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Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection

Management of Medication Toxicity or Intolerance

Hematologic Effects

(Last updated: March 1, 2016; last reviewed: March 1, 2016)

Table 12d. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Hematologic Effects
Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/ Monitoring Management
Anemiaa Principally ZDV Onset:
  • Variable, weeks to months
Most Commonly:
  • Asymptomatic or mild fatigue
  • Pallor
  • Tachypnea
  • Congestive heart failure
HIV-Exposed Newborns:
  • Severe anemia is uncommon, but may be seen coincident with physiologic Hgb nadir.
HIV-Infected Children on ARVs:
  • 2–3 times more common with ZDV-containing regimens; less frequent with currently recommended dosing of ZDV
HIV-Exposed Newborns:
  • Premature birth
  • In utero exposure to ARVs
  • Advanced maternal HIV
  • Neonatal blood loss
  • Combination ARV prophylaxis, particularly with ZDV plus 3TC
HIV-Infected Children on ARVs:
  • Underlying hemoglobinopathy (e.g., sickle cell disease, G6PD deficiency)
  • Myelosuppressive drugs (e.g., TMP-SMX, rifabutin)
  • Iron deficiency
  • Advanced or poorly controlled HIV disease
  • Malnutrition
HIV-Exposed Newborns:
  • Obtain CBC at birth.
  • Consider repeat CBC at 4 weeks for neonates who are at higher risk (e.g., those born prematurely or known to have low birth Hgb).
HIV-Infected Children on ARVs:
  • Avoid ZDV in children with moderate to severe anemia when alternative agents are available.
  • Obtain CBC as part of routine care.
HIV-Exposed Newborns:
  • Rarely require intervention unless Hgb is <7.0 g/dL or anemia is associated with symptoms.
  • Consider discontinuing ZDV if 4 weeks or more of a 6-week ZDV prophylaxis regimen are already completed (see the Perinatal Guidelinesb).
HIV-Infected Children on ARVs:
  • Discontinue non-ARV, marrow-toxic drugs, if feasible.
  • Treat coexisting iron deficiency, OIs, malignancies.
  • For persistent severe anemia thought to be associated with ARVs, change to a non-ZDV-containing regimen; consider a trial of erythropoietin if essential to continue ZDV.
Macrocytosis Principally ZDV; also d4T Onset:
  • Within days to weeks of starting therapy
  • MCV often >100 fL
  • Most often asymptomatic
  • Sometimes associated with anemia (occurs more often with ZDV than with d4T)
>90% to 95%, all ages None Obtain CBC as part of routine care. None required unless associated with anemia
Neutropeniaa Principally ZDV Onset:
  • Variable
  • Most commonly asymptomatic. Complications appear to be less than with neutropenias associated with cancer chemotherapy.
HIV-Exposed Newborns:
  • Rare
HIV-Infected Children on ARVs:
  • 2.2% to 26.8% of children on ARVs, depending upon the ARV regimen. 2.2% for ZDV/3TC
  • Highest rates with ZDV-containing regimens
HIV-Exposed Newborns:
  • In utero exposure to ARVs
  • Combination ARV prophylaxis, particularly with ZDV plus 3TC
HIV-Infected Children on ARVs:
  • Advanced or poorly controlled HIV infection
  • Myelosuppressive drugs (e.g., TMP-SMX, ganciclovir, hydroxyurea, rifabutin)
HIV-Infected Children on ARVs:
  • Obtain CBC as part of routine care.
HIV-Exposed Newborns:
  • No established threshold for intervention; some experts would consider using an alternative NRTI for prophylaxis if ANC <500 cells/mm3, or discontinue ARV prophylaxis entirely if ≥4 weeks of 6-week ZDV prophylaxis have been completed (see the Perinatal Guidelinesb).
HIV-Infected Children on ARVs:
  • Discontinue non-ARV marrow-toxic drugs, if feasible.
  • Treat coexisting OIs and malignancies.
  • For persistent severe neutropenia thought to be associated with ARVs, change to a non-ZDV-containing regimen. Consider a trial of G-CSF if essential to continue ZDV.
a HIV infection itself, OIs, and medications used to prevent OIs, such as TMP-SMX, may all contribute to anemia, neutropenia, and thrombocytopenia.
b Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States

Key to Acronyms: 3TC = lamivudine; ANC = absolute neutrophil count; ARV = antiretroviral; CBC = complete blood count; d4t = stavudine; dL = deciliter; fL = femtoliter; G6PD = glucose-6-phosphate dehydrogenase; G-CSF = granulocyte colony-stimulating factor; Hgb = hemoglobin; MCV = mean cell volume; NRTI = nucleoside reverse transcriptase inhibitor; OI = opportunistic infection; TMP-SMX = trimethoprim-sulfamethoxazole; ZDV = zidovudine


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