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

12th World AIDS Conference

Abstracts 12158-12162 43

12158 Improved outcome of patients with CMV retinitis after
adoption of 1996 IAS-USA recommendations
Pedro Cahn1, Hector Perez1, C. Ochoa1, M. Vazquez', S. Puente',
M. Callegar2, R. Glancszpigel2, C. Zala3. 1Infectologia-Hospital Fernandez,
Angel Peluffo 3932 (1181), Buenos Aires; 2Edyabe SA, Buenos Aires;
3Fundacion Huesped, Buenos Aires, Argentina
Objectives: To assess clinical outcome of patients with CMV retinitis in the era
of HAART.
Patients and Methods: Charts review from all patients with CMV retinitis
diagnosed at the Ophthalmology Clinic and followed at the Infectious Diseases
Unit in a tertiary Hospital since protease inhibitors (PIs) became available in
Argentina. Since Jun 96 antiretroviral therapy was prescribed according to the
1996 IAS-USA Recommendations. SQV, RTV and IDV were available to this
cohort. A random sample of patients (n:91) diagnosed with CMV retinitis prior
to PIs were in place, were also analyzed with regard to survival and time free
of relapse (Group B). Standard therapy with Ganciclovir and/or Foscarnet were
administrated to all study subjects following local therapeutic guidelines. Survival
and free survival times were estimated using Kaplan Meier method.
Results: From Jun 96 to Dec 97 a total of 43 patients (15 women) were
identified. Mean follow up was 331.1 days (30-761). The median of survival time
from a diagnosis of CMV retinitis was 519.4 days ~ 70.0 (196.0 ~ 19.2 for Group
B). 10/43 (23%) patients relapsed while receiving PIs. Median ~ SE time free of
relapse since inititation of a PIs based regimen was 243.4 ~ 38.8 days. (Group
B: 141.0 ~ 15.2 days)
Conclusion: In this cohort, introduction of Pis based regimens seems to prolong survival and time free of active CMV retinitis, however, a significant number
of patients will ultimately relapse.
S12159 Congenital HIV and Chagas' disease: Case report
Omar Atilio Marin, Maria Beatriz, E. Bogdanowicz, G. Reboredo. AV Cordoba
2351 Piso3 Sala 2 CAp. Fed., Infectious Disease Unit-Mtal. Clinican Buenos
Aires, Argentina
Description of the case: A 3 month preterm bronchodisplasic infant was admitted to the hospital due to respiratory distress and sepsis syndrome. His mother
had lived in a rural area until she was fourteen, was an IV drug abuser and was
seropositive for Chagas disease (IgG 1/32) and toxoplasmosis (1/512). She had
an uncontrolled pregnancy. The children was born with a weight of 1080g, Apgar
score of 4 and 7/10. Soon after birth, he turned poorly responsonive, letargic,
hypotonic, with enlargement of the liver and spleen, with vitreal hemorrhage,
retinopathy episodes of sudden apneas, tachypnea, cyanosis and hypoglycemia
and hyperbilirrubinemia. The chest radiograph showed diffuse intersticial bilateral
infiltrates. A diagnosis of sepsis was made and started treatment with ceftriaxone plus gentamicin, but failed to respond to multiple antimicrobials. Hematologic
findings were leucocytosis, thrombocytopenia and anemia. Antibody test for Toxoplasma, Rubella, CMV and HSV were negative. The CT scan showed hypodensity
of ventricles wich appeared dilated and alteration of basal ganglia with microcalcifications. The 2D echocardiography revealed moderate anterior pericardial
effusion and persistent ductus arteriosus. Auditory evoked potentials showed
severe compromise of central origin. CSF pressure was high, with mononuclear
pleocytosis and low levels of glucose. The direct examination and Giemsa stain
showed circulating trypomastigotes. The number of parasites per ml. of blood
was 250,000 (microhematocrit test). Treatment with benznidazole 10 mg/kg/d was
started. The sreening for HIV yielded positive ELISA, WB and PCR in peripheral
blood). CD4 360//l. His condition worsened and died on the 18th hospital day
Both parents were HIV positive.
Conclusions: The aim of this case report is to show the clinical presentation
of congenital HIV and Chagas disease, for wich there should be a high level of
suspicion present, especially in areas where hte disease is endemic
121601 Mortality and neoplasms of HIV-1 infected children:
Long-term follow-up of pediatric AIDS Clinical Trials
Group (PACTG) participants (PACTG 219)
James Oleske', M.T. Brady2, S. Lee3, M.G. Fowler", B. Cunningham5,
M. Culnane4, L.M. Mofenson6. University of Medicine of New Jersey, Newark
NJ; 2Ohio State University, Columbus, OH; 3Harvard School of Public Helath,
Boston, MA; 4Division of AIDS NIAID, Bethesda, MD; 5Statistical & Data
Management Center, Amherst, NY; 6NICHD, rockville, MD, USA
Following completion of PACTG perinatal and therapeutic clinical trials, 2,163
children (including 289 uninfected children from perinatal trials) have been enrolled for long-term follow-up (to age 21 years or death) to assess HIV- and
treatment-related outcomes. As of 11/1/97 (median duration of follow-up = 23.6
months), there were 168 deaths [162 (10%) of 1627 in therapeutic trials and
6 (1.1%) of 536 in perinatal trials]. Prior to 5/96, the mean age at death was
6.4 years. The mean age of death for the last 48 children (after 5/96) was 7.4
years. The primary causes of death were: infections - 103 (62%); non-infectious

