Liliana Martinez Peralta

Two HIV-1 epidemics in Argentina: different genetic subtypes associated with different risk groups.

Summary: This study determined the risk behaviors and viral subtypes of HIV‐1 found in 134 heterosexual HIV‐seroprevalent maternity patients, 41 of their sexual partners (men who have sex with women [MSW]), and 95 homosexual men (men who have sex with men [MSM]) from Buenos Aires, Argentina. Peripheral blood mononuclear cells (PBMCs) were purified from blood and used for DNA extraction, amplification, and genotyping by the envelope heteroduplex mobility assay (env HMA). Most of the women had been infected by having sex with an already infected partner (84%), whereas most of the male partners had been infected via drug use (76%). Both the patients and their sexual partners were poorly educated, only 30% having completed secondary school. The MSM study subjects, however, were significantly better educated and had a lower prevalence of injecting drug use. Env HMA subtype F was found in 77% (103 of 134) of the maternity patients, with similar rates in their partners (73%). Most of the remaining samples were env subtype B. All but one of the couples was concordant in subtype. In the MSM risk group, however, only 10% were env HMA subtype F. Ninety percent of the MSM samples were subtype B. There are at least two independent epidemics of HIV‐1 infection in Buenos Aires, Argentina. One, in heterosexual men and women, is dominated by env subtype F whereas the other, in homosexual men, is dominated by env subtype B, as determined by env HMA.

High Seroprevalence of Bloodborne Viruses among Street-Recruited Injection Drug Users from Buenos Aires, Argentina

Injection drug use is the main mechanism of human immunodeficiency virus (HIV) transmission in Argentina (40% of reported AIDS cases in Argentina). This study was conducted among street-recruited injection drug users (IDUs) from Buenos Aires, with the aim of estimating seroprevalence and coinfection of HIV, hepatitis B virus (HBV), hepatitis C virus (HCV), and human T-lymphotropic viruses (HTLVs). A total of 174 volunteers participated in this study; 137 were men (78.7% of volunteers). The average age of the participants was 30 years. Only 64 of participants (37%) had no viral infection, whereas 110 (63%) were infected with > or =1 viruses. Seroprevalences were 44.3% for HIV, 54.6% for HCV, 42.5% for HBV, 2.3% for HTLV-I, and 14.5% for HTLV-II. Among the 77 HIV-infected persons, only 6.5% (5 persons) were not coinfected with other viruses; 88.3% (68) were coinfected with HCV and 68.8% (53) were coinfected with HBV. We demonstrated the existence of multiple viral infections with a high rate of prevalence in IDUs in Buenos Aires, Argentina.

Intersubtype BF recombinants of HIV-1 in a population of injecting drug users in Argentina.

Summary:The presence of recombinant intersubtypes of HIV-1 in Argentina has been reported since the mid-1990s. In this study, sequences of a region of the gag, pol, and vpu genes of HIV-1 were analyzed in samples of 21 injection drug users (IDUs) residing in the suburbs of the city of Buenos Aires. Genomic characterization and identification of recombination sites were made comparing the 3 regions with reference isolation sequences of subtypes B, F, C, A, and B/F recombinants: CRF12_BF and non-CRF12_BF sequences. Subtype assignment of the analyzed segments was phylogenetically confirmed. All the samples turned out to be BF recombinants in at least 1 of the 3 studied genes. Twelve samples (57%) had the same pattern as the Argentinean CRF12_BF, whereas in the rest, the pattern differed in at least 1 of the 3 genes. The relation of these fragments to the CRF12_BF was phylogenetically verified. These results indicate the predominance of BF recombinants and the presence of a high percentage of sequences closely related to the CRF12_BF in the IDU population in Argentina and suggest a possible association between viral variants and the transmission route.

Lack of viral selection in human immunodeficiency virus type 1 mother-to-child transmission with primary infection during late pregnancy and/or breastfeeding

Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) as described for women with an established infection is, in most cases, associated with the transmission of few maternal variants. This study analysed virus variability in four cases of maternal primary infection occurring during pregnancy and/or breastfeeding. Estimated time of seroconversion was at 4 months of pregnancy for one woman (early seroconversion) and during the last months of pregnancy and/or breastfeeding for the remaining three (late seroconversion). The C2V3 envelope region was analysed in samples of mother-child pairs by molecular cloning and sequencing. Comparisons of nucleotide and amino acid sequences as well as phylogenetic analysis were performed. The results showed low variability in the virus population of both mother and child. Maximum-likelihood analysis showed that, in the early pregnancy seroconversion case, a minor viral variant with further evolution in the child was transmitted, which could indicate a selection event in MTCT or a stochastic event, whereas in the late seroconversion cases, the mothers and childs sequences were intermingled, which is compatible with the transmission of multiple viral variants from the mothers major population. These results could be explained by the less pronounced selective pressure exerted by the immune system in the early stages of the mothers infection, which could play a role in MTCT of HIV-1.

Efficacy of strategies to reduce mother-to-child HIV-1 transmission in Argentina, 1993-2000.

