Bridging the Gap: Conference Record [Abstract book, International Conference on AIDS (12th: 1998: Geneva, Switzerland)]

12th World AIDS Conference

Abstracts 23279-23282 397

23279 Induced /3-chemokine and cytokine response in
pregnant HIV-1 infected women and risk of perinatal
transmission
Kenneth C. Rich1, J.N. Siegel2, S.E. Leurgans2, A.L. Landay2. 1Dept Pediatrics,
Univ of Illinois, MC856 840 South Wood St, Chicago, IL 60612; 2Ruch Medical
College Chicago, USA
Objectives: To determine whether induced /-chemokine and cytokine responses
in pregnant women are associated with perinatal HIV-1 transmission to the infant.
Methods: Cryopreserved peripheral blood mononuclear leukocytes from the
third trimester of pregnant HIV-1 infected women enrolled in the Women and
Infants Transmission Study (WITS) were studied. Induced /f-chemokines and
Type 1 and Type 2 cytokine (IL2, IL4, IL10 and IFNy) concentration was assessed by ELISA of culture supernatant after stimulation with anti-CD3 or PHA.
These results and lymphocyte phenotypes, HIV-1 viral load by RNA PCR, and
concurrent antiretroviral therapy were examined for their association with transmission.
Results: Transmitting women had significantly lower PHA induced
/-chemokine and cytokine levels (pg/ml) than did non-transmitting women (*p <
0.05; 0.4 pg/ml = <level of detection). They also had higher CD8+% (p = 0.023)
and a trend towards higher expression of the activation marker CD8+HLA-DR+.
There was no relation between transmission and RANTES, CD4+%, antiretroviral
therapy, or viral load.

Uninfected infant
HIV-1 infected infant
Seronegative non-pregnant

n MIP l MIP 1~ IL2 IL4 IL10 IFNy
17 4062 3075 220 20 56 26
7 1416 980 60 0.4 5 0.4
7 9873 8001 578 53 737 75

Conclusions: Pregnant HIV-1 infected women with near normal /-chemokine
and cytokine responses were less likely to transmit HIV-1 to their infants than
those with lower concentrations. The maternal functional immune activity during
pregnancy may be an independent factor determining the risk of HIV-1 transmission to her fetus.
31 *23280 Study drug adherence and tolerance within a
randomized clinical trial to evaluate a short-course
regimen of zidovudine to reduce mother-to-child
transmission of HIV-1 in Abidjan, C6te d'lvoire
Ehounou Rene A. Ekpini1, T.S. Sibailly2, E. Boni-Ouattara2, A. Kamelan-Tano2,
I.M. Coulibaly3, C. Maurice2, M. Kouassi2, T.H. Roels4, A.E. Greenberg4,
S.Z. Wiktor4. '01 BP 1712, Abidjan 01; 2Projet Retro-CI, Abidjan; 3National
AIDS/STD/TB Control Program, Abidjan, Cote d'lvoire; 4Centers for Disease
Control and Prevention, Atlanta, USA
Objective: To evaluate adherence and tolerance to a self-administered prenatal
and intrapartum drug regimen by HIV-1-positive women enrolled in a randomized clinical trial to evaluate a short-course zidovudine (ZDV) regimen to reduce
mother-to-child transmission of HIV-1 in Abidjan, C6te d'lvoire.
Methods: Since April 1996, all consenting, eligible HIV-1-positive pregnant
women attending a public antenatal clinic in Abidjan are enrolled at 36 weeks
gestation and are randomized to receive either ZDV (300 mg tablets) or placebo.
Women are instructed to take I tablet of study drug twice daily until the onset of
labor, I tablet loading dose at the onset of labor, and then I tablet every three hours
until delivery. Study drug adherence (number of tablets taken/expected number)
is assessed by questionnaire and pill counts at biweekly prenatal visits and at
delivery, while tolerance to study drug is assessed by questionnaire, physical
examination and laboratory evaluation.
Results: To date, 272 HIV-1 seropositive women have been enrolled (mean
age 26 years, range 15-42). Among the 259 women who have delivered, the
median duration of prenatal drug regimen was 26 days (range 1-80 days). The
overall median study drug adherence during the prenatal period was 93% (range
29%-100%). The median duration of labor was 10 hours (range 1-44 hours);
11.6% of women delivered at home and 41% of women delivering in the clinic
spent <1 hour in the delivery room. 82.2% (63.3% for home and 87.6% for clinic
deliveries) of women took the loading dose at onset of labor. Median intrapartum
study drug adherence was 37% (10% for home and 43% for clinic deliveries),
while 17.4% of the women took no study drug during labor and only 5.4% took
all of the expected intrapartum dose. Tolerance to the drug regimen has been
excellent; with no permanent and only three temporary study drug interruptions
due to clinical or laboratory adverse events.
Conclusion: Adherence to self-administered oral study drug by HIV-1-infected
pregnant women is excellent during the prenatal period, is good for the oral
loading dose at the onset of labor, but relatively poor for the remainder of the
intraparturn period; while tolerance is excellent. If this ZDV regimen proves effective, it will be critical to gain a better understanding to the barriers to intrapartum
adherence.

