditions in clinical category B include, but are not limited to, the following: - Anemia (<8gr/dl), neutropenia (<1000/mm³), or thrombocytopenia (<100000/mm³) for 30 dd - bacterial meningitis, pneumonia or sepsis (single episode) - candidiasis, orofaryngeal persisting for > 2 mm in children aged > 6 mm - cardiomyopathy - CMV infection with onset before age 1 month - diarrhea, recurrent or chronic - hepatitis, nephropathy - HSV stomatitis, recurrent (I.e. > 2 episodes/year) - HSV bronchitis, pneumonitis or esofagitis with onset before age 1 month - Herpes Zoster involving at least two distinct episodes or more than one dermatome - LIP or pulmonary lymphoid hyperplasia complex -... Category C: Severe symptomatic Children who have any condition listed in the 1987 surveillance case definition for acquired immunodeficiency syndrome, with the exception of LIP

42 Table 3:Association of baseline CD4 T cell % with long-term risk for death in HIV- infected children DEA THS BASELINE # PATIENTS # % < 5% 5%-9% 10%-14% 15%-19% 20%-24% 25%-29% 30%-34% 35%

43 Table 4:Association baseline # HIV RNA Copy with long-term risk for death in HIV-infected children DEA THS BASELINE # PATIENTS # % Total

44 Table 5:Association baseline # HIV RNA copy & CD4 T cell % with long term risk for death in HIV infected children Baseline HIV RNA / Baseline CD4 T cell % DEA THS # PATIENTS # % % < 15% % < 15%

45 Table 6: Indications for initiation of antiretroviral therapy in children with Until HIV 2016 Start infection treatment? when? and how? Clinical symptoms associated with HIV infection (cfr Tabel 2: Clinical cat. A,B or C) Evidence of immune suppression, indicated by CD4 T cell absolute number of percentage (Cfr. Table 1: Immune cat. 2 or 3) Age < 12 mm, regardless of clinical, immunologic or virologic status For asymptomatic children aged 1 year with normal immune status, two options can be considered: 1. Initiate therapy, regardless of age or symptom status 2. Defer treatment in situations in which the risk for clinical disease progression is low and other factors favor postponing treatment. In such cases, the health care provider should regularly monitor virologic, immunologic, and clinical status. Factors to be considered in deciding to initiate therapy include the following: - High or increasing HIV RNA copy number - Rapidly declining CD4 T cell number or percentage to values approaching those indicative of moderate immune suppression (Cfr. Table 1: Immune cat. 2) - Development of clinical symptoms

46 Tabel 8: Indications for initiation of antiretroviral therapy in children >12 mm with HIV infection Until 2016 Start treatment? when? and how? Clinical categoria CD4+ Cell % Plasma HIV RNA copy # Recommandation AIDS (Clinical cat. C) <15% (Immuun cat. 3) Any VL Treat Mild symptomatic(clinical cat. A or B) Asymptomatic (Clinical cat.n) OR OR 15-25% (Immuun cat.2) >25% AND (Immuun cat. 1) >= c/ml Consider treatment OR < c/ml Many experts would rather wait to start a treatment, but with close FU AND

47 And now 2017 Start treatment? when? Based on data from the multinational START and PENPACT1 trials, the Panel now recommends antiretroviral treatment (ART) for all HIV-infected children, regardless of clinical symptoms, viral load or CD4 T lymphocyte (CD4) count. The strength of the Panel's recommendations varies by age and pretreatment CD4 cell count due to fewer available pediatric data regarding benefits and risks of therapy in asymptomatic HIV-infected children than in adults. The text offers guidance on the urgency of initiation of ART based on age, clinical status and CD4 cell counts.

48 And now 2017 Start treatment? when?

49 And now 2017 Start treatment? how? What Drugs to Start: Initial Combination Therapy for Antiretroviral Treatment-Naive Children Content has been reorganized to enhance usability, and a figure has been added to provide an overview of Preferred and Alternative regimens for initiation of ART in treatment -naive children.

50 And now 2017 Start treatment? how? The Panel has added the tenofovir alafenamide (TAF) containing fixed dose combination tablet elvitegravir/cobicistat/emtricitabine/taf (Genvoya) as a preferred integrase strand transfer inhibitor (INSTI) regimen in adolescents 12 years and older. Darunavir boosted with ritonavir is now considered a preferred protease inhibitor (PI) in children and adolescents aged 3 years and older. Dolutegravir is now considered a preferred INSTI in adolescents aged 12 years and older. Raltegravir is now considered a preferred INSTI in children aged 2 to 12 years. The Panel has determined that fosamprenavir, nelfinavir, stavudine, and unboosted atazanavir should not be used for initial therapy.

51 What HAART to start with?

52 What HAART to to start start with? with? Nucleoside Reverse Transcriptase Inhibitors Non-Nucleoside reverse Transcriptase Inhibitors Nucleotide reverse transcriptase Inhibitors Protease Inhibitors Integrase Inhibitors Fusie Inhibitors

53 Workingmechanisms RNA and reverse transcription Injection of capsid contents NNRTI work here NRTI work here Transcription Protease Translation Protein cleavage PI work here Viral assembly RNA DNA Provirus (circular structure) Integrase Maturation Integration of Provirus DNA into Host DNA HIV particle Binding FI work here Completed HIV particle

54 What HAART to start with?

55 What HAART to start with?

56 What HAART to start with?

57 HIV PART 1: pmtct Epidemiology Risk factors of transmission PART 2: HIV in Children HIV in general: World report HIV in Belgium: HIV plan HIV in Children PART 3: Transition of adolescents PART 4: Local experience: CBSK

