BACKGROUND
Concepts Considered in the Formulation of Pediatric Treatment Guidelines
Go to the NIH Guidelines for Pediatric Antiretroviral Use Menu
Go to the NIH Report & Guidelines Menu
Go to the HIVpositive.us Main Menu
Concepts Considered in the Formulation of Pediatric Treatment Guidelines
The following concepts were considered in the formulation of these guidelines:
*In areas where enrollment in clinical trials is possible, enrolling the child in available trials should be discussed with the caregivers of the child. Information about clinical trials for HIV-infected adults and children can be obtained from the AIDS Clinical Trials Information Service, telephone (800) 874-2572 ([800] TRIALS-A).
Identification of Perinatal HIV Exposure
Early identification of HIV-infected women is crucial for the health of such women and for care of HIV-exposed and HIV-infected children. Knowledge of maternal HIV infection during the antenatal period enables a) HIV-infected women to receive appropriate antiretroviral therapy and prophylaxis against opportunistic infections for their own health; b) provision of antiretroviral chemoprophylaxis with ZDV during pregnancy, during labor, and to newborns to reduce the risk for HIV transmission from mother to child (4,6,7); c) counseling of infected women about the risks for HIV transmission through breast milk and advising against breastfeeding in the United States and other countries where safe alternatives to breast milk are available (11); d) initiation of prophylaxis against Pneumocystis carinii pneumonia (PCP) in all HIV-exposed infants beginning at age 4-6 weeks in accordance with PHS guidelines (12); and e) early diagnostic evaluation of HIV-exposed infants to permit early initiation of aggressive antiretroviral therapy in infected infants.
If women are not tested for HIV during pregnancy, counseling and HIV testing should be recommended during the immediate postnatal period. For newborns in whom maternal serostatus was not determined during the prenatal or immediate postpartum period, HIV antibody should be tested for following counseling and consent of the mother. The HIV-exposure status of infants should be determined rapidly because the neonatal component of the recommended ZDV chemoprophylaxis regimen should begin as soon as possible after birth and because PCP prophylaxis should be initiated at age 4-6 weeks in all infants born to HIV-infected women. Those infants who have been abandoned, are in the custody of the state, or have positive toxicology screening tests should be considered at high risk for exposure to HIV, and mechanisms to facilitate rapid HIV screening of such infants should be developed.
Diagnosis of HIV Infection in Infants
HIV infection can be definitively diagnosed in most infected infants by age 1 month and in virtually all infected infants by age 6 months by using viral diagnostic assays. A positive virologic test (i.e., detection of HIV by culture or DNA or RNA polymerase chain reaction [PCR]) indicates possible HIV infection and should be confirmed by a repeat virologic test on a second specimen as soon as possible after the results of the first test become available. Diagnostic testing should be performed before the infant is aged 48 hours, at age 1-2 months, and at age 3-6 months. Testing at age 14 days also may be advantageous for early detection of infection. HIV-exposed infants should be evaluated by or in consultation with a specialist in HIV infection in pediatric patients.
HIV DNA PCR is the preferred virologic method for diagnosing HIV infection during infancy. A metaanalysis of published data from 271 infected children indicated that HIV DNA PCR was sensitive for the diagnosis of HIV infection during the neonatal period. Thirty-eight percent (90% confidence interval [CI]=29%-46%) of infected children had positive PCR tests by age 48 hours (13). No substantial change in sensitivity during the first week of life was observed, but sensitivity increased rapidly during the second week, with 93% of infected children (90% CI=76%-97%) testing positive by PCR by age 14 days.
Assays that detect HIV RNA in plasma also may be useful for diagnosis of perinatal infection and may prove to be more sensitive than DNA PCR for early diagnosis of HIV infection in HIV-exposed infants (14). However, data are more limited regarding the sensitivity and specificity of HIV RNA assays compared with HIV DNA PCR for early diagnosis.
HIV culture has a sensitivity similar to that of DNA PCR for the diagnosis of infection (15). However, HIV culture is more complex and expensive to perform than DNA PCR, and definitive results may not be available for 2-4 weeks. Although use of standard and immune-complex-dissociated p24 antigen tests are highly specific for HIV infection and have been used to diagnose infection in children, the sensitivity of these tests is less than the sensitivity of other HIV virologic tests. The use of p24 antigen testing alone is not recommended to exclude infection or for diagnosis of infection in infants aged <1 month because of a high frequency of false-positive assays during this time (16).
Initial testing is recommended by age 48 hours because nearly 40% of infected infants can be identified at this time. Because of concerns regarding potential contamination with maternal blood, blood samples from the umbilical cord should not be used for diagnostic evaluations. Working definitions have been proposed for acquisition of HIV infection during the intrauterine and intrapartum periods. Infants who have a positive virologic test at or before age 48 hours are considered to have early (i.e., intrauterine) infection, whereas infants who have negative virologic tests during the first week of life and subsequent positive tests are considered to have late (i.e., intrapartum) infection (17). Some researchers have proposed that infants with early infection may have more rapid disease progression than those with late infection and therefore should receive a more aggressive therapeutic approach (18,19). However, recent data from prospective cohort studies have demonstrated that although early differences in HIV RNA levels have been present between infants with positive HIV culture within 48 hours of birth and those with a first positive culture after age 7 days, these differences were no longer statistically significant after age 2 months (20). HIV RNA copy number after the first month of life was more prognostic of rapid disease progression than the time at which HIV culture tests were positive (20). Repeat diagnostic testing also can be considered at age 14 days in infants with negative tests at birth, because the diagnostic sensitivity of virologic assays increases rapidly by age 2 weeks and early identification of infection would permit modification of antiretroviral therapy from the standard 6-week course of neonatal ZDV chemoprophylaxis to more aggressive combination antiretroviral therapy.
Infants with initially negative virologic tests should be retested at age 1-2 months. With increasing use of ZDV to reduce perinatal transmission, most HIV-exposed neonates will receive 6 weeks of antiretroviral chemoprophylaxis. Although prophylactic antiretroviral therapy theoretically could affect the predictive value of HIV virologic testing in neonates, ZDV monotherapy did not delay the detection of HIV by culture in infants in PACTG protocol 076 and has not decreased the sensitivity and predictive values of many virologic assays (4, 21). However, whether the current, more intensive combination antiretroviral regimens women may receive during pregnancy for treatment of their own HIV infection will affect diagnostic test sensitivity in their infants is unknown.
HIV-exposed children who have had repeatedly negative virologic assays at birth and at age 1-2 months should be retested again at age 3-6 months. HIV infection is diagnosed by two positive HIV virologic tests performed on separate blood samples. HIV infection can be reasonably excluded among children with two or more negative virologic tests, two of which are performed at age >1 month, and one of those being performed at age >4 months (12). Two or more negative HIV immunoglobulin G (IgG) antibody tests performed at age >6 months with an interval of at least 1 month between the tests also can be used to reasonably exclude HIV infection among children with no clinical evidence of HIV infection. HIV infection can be definitively excluded if HIV IgG antibody is negative in the absence of hypogammaglobulinemia at age 18 months and if the child has both no clinical symptoms of HIV infection and negative HIV virologic assays.
Go to the NIH Guidelines for Pediatric Antiretroviral Use Menu
Go to the NIH Report & Guidelines Menu
Go to the HIVpositive.us Main Menu