Background: The role of maternal autologous neutralizing antibody (ANAB) in perinatal HIV transmission and disease progression is controversial. Some, but not all, studies have shown a protective effect of ANAB on perinatal transmission and there is limited data on the role of ANAB in disease progression in perinatally infected infants.

Methods: As part of a prospective study of perinatal HIV transmission, we studied 21 transmitting (T) mother/infant pairs and 17 non-transmitting (NT) mothers who did not receive ZDV. Sequential samples of virus/serum/cells were collected in mothers during gestation and at delivery and in infected infants at birth and q2 wks to 6 months and q3 mos to 5 yrs. The timing of transmission was defined as in utero (IU) or intrapartum (IP) by the presence/absence of HIV at birth and infants were characterized as rapid (RP) intermediate (IP) or slow progressors (SP) based clinical and lab criteria. ANAB titers were determined by PBMC assay against titrated autologous HIV stocks. HIV env gene diversity was measured by HMA.

Results: We found that only 2/14 (14%) of IU vs 6/7 (86%) of IP transmitters had ANAB > 20 at delivery (p ≤ 0.01). In contrast ,12/17 (73%) non-transmitters had ANAB > 20 at delivery (p ≤ 0.01). Five (5) out of 6 IP transmitting mothers could also neutralize their infant’s first isolate. ANAB in infected infants with rapid (n = 6), intermediate (n = 3) or slow progression (n = 6) was assessed against first infant isolates and concurrent virus over time. Infants with rapid progression had NAB titers < 20 against past and concurrent virus. Infants with intermediate progression showed no ANAB for 6 months (mos) but increasing ANAB against past and concurrent isolates by 1 yr. In contrast, SP showed NAB against transmitted virus < 3 mos with enhanced ability to produce ANAB to past and concurrent virus over time.

Conclusions: Mothers who transmit in utero are significantly less likely to have ANAB to their own virus or their infants first isolate and their infected infants are more likely to be rapid progressors. The fact that virus can be transmitted intrapartum despite the presence of ANAB and mothers can more often neutralize their infant’s isolates suggest different mechanism of transmission. The ability to produce ANAB by infants also correlated with the rate of disease progression and viral diversity. Taken together, these data suggest that ANAB has a protective role in both transmission and disease progression in infants.