Abstracts Vol. 1 [International Conference on AIDS (11th: 1996: Vancouver, Canada)]

Tu.C.441 - Tu.C.445

Tuesday, July 9, 1996

Tu.C.44 I
PERINATAL HIV TRANSMISSION RISK AND THE EFFECT OF PREGNANCY OR
INFANT ZIDOVUDINE USE IN A MULTICENTER STUDY, 1994-1995.
Steketee, Richard W. Simonds RJ, Abrams E, Nesheim S,Vink P Palumbo, P for the Penatia!
AIDS Collaborative Transmnission Study (PACTS), Centers for Disease Control and
Prevention, Atlanta, GA.
Objective: To determine risk factors for -perinatal HIV transmission (PHTi) anrd the impact of
zidovudine (ZDV) in pregnarincy (Preg: antenatal or intrapar turn) and/or earl Infrncy (Inf) in
a multicenter study during 199 1-1995.
Methods: Severn PACTS sites have enrolled HIVinfected pregnant women and their chil
dren in a prospective study of PH1. iData on maternal and infant characteristics including
Preg- and Inf ZDV use were collected. Infants testing positive twice by virologic tests (culture, DNA PCR, p24Ag) or by HIV antibody 5 months of age were considered infected
(HIV+); infants testing negative twce by virologic tests (1 test after 2 months of age) or
by HIV antibody were considered uninfected (HIV-). PHT rates for infants born in 1994 -199 were compired an o full,r talad non-users of ZDV while coniroling for
maternal and deiver ris charactt tstcs.
Results: A total of 269 HIV( )womer and their Infants had known PHT outcome; 101
(38%) received both Proeg ZDV anid Inf Z[)V 27 (I 0%) received only Preg- ZDV, 22 (8%)
received only Inf ZDV and t 19 (44%) rece ived no ZDV PHT rates were similar: 3.9%,
14.8%, 9.1%, and 14.3%, respectively. PHIT rates armon g mnother irnfant pairs receiving any
Preg-ZDV or any Inf ZDV were I14. 1% and I 3.070, respectively After adjusting for ZDV-use,
signiricant risk factors for PHT in this cohort included CD4 count <200 (RR=3.07,
95%C1= 1.32 7. 1i3) and rupture of membr anes (ROM) >4 hours (RR-2.16, 95%CI= I.12 -4.17). Compared to women without the characteristic, PHT was higher in women with
class-C disease (19% vs. I 3%, p=0.26) and in women with long use of Preg-ZDV (2! 8wks
vs.< 18wks: 18% vs: 8%, p0. I I). Amrong mother -infant pairs with a risk factor (low CD4
count or prolonged ROM), PHT rates did not differ by ZDVuse, however among those
without the above risks, those receiving Preg and/or Inf ZDV tended to have lower PHT
rates than non-ZDV users (7% vs 2%, p= 0.2).
Conclusion: In 1994 1995, penatal HFIV transmissiorn was low and similar among full-, partial- and non-users of ZDV. Materna and delivery characteristics persisted as risk factors
despite ZDV use. Additionrl studies to examine the ntical time of antiretroviral use to prevent pennatal transmission are warranted.
Dr Richard W Steketee, Mailstop ['E15, DHAP NCHSPP Centers for Disease Control and
Prevention, 1600 Clfton Rd, Atlanta, GA 30333, USA.Tel:[phone]; Fax [phone];
email: risl(rcidhivL em.cdc.ov
Tu.C.442
EFFECTS OF ZIDOVUDINE PROPHYLAXIS AND ELECTIVE CESAREAN SECTION
ON VERTICAL HIV TRANSMISSION
Kind, Chrstian fr the Swiss Neonal ItV Study GroupDi 'vDision of Neonatology,
Frauenklnik, Kantonssplti, CH-9007 St.Gallen, Switzerland
