HIV Drug Resistance in Adults Initiating or Reinitiating Antiretroviral Therapy in Uruguay-Results of a Nationally Representative Survey, 2018-2019.

The first nationally representative cross-sectional HIV drug resistance (HIVDR) survey was conducted in Uruguay in 2018-2019 among adults diagnosed with HIV and initiating or reinitiating antiretroviral therapy (ART). Protease, reverse transcriptase, and integrase genes of HIV-1 were sequenced. A total of 206 participants were enrolled in the survey; 63.2% were men, 85.7% were >25 years of age, and 35.6% reported previous exposure to antiretroviral (ARV) drugs. The prevalence of HIVDR to efavirenz or nevirapine was significantly higher (OR: 1.82, p < 0.001) in adults with previous ARV drug exposure (20.3%, 95% CI: 18.7-22.0%) compared to adults without previous ARV drug exposure (12.3%, 11.0-13.8%). HIVDR to any nucleoside reverse transcriptase inhibitors was 10.3% (9.4-11.2%). HIVDR to ritonavir-boosted protease inhibitors was 1.5% (1.1-2.1%); resistance to ritonavir-boosted darunavir was 0.9% (0.4-2.1%) among adults without previous ARV drug exposure and it was not observed among adults with previous ARV drug exposure. Resistance to integrase inhibitors was 12.7% (11.7-13.8%), yet HIVDR to dolutegravir, bictegravir, and cabotegravir was not observed. The high level (>10%) of HIVDR to efavirenz highlights the need to accelerate the transition to the WHO-recommended dolutegravir-based ART. Access to dolutegravir-based ART should be prioritised for people reporting previous ARV drug exposure.

Analysis of human papillomavirus 16 E6, E7 genes and Long Control Region in cervical samples from Uruguayan women.

OBJECTIVE: This study aims to investigate the HPV16 variant distribution by sequence analyses of E6, E7 oncogenes and the Long Control Region (LCR), from cervical cells collected from Uruguayan women, and to reconstruct the phylogenetic relationships among variants. METHODS: Forty-seven HPV16 variants, obtained from women with HSIL, LSIL, ASCUS and NILM cytological classes were analyzed for LCR and 12 were further studied for E6 and E7. Detailed sequence comparison, genetic heterogeneity analyses and phylogenetic reconstruction were performed. RESULTS: A high variability was observed among LCR sequences, which were distributed in 18 different variants. E6 and E7 sequences exhibited novel non-synonymous substitutions. Uruguayan sequences mainly belonged to the European lineage, and only 5 sequences clustered in non-European branches; 3 of them in the Asian-American and North-American linage and 2 in an African branch. Additionally, 6 new variants from European and African clusters were identified. CONCLUSIONS: HPV16 isolates mainly belonged to the European lineage, though strains from African and Asian-American lineages were also identified. Herein is reported for the first time the distribution and molecular characterization of HPV16 variants from Uruguay, providing novel insights on the molecular epidemiology of this infectious disease in the South America. SYNOPSIS: A high variability among HPV 16 isolates mainly belonged to European lineage, provides an extensive sequence dataset from a country with high burden of cervical cancer.

Longitudinal analysis of HIV-1 BF1 recombinant strains in vertically infected children from Argentina reveals a decrease in CRF12_BF pol gene mosaic patterns and high diversity of BF unique recombinant forms.

