María Rosa Agosti

Epidemiological and Molecular Evidence of Two Events of Father-to-Child HIV Type 1 Horizontal Transmission

HIV-1 infection in children less than 15 years of age is mainly due to mother-to-child transmission. The aim of this work was to investigate molecular evidence to prove father-to-be horizontal transmission in two possible events of transmission. In the first event a boy was identified as HIV infected at 2-3 years of age. At the same time infection was confirmed in the father, while mother and siblings were negative. In the second event a girl was negative for HIV at age 1 and identified as HIV-1 infected at age 6. The fathers HIV infection was diagnosed in the same period while the mother was repeatedly negative. No evidence of sexual assault or transfusion was recorded in any case. Peripheral blood mononuclear cells were obtained from both fathers and children. After PCR amplification, the C2V3 region of the envelope gene and the region coding for amino acid 132 of p24 up to amino acid 40 of p7 of the gag gene were sequenced. Genetic distance measurements and phylogenetic tree analysis showed that in both cases the fathers and childs viral sequences were closely related. They were distinct when compared to Argentina sequences including sequences from the same geographic region. Epidemiological and molecular data strongly suggest that horizontal transmission had occurred, probably related to the close father-to-child contact.

Evaluation of minority populations of HIV type-1 with K103N and M184V drug resistance mutations among children in Argentina.

BACKGROUND The aim of this study was to describe the frequency of minority populations of viruses carrying mutations K103N and M184V in drug-naive HIV type-1 (HIV-1)-infected children, and to further evaluate their effect on the selection of drug-resistant viruses within highly active antiretroviral therapy (HAART). METHODS Newly diagnosed vertically HIV-1-infected children were evaluated. The HIV-1 pol gene was sequenced for subtyping and antiretroviral drug resistance analysis. Standard genotypic sequencing and sequence-selective real-time PCR (SPCR) to quantify minority viral populations were used. RESULTS From December 2004 to July 2006, we included 35 children who were studied at baseline and during their first HAART regimen (follow-up median time 29.4 months). Of them, 82.9% were infected with intersubtype B/F recombinant variants. At baseline, all children had a drug-susceptible viral population that was studied by bulk sequencing. SPCR showed that 4 children had between 2-10% of M184V, 11 had <0.7%, 18 had no detectable mutation and 2 could not be amplified. No K103N minority populations were found. Once under HAART, children who had 2-10% of M184V at baseline further selected it in percentages >20% in less time than those with -0.1-0.6% or without minority populations (P=0.01). CONCLUSIONS It was shown that having 2-10% of M184V at baseline enhanced its selection in high percentages in a short time after HAART initiation. Further research regarding the presence of minority quasispecies before initiation of HAART in large paediatric populations should be undertaken to evaluate their clinical effect during HAART.

Two cases of mother-to-child transmission of HIV and Trypanosoma cruzi in Argentina

Since numerous tropical pathogens lead to opportunistic infections in the context of the human immunodeficiency virus (HIV), coinfection could have significant effects on the course of HIV infection. 1 In this article we report two cases coinfected with HIV and Trypanosoma cruzi presenting unfavorable evolution despite correct treatment. Both patients were infected with both pathogens by mother-to-child transmission (MTCT) route, and both died due to a Klebsiella pneumoniae sepsis. Case 1: Child 1 was admitted to the Central Childrens Hospital in La Plata at age 1 month with respiratory difficulty and diarrhea. The patient was a preterm newborn with good weight for the gestational age, with no prenatal care. Both parents were illiterate, and were living with HIV for a year but without treatment, including during pregnancy. The father was an intravenous drug abuser, and had been incarcerated; a 2-year-old brother was HIV-negative but an elder sister had died of HIV/acquired immunodeficiency syndrome (AIDS). Chagas infection in the mother was probably congenital, since her mother emigrated from a high endemic zone. The child presented severe malnutrition and congenital heart disease (interventricular communication). The child started with shortness of breath and diarrhea with a 48-hour evolution, and also presented bilateral inguinal and cervical micropoliadenopaty, splenomegaly, thrush, hypoxemia, and opisthotonus position. Disturbances in the cerebrospinal fluid cell count became apparent and Streptococcus pneumoniae was cultivated. Therefore, the patient was received ceftriaxone at appropriate doses for meningitis treatment for ten days, and an erythrocyte transfusion was performed. Vaccination with DPT-HB-Hib and Salk was indicated. During hospitalization, he presented two episodes of seizures related with fever. Serologies for several pathogens were performed, and antibodies for T. cruzi, Toxoplasma gondii, Epstein-Barr virus (EBV), and HIV were detected. HIV infection was confirmed by polymerase chain reaction (PCR), and T. cruzi infection, by Microstrout (both infections were confirmed in at least two separate samples). Electroencephalography (EEG) and cerebral computed tomography (CT) were abnormal, with muscular hypertonia and opisthostonus, both bilateral clonus and positive Babinsky. The symptoms were interpreted as brain damage due to pneumococcocal meningoencephalitis. At the age of six months, he was released after 155 days in hospital. Then, at the age of 22 months, he presented with diarrhea and sepsis by K. pneumoniae with secondary dehydration. The patient died ten days later; he had been treated with zidovudine since delivery and for two months with combined HAART (lamivudine, stavudine, nelfinavir) and benzonidazol. Three resistance tests …

High frequency of belated HIV diagnoses in pediatric population in Buenos Aires, Argentina

Background The ready availability of HIV prevention, testing and treatment services has lowered HIV mother-to-child transmission (MTCT) rates to less than 2% in high-income countries. Argentina has laws that guarantee universal and free antiretroviral therapy (ART) to every HIV-infected person and makes the offering of an HIV test to every pregnant woman mandatory. In spite of this, HIV MTCT is still present. The aim of this report is to call the attention of general paediatricians of belated HIV diagnoses in children.