Untitled Document

Antiretroviral Treatment of HIV-Infected Children

Adapted from
Working Group on Antiretroviral Therapy and Medical Management of
HIV-Infected Children. Guidelines for the Use of Antiretroviral Agents
in Pediatric HIV Infection (2009) Adobe PDF document

The pathology and treatment of HIV/AIDS is similar across patient groups. However, children present unique treatment considerations.

Most children are infected through perinatal exposure.
Depending on prenatal care, the infant may have received zidovudine in utero or postpartum.
Age-specific differences in CD4 cell counts.
Drug metabolism and clearance differ depending on systems maturation.
Neonatal serologic tests can be effected by maternal antibodies.
Clinical presentations differ in the immature body.
Psychosocial needs vary with age.
Special compliance issue.

Prenatal exposure

Prenatal HIV testing and counseling is the standard of care for all pregnant women in the United States. Testing may be offered on an opt-out basis. Repeat testing in the third trimester for high risk HIV negative women is suggested. Rapid HIV antibody screening and intrapartum antiretroviral prophylaxis prior to delivery is recommended for women of unknown HIV status. In the absence of laws requiring HIV testing, rapid antibody testing, counseling and antiretroviral prophylaxis should be offered as soon as possible after delivery when maternal HIV status is unknown.

Diagnosis in infants

The presence HIV RNA in the blood can be confirmed in most infected infants by age 1 month and in virtually all infected infants by age 6 months, using cell culture, polymerase chain reaction or RNA assays. HIV antibody screening is not useful prior to 18 months of age due to the possible presence of circulating maternal antibodies. Children older than 18 months may be tested with antibody assays.Early diagnosis allows early treatment. A number of studies demonstrate that early HAART slows progression to AIDS or death.

Goals of HAART

Reduce HIV related morbidity and mortality
Restoring and/or preserving immune function
Maximally supress viral replication for as long as possible
Minimize side effects
Promote normal development
Improved quality of life.

Initiate HAART (Recommendation)

Age	Criteria	Recommendation
Antiretroviral drug-resistance testing is recommended prior to initiation of therapy in all treatment-naïve children.
<12 months	Regardless of clinical symptoms, immune status, or viral load	Treat
1 to <5 years	AIDS or significant HIV-related symptoms	Treat
	CD4 <25%, regardless of symptoms or HIV RNA level	Treat
	Asymptomatic or mild symptoms and CD4 ≥25% and HIV RNA ≥100,000 copies/mL	Consider treament
	Asymptomatic or mild symptoms and CD4 ≥25% and HIV RNA <100,000 copies/mL	Defer treatment
≥5 years	AIDS or significant HIV-related symptoms	Treat
	CD4 <350 cells/mm3	Treat
	Asymptomatic or mild symptoms and CD4 ≥350 cells/mm and HIV RNA ≥100,000 copies/mL	Consider treament
	Asymptomatic or mild symptoms CD4 ≥350 cells/mm HIV RNA <100,000 copies/mL	Defer

Which HAART regimen?

As of February 2009 there are 25 antiretroviral medications approved for use in the U.S. Of these 17 are available for use in children.

Antiretroviral drug resistance testing is recommended prior to initiation of HAART in all treatment naive children.
"Infants who are identified as HIV- infected during the first 6 weeks of life while receiving zidovudine chemoprophylaxis should have zidovudine discontinued and should be assessed to determine the need for initiation of standard combination treatment."
"Combination therapy with at least 3 drugs, including either a protease inhibitor or non-nucleoside reverse transcriptase inhibitor plus a dual nucleoside analogue reverse transcriptase inhibitor backbone, is recommended for initial treatment of HIV-infected children."
The goal of therapy in treatment-naïve children is to reduce HIV RNA levels to below the level of
detection (if possible, as determined using ultrasensitive assays) and to preserve immune function for as long as possible.

Preferred Components for Initial HAART in Children
Preferred NNRTI	Children ≥3 years old: Two NRTIs plus efavirenz Children <3 years old or who can’t swallow capsules: Two NRTIs plus nevirapine Alternative: Two NRTIs plus nevirapine1 (children ≥3 years old) Avoid Efavirenz in pubescent females d/t potential birth defects.
	Nevirapine in combination with 2 NRTIs for children age < 3 years or who require a liquid formulation

Preferred PI	Two NRTIs plus lopinavir/ritonavir Alternative: Two NRTIs plus atazanavir plus low-dose ritonavir (children >6 years old) Two NRTIs plus fosamprenavir plus low-dose ritonavir (children >6 years old) Two NRTIs plus nelfinavir (children >2 years old)

Preferred 2NRTI Backbone	Abacavir + (lamivudine or emtricitabine) abacavir should not be given to a child who tests positive for HLA B*570 Didanosine + emtricitabine Zidovudine + (lamivudine or emtricitabine) Tenofovir + (lamivudine or emtricitabine) Postpubertal adolescents

Antiretroviral Regimens or Components that Should Not Be Offered for Treatment of Human Immunodeficiency Virus Infection in Children (July 29, 2008)
Regimens NOT Recommended	Rationale	Exceptions
Monotherapy	Rapid development of resistance Inferior antiviral activity compared to combination with >3 antiretroviral drugs	HIV-exposed infants (with negative viral testing) during 6-week period of prophylaxis to prevent perinatal transmission
2 NRTIs alone	Rapid development of resistance Inferior antiviral activity compared to combination with >3 antiretroviral drugs	Not recommended for initial therapy; for patients currently on this treatment, some clinicians may opt to continue if virologic goals are achieved
Tenofovir + abacavir + (lamivudine or emtricitabine) as a triple NRTI regimen	High rate of early virologic failure when this triple NRTI regimen was used as initial therapy in treatment-naive adults	No exception
Tenofovir + didanosine + (lamivudine or emtricitabine) as a triple NRTI regimen	High rate of early virologic failure when this triple NRTI regimen was used as initial therapy in treatment-naive adults	No exception
Efavirenz in first trimester or for sexually active girls of childbearing potential	Potential for teratogenicity	When no other antiretroviral option is available and potential benefits outweigh risks
Nevirapine initiation in adolescent girls with CD4 cell count >250/mm3 or adolescent boys with CD4 cell count >400/mm3	Increased incidence of symptomatic (including serious and potentially fatal) hepatic events in these patient groups	Only if benefit clearly outweighs risk
Saquinavir as single sole PI	Poor oral bioavailablity Inferior virologic activity compared to other PIs	No exception

HAART evaluation

Children who start a new antiretroviral regimen should be evaluated in person or by a phone call within 1 to 2 weeks of starting medication to screen for clinical side effects and to assure that they are taking medication properly.
Children should be seen within 4 to 8 weeks to assess for possible side effects and to evaluate initial response to therapy. More frequent evaluation may be needed following initiation or change in therapy to support adherence to the regimen.
Subsequently, children should have a monitoring visit at least every 3 to 4 months to assess both efficacy and potential toxicity of their antiretroviral regimens.