Objective: To deter mine the iropct o f rec ornmending zidovudine prophylaxis (ZDV) on
vertcal HIV tran.mir son n the context of mode of delivery and otherrisk f/rctors in an
ongoing natio /al cohort study
Methods: Up to [Dcerrer / st 1995, 143 chldren of HIV infected mothers were followed
up prospectvely from birth for at least 6 onths. Infection status was determined in 368 of
themn by concr ordanrt result of PCR and p24 antigen detection after heat medialed disruption
of immune corp exes in it least 2 samples taken after the age of I month. 62 were found to
be infected, giving a transmission rate (T R) of I 6.8%, 95%-confidence interval (CI) I 13.3 -19.5%.
ZDV was universally reconienrded forHIV positive pregnant women in Switzernd in mid
199'. Association of risk factor s withT R were investigated by univariate and multariate
(logistic reression) analysis. Odds rtlos (OR) with CI and X --tests were used.
Results: ZDV ias apphed in 45 c,e, I r (75% of ll Lregsterec pregnanes since mid 1994).
Infection status was knowr in 23 chidren,. 2 (8.7%) were infected (OR 0.35, CI 0.1 -1.98,
not significotn vs. no ZV) TR was freduced itfter elective cesarean section (FCS) with irntact
rserlbranes and withot previous labor: OR 0.35, 0.1 4 0.89, p < 0.05. Other factors
associated with (R were matern al I tiVelated sIrymptoms (OR 2.8, CI 1.5 92, p "< 0.01), a
history of abori (OR, P I.. p -0.01) and duration of pregnancy: 40 weeks
(OR 2.2, CI 1.1 7 p /( 5 n o tic /effectt of DV aid fCS are shown in the table.
/S r1>55 kCS risk difference for t C
ZDV 0,, (0',o, 1/1,1 (i 4.3%)' 14.31i
no ZU'V '/8 ( )'8 ") 1/260 (O0.l 12.2
risk Jnlfferitrce for Z.V 5.6 6 'N infected / N of chldrer (% infected)
Conclusions: Our pr elirinar y dat a are c ompatible with an additive protective effect of both
zidovudine prophylaxis rnd elective esre n sect on. A history of abortion and prolonged
pregnancy were found as new ptnltlai risk fctors associated with increased tranrsmission.
C. Kind, NeI-onato ro.. Frauek nik, K I ntorsspital, CH 9007 St. Gaen, Switzerland i
Telephone: '1 // 21 f r' Fa: H! 7t 26 28 8.
Tu.C.443
THE EFFECTIVENESS OF ORAL ZIDOVUDINE ADMINISTERED IN LATE
PREGNANCY IN LOWERING PLASMA AND CERVICOVAGINAL HIV-I VIRAL LOAD
IN HIV-INFECTED PREGNANT WOMEN IN ABIDJAN COTE D'IVOIRE
Wiktor Stefan Z 12, Ekpin ERI, ibal IlryS, Diaby LI, Brown T2, Fransen K3, Steketee R,
Coulibaly HLaga M Kahi M, treenbery AE l.3 Projet RETRO Cl, Abidian Cte
dlvo ire; fCC I Atlant. A USA; 3Niat on0DIS/STD/B Control Proyr-am, Abidjan, Cte
dIvoire;.t ITH, Antwverlp Belgium
Objective:-o freasur te If efecteness of oral zdovudne (ZDV) administered in late preg
ianc7 in lowenn plasmi and cericov gir HIV / viral load rn pregnant women in Abidan,
C~te d'Ivorre
Methods: In preparatort for a lre clic tal companun the efficacy of ZDV vs. placebo
administered late r lienani to rcle 'ri/erto child HIV-I transrnisson, pilot study is
beiny conducted to a /3ses ZDV tolera ce and its effect on HIVtI viral load Since October
1995, consenti p, c abre fIV infe ted preg at women attendiny a public antenatal clinic