&NA; This study evaluated the success of a national program for the prevention of mother‐to‐child transmission (MTCT) of HIV‐1 in 874 mother‐infant pairs from Buenos Aires and surroundings. This population was referred to the National Reference Center for AIDS for diagnosis of neonatal infection during 1993‐2000. The data revealed an increase in the use of antiretroviral therapy during pregnancy from 3.2% in 1993‐1994 to 73.1% in 1999‐2000 and in the use of cesarean delivery (reaching 54.8% in 1999‐2000). However, the proportion of HIV‐infected women who continued to breast‐feed their children remained steady (around 12%). General improvement of the conditions for decreasing MTCT resulted in a significant decrease in the proportion of infected infants from 37.3% before 1995 to 10.7% in 1999‐2000 and even 6.5% during 2001. Data on the time of diagnosis indicated that only 42.7% of the women knew about their HIV status before pregnancy, 44.8 knew during pregnancy, and 12.3% knew after the birth of their child. The main risk factor for HIV infection in the mothers was heterosexual contact (73%), and in the fathers, it was injection drug use (67%). These results point out the urgent need to develop additional strategies for prevention of MTCT of HIV‐1 to generalize education, counseling, and testing of young women.

Detection of HIV-1 dual infections in highly exposed treated patients

BackgroundGenetic characterization of HIV-1 in Argentina has shown that BF recombinants predominate among heterosexuals and injecting drug users, while in men who have sex with men the most prevalent form is subtype B.ObjectivesThe aim of this work was to investigate the presence of HIV dual infections in HIV-infected individuals with high probability of reinfectionStudy designBlood samples were collected from 23 HIV positive patients with the risk of reinfection from Buenos Aires. A fragment of the HIV gene pol was amplified and phylogenetic analyses were performed. Antiretroviral drug resistance patterns of all the sequences were analyzed.ResultsFive dual infections were detected with four patients coinfected with subtype B and BF recombinants and one patient was coinfected with two BF recombinants presenting different recombination patterns. Prolonged infection with a stable clinical condition was observed in the five individuals. Resistance mutation patterns were different between the predominant and the minority strains.ConclusionsOur results show that HIV dual infection can occur with closely related subtypes, and even with different variants of the same recombinant form in certain populations. Clinical observations showed neither aggressive disease progression nor impact on the resistance patterns in the dually-infected patients.

Inhibition of HIV-1 Replication in Human Monocyte- Derived Macrophages by Parasite Trypanosoma cruzi

Background Cells of monocyte/macrophage lineage are one of the major targets of HIV-1 infection and serve as reservoirs for viral persistence in vivo. These cells are also the target of the protozoa Trypanosoma cruzi, the causative agent of Chagas disease, being one of the most important endemic protozoonoses in Latin America. It has been demonstrated in vitro that co-infection with other pathogens can modulate HIV replication. However, no studies at cellular level have suggested an interaction between T. cruzi and HIV-1 to date. Methodology/Principal Findings By using a fully replicative wild-type virus, our study showed that T. cruzi inhibits HIV-1 antigen production by nearly 100% (p<0.001) in monocyte-derived macrophages (MDM). In different infection schemes with luciferase-reporter VSV-G or BaL pseudotyped HIV-1 and trypomastigotes, T. cruzi induced a significant reduction of luciferase level for both pseudotypes in all the infection schemes (p<0.001), T. cruzi-HIV (>99%) being stronger than HIV-T. cruzi (∼90% for BaL and ∼85% for VSV-G) infection. In MDM with established HIV-1 infection, T. cruzi significantly inhibited luciferate activity (p<0.01). By quantifying R-U5 and U5-gag transcripts by real time PCR, our study showed the expression of both transcripts significantly diminished in the presence of trypomastigotes (p<0.05). Thus, T. cruzi inhibits viral post-integration steps, early post-entry steps and entry into MDM. Trypomastigotes also caused a ∼60-70% decrease of surface CCR5 expression on MDM. Multiplication of T. cruzi inside the MDM does not seem to be required for inhibiting HIV-1 replication since soluble factors secreted by trypomastigotes have shown similar effects. Moreover, the major parasite antigen cruzipain, which is secreted by the trypomastigote form, was able to inhibit viral production in MDM over 90% (p<0.01). Conclusions/Significance Our study showed that T. cruzi inhibits HIV-1 replication at several replication stages in macrophages, a major cell target for both pathogens.

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.

The Tacaribe Complex

The Tacaribe complex of Arenaviridae is comprised of a group of 10 serologically cross-related viruses that are transmitted by rodents living in different geographic locations of the Western hemisphere from Florida to Argentina. So far, members of the Tacaribe group, also referred to as the New World arenaviruses, include Junin (the agent of Argentine hemorrhagic fever), Machupo (the agent of Bolivian hemorrhagic fever), Guanarito (the agent of Venezuelan hemorrhagic fever), and Pichinde, Tacaribe, Tamiami, Latino, Amapari, Flexal, and Parana viruses, none of which are currently known to be naturally infectious or pathogenic for humans (Howard, 1986).

FIRST REPORT OF HIV-2 INFECTION IN ARGENTINA

Described in this letter is the first reported case of HIV-2 in Argentina. The patient a 28-year-old Black woman was born in Guinea but spent most of her life in Senegal until emigrating to Buenos Aires Argentina in 1993 as a political prisoner. Her husband and two children remained in Senegal. In 1995 she gave birth to a baby fathered by a Senegalese man also living in Buenos Aires. An HIV test administered as part of a routine pregnancy work-up provided inconclusive results for HIV-1 but was positive for HIV-2. Repeat analysis at a Canadian laboratory where a different test was used revealed coinfection with HIV-1 and -2. The woman was asymptomatic. She reported no sexual contacts with Argentineans and her Senegalese partner returned to his country. She had not injected drugs or donated or received blood. Epidemiologic data suggest the infection was acquired either in Africa or from an African. This report should be considered as an alert of the onset of a new epidemiologic chain in South America with eventual autochthonous cases.