Clinical Guidelines Portal
- What's New in the Guidelines
- Guidelines Panel Members
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- Preconception Counseling and Care for HIV-Infected Women of Childbearing Age
- Antepartum Care
- Intrapartum Care
- Postpartum Care
- Appendix A: Review of Clinical Trials of Antiretroviral Interventions to Prevent Perinatal HIV Transmission
- Appendix B: Supplement: Safety and Toxicity of Individual Antiretroviral Agents in Pregnancy
- Nucleoside and Nucleotide Analogue Reverse Transcriptase Inhibitors
- Non-Nucleoside Reverse Transcriptase Inhibitors
- Protease Inhibitors
- Amprenavir (Agenerase, APV)
- Atazanavir (Reyataz, ATV)
- Darunavir (Prezista, DRV)
- Fosamprenavir (Lexiva, FPV)
- Indinavir (Crixivan, IDV)
- Lopinavir + Ritonavir (Kaletra, LPV/r)
- Nelfinavir (Viracept, NFV)
- Ritonavir (Norvir, RTV)
- Saquinavir (Invirase [Hard Gel Capsule], SQV)
- Tipranavir (Aptivus, TPV)
- Entry Inhibitors
- Integrase Inhibitors
- Antiretroviral Pregnancy Registry
- Appendix C: Acronyms
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
Long-Term Follow-Up of Antiretroviral Drug-Exposed Infants
(Last updated:3/28/2014; last reviewed:3/28/2014)
- Children with in utero/neonatal exposure to antiretroviral (ARV) drugs who develop significant organ system abnormalities of unknown etiology, particularly of the nervous system or heart, should be evaluated for potential mitochondrial dysfunction (CIII).
- Follow-up of children with exposure to ARVs should continue into adulthood because of the theoretical concerns regarding the potential for carcinogenicity of nucleoside analogue ARV drugs (CIII).
|Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials with clinical outcomes and/or validated laboratory endpoints; II = One or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = Expert opinion
Data remain insufficient to address the effect that exposure to zidovudine or other antiretroviral (ARV) agents in utero might have on long-term risk of neoplasia or organ system toxicities in children. Data from follow-up of PACTG 076 infants through age 6 years did not indicate any differences in immunologic, neurologic, and growth parameters between infants who were exposed to the zidovudine regimen and those who received placebo, and no malignancies were noted.1-3 Data are conflicting regarding whether mitochondrial dysfunction is associated with perinatal exposure to ARV drugs. Children with in utero exposure to ARVs who develop significant organ system abnormalities of unknown etiology, particularly of the nervous system or heart, should be evaluated for potential mitochondrial dysfunction.4-6 It is also unclear from laboratory-based and long-term clinical studies of infants and preadolescent children with in utero exposure to ARV drugs whether residual effects of these medications result in clinical consequences.7-11 Studies should continue into adulthood because of the theoretical concerns regarding the potential for carcinogenicity of the nucleoside analogue ARV drugs. Long-term follow-up should include annual physical examinations of all children exposed to ARV drugs. Innovative methods are needed to provide follow-up of infants, children, and youth with in utero exposure to ARV drugs. Information regarding such exposure should be part of ongoing permanent medical records for children, particularly those who are uninfected.
Evaluation is ongoing of early and late effects of in utero exposure to ARV drugs, including the Pediatric HIV/AIDS Cohort Study, Surveillance Monitoring of Antiretroviral Toxicity Study, natural history studies, and HIV/AIDS surveillance conducted by state health departments and the Centers for Disease Control and Prevention. Because most of the available follow-up data relate to in utero exposure to antenatal zidovudine alone and most HIV-infected pregnant women currently receive combination ARV drug regimens, it is critical that studies to evaluate potential adverse effects of in utero drug exposure continue to be supported. HIV surveillance databases from states that require HIV reporting provide an opportunity to collect population-based information concerning in utero exposure to ARV drugs. To the extent permitted by federal law and regulations, data from these confidential registries can be compared with information from birth defect and cancer registries to identify potential adverse outcomes.
- Culnane M, Fowler M, Lee SS, et al. Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women. Pediatric AIDS Clinical Trials Group Protocol 219/076 Teams. JAMA. 1999;281(2):151-157. Available at http://www.ncbi.nlm.nih.gov/pubmed/9917118.
- Hanson IC, Antonelli TA, Sperling RS, et al. Lack of tumors in infants with perinatal HIV-1 exposure and fetal/neonatal exposure to zidovudine. J Acquir Immune Defic Syndr Hum Retrovirol. 1999;20(5):463-467. Available at http://www.ncbi.nlm.nih.gov/pubmed/10225228.
- Brogly S, Williams P, Seage GR, 3rd, Van Dyke R. In utero nucleoside reverse transcriptase inhibitor exposure and cancer in HIV-uninfected children: an update from the pediatric AIDS clinical trials group 219 and 219C cohorts. J Acquir Immune Defic Syndr. 2006;41(4):535-536. Available at http://www.ncbi.nlm.nih.gov/pubmed/16652068.
- Blanche S, Tardieu M, Rustin P, et al. Persistent mitochondrial dysfunction and perinatal exposure to antiretroviral nucleoside analogues. Lancet. 1999;354(9184):1084-1089. Available at http://www.ncbi.nlm.nih.gov/pubmed/10509500.
- Barret B, Tardieu M, Rustin P, et al. Persistent mitochondrial dysfunction in HIV-1-exposed but uninfected infants: clinical screening in a large prospective cohort. AIDS. 2003;17(12):1769-1785. Available at http://www.ncbi.nlm.nih.gov/pubmed/12891063.
- Spector SA, Saitoh A. Mitochondrial dysfunction: prevention of HIV-1 mother-to-infant transmission outweighs fear. AIDS. 2006;20(13):1777-1778. Available at http://www.ncbi.nlm.nih.gov/pubmed/16931943.
- Cade WT, Waggoner AD, Hubert S, Krauss MJ, Singh GK, Overton ET. Reduced diastolic function and left ventricular mass in HIV-negative preadolescent children exposed to antiretroviral therapy in utero. AIDS. 2012;26(16):2053-2058. Available at http://www.ncbi.nlm.nih.gov/pubmed/22874520.
- Hernandez S, Moren C, Lopez M, et al. Perinatal outcomes, mitochondrial toxicity and apoptosis in HIV-treated pregnant women and in-utero-exposed newborn. AIDS. 2012;26(4):419-428. Available at http://www.ncbi.nlm.nih.gov/pubmed/22156962.
- Jitratkosol MH, Sattha B, Maan EJ, et al. Blood mitochondrial DNA mutations in HIV-infected women and their infants exposed to HAART during pregnancy. AIDS. 2012;26(6):675-683. Available at http://www.ncbi.nlm.nih.gov/pubmed/22436539.
- Kirmse B, Hobbs CV, Peter I, et al. Abnormal newborn screens and acylcarnitines in HIV-exposed and ARV-exposed infants. Pediatr Infect Dis J. 2013;32(2):146-150. Available at http://www.ncbi.nlm.nih.gov/pubmed/22935866.
- Kunz A, von Wurmb-Schwark N, Sewangi J, et al. Zidovudine exposure in HIV-1 infected Tanzanian women increases mitochondrial DNA levels in placenta and umbilical cords. PLoS One. 2012;7(7):e41637. Available at http://www.ncbi.nlm.nih.gov/pubmed/22848552.