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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
Abstract
ABSTRACT
Objective: To investigate the effects of short-course nucleoside reverse transcriptase
inhibitor (Zidovudine, ZDW/AZT) on maternal immune responses and risk of infant
infection with HIV-1 among rural-based mothers in western Kenya.
Design: A prospective cohort study involving HIV-1 seropositive pregnant mothers and
their infants.
Subjects: One hundred and seven HIV-1 seropositive asymptomatic pregnant women
and their infants.
Methods: After informed consent, the women were enrolled at gestation age between
16-24 weeks. For cultural and economic reasons, all mothers were allowed to breast
feed their infants. Short-course antepartum regime of AZT was administered to all
mothers 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 samples
sequentially taken at 1, 2, 3, 4, 6 and 9 months and confirmed by serology at 18 months
of age.
Interventions: Antepartum short-course orally administered AZT: 300mg twice-daily
starting at 36 weeks gestation until start of labour, 300mg at labour onset and 300mg
every 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 qualified
for 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 rise
in all mothers (P = 0.01). This increase in CD4+ T cells was not significant among
mothers who infected their infants with HIV-1 (P = 0.474). However, a significant rise
in CD4+ T cells following AZT therapy was observed only in mothers who did not
transmit HIV-1 to their infants (P=0.014).
Conclusion: These data suggest that a rise in the CD4+ T cell counts following short
AZT regimen, now widely in use in resource-weak countries, may be evidence of the
active suppression of the replication of HIV. However, further studies to examine the
multi-factorial effect of CD4+ lymphocytes and pregnancy on MTCT of HIV need to
be carried out to help fully explain the effect of AZT on immune response and whether
the CD4+T cell count can be used as a true test of immunological normalisation during
antiretroviral therapy.
Objective: To investigate the effects of short-course nucleoside reverse transcriptase
inhibitor (Zidovudine, ZDW/AZT) on maternal immune responses and risk of infant
infection with HIV-1 among rural-based mothers in western Kenya.
Design: A prospective cohort study involving HIV-1 seropositive pregnant mothers and
their infants.
Subjects: One hundred and seven HIV-1 seropositive asymptomatic pregnant women
and their infants.
Methods: After informed consent, the women were enrolled at gestation age between
16-24 weeks. For cultural and economic reasons, all mothers were allowed to breast
feed their infants. Short-course antepartum regime of AZT was administered to all
mothers 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 samples
sequentially taken at 1, 2, 3, 4, 6 and 9 months and confirmed by serology at 18 months
of age.
Interventions: Antepartum short-course orally administered AZT: 300mg twice-daily
starting at 36 weeks gestation until start of labour, 300mg at labour onset and 300mg
every 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 qualified
for 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 rise
in all mothers (P = 0.01). This increase in CD4+ T cells was not significant among
mothers who infected their infants with HIV-1 (P = 0.474). However, a significant rise
in CD4+ T cells following AZT therapy was observed only in mothers who did not
transmit HIV-1 to their infants (P=0.014).
Conclusion: These data suggest that a rise in the CD4+ T cell counts following short
AZT regimen, now widely in use in resource-weak countries, may be evidence of the
active suppression of the replication of HIV. However, further studies to examine the
multi-factorial effect of CD4+ lymphocytes and pregnancy on MTCT of HIV need to
be carried out to help fully explain the effect of AZT on immune response and whether
the CD4+T cell count can be used as a true test of immunological normalisation during
antiretroviral therapy.
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