Background:  Determining the infection status of newborns exposed to HIV is critical for the clinical management of both mother and infant, particularly in parts of the world where breastfeeding is critical to infant survival.

Methods:  In a study designed to explore virological and immunological parameters associated with perinatal transmission of SHIV-SF162P3 in Macaca nemestrina, we examined viral replication and de novo antibody responses in newborn macaques. This virus produces high acute viremia and variable post-acute viremia with no rapid CD4⁺ T cell loss in adult in 17 of 18 juvenile M. nemestrina infected intravenously.

Results:  Of 4 newborns exposed orally to this R5 virus, 3 experienced rapid loss of CD4⁺ T cells and high, unchecked viremia. This pattern was also seen in a newborn that acquired infection during gestation. In marked contrast, 3 infants born to viremic, SHIV-infected dams were virus-negative on the day of birth but subsequently had virologic and/or immunologic evidence for infection and undetectable virus after a few weeks. Phylogenetic analysis of env sequences in dams and infants showed that the infant infected in utero had rapid viral evolution; analysis of gut and lymphoid tissues in this infant confirmed env sequence divergence of 1.7 to 2.2% from the inoculum. In infants with highly controlled viremia, the transmitted virus was <1% divergent from the inoculum. Examination of tissues from the gut and mucosa of infants using limiting dilution nested multiplex PCR to detect and quantify SHIV gag and nef DNA showed <1 copy per million cells. Despite the paucity of virus, macaques had de novo IgG responses to Env gp120 and gp41 and developed neutralizing antibodies detectable after the decay of passively acquired maternal IgG.

Conclusions:  Mechanisms accounting for low-level viral persistence in these neonates are presently unclear. A minority of adults exposed repeatedly to HIV can remain seronegative; in some cases these exposed seronegative individuals have HIV-1 DNA persisting in resting CD4⁺ T cells at levels below the detection limit of conventional PCR assays. Maternal IgG could contribute to rapid viral control, although at least some of the infant transmitted envs in pseudotyped virus are resistant to maternal neutralizing antibodies. Understanding the control of SHIV infection in newborn macaques at such low levels has implications for lentiviral pathogenesis and potential vaccine strategies to limit breast-milk transmission.