The HIV-1 epidemic associated to BF1 recombinants in South America is both complex and intriguing, with an underestimated diversity of recombinant structures. Our aim was to explore the characteristics and temporal dynamics of the HIV-1 BF1 epidemic in Argentina, through the study of 172 HIV-1 pol BF1 recombinant sequences obtained from HIV-1 vertically infected patients born from 1986 to 2008. Recombination patterns were characterized by bootscanning, subtype signature analysis, and phylogenetic approaches. Proportion of sequences sharing common ancestry and recombination breakpoints with the Circulating Recombinant Form (CRF) CRF12_BF was compared against sequences with a non-CRF12_BF pattern in three study periods, and by fitting the data to a logistic model. Twenty-eight HIV-1 pol BF1 mosaic structures were identified, including four of the seven South-American CRF_BF-like patterns. However, common ancestry of these sequences with reference CRF strains only confirmed the presence of CRF12_BF (51.1%) and CRF17_BF (1.2%) among the Argentine BF pol sequences. Most non-CRF_BF-like recombinant patterns shared at least one common recombination breakpoint with CRF12_BF. The number of transmissions caused by CRF12_BF viruses decreased in a linear way over time, from 69% in the period 1986-1993 to 46% in 2001-2008. In conclusion, the diversity of HIV-1 pol BF1 recombinant structures in Argentina is much more complex than previously described, with at least two CRFs_BF and 26 BF1 unique recombinant forms. For the first time, we provide evidence of a decrease in the proportion of CRF12_BF viruses transmitted from mother-to-child since the start of the epidemic to the present time in Argentina.

Phylodynamics of HIV-1 circulating recombinant forms 12_BF and 38_BF in Argentina and Uruguay.

BACKGROUND: Although HIV-1 CRF12_BF and CRF38_BF are two epidemiologically important recombinant lineages circulating in Argentina and Uruguay, little is known about their population dynamics. METHODS: A total of 120 "CRF12_BF-like" and 20 "CRF38_BF-like" pol recombinant sequences collected in Argentina and Uruguay from 1997 to 2009 were subjected to phylogenetic and Bayesian coalescent-based analyses to estimate evolutionary and demographic parameters. RESULTS: Phylogenetic analyses revealed that CRF12_BF viruses from Argentina and Uruguay constitute a single epidemic with multiple genetic exchanges among countries; whereas circulation of the CRF38_BF seems to be confined to Uruguay. The mean estimated substitution rate of CRF12_BF at pol gene (2.5 x 10-3 substitutions/site/year) was similar to that previously described for subtype B. According to our estimates, CRF12_BF and CRF38_BF originated at 1983 (1978-1988) and 1986 (1981-1990), respectively. After their emergence, the CRF12_BF and CRF38_BF epidemics seem to have experienced a period of rapid expansion with initial growth rates of around 1.2 year-1 and 0.9 year-1, respectively. Later, the rate of spread of these CRFs_BF seems to have slowed down since the mid-1990s. CONCLUSIONS: Our results suggest that CRF12_BF and CRF38_BF viruses were generated during the 1980s, shortly after the estimated introduction of subtype F1 in South America (~1975-1980). After an initial phase of fast exponential expansion, the rate of spread of both CRFs_BF epidemics seems to have slowed down, thereby following a demographic pattern that resembles those previously reported for the HIV-1 epidemics in Brazil, USA, and Western Europe.

Serologic evidence of influenza A and B viruses in South American fur seals (Arctocephalus australis).

The aim of this work was to detect serologic evidence of influenza virus infections in South American fur seals (Arctocephalus australis) that inhabit the Uruguayan coast. In 29 of 37 serum samples that were analyzed, we identified antibodies to at least one of the following antigens: H1N1 (A/NewCaledonia/20/99), B/Beijing/184/93-like viruses, B/Hong Kong/330/01, and B/Sichuan/379/99 by means of the hemagglutination inhibition assay (HAI). Results confirmed that influenza A viruses circulate in marine mammals and also showed, for the first time, indirect evidence of influenza B infections in Arctocephalus australis.

Identification of a new HIV Type 1 circulating recombinant form (CRF38_BF1) in Uruguay.