123281 Antiretroviral use in pregnancy in PACTG 316: A phase III
randomized, blinded study of single-dose
intrapartum/neonatal nevirapine to reduce mother to
infant HIV transmission
Alejandro Dorenbum-Kracer1, J. Sullivan2, R. Gelber3, L. Mofeson4
M. Culnane1, C. Cunningham5, G. Brown6, K. Beckerman7, K. Dransfield8. 1505
3Harvard School of Public Health, Boston, MA; 4National Institutes of
Health-NICHD, Rockville, MD; 5Sunny-Syracuse, Syracuse, NY; 6Columbia
Presbiterian Medical Center, New York, NY; 7University of California, San
Francisco, San Francisco; 8Boehriner - Ingelheim Pharmaceuticals, Ridgefield,
CT, USA
Objective: PACTG 316 is a randomized, double-blind phase III trial to determine
if nevirapine (NVP) given to the mother during labor and to the neonate at age
48-72 hours can reduce mother to infant HIV transmission (MIT); women/infants
arc are randomized to receive NVP or placebo (PL). We evaluated antiretroviral
use during pregnancy in the context of this trial.
Methods: PACTG 316 enrolls HIV-infected pregnant women as of the 28 Th.
week of gestation. Women can receive any combination of antiretrovirals needed
for their own health including ZDV prophylaxis with the exclusion of non-nucleoside reverse transcriptase inhibitors; Thus, at enrollment, the antiretrovirals used
reflect the range of treatment modalities offered to HIV infected pregnant women
in multiple centers across the US. The sample size of 1,244 mother/infant pairs
has 80% power to detect a decrease in MIT from 5% in the PL arm to 2% in the
NVP arm. The study opened to enrollment in PACTG sites in the US in May 1997,
and will expand to European sites during 1998.
Results: Between May 13, 1997 and January 13, 1998, 148 women enrolled in
PACTG 316, 102 of whom have delivered. This report is based on the characteristics at entry for the 102 women who have delivered. Median age at enrollment
was 26 years and 85% were of minority race/ethnicity; 49% of women received
their initial diagnosis of HIV infection during the current pregnancy. Median entry
CD4 count was 424/ul. Delivery was by cesarean section in 29%. Antiretroviral,
therapy received during the current pregnancy was: ZDV alone in 29%; combination ZDV and 3TC in 46%; other combination nucleoside analogue regimens in
5%; and combination therapy including a protease inhibitor in 20%.
Conclusions: Antiretroviral use in PACTG 316 reflects the current therapy
received by HIV infected pregnant women during 1997; all women in this trial
received antiretroviral therapy and 71% were given combination therapy. However, at enrollment, only 20% of the pregnant women were receiving combination
therapy with a protease inhibitor; the recommended treatment for non-pregnant
adults with HIV infection in the US.
S23282 Prevention of perinatal transmission in the US:
A population-based evaluation of prevention efforts in 4
states
Pascale M. Wortley1, P.L. Fleming1, M.L. Lindegren', L. Dimasi2, N. Harris3,
H. Malamud4, S. Troxler5. 1Centers For Disease Control & Prevention 1600
Cliton RD. MS E-47, Atlanta GA, 30333; 2New Jersey State Department of
Health Trenton NJ; 3South Carolina Department Of Health Columbia SC;
4Detroit health Department Detroit MI; 5Louisiana Department Of Health New
Orleans LA, USA
Objective: To determine the change in proportion of HIV-infected pregnant women
tested for HIV before giving birth in 4 states (MI, NJ, LA, SC) between 1993 and
1996, and to determine what proportion of women received prenatal care (PNC)
and were offered zidovudine (ZDV).
Methods: States matched HIV/AIDS registries to birth registries to identify
mother-infant pairs and to review medical records. Mothers were considered to
have had an HIV diagnosis before delivery if their HIV test date preceded the
infant's date of birth. To estimate the 1993 proportion of pregnant HIV-infected
women diagnosed before delivery we used data from the 1993 seroprevalence
survey of childbearing women (SCBW) as the denominator. For 1996 we used
the last SCBW year available ('95 for MI and LA, '96 for SC). Because NJ has
experienced a significant decline in HIV-infected women giving birth over time,
we used a state 1996 estimate (linear extrapolation from 1989-95 results).
Results: The proportion of HIV-infected pregnant women identified before
birth in these 4 states increased from 68% (503/742) in 1993 to 80% (508/645) in
1996. One state consistently identified over 80% of HIV-infected pregnant women.
Among 436 women identified before birth whose charts have been reviewed to
date (265 for '93, 171 for '96), the proportion offered ZDV in pregnancy, intrapartum (IP), and neonatally increased from 28% to 91%, 5% to 82%, and 7% to
82%, respectively. Less than 4% refused treatment. In 1993 and 1996 combined,
13% and 22% of women had zero and 1-4 PNC visits. They were 5.0 and 1.5
times less likely to be offered ZDV, and were 3.4 and 2.1 times more likely to
report illicit drug use in pregnancy than women with >5 visits. In 1996, delivery
before or within 45 min. of admission accounted for 17/30 failures to receive IP
ZDV. Among 106 women tested after birth whose charts have been reviewed to
date, 70% had <5 PNC visits.

Conclusions: In 1996 a minimum of 80% of HIV-infected pregnant women in
4 these states were diagnosed with HIV infection before delivery, a conservative
estimate because of delays in complete matching, and the great majority of
women receiving some PNC were offered ZDV. Failure to receive adequate PNC,
however, remains a major barrier to full implementation of prevention measures.
Outreach must be strengthened to reach these women, both for their own care
and to prevent perinatal transmission.