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

394 Abstracts 23265-23269

12th World AIDS Conference

Conclusion: HCV infection is high in thalassemic patients. Blood transfusion
appears to be an important way for HCV infection. HIV is absent. HIV infection
still an uncommon infection in EGYPT.
462* /232651 Risk factors for perinatal HIV transmission in
women/infants receiving standard zidovudine
(ZDV) prophylaxis
John Lambert1, L. Mofenson3, E.R. Stiehm7, J. Bethel6, W. Meyer2,
P. Reichelderfer4, G. Nemo5. 1Inst. Human Virology, UMD-Baltimore, Room
S521, 725 W Lombard St., Baltimore; 2Quest Diagnostics, Baltimore, MD;
3NICHD-NIH, 4NIAID-NIH, 5NHLBI-NIH, Rockville; 6WESTAT, Incorp., Rockville,
MD; 7UCLA, Los Angeles, CA, USA
Background: Determining factors associated with perinatal transmission in the
presence of antenatal/intrapartum/neonatal ZDV prophylaxis (which is now standard in the US) may permit development of improved preventive interventions to
further reduce transmission.
Methods: Risk factors were evaluated in 473 infected pregnant women enrolled in perinatal trial PACTG 185 [comparing efficacy of ZDV+HIV hyperimmune
globulin (HIVIG) vs ZDV+IVIG]; all mother/infant pairs received standard ZDV
prophylaxis. Infant infection was determined by serial HIV culture through age 6
months. Stored plasma HIV RNA level was evaluated by NASBA assay.
Results: In univariate analyses, entry CD4 [p =.016; Odds Ratio (OR) 0.59
per 100 cell increment (T)] & HIV culture titer (IUPM) (p =.04; OR 1.7 per 1 log T)
& HIV RNA (per 1 log T) both at entry (p =.003; OR 3.8) & delivery (p =.005; OR
3.3) were associated with transmission. Delivery IUPM, study arm (HIVIG/IVIG),
gestational age, delivery mode, duration of membrane rupture & birthweight were
not associated with transmission. 11% of women with entry CD4 in the lowest
quartile (<210/mm3) transmitted compared to 3% with CD4 in the other quartiles
(p =.001). 12% of women with entry RNA in the highest quartile (>4.6 log)
transmitted compared to 2% in the other quartiles (p =.002). Transmission was
0% (0/48) for delivery RNA <500 (below the level of detection of the assay) vs 5%
for >500 (p =.10). In multivariate logistic regression models including (entry CD4
count, IUPM, & RNA} or {delivery IUPM & RNA}, only RNA remained significantly
associated with transmission (at entry: p =.03, OR 2.8; at delivery: p =.003, OR
4.2).
Conclusions: Our results suggest that in women already receiving ZDV prophylaxis, attempts to reduce maternal viral load to <500 copies/mL may further
reduce perinatal transmission. The effect of maximal RNA suppression by newer
potent antiretroviral regimens on perinatal transmission should be evaluated.
456*/ 23266 Late postnatal mother-to-child transmission (LPT)
of HIV-1: International multicentre pooled analysis
Valeriane Leroy1, M.L. Newell2, F. Dabis1, C. Peckham2. 1/nserm U. 330,
Bordeaux 2, 146 rue Leo Saignat 33076, Bordeaux, France; 2lnstitute of Child
Health, London, United Kingdom
Background: Understanding the risk and timing of mother-to-child transmission
of HIV-1 in the postnatal period is important for the development of public health
strategies to reduce vertical transmission of HIV in the developing world.
Methods: An international multicentre pooled analysis of individual data from
prospective cohort studies of children born to HIV infected mothers followed from
birth.to estimate the rate of LPT of HIV. All children diagnosed as uninfected
by HIV DNA PCR and/or HIV serology were enrolled. LPT was considered to
have occurred if a child subsequently became infected. Duration of follow-up for
each child was calculated from the time of negative diagnosis to the date of the
last laboratory follow-up, or for cases to the mid-point between the date of last
negative and first positive results.
Results: Fewer than 5% of the 2807 children enrolled in 4 cohorts from industrialized countries (USA, Switzerland, France and Europe) were breastfed and
no case of LPT was diagnosed. In constrast, there were 49 cases of LPT in 902
children enrolled in 4 cohorts from developing countries, where breastfeeding
was the norm (Rwanda [2], Ivory Coast, Kenya), yielding an overall estimated
risk of LPT of 3.2 per 100 child-years of breastfeeding, with similar estimates in
individual studies. Exact information on timing of infection and breastfeeding was
available for 20 of the 49 LPT cases. Depending on assumptions about the timing
of LPT in the interval between tests, LPT would have occurred in a minimum of
none and a maximum of 2 cases if breastfeeding had ceased at 4 months, and 3
or 4 if breastfeeding had ceased at 6 months of age.
Conclusion: The similarity in estimated risk of LPT between studies strengthens the reliability of the overall estimate, which shows that breastfed children
born to HIV positive mothers are at substantial risk of LPT. This risk should be
balanced against the effect of early weaning on infant mortality and morbidity and
maternal morbidity and fertility.
23267 Sustained release antiviral implants for the prevention of
maternal transmission of HIV in the developing world: In
vitro release studies

