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 transcriptase inhibitor (Zidovudine, ZDW/AZT) on maternal immune responses and risk of infant infection with HIV-1 among rural-based mothers in western Kenya.


METHODS
A prospective cohort study involving HIV-1 seropositive pregnant mothers and their infants.


METHODS
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.


METHODS
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.


METHODS
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).


CONCLUSIONS
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.
Makokha
E P
EP
Department of Immunology, Faculty of Health Sciences, Moi University, PO Box 4606, Eldoret, Kenya.
Songok
E M
EM
Orago
A A
AA
Koech
D K
DK
Chemtai
A K
AK
Kobayashi
N
N
Mpoke
S
S
Tukei
P M
PM
Andayi
F A
FA
Lihana
R W
RW
Adungo
N I
NI
Vulule
J M
JM
D000328:Adult; D019380:Anti-HIV Agents / Q000276:immunology* / Q000627:therapeutic use*; D001942:Breast Feeding; D018791:CD4 Lymphocyte Count; D005260:Female; D006679:HIV Seropositivity / Q000188:drug therapy* / Q000276:immunology* / Q000635:transmission; D015497:HIV-1; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control* / Q000706:statistics & numerical data; D007630:Kenya / Q000453:epidemiology; D008297:Male; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D011256:Pregnancy Outcome / Q000453:epidemiology; D011263:Pregnancy Trimester, Third; D011295:Prenatal Care / Q000379:methods*; D011446:Prospective Studies; D012307:Risk Factors; D012423:Rural Health / Q000706:statistics & numerical data; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology; D015215:Zidovudine / Q000276:immunology* / Q000627:therapeutic use*
D019380:Anti-HIV Agents; D015215:Zidovudine