Recombination has been shown to be an important force in HIV-1 evolution. Recombination contributes to an increase in genetic variation and hinders vaccine design efforts. Several molecular epidemiology studies in South America described the circulation of subtypes B, F, and C as well as several B/F1 recombinants. This study performed by nucleotide sequencing in at least two genes of 89 samples from Uruguay has shown a complex HIV-1 epidemic characterized by the cocirculation of subtype B, and subtype C strains, together with an important group of BF1 recombinant viruses, including isolates similar to CRF12_BF. In addition we identified a new circulating recombinant form, designated CRF38_BF(1), which was dominant in the recombinant virus group.

Influenza B viruses isolated in Uruguay during the 2002-2005 seasons: genetic relations and vaccine strain match.

Monitoring antigenic and genetic variations of circulating influenza viruses is critical for the selection of annual vaccine strains. In order to gain insight into the molecular evolution of Influenza B viruses (IBV) isolated in Uruguay in 2002 and 2005 outbreaks, antigenic and phylogenetic studies were carried out for the Hemagglutinin (HA) gene. Antigenic relations among Uruguayan and reference strains isolated elsewhere were performed by means of hemagglutination inhibition assays (HAI). Genetic relations of HA genes from Uruguayan as well as 41 IBV strains isolated elsewhere were established by means of the construction of phylogenetic trees. HAI assays showed a distant antigenic relationship among the 2002 Uruguayan isolates and the 2002 vaccine strain B/Sichuan/379/99. Phylogenetic analysis also revealed a distant genetic relationship among Uruguayan and 2002 vaccine strains. All 2005 IBV Uruguayan strains were both antigenically and genetically related to B/Victoria lineage-viruses. The results of these studies revealed that 2002 IBV Uruguayan strains have a distant antigenic and genetic relation with the 2002 IBV vaccine strain used in Uruguay. The high rate of susceptible individuals in the youngest cohort (<25 years) might be related to the fact that the B/Victoria lineage-viruses were not previously circulating in Uruguay.

Serologic evidence of human metapneumovirus circulation in Uruguay

First identified in 2001, the human metapneumovirus (hMPV), is a respiratory tract pathogen that affects young children, elderly, and immunocompromised patients. The present work represents the first serologic study carried out in Uruguay. It was performed with the purpose of obtaining serological evidence of hMPV circulation in Uruguay and to contribute to the few serologic reports described until now. Sixty nine serum samples collected between 1998 and 2001 by vein puncture from patients without respiratory symptoms or underlying pathology aged 6 days to 60 years were examined using an indirect immunofluorescence assay (IFA). The global seropositivity rate of the samples was 80 percent (55/69). Rates of 60 percent (15/25) and 91 percent (40/44) were observed for the pediatric and adult cohorts, respectively. Results obtained from a longitudinal analysis of 6 children aged 6 days to 18 months are discussed. These results are a clear evidence of hMPV circulation in Uruguay, at least since 1998, and reinforce the previous data on worldwide circulation of this virus.

Seroincidence and phylogeny of human immunodeficiency virus infections in a cohort of commercial sex workers in Montevideo, Uruguay.

A cohort study involving 60 human immunodeficiency virus (HIV)-negative male transvestite commercial sex workers (CSWs) was conducted in Montevideo, Uruguay in 1999-2001. Serum samples were tested for HIV by an enzyme-linked immunosorbent assay screening with immunoblot confirmation. Six participants seroconverted for an incidence-density rate of 6.03 (95% confidence interval = 2.21-13.12) per 100 person-years. Inconsistent condom use during client sex (adjusted hazard ratio [AHR] = 6.7), during oral sex (AHR = 5.6), and at the last sexual encounter (AHR = 7.8), and use of marihuana (AHR = 5.4) were marginally associated with HIV seroconversion. Five samples were genotyped in the protease and reverse transcriptase regions; three were subtypes B and two were BF recombinants. Full genome analysis of four samples confirmed all three subtype B samples and one of the two BF recombinants. Male transvestite CSWs sustained a high rate of HIV infection. Larger prospective studies are required to better define subtypes and associated sexual and drug-related risk factors.