58 Care and treatment support of HIV-Infected Adolescents

59 Topic outline Two Epidemiological Subgroups Adolescents: Behavioral vs perinatal Differences in HIV Care Models: Pediatric vs. Adolescent vs. Adult Transition Local experience 19 DEC 2014

60 Two Epidemiologic Subgroups Adolescents 19 DEC 2014

61 Two Epidemiologic Subgroups Adolescents 1. Perinatally Infected with HIV 2. Behaviorally Infected with HIV These two groups have both distinct as well as shared clinical and psychosocial characteristics 19 DEC 2014

62 Unique Clinical Issues in Perinatally Infected vs. Behaviorally Infected Youth Behavioral: more likely to be in earlier stages of HIV disease less OI complications no previous ARV exposure less likely to be resistant to ARV s less likely to require HAART when HAART required can give simpler regimens treatment adherence problems may be relatively simpler to manage than perinatal group more likely to achieve functional autonomy

63 Unique Clinical Issues in Perinatally Infected vs. Behaviorally Infected Youth Perinatal: more likely to be in more advanced stages of HIV disease and immunosuppression more likely to have OI s with complications/disabilities (eg. blindness, O 2 dependent, chronic renal failure) more likely to have heavy ARV exposure and therefore more likely to have multi-drug resistant virus more likely to require HAART to control viremia, low CD4 counts

64 Unique Clinical Issues in Perinatally Infected vs. Behaviorally Infected Youth Perinatal (cont.): more complicated ARV regimens (eg. mega-haart ) more complicated non-arv medications such as OI prophylaxis/treatment greater obstacles to achieving functional autonomy due to physical and developmental disabilities/greater dependency on family (eg. adult vulnerable child) significant prevalence developmental delay and regression (eg. ADHD 15% - Behavioral problems 29%) when pregnant, higher risk of complications during more advanced stages of disease and of second generation HIV transmission due to multiple-drug resistance

65 Differences in HIV Care models: Pediatric vs. Adolescent vs. Adult 19 DEC 2014

66 Differences in HIV Care models: Pediatric vs. Adolescent vs. Adult Pediatric: family-centered and multidisciplinary care with pediatric expertise medical provider has more long standing relationship with care giver at home primary care approach integrated into HIV care issues of HIV disclosure to patient and youth s confidentiality/right to consent care usually offered in discreet, child-friendly and intimate setting teen services supplemental to existing services

67 Differences in HIV Care models: Pediatric vs. Adolescent vs. Adult Adolescent: teen-centered and multidisciplinary care; provider may have minimal to no relationship with parent/care giver primary care approach integrated into HIV care youth often does not disclose HIV status to family issues of confidentiality and consent; care usually offered in discreet, teen-friendly and intimate setting teen services core to clinic-sexuality, pelvic examinations/pap smears, rights to confidentiality and consent, treatment education and adherence approaches

68 Differences in HIV Care models: Pediatric vs. Adolescent vs. Adult Adult: adult-oriented care based on strict medical model Adult medical providers more often ID specialists than are pediatric or adolescent providers young person s transitional issues usually not given any systematic specialized focus clinics tend to be very large and easy for transitioning patients to slip through the cracks unless very motivated

69 Transition

70 Transition Transition is a multifaceted, active process that attends to the medical, psychosocial, and educational or vocational needs of adolescents as they move from the child-focused to the adultfocused health-care system. Health care transition facilitates transition in other areas of life as well (eg. work, community, and school). Reiss, J, Gibson R. Health Care Transition: Destinations Unknown. Pediatrics. 2002;110: DEC 2014

71 Transition Most developmental transitions create anxiety timing of the transition will depend on developmental readiness, complexity of the health problems, characteristics of the adolescent and family, and the availability of skilled adult health providers. Transition is more complex and generally more difficult for those with more severe functional limitations or more complicated medical conditions. Reiss, J, Gibson R. Health Care Transition: Destinations Unknown. Pediatrics. 2002;110: DEC 2014

72 Transition Principles of Healthcare Transition Begin healthcare transition early Continuity of care is the goal Transition planning should be comprehensive Involve teen and family Providers and parents should be prepared to facilitate movement Service coordination, communication and collaboration between providers is essential

73 Transition Interventions & Strategies Maintain a relationship with teen and family Stimulate discussion about teen s future Understand the nature and implications of teen s chronic illness Determine time for transition discussions based on teen's development and needs Practice family-centered care

74 Transition What can young people do? Start talking about upcoming transition Acknowledge and accept developmental change Accept adulthood responsibly Take charge of healthcare information

75 HIV PART 1: pmtct Epidemiology Risk factors of transmission PART 2: HIV in Children HIV in general: World report HIV in Belgium: HIV plan HIV in Children PART 3: Transition of adolescents PART 4: Local experience: CBSK

76 Local experience CBSK since 1990 Total seropositive children in FU = seropositive children in FU = 27 Perinatal/behavioral = 27/03 Total MTCT in FU > MTCT in FU = 91

77 Local experience CBSK in 2017 PATIENTS < 14Y = 7/27 HAART: 6/ Y = 4/27 HAART: 3/ Y = 5 (à 8)/27 HAART: 4/5 > 18Y = 11/27 HAART: 11/11

78 Local experience CBSK in 2017 TRANSITIONS TO PLAN 2015 = 4/ = 4/ = 3/19 (waarvan 1 naar Gent) 2018 = 2/ = 3/14 (waarvan 2 naar Gent) 2020 = 3/11 (waarvan 1 naar Brugge)

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