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Guidances
- 1. Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection A comparison of WHO and HHS recommendations for 2010 . Robert D. Johnson
- 24. (HHS) ARV AE and Management Recommendations
Notas do Editor
- Preferably < 36 weeks Behaviors: Sex, drugs (>1 sex partner during pregnancy -or- NEW STD in pregnancy) (1 HIV-infected pregnant woman/1000 women screened is HIGH-prevalence) (+) Pos Rapid tests to be followed with WESTERN OR IFA. AND IMMEDIATE antiretroviral prophylaxis with NO breastfeeding in both while pending results of confirmatory test.
- HIV DNA PCR and HIV RNA assays are preferred. DNA PCR requires Whole blood, DBS RNA PCR requires Plasma, DBS
- Virologic testing at 4-6 weeks will identify 95% of infants exposed in utero/itrapartum.
- Because of maternal antibodies 18 months is our cutoff date for serology. Nucleic acid amplification tests should have a Sens and Spec of 95 and 98 respectively. P24 – South Africa used heat shock method to optimize p24 dipsticks and got good results in 40 minutes with only 25 microliters plasma. Up24 Ag should NOT be used in areas where HIV SUBTYPE D is common (Central/East Africa)
- By age 2, over half of HIV-infected kids will die w/o tx. WHO Stage 3 : unexplained fever, weight loss, diarrhea. Oral hairy leukoplakia, candidiasis and TB in last two (2) years. WHO Stage 4: Wasting syndrome, PCP, EXTRAPULMONARY TB , KS, Toxo, Encephalopathy
- Some similarities, some mild distinctions/departures
- “ Exposed” means to Nevirapine or other NNRTI's used for PMTCT (LOPINAVIR/RITONAVIR) a PI In order to preserve a potent new class for second-line regimens, PI's are not usually used in first-line therapy, unless exposure to NNRTI's has occured.
- There is no established dosing for Efavirenz in kids <3 and it has CNS tox. Efavirenz would otherwise be preferred. (Tenofovir and emtricitabine) Heart of it in this order: You want to use 3TC (Lamivudine) and AZT or 3TC and abacavir or 3TC and Stavudine Triple regimen might be: NELFINAVIR plus 2 NRTI's (safe but only tested in kids with PRIOR NRTI tx). -->in HHS, Nelfinavir has been removed as an initial tx
- HLA-B*5701 (South Africa, India, Spain) drug-induced inflammatory skin reactions (also ½ the combo of “KIVEXA”, so Epzicom may not be right for everybody) No tenofovir (TDF) in Tanner Stages 1-3 (Bone tox) Triple class not tested as initial tx No PK/safety data in kids for these newer drugs (an entry, integrase and fusion inhibitor)
- Differences: 2 NRTI's plus NEVIRAPINE is being suggested as an ALTERNATIVE regimen. US experts state LVP/r is less hepatotoxic than NVP and that NVP has a higher failure rate, they admit studies are lacking however. R-Ritonavir is a booster – you can use lower amounts of others drugs often as it is a STRONG 3A4 inhibitor.
- CD4 (Strong recommendation, low quality of evidence), pretty much same for HHS (AIII) for they are on par with WHO on CD4 situation except for timeframe. If CD4 is limited in its availability, then save it for sudden clinical changes. Routine Labs WBC's and Hb. Any labs for tox. Strong rec, Very Low quality of evidence
- In children younger than 5 y/o, CD4 PERCENTAGE is preferred. There are 5 FDA approved VL assays The one with the lowest Lower Limit of Detection is the Abbot Real Time HIV-1 test <40 copies/mL. They say use the same assay consistently however due to variability... .
- First few weeks are particularly difficult.: 1-2 weeks quick assessment of Effectiveness, Adherence, Tolerability Rx like DIDANosine require Pancreatic enzymes too. Kids on Nevirapine need LFT's every 2 weeks (1 st month), monthly (3 months) then q3-4 months.
- Who suggests potentially more frequent follow-ups.
- Treatment failure as defined as VIROLOGIC, IMMUNOLOGIC or CLINICAL failure VIRO: Incomplete viral response or viral rebound IMMUNO: Failure to improve or sustained decline in CD4 cells. CLINICAL: Neurodevelopmental deterioration. Growth Failure New OI's MUST Rule out IRIS (Immune Reconstitution Inflammatory Syndrome) (There may be lag in immune functions improvement or even a seemingly paradoxical decrease in immune function.) ADHERENCE is the MCC of treatment failure. FOR EXAMPLE: “ Poor adherence and limited levels of success in adolescents due to local site reactions “ ARV DRT: 1. prior to starting tx, 2. prior to changing tx, 3. for virologic failure while pt is still on failing regimen, 4. Tropism assays (Phen oscrtipt or Trofile) for those on CCR5antagonists like maraviroc)
- TB is the MC OI-treatment ASSOCIATED with IRIS children. Do not get confused! LVP/r was their best-evidence recommendation.
- A quick aside, page 68 in the WHO document.
- Tenofovir causes loss of bone density in kids. Drug substitution may not be possible in resource-limited settings Say NVP-induced SJS would mean not switching to another NNRTI (due to class-specific tox but switching to say a TRIPLE REGIMEN or substituting a PROTEASE INHIBITOR for NVP). .
- Similar to WHO
- TB exposure? As evidenced by: Poor weight gain/cough/fever/TB contacts? Isoniazid Preventative Therapy for all: STRONG REC BUT VL Qual of Evidence IPT as a package of care= 6 Months INH EVEN if unexposed and no active dz. Greater quality of evidence for children getting IPT than infants NOT getting IPT. Nothing about B6 supplementation...?