HIV AIDS infection in infants
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
The use of ART during pregnancy in HIV-infected women has resulted in a dramatic decrease in the transmission rate to infants, which is currently less than 2% in the United States, and the number of infants with AIDS in the United States continues to decline. Finally, children living with HIV infection are, as a group, growing older, bringing new challenges of adherence, drug resistance, reproductive health planning, management of multiple drugs, and long-term complications from HIV and its treatments.
Unique properties of HIV infection in pediatric age group
- Acquisition of infection through perinatal exposure for most infected children.
- In utero, intrapartum, and/or postpartum neonatal exposure to zidovudine and other ARV drugs in most perinatally infected children.
- Requirement for use of HIV virologic tests to diagnose perinatal HIV infection in infants younger than 18 months.
- Age-specific differences in CD4 cell counts.
- Changes in pharmacokinetic (PK) parameters with age caused by the continuing development and maturation of organ systems involved in drug metabolism and clearance.
- Differences in the clinical and virologic manifestations of perinatal HIV infection secondary to the occurrence of primary infection in growing, immunologically immature persons.
- Special considerations associated with adherence to ARV treatment for infants, children, and adolescents.
Diagnosis
Pediatric Classification system
Treatment
General Considerations
- A number of factors need to be considered in making decisions about initiating and changing antiretroviral therapy (ART) in children, including:
- Severity of HIV disease and risk of disease progression, as determined by age, presence or history of HIV-related or AIDS-defining illnesses, level of CD4 cell immunosuppression, and magnitude of HIV plasma viremia.
- Availability of appropriate (and palatable) drug formulations and pharmacokinetic (PK) information on appropriate dosing in the child’s age group.
- Potency, complexity (e.g., dosing frequency, food and fluid requirements), and potential short- and long-term adverse effects of the ARV regimen.
- Effect of initial regimen choice on later therapeutic options.
- the child’s ARV treatment history.
- Presence of ARV drug-resistant virus.
- Presence of comorbidity, such as tuberculosis (TB), hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, or chronic renal or liver disease, that could affect drug choice.
- Potential ARV drug interactions with other prescribed, over-the-counter, or complementary/alternative medications taken by the child.
- The ability of the caregiver and child to adhere to the regimen.
Goals of Antiretroviral Treatment
The goals of ART for HIV-infected children include:
- Reducing HIV-related mortality and morbidity.
- Restoring and/or preserving immune function as reflected by CD4 cell measures.
- Maximally and durably suppressing viral replication.
- Preventing emergence of viral drug-resistance mutations.
- Minimizing drug-related toxicity.
- Maintaining normal physical growth and neurocognitive development.
- Improving quality of life.
Recommendations
Identification of Perinatal HIV Exposure
- HIV testing early in pregnancy is recommended as standard of care for all pregnant women in the United States (AII).
- Repeat HIV testing in the third trimester is recommended for women who have negative HIV antibody tests earlier in pregnancy if they are at high risk of HIV infection because of behavior or residence in a high-prevalence area (AII).
- Women seen at labor with undocumented HIV status should undergo rapid HIV antibody testing, and women with a positive antibody test should initiate intrapartum antiretroviral (ARV) prophylaxis (AII).
- If acute HIV infection is suspected in a pregnant woman, a virologic test (e.g., plasma HIV RNA assay) should be performed because serologic testing may be negative at this early stage of infection (AII).
- Women who have not been tested for HIV before to or during labor should undergo rapid HIV antibody testing during the immediate postpartum period or their newborns should undergo rapid HIV antibody testing. If the mother or infant is HIV antibody positive, infant ARV prophylaxis should be initiated as soon as possible and the mother advised not to breastfeed pending results of confirmatory HIV antibody testing (AII).
Diagnosis of HIV Infection in Infants
- Virologic assays that directly detect HIV must be used to diagnose HIV infection in infants younger than 18 months (AII). HIV antibody testing cannot establish HIV infection in this age group because maternal HIV antibodies may persist and interfere with the interpretation of a positive HIV antibody test.
- Virologic diagnostic testing is recommended in infants with known perinatal HIV exposure at ages 14–21 days, 1–2 months, and 4–6 months ( AII ).
- Virologic diagnostic testing at birth should be considered for infants at high risk of HIV infection (BIII).
- HIV DNA polymerase chain reaction (PCR) and HIV RNA assays are recommended as preferred virologic assays (AII).
- Confirmation of HIV infection should be based on two positive virologic tests obtained from separate blood samples (AI).
- Definitive exclusion of HIV infection (in the absence of breastfeeding) should be based on at least two negative virologic tests (one at >1 month and one at ≥4 months of age) (AII).
- Some experts confirm the absence of HIV infection at 12–18 months of age in infants with prior negative virologic tests by performing an antibody test to document loss of maternal HIV antibodies (BIII).
- In children ≥18 months of age, HIV antibody assays alone can be used for diagnosis (AII)
Laboratory monitoring of pediatric HIV infection before initiation of therapy
- The age of the child must be considered when interpreting the risk of disease progression based on CD4 percentage or count and plasma HIV RNA level (AII). For any given CD4 percentage or count, younger children, especially those in the first year of life, face higher risk of progression than do older children.
- In children younger than 5 years of age, CD4 percentage is preferred for monitoring immune status because of age-related changes in absolute CD4 count in this age group (AII).
- CD4 percentage or count should be measured at the time of diagnosis of HIV infection and at least eve