MATERNAL IMMUNE RESPONSES AND RISK OF INFANT INFECTION WITH HIV-1 AFTER A SHORT COURSE ZIDOVUDINE IN A COHORT OF HIV-1 INFECTED PREGNANT WOMEN IN RURAL KENYA

Objective: To investigate the effects of short-course nucleoside reverse transcriptaseinhibitor (Zidovudine, ZDW/AZT) on maternal immune responses and risk of infantinfection with HIV-1 among rural-based mothers in western Kenya.Design: A prospective cohort study involving HIV-1 seropositive pregnant mothers andtheir infants.Subjects: One hundred and seven HIV-1 seropositive asymptomatic pregnant womenand their infants.Methods: After informed consent, the women were enrolled at gestation age between16-24 weeks. For cultural and economic reasons, all mothers were allowed to breastfeed their infants. Short-course antepartum regime of AZT was administered to allmothers starting at 36 weeks gestation until start of labour. Maternal absolute CD4+T cell subset assays were performed before 3rd trimester (about 36 weeks gestation)and after a 4-week therapy of AZT (at least one month post-nuptially). Infant HIV-1 status was determined by HIV-1 DNA polymerase chain reaction (PCR) on samplessequentially taken at 1, 2, 3, 4, 6 and 9 months and confirmed by serology at 18 monthsof age.Interventions: Antepartum short-course orally administered AZT: 300mg twice-dailystarting at 36 weeks gestation until start of labour, 300mg at labour onset and 300mgevery three hours during labour until delivery.Main Outcome Measures: Maternal CD4+ T cell counts before and after AZT treatment.Determination of infant HIV-1 infection status.Results: Among 107 women sampled, only 59 received full dose of AZT and thus qualifiedfor present analysis. Of these, 12 infected their children with HIV, while 47 did not.Comparison of CD4+ T cells before and after AZT treatment scored a significant risein all mothers (P = 0.01). This increase in CD4+ T cells was not significant amongmothers who infected their infants with HIV-1 (P = 0.474). However, a significant risein CD4+ T cells following AZT therapy was observed only in mothers who did nottransmit HIV-1 to their infants (P=0.014).Conclusion: These data suggest that a rise in the CD4+ T cell counts following shortAZT regimen, now widely in use in resource-weak countries, may be evidence of theactive suppression of the replication of HIV. However, further studies to examine themulti-factorial effect of CD4+ lymphocytes and pregnancy on MTCT of HIV need tobe carried out to help fully explain the effect of AZT on immune response and whetherthe CD4+T cell count can be used as a true test of immunological normalisation duringantiretroviral therapy

MATERNAL IMMUNE RESPONSES AND RISK OF INFANT INFECTION WITH HIV-1 AFTER A SHORT COURSE ZIDOVUDINE IN A COHORT OF HIV-1 INFECTED PREGNANT WOMEN IN RURAL KENYA

ABSTRACTObjective: To investigate the effects of short-course nucleoside reverse transcriptaseinhibitor (Zidovudine, ZDW/AZT) on maternal immune responses and risk of infantinfection with HIV-1 among rural-based mothers in western Kenya.Design: A prospective cohort study involving HIV-1 seropositive pregnant mothers andtheir infants.Subjects: One hundred and seven HIV-1 seropositive asymptomatic pregnant womenand their infants.Methods: After informed consent, the women were enrolled at gestation age between16-24 weeks. For cultural and economic reasons, all mothers were allowed to breastfeed their infants. Short-course antepartum regime of AZT was administered to allmothers starting at 36 weeks gestation until start of labour. Maternal absolute CD4+T cell subset assays were performed before 3rd trimester (about 36 weeks gestation)and after a 4-week therapy of AZT (at least one month post-nuptially). Infant HIV-1 status was determined by HIV-1 DNA polymerase chain reaction (PCR) on samplessequentially taken at 1, 2, 3, 4, 6 and 9 months and confirmed by serology at 18 monthsof age.Interventions: Antepartum short-course orally administered AZT: 300mg twice-dailystarting at 36 weeks gestation until start of labour, 300mg at labour onset and 300mgevery three hours during labour until delivery.Main Outcome Measures: Maternal CD4+ T cell counts before and after AZT treatment.Determination of infant HIV-1 infection status.Results: Among 107 women sampled, only 59 received full dose of AZT and thus qualifiedfor present analysis. Of these, 12 infected their children with HIV, while 47 did not.Comparison of CD4+ T cells before and after AZT treatment scored a significant risein all mothers (P = 0.01). This increase in CD4+ T cells was not significant amongmothers who infected their infants with HIV-1 (P = 0.474). However, a significant risein CD4+ T cells following AZT therapy was observed only in mothers who did nottransmit HIV-1 to their infants (P=0.014).Conclusion: These data suggest that a rise in the CD4+ T cell counts following shortAZT regimen, now widely in use in resource-weak countries, may be evidence of theactive suppression of the replication of HIV. However, further studies to examine themulti-factorial effect of CD4+ lymphocytes and pregnancy on MTCT of HIV need tobe carried out to help fully explain the effect of AZT on immune response and whetherthe CD4+T cell count can be used as a true test of immunological normalisation duringantiretroviral therapy