To the Editors:
We read the article of Millar et al1 on the diagnosis of a child infected with HIV. In their report, a female child was defined to be infected with HIV at 5 months of age based on >107 copies/mL of plasma HIV RNA. At 19 hours of age, this child showed borderline HIV positive in a total nucleic acid PCR point-of-care test on whole blood. While this child did not show positive results in detecting HIV RNA in her plasma and in HIV total nucleic acid PCR on dried blood from first day to 3 months age, the authors diagnosed the infection acquired in utero, based on the findings of detectable HIV cell-associated DNA at day 1 and at day 10 of age respectively and the homology of HIV gag sequences between the child and mother. However, we consider that the results should be interpreted with caution. It is more likely that this child acquired infection intrapartum or after birth, rather than in utero, because of following reasons.
First, an established in utero infection of HIV is characterized with persistent HIV positive ever since birth. But this child showed HIV negative in various tests at least during the first 3 months of life.
Second, virginal delivery can increase maternal cells and other components in fetal cord blood through mother-to-fetus transfusion during delivery caused by repetitive, strong uterine contractions.2 Since this child was virginally delivered, during which maternal cells and other components, including HIV, were able to enter into fetus. This may explain that this child was borderline positive for HIV at 19 hours age, and had detectable, but relatively much lower, HIV cell-associated DNA after birth. These HIV-positive markers were derived from the mother, but not produced by the child; at that moment, the child was exposed to, but not yet infected with HIV. This is similar to mother-to-child transmission of hepatitis B virus (HBV); the presence of HBV DNA in umbilical cord blood or circulation of neonates just indicates exposure to, but not infection with HBV.3 Passive-active immunoprophylaxis can protect absolute majority of neonates with cord blood positive HBV DNA against HBV infection.3 Unfortunately, immunoprophylaxis against HIV is not yet available.
Third, this baby received exclusive breast-feeding, while her mother had HIV RNA level 12,000–212,000 copies/mL. But prophylaxis with antiretroviral therapy (ART) in this child was stopped after 3 months age. Breast-feeding can increase mother-to-child transmission of HIV. Infants on receiving ART prophylaxis should continue prophylaxis for 1 week after breast-feeding is fully stopped.4
Fourth, the homology of HIV sequences between the child and mother can validate mother-to-child transmission, but cannot demonstrate in utero infection.
Finally, maternal ART, in combination with elective cesarean section, neonatal ART prophylaxis, and avoidance of breast-feeding, can reduce the transmission <1%,5 indicating that mother-to-child transmission mostly occurs intrapartum and/or postnatal close contacts, and true in utero infection should be rare.
Haiqin Lou, MD
Department of Mass Health Care, Nantong Municipal Maternal and Child Health Hospital, Nantong 226018, Jiangsu, China
Yi-Hua Zhou, MD, PhD
Departments of Laboratory Medicine and Infectious Diseases, Nanjing Drum Tower Hospital and Jiangsu Key Laboratory for Molecular Medicine, Nanjing University Medical School, Nanjing 210008, Jiangsu, China
1. Millar JR, Mvo Z, Bengu N, et al; Ucwaningo Lwabantwana Consortium Group. Increasing diagnostic uncertainties in children with in utero HIV infection. Pediatr Infect Dis J. 2019;38:e166–e168.
2. Masuzaki H, Miura K, Miura S, et al. Labor increases maternal DNA contamination in cord blood. Clin Chem. 2004;50:1709–1711.
3. Liu J, Xu B, Chen T, et al. Presence of hepatitis B virus markers in umbilical cord blood: exposure to or infection with the virus? Dig Liver Dis. 2019;51:864–869.
4. World Health Organization. Guideline updates on HIV and infant feeding. 2016. Available at: https://www.ncbi.nlm.nih.gov/books/NBK379872/pdf/Bookshelf_NBK379872.pdf
Accessed August 17, 2019.
5. Selph SS, Bougatsos C, Dana T, et al. Screening for HIV infection in pregnant women: updated evidence report and systematic review for the US preventive services task force. JAMA. 2019;321:2349–2360.