Evidence for extended age dependent maternal immunity in infected children: mother to child transmission of HIV infection and potential interventions including sulfatides of the human fetal adnexa and complementary or alternative medicines.

Abstract

The two neighboring southwestern states of India, Karnataka and Maharashtra, have high incidence of HIV/AIDS and are among the six most high prevalence HIV infected states. In Karnataka state, the northern districts of Bagalkot, Belgaum and Bijapur (the three Bs) and in Maharashtra state, the southern districts of Sangli, Satara, and Solapur (the three Ss) are the areas with the highest incidence of HIV/AIDS. We have evaluated the incidence of maternal to child transmission (MTCT) of HIV-1 infection in Belgaum District which is more than 500 kilometers distance by road from the campus in greater Bangalore (Karnataka State). We have obtained the prenatal CD4 counts of HIV infected pregnant mothers. We have also screened the HIV infected children in two orphanages (rehabilitation centres for HIV infected children) in Belgaum District. The clinical conditions of these infected children were assessed for their CD4 counts, anti-retroviral therapy (ART) intake status, outpatient illnesses and body composition. We have observed that there is an influence of the age factor on the CD4 counts of the HIV infected children. Further, in view of the role of our recently found involvement of sulfatide, 3-O- galactosylceramide, in inhibition of HIV-1 replication and enhancement of hematopoiesis which is otherwise inhibited due to such infection, we have discussed the possible role of sulfatides that biologically occur in the fetal adnexa (placentatrophoblasts /amnion/chorion-umbilical cord), in containing HIV infection as a potential safer alternative to the ART regimens currently approved to be clinically practiced. Lastly, we have discussed the complementary and alternative medicine (CAM) therapies such as evidence based yoga and ayurveda as add-on to ART in potential elimination of MTCT of HIV infection. Out of a total of 150 children delivered by HIV infected mothers, 13 children were found to be positive as determined by the dried blood smear (DBS) for virological testing, giving an incidence of about 8.66% in the Belgaum district during the last two years, in spite of the prescription of currently available ART regimens. All the 13 HIV-transmitting mothers had normal vaginal deliveries. Though 12% of the total 150 deliveries required lower segment caesarean section (LSCS), none among them resulted in MTCT of HIV. Comparison of the prenatal CD4 counts between transmitting and non-transmitting mothers did not show significant differences (p=0.25) thus suggesting indirectly that HIV-1 proviral loads (undetermined / unavailable) need not necessarily determine the fate of incidence of vertical transmission. The mean age of 44 HIV infected children (14 females, 30 males) that were screened in two orphanages was 10.8±3.1 years. Out of these 44 children, 27 were taking ART (61.36%) with mean duration of consumption being 2.8±2.28 years. Fifty percent (n=22) of the children were suffering from at least one outpatient illness, out of which 13 were taking ART. Their mean basal metabolic rate (BMR), body mass index (BMI), muscle mass, fat mass and fat % were 795.45±106.9, 14.55±1.9 kg/m(2), 9.54±3.4 kg, 3.69±2.24 kg and 15.04±7.8% respectively. Comparison between the children taking ART (on-ART, n=27) and those not taking ART (non-ART, n= 17) showed that though there was no significant difference in the average age of the two groups, on-ART children had significantly higher BMR (p=0.05), and muscle mass (p=0.004), than non-ART. The CD4 counts, BMI, fat mass and fat percentage did not show significant statistical differences between the two groups. The CD4 counts of the children (both on-ART and non-ART) of age 8 years and below (n=12) were found to be significantly higher (p=0.04) than those of age 14 and above (n=10). All the children in age group of 14 years and above (n=10) except one child were on ART, whereas 7 out of 12 children in age group of 8 years and below were on-ART. In one of the rehabilitation centers called Aadhar, among non-ART children, a significant correlation was observed between the age of the child and CD4 counts (measured separately in the months of June 2011 and December 2011). Both the CD4 counts measured in June 2011 (n=6; r=-0.82, p= 0.04) as well as in December 2011 (n=6; r=-0.97, p=0.001) showed a significant decline as the age progressed. Also, at the same center, among on-ART children, the CD4 counts in June 2011 (n=7) and December 2011 (n=8) were significantly different between the children in the age group of 8 below years, and those in the age group of 14 years and above (p= 0.005). As HIV infected children grow in age, they may lose maternal derived immunity as shown by the decrease in CD4 counts, irrespective of their ART status. It is to be expected from these results that the conferred maternal immunity (possibly primarily humoral and secondarily cytotoxic immune responses) to the virus acquired at child birth taper off and eventually overcome by the generation of mutant HIV strains in the children, as the life spans of the infected children progress. We have discussed safer therapeutic interventions whose efficacy on HIV/AIDS may be synergistic to or even substitute the existing treatment strategies. Some of such interventions may even be customized to help eliminate MTCT. Further, these virus infected pregnant mother patient blood / serum samples could prove useful in the vaccine development against HIV infection.