- 58 (34%); unknown -7 (4%). The most common infections that contributed to
death (primary/secondary) were: Mycobacterium avium-intracellulare (MAI) - 48;
invasive bacterial - 18; invasive Candida - 15; Pneumocystis carinii pneumonia
(PCP) - 12; and cryptosporidium - 8. Nonspecific pneumonias occurred in 32.
Common non-infectious contributing factors were: HIV encephalopathy - 29;
wasting syndrome - 29; and cardiomyopathy - 27. Median of the last CD4+ cell
count of the children who died was 18 (mean = 140 ~ 322; range: 0 - 1722). A "Do

Not Resuscitate" notification was made prior to death in 37 of the 168 children; 28
of these children died at home. There were 9 neoplasms identified (non-Hodgkin's
lymphoma - 2; Burkitt lymphoma - 2; B cell lymphoma - 2; Hodgkin's lymphoma
- 1; thymoma - 1; leiomyosarcoma - 1); all HIV-related. Five (55%) contributed
to the child's death. There were no deaths or neoplasms among HIV-uninfected
children who received zidovudine perinatally. Except for two cases of pancreatitis,
antiviral drugs were not implicated as a contributor to mortality.
Conclusion: Opportunistic infections, particularly MAI and invasive bacterial,
still play a prominent role in the demise of HIV-infected children. Encephalopathy, wasting, and cardiomyopathy, the most common non-infectious diagnoses,
contributed significantly to mortality of participants in PACTG 219. Neoplasms
are not common, but when present may contribute to death. For the perinatal
group, no apparent relationship was found between mortality or neoplasm with
investigational drug.
112161 ] Prevalence of congenital CMV in children born to
HIV-infected women
Jesus Saavedra Lozano, J.T. Ramos Amador, A. Bodas, V. Rodriguez-Cerrato,
J. Ruiz-Contreras, J. Otero. 'Pediatrician MD, Hospital 12 de Octubre DPTO
Pediatria CTRA de Andalucia Km.5, 4, 28041 Madrid, Spain
Background: The rate of congenital cytomegalovirus (CMV) infection in infants
born to HIV-infected women is unknown.
Objectives: 1) To determine the rate of congenital transmission of CMV in perinatally HIV-exposed children and 2) to evaluate possible risk factors associated
with congenital CMV infection in this population.
Patients and Methods: We prospectively studied the cohort of children born
to HIV-infected women between 1987-1997. Newborn CMV urine cultures were
scheduled at birth and serially thereafter. Congenital CMV infection was defined
as a positive CMV culture obtained during the first 3 weeks of life. We only
analyzed the cohort of children born at our hospital followed from birth.
Results: Ten children out of 156 born to HIV-infected mothers had a congenital
CMV infection (transmission rate 6.4%, CI 95: 3.3-11.1%). CD4 cell counts and
viral load were not different between transmitting and nontransmitting mothers.
We found a significant association between duration of rupture of obstetric membranes and both CMV-infection and HIV-infection. Overall 21 children (13.5%)
became HIV-infected. Five (23.8%) of these 21 children were diagnosed with congenital CMV infection, whereas only 5 (3.7%) of 135 children who seroreverted
had a congenital CMV infection (p = 0.005; Fisher exact test)
Conclusions: The prevalence of congenital CMV infection in children born
to HIV-infected women between 1987-1997 in our hospital was 6.4%, higher
than the prevalence in the general population in our setting. Univariate analysis
showed an association between perinatal transmission of HIV and CMV. Whether
CMV is an independent risk factor for HIV -transmission or not remains to be
elucidated.
12162 Role of CCR5 chemokine receptor gene in vertical HIV-1
transmission and disease progression
Nicola Principi1, Susanna Esposito1, C. Colasante2, G.V. Zuccotti3, G. Ferraris4,
M. Clerici5, L. Galli6, M. Galli3. 'Pediatric Dept. 4 University of Milan, Milan;
2Infect Dis Dept. 5 University of Milan, Milan; 3Pediatric Dept. 5 University of
Milan, Milan; 4Maternal Infant Center USSL 75/1 Milan; 51mmulogy Dept., Milan;
6Pediatric Dept. 3 University of Milan, Milan, Italy
Background: In adults, a 32-nucleotide deletion (CCR5del32) within the gene
encoding CCRS, the co-receptor for macrophage-tropic strains of HIV-1, has been
associated with protection from parenterally and sexually transmitted infection if
present on both alleles and with a more benign pattern of disease progression if
present on one of the two alleles
Objectives: To analyse the polymorphism of CCR5 gene in HIV-1 vertically
infected and HIV-1 vertically exposed but uninfected children in order to define
the role of CCR5del32 in perinatal HIV-1 transmission and disease progression.
Methods: CCR5 sequences were amplified by polymerase chain reaction
(PCR) from DNA of peripheral blood mononuclear cells. Samples from 208
Caucasian children, of whom 83 were HIV-1 vertically infected and 125 were
perinatally HIV-1 exposed but uninfected, were tested for the detection of the 32
base-pair deletion.
Results: CCR5de132 heterozygous condition was represented in 9.6 and 10.4%
of HIV-1 vertically infected and HIV-1 exposed but uninfected children, respectively. None was homozygous for CCR5de132 allele. Mothers of heterozygous
children did not seem to have been preferentially infected by a specific route
(42.9% heterosexual, 57.1% drug users). No differences were observed between
HIV-1 infected children with and without CCR5de132 as regards clinical manifestations of disease, pattern of disease progression, degree of immunosuppression,
and level of viral load.
Conclusions: CCR5de132 does not confer any absolute protection against
vertical transmission of HIV-1 infection and disease progression, suggesting that
both CCR5 is not essential as a co-receptor for vertically transmitted infections,

and that infection may advance independently of the presence of a functional
CCR5 co-receptor. More accurate analyses on the interaction between the virus
and its cellular receptors are needed to better define the factors that play the
main role in perinatal HIV-1 transmission and disease progression.