1 / 29

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. DR. S.K CHATURVEDI DR. KANUPRIYA CHATURVEDI. Antiretroviral (ARV) Therapy in Adults and Children. Similar pathogenesis of HIV infection General virologic and immunologic principals for antiretroviral therapy apply

xandy
Download Presentation

Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection DR. S.K CHATURVEDI DR. KANUPRIYA CHATURVEDI

  2. Antiretroviral (ARV) Therapy in Adults and Children • Similar pathogenesis of HIV infection • General virologic and immunologic principals for antiretroviral therapy apply • Unique considerations in infants, children, and adolescents

  3. Special Considerations in Pediatric ARV Therapy • Diagnostic issues • Pharmacokinetic changes • Availability of pediatric formulations • Natural history differences in virologic and immunologic markers • Adherence issues

  4. Changing Pharmacokinetics • Age-related differences between children & adults • Body composition • Renal excretion • Liver metabolism • Gastrointestinal function • Enzyme maturation • Drug distribution, metabolism and clearance • Drug dosing and toxicities Lead to potential differences in:

  5. Diagnostic Issues • Early identification = all pregnant women must be offered HIV counseling and testing • Perinatal infection = primary infection • Early diagnosis = starting therapy during primary/early infection

  6. Diagnostic Issues in Infants • HIV is diagnosed by 2 positive HIV virologic tests performed on blood samples 2 separate dates • Use DNA PCR or HIV culture for diagnosing at: • Birth (<48 hours) • 14 days (optimal) • 1–2 months • 3–6 months

  7. Diagnostic Issues in Infants • HIV is reasonably excluded with: • 2 or more negative virologic tests • One at age >1 month • One at age >4months • 2 or more negative HIV antibody tests at >6 months (in the absence of breast feeding)

  8. Pediatric HIV ClassificationAge-Specific CD4+ Immunologic Categories

  9. Pediatric HIV Classification Clinical Categories • Category E: Perinatally Exposed • Category N: Not Symptomatic • Category A: Mildly Symptomatic • Category B: Moderately Symptomatic • Category C: Severely Symptomatic

  10. Immunologic Parameters in Children • Absolute CD4+ counts in healthy children are much higher than in adults • Normal absolute CD4+ counts slowly decline to adult levels by age 6 • If using CD4+ count for ARV decision, use appropriate levels • CD4 percent varies less with age and may be a better immunologic parameter to follow in children <6 years

  11. Immunologic Parameters in Children • Obtain baseline CD4 assays when child is clinically stable • Confirm CD4 changes with a second test before making therapy decisions (when to initiate therapy, when to change therapy, etc.)

  12. HIV RNA and Children:Clinical Considerations • HIV RNA and CD4 assays are independently predictive of risk of disease progression • Both help determine when to start and when to change ARV therapy • A 5-fold change in HIV RNA copies/mL in infants or 3-fold change in children is biologically and clinically significant

  13. HIV RNA and Children:Clinical Considerations • Low levels at birth rise to >100,000 copies/mL to several million copies within the first 1–2 months of life • Without treatment, very slow decline over several years to reach “set point”

  14. HIV RNA and Children:Clinical Considerations • Children >12 months with HIV RNA >100,000 copies/mL are at higher risk for disease progression and death • Predictive value of HIV RNA in infants <12 months old less than older children • In infants, HIV RNA levels are much higher and overlap with rapid and non-rapid progressors • CD4+ counts/percentages may be more useful in evaluating risk in infants <12 months than HIV RNA; in older children both parameters are useful

  15. HIV RNA in Children:Clinical Considerations • Moderate predictive value of specific HIV RNA levels for disease progression/death in individual child • HIV RNA levels difficult to interpret in first year of life • CD4+ and HIV RNA level provide complimentary and independent information about prognosis • Assess HIV RNA every 3-4 months

  16. HIV RNA and Children:Clinical Considerations • Obtain 2 baseline HIV RNA tests when child is clinically stable • Confirm HIV RNA changes with a second test before making therapy changes • Consult pediatric HIV specialist when interpreting HIV RNA for clinical decision-making

  17. Antiretroviral Treatment Guidelines for Children with HIV Infection

  18. Decision Factors about ARV Initiation in Children • Disease severity and risk of progression—presence/hx of serious illness, CD4+ count, HIV RNA • Availability of appropriately formulated and palatable drugs

  19. Decision Factors about ARV Initiation in Children • Complexity of regimen and potential adverse effects • Effect of initial choice on later therapeutic options

  20. Decision Factors about ARV Initiation in Children • Presence of comorbidities (e.g. TB, Hep B or C, or chronic renal/liver disease) • Potential ARV interaction with child’s other medications • Ability of the child and caregiver to adhere to the regimen

  21. Early Initiation of Therapy: Potential Advantages Starting ARVs in the asymptomatic patient: • Controls viral replication while genetic quasispecies are relatively homogeneous and before significant viral mutations occur • Could control development of heterogeneous viral strains/mutations • Potentially leads to less drug resistance • Could lower “viral setpoint”fewer viral strains • Slows immune system destruction preserving immune function and preventing clinical progression

  22. Delayed Initiation of Therapy: Potential Advantages Delaying ARV therapy until symptomatic: • Could reduce evolution of drug-resistant virus due to lack of drug selection pressure exerted by early ARV use • May support greater adherence when symptomatic • Reduces or delays adverse effects of ARVs

  23. ARV Therapy for Infants <12 Months • Risk of disease progression is inversely correlated with age • Limited data on rapid v. slower disease • Limited clinical trial data on early aggressive therapy • Limited information on drug dosing • Potential ARV toxicities over the long term

  24. ARV Therapy for Infants <12 Months • Initiate treatment for any infant with clinical or immunologic symptoms • Consider treatment for infants who are asymptomatic with normal immune function The Working Group recommends:

  25. Indications for Initiation of ARV Therapy in Children <12 Months of Age

  26. ARV Therapy for Children Age 12 Months and Older • Risk of disease progression is less in older children than in infants • Children with fewer clinical symptoms or only moderate immune suppression are at lower risk for progression than those with more advanced clinical symptoms/immune disease • In children >12 months, plasma HIV RNA may provide information about progression risk as an adjunct to clinical/immune parameters and can assist in making ARV decisions

  27. ARV Therapy for Children Age 12 Months and Older • Start treatment in children with AIDS or severe immune suppression • Consider treatment for children with • Mild-moderate clinical symptoms • Moderate immune suppression and/or • Confirmed plasma HIV RNA level >100,000 copies/mL The Working Group recommends:

  28. ARV Therapy for Children Age 12 Months and Older • Defer treatment in asymptomatic children with normal immune status with low risk of clinical disease (HIV RNA <100,000 copies/mL) when adherence factors favor postponing • Monitor virologic, clinical, and immunologic status

  29. ARV Therapy for Children Age 12 Months and Older • Factors to consider in deciding when to initiate therapy • Increasing HIV RNA levels (>100,000 copies/mL) • Rapidly declining CD4+ count or percentage to values approaching severe suppression • Development of clinical symptoms • Ability of caregiver and child to adhere to regimen

More Related