in Abidjan were gi pve oral ZDV 250mg twice daily starting at about 36 weeks gestation followed by 500,,p ZDV oraly at onset of labor, 250mg ZDV orally every two hours until
delivery and n( ZDV after delivery Blood samples were drawn and cervicovaginal lavages
were done o t enrollmen and two weeks prenatally and blood samples were again drawn
two weeks p-ti ll C uanrtitative plasma HIVI viral load (PVL) was done by the NASBA
method (Orga 'n Teknik ) and is expressed in copies/ml or not detectable (ND).
Qualitative cervicoviginal vi ral load (CVL) was done by PCR testing of the lavage supernatant and is expressed as positive (P) or negative (N).
Results: Thus far; 15 HIV I positive women have been enrolled in the pilot study Data on
the first four womern who took ZDV for a median of 28 days (range 14-38) are available.

Visit
enrollment
2 weeks prenatal
delivery
2 weekspostnatal

Subjlect A
PVLCVL
6 1,000/N
25,000/N
21,000/na! 30,000/na

Subject B
PVL/CVL
4,700/N
2,500/N
2,600/na
na/na.

Subject C
PVL/CVL
98,000/P
39,000/N
na/na
na/na

Subject D
PVL/CVL
ND/N
ND/N
ND/N
ND/na

Conclusions:WiVthin two weeks of initiating oral ZDV PVL was reduced by approximately
50% in three women, and CVL became undetectable in the only woman in whom it was
detected at enrollment. In one woman, the postnatal PVL was more than twice the enrollment sample PVL. Follow up of these and other- women and their babies will enable us to
further explore the changes in viral load during and following ZDV therapy and to assess
the relationship between viral load and mother-to -child transmission of HIV-I.
Stefan Wiktor, 31 B.P 17 12, Abidjan 01, Cote d'Ivoire Telephone: [phone]
Fax: [phone]
Tu.C.444
ZIDOVUDINE TO DECREASE MOTHER-TO-CHILD TRANSMISSION OF HIV-I:A
PHASE II STUDY IN WEST AFRICA, 1995-1996 (ANRS 049A)
Dabis, Francois* Meda, N ", HMsellati, P **, Cartoux, M "**,Welffens- Ekra. C. Mandelbrot,
Lt*. INSERMP U. 330, Universite de Bordeaux II, Bordeaux (France) "* Centre Muraz, Bobo
Dioulasso (Burkna Faso) ** ORSTOPM Petit Bassam, Abidjan (Cote d'lvoire)( Centre
Hospitalier Urniversitaire de Yopougon, Abidjant Maternite Cochin - Pcrt Royal, Pas
Objectives: Zidovudne (ZDV) is now the gold standard to reduce mother-to-child transmission of HIV I in industrialzed countries.The applicability tolerance and efficacy of this
intervention deserve investigation in developing countries, assuming that it can be applied
to breast fed populations in a simple manner
Methods: A phase II tolerance and acceptability study of ZDV versus placebo has been
designed in two urban centers of West Africa: Abidjan (Cote d'lvoire) and Bobo Dioulasso
(Burkina Faso). After HIV testing and counsellng and in the absence of severe anemia
(hemoglobin >7g/dl), women who accept the principles of the trial are randomized and
treated starting at 37 weeks of gestation: ZDV 250 mg bid until delvery oral loading dose
of 500 mg at entry in the delivery room and 250 mg bid during the first week after dehivery The sample size is 2 x 75 pregnant women with HIV I or dual infection. Follow-up of
mothers and chidren is schleduled until 15 months after delivery/birth. Iron/folates supplementation is systenmatic.
Results: Acceptance of HIV test varies from 56 to 90% according to site. HIV screening has
been applied to 2800 pregnant womren, with an overall HIV prevlence of 12.1% (range:
9.5- 12.5%).The proportion of women returning for their test results varies from 45 to 80%.
As of January 2'7, 1996, 37 women have been enrolled in the trial. Compliance is good. No
severe neutropenia or increase in liver enzymes has been noticed during short-term follow up
(until 4 weeks post-paritum) and no side effect has been noticed in newborns. Both groups
combined, mean maternal HbI was 9. 6 g at entry It increased by 1.2 g at the end of the treatment period Inclusions and short termn follow-up will be completed by June 30, 1996.
Conclusions: Interventions requir ing HIV testing during pregnancy may be difficult to implement in Africa. for women who consenl, a sirmpol fied regimen of ZDV may be an acceptable
and safe intervention,
I. Dabis, INSERM U 330, Universite de Bordeaux II. 33076 Bordeaux (France)
Telephone: [phone] Fax: [phone] E ma ii vu330u- bordeaux2.fr
Tu.C.445
THE PHARMACOKINETICS OF 3TC ADMINISTERED TO HIV- I INFECTED WOMEN
(PRE-PARTUM, DURING LABOUR AND POST-PARTUM) AND THEIR OFFSPRING
Johnson A. 1,Goodwin C,Yuen GJ. Gray MD, Plumb R, *Coovadia Pro. H, *Pilay K,
*Moodley D, *Moodley Prof J, *"Saba J. Clinical Pharmacology Division, Glaxo Wellcome
plc, Greenford, UIK, Department of Obstetrics, Gynaecology and Paediatrics, University of
Natal, Durban, SA; **WHO), Geneva, Switzerland.
Objectives: Recently pubitshed data has shown that Retrovir given in pregnancy during
delivery and to the neonate can substantially reduce the transmissionr of HIV infection from
25.5% (placebo) to 8.3% [Connor EM e al 1994]. Comnbination of lamivudine (3TC) and
Retrovir, have demonstrated a greater effect on viral load and immunological markers than
either drug as monotherapy.
Methods: This study was designed to investigate the safety and pharmacokinetics of 3TC
alone (300mg bid ie. about 8mg/kg/day) and in combination with Retrovir ( 150mg bid 3TC,
300mg bid Retrovir), when given orally to pregnant women from week 38 of pregnancy,
through labour and up to I week post -birth. All neonates were dosed orally with 3TC
alone (8mg/kg/day) or in combination with Retrovir (8mg/kg/day) depending on what their
mother received duning pregnancy. Dosing of the neonates began 12 hours post-birth and
continued (bid) for I week. Samples of blood, amniotic fluid. vaginal secretions and breast
milk were taken as appropriate.
Results: Preliminary pharmacokinetic data are available from thirteen mothers and their
neonates (birthweight 2.7 3.7kg).The parameters of Clo, Cmax, AUC, tmax and t in preg
nant women are similar to those obtained in non-pregnant adults and exhibit proportionali
ty between low and high 3TC doses. 3TC freely crossed the placenta as the serum concentrnations at birth in mothe umrbilical cord and neonate are very similar Following birth,
maternal 3TC pharmacokinetics do not appear different from non-pregnant adults.
Neonates have immature organ function at birth, but the kidneys attain moderate function

249