Table 15d. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Hematologic Effects

Body
Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/Monitoring Management
Anemiaa ZDV Onset:
  • Variable; weeks to months after starting therapy
Presentation
More Common:
  • Asymptomatic
  • Mild fatigue
  • Pallor
  • Tachypnea
Rare:
  • Congestive heart failure
Newborns Exposed to HIV:
  • Severe anemia is uncommon but might be coincident with physiologic Hgb nadir.
Children with HIV Who Are Taking ARV Drugs:
  • Anemia is two to three times more common with ZDV-containing regimens than with all other regimens.
Newborns Exposed to HIV:
  • Premature birth is the most common risk factor
  • In utero exposure to ZDV-containing regimens.
  • Advanced maternal HIV
  • Neonatal blood loss
  • Combination ARV prophylaxis or presumptive HIV therapy, particularly ZDV plus 3TC and NVP
Children with HIV Who Are Taking ARV Drugs:
  • Underlying hemoglobinopathy (e.g., sickle cell disease, G6PD deficiency)
  • Myelosuppressive drugs (e.g., TMP-SMX, rifabutin)
  • Iron deficiency
  • Advanced or poorly controlled HIV disease
  • OIs of the bone marrow
  • Malnutrition
Newborns Exposed to HIV:
  • Obtain CBC at birth.
  • Consider repeating CBC at 4 weeks for neonates who are at higher risk (e.g., those born prematurely or who are known to have low birth Hgb) and for neonates who receive ZDV beyond 4 weeks.
Children with HIV Who Are Taking ARV Drugs:
Newborns Exposed to HIV: Children with HIV Who Are Taking ARV Drugs:
  • Discontinue non-ARV, marrow-toxic drugs, if feasible.
  • Treat coexisting iron deficiency, OIs, and malignancies.
  • For persistent, severe anemia that is thought to be associated with ARV drugs (typically macrocytic anemia), switch to a regimen that does not contain ZDV.
Macrocytosis ZDV Onset:
  • Within days or weeks of starting therapy
Presentation:
  • Asymptomatic, but MCV often is >100 fL
  • Sometimes associated with anemia
>90% to 95% for all ages None No monitoring required—macrocytosis can be detected if CBC is obtained as part of routine care (see Clinical and Laboratory Monitoring of Pediatric HIV Infection). No management required.
Neutropeniaa ZDV Onset:
  • Variable
Presentation:
  • Asymptomatic
Newborns Exposed to HIV:
  • Rare
Children with HIV Who Are Taking ARV Drugs:
  • 2% to 4% of children on ARV drugs
  • Highest rates occur in children on ZDV-containing regimens
Newborns Exposed to HIV:
  • In utero exposure to ARV drugs
  • Combination ARV prophylaxis, particularly ZDV plus 3TC and NVP
Children with HIV Who Are Taking ARV Drugs:
  • Advanced or poorly controlled HIV infection
  • Myelosuppressive drugs (e.g., TMP-SMX, ganciclovir, hydroxyurea, rifabutin)
Children with HIV Who Are Taking ARV Drugs:
  • Obtain CBC as part of routine care.
Newborns Exposed to HIV: Children with HIV Who Are Taking ARV Drugs:
  • Discontinue non-ARV, marrow-toxic drugs, if feasible.
  • Treat coexisting OIs and malignancies.
  • In cases of persistent, severe neutropenia that is thought to be associated with ARV drugs, switch to a regimen that does not contain ZDV.
a HIV infection itself, OIs, and medications that are used to prevent OIs (e.g., TMP-SMX) can all contribute to anemia and neutropenia. Prolonged use of NVP with ZDV in three drug regimens for the prevention of perinatal HIV transmission has been associated with increased rates of anemia and neutropenia in some, but not all, studies. The effects are of uncertain clinical significance and appear to be transient.

Key: 3TC = lamivudine; ANC = absolute neutrophil count; ARV = antiretroviral; CBC = complete blood count; fL = femtoliter; G6PD = glucose-6-phosphate dehydrogenase; g/dL = grams per deciliter; Hgb = hemoglobin; MCV = mean cell volume; NRTI = nucleoside reverse transcriptase inhibitor; NVP = nevirapine OI = opportunistic infection; TMP-SMX = trimethoprim-sulfamethoxazole; ZDV = zidovudine