Jianbing Chen, H. Guo, T. Smith, P. Ashton, R. Shimizu. Control Delivery
Systems, 86 Rosedale Rd, Watertown, MA, USA
Objectives: To reduce the incidence of maternal transmission of HIV in the
developing world by developing a sustained release antiviral Norplant-like device
which will provide therapeutic antiviral blood levels for a period of one year. If

breast feeding is to take place, as is advocated in many countries, then such
a prolonged period of therapy may be necessary. It has been established that
antiviral therapy with zidovudine reduces maternal transmission of HIV. We hypothesize that dideoxycytosine (ddC), which uses active transcellular transport
and therefore requires much lower dosing, may also prevent transmission. We
are testing this hypothesis in the feline immunodeficiency model of maternal
transmission. Antiviral efficacy and toxicity are also being tested. We describe
here the in vitro experiments which forms the basis for this work.
Design: Laboratory study: in vitro release, sterilization and stability studies.
Methods: We designed and manufactured a polymer based sustained release
implant for the antiviral ddC using technology similar to that we developed for
ganciclovir in the VitrasertTM system. In vitro release rates were measured and
the polymer coatings modified to give the appropriate release. The effect of
sterilizing the implants was studied and stability studies have been initiated.
Results: Devices were constructed in order to have the external dimensions
of the Norplant birth control device. These devices released at 1.8 ~ 0.2 mg. per
day (mean ~ s.d.). The devices contain 600 mg. of drug and thus release drug for
330 ~ 30 days. Sterilizing the devices had no effect on release rates and stability
studies to date have shown no breakdown of the drug or polymers.
Conclusion: Maternal antiviral therapeutic levels for about one year can be
achieved from a single therapeutic intervention. This device can be inexpensively
manufactured and could be part of a practicable program to reduce maternal
transmission of HIV in developing countries.
Supported in part by SBIR grants R44EY-11316 & R43AI 36548 from the
National Institutes of Health.
1461 */23268 Association between placental malaria infection
and increased risk of mother-to-infant
transmission of HIV-1 in western Kenya
Richard Steketee1, Bernard Nahlen2, J. Ayisi3, A. Van Eijk3, J. Otieno3,
A. Misore3, M. Rayfield3, K. Udhayakumar4. 11600 Clifton road N.E. E46 (CDC)
Atlanta Georgia 30333; 2CDC DHAP-SE Atlanta GA; 4CDC Atlanta GA, USA;
3Kenya Medical Research Institute Kisumu, Kenya
Background: Malaria and HIV-1 are common infections in reproductive-age
women in sub-Saharan Africa. In Malawi, infants born to HIV(+) women with
placental malaria infection had a 3.4-fold increased risk of post-neonatal death
compared with infants born to HIV(+) women without placental parasitemia,
suggesting that placental malaria infection may promote mother-to-infant HIV
transmission. In August 1996 we began a prospective study to assess this
possible interaction in western Kenya.
Methods: Between August 1996 and September 1997, consecutive pregnant
women attending an antenatal clinic in Kisumu, Kenya, were counseled and
offered HIV testing (CT). At delivery placental blood smears were examined for
malaria parasitemia, and infants born by spontaneous vaginal delivery to asymptomatic HIV(+) mothers were enrolled into the study. Infants were seen monthly
for a clinical exam, or more frequently for intercurrent illness. Infant HIV DNA-PCR
was drawn at 2, 3, and 6 months.
Results: Among 2976 pregnant women who received CT, 790 (26.5%) were
HIV(+). Overall, 18.2% (277/1521) of women had placental malaria infection, and
HIV(+) women had higher rates of placental malaria than HIV(-) women (OR
2.06, 95% CI 1.55-2.73). Preliminary results of the 365 infants with follow-up
indicate that infants born to HIV(+) mothers with placental malaria infection are
more likely to be PCR(+) within the first 3 months of life compared with infants
born to mothers without placental parasitemia, although the difference in HIV
transmission rates does not yet attain statistical significance.
Conclusions: HIV-1 and malaria are common in pregnant Kenyan women.
Preliminary results indicate that HIV(+) women are at increased risk for malaria,
and placental malaria may infant HIV transmission. A safe, cost-effective strategy
to prevent placental malaria is available and may reduce mother-to-infant HIV
transmission in malarious areas. Updated results from this study will be presented.
171*/ 23269 Implementation of recommendations for the
medical care of HIV-exposed infants in the first
year of life, USA
Jeanne Bertolli1, R.J. Simonds1, P. Thomas2, S. Melville3, I. Ortiz4, L. Mascola5,
C. Wilfert6, T. Rakusan7, H. Hsu8, Y. Maldonado9. 1Div. HIV/AIDS Prevention,
Centers for Disease Control, 1600 Clifton Road, Atlanta, GA; 2New York City
Department of Health, New York, NY; 3 Texas Department of Health, Austin, TX;
4Puerto Rico Department of Health, Rio Piedras, PR; 5Los Angeles Country
Health Department, Los Angeles, CA; 6Duke University, Durham, NC; 7Childrens
National Medical Center, Washington, DC; 8 University of Massachusetts,
Worcester, MA; 9Stanford University, Stanford, CA, USA
Background: Current standard of care in the US is to give zidovudine (ZDV)
to HIV-infected women in pregnancy and labor and to their newborns (full 076
Rx) to prevent perinatal HIV transmission; prophylaxis against Pneumocystis
carinii pneumonia (PCP) is recommended for all HIV-exposed children at age
4-6 weeks.

Methods: Data were collected retrospectively from the medical records of
1145 children born to HIV-infected women in 1995 and enrolled in the Pediatric
Spectrum of HIV Disease Project (PSD) in eight US sites. We compared risk of
HIV infection and PCP diagnosis among children receiving full 076 Rx and PCP
prevention, respectively. HIV infection status was determined using of viral and
antibody detection tests.