Serologic evidence of human metapneumovirus circulation in Uruguay.

First identified in 2001, the human metapneumovirus (hMPV), is a respiratory tract pathogen that affects young children, elderly, and immunocompromised patients. The present work represents the first serologic study carried out in Uruguay. It was performed with the purpose of obtaining serological evidence of hMPV circulation in Uruguay and to contribute to the few serologic reports described until now. Sixty nine serum samples collected between 1998 and 2001 by vein puncture from patients without respiratory symptoms or underlying pathology aged 6 days to 60 years were examined using an indirect immunofluorescence assay (IFA). The global seropositivity rate of the samples was 80% (55/69). Rates of 60% (15/25) and 91% (40/44) were observed for the pediatric and adult cohorts, respectively. Results obtained from a longitudinal analysis of 6 children aged 6 days to 18 months are discussed. These results are a clear evidence of hMPV circulation in Uruguay, at least since 1998, and reinforce the previous data on worldwide circulation of this virus.

Antigenic and genetic variability of human respiratory syncytial viruses (group A) isolated in Uruguay and Argentina: 1993-2001.

The antigenic and genetic diversity of G glycoprotein from 25 human respiratory viruses (group A) isolated during nine consecutive epidemics (1993-2001) in Montevideo, Uruguay, and 7 strains isolated in Buenos Aires, Argentina, in the same period were analyzed. Genetic variability was evaluated by partial sequence of the G protein gene. Phylogenetic analysis indicated that most Uruguayan and Argentinean group A isolates clustered into three genotypes: GA5, GA2, and GA1. Some strains clustered into the GA3 genotype characterized previously. The antigenic analysis was carried out with a panel of anti-G monoclonal antibodies that recognized conserved and strain-specific epitopes. A close correlation between the antigenic and genetic relatedness of the strains analyzed was observed.

Evaluación de la quimioprofilaxis con zidovudine a la mujer embarazada VIH(+) y su hijo / Evaluation of zidovudine chemoprophylaxis in VIH (+) pregnant women and their son

En 1994 se publicaron los resultados del protocolo ACTG 076 sobre quimioprofilaxis (QP) con zidovudine (AZT) para reducir la transmisión vertical del VIH. El grupo de madres que recibió QP con AZT tuvo un porcentaje de transmisión de 8,4 por ciento, comparado con el 24,2 por ciento de los que recibían placebo. Material y métodos: Se analizaron en forma retrospectiva los datos de 304 binomios madre - hijo captados en la Policlínica materno-infantil del CHPR desde junio de 1990 al 31 de diciembre de 1998. Se definió QP completa cuando la mujer VIH(+) embarazada recibió AZT vía oral las primeras 6 semanas. Se definió QP incompleta, cuando faltaron una o dos fases del tratamiento. Los niños fueron clasificados como serorevertidos (S), infectados (I), o perinatalmente expuestos (E), según criterios del CDC. Resultados. Hasta el 31 de diciembre de 1994 se estudiaron 116 binomios madre - hijo, y el porcentaje de trasmisión vertical fue de 28,4 por ciento. En 1995, en 31 binomios, el porcentaje de transmisión fue 29,03 por ciento, ningún binomio recibió QP completa y 5 (15,6 por ciento) la recibieron en forma incompleta. En 1996, en 60 binomios, el porcentaje de transmisión fue 31,6 por ciento, 7 (11,66 por ciento) recibieron QP completa y 22 (36 por ciento) incompleta. En 1997, en 50 binomios, el porcentaje de transmisión fue de 12 por ciento, 26 (52,9 por ciento) recibieron QP completa 16 (31,3 por ciento) e incompleta. En 1998, en 47 binomios, el porcentaje de transmisión fue de 8,5 por ciento, recibieron QP completa 31 (65 por ciento) e incompleta 14 (29,78 por ciento). Analizados desde el 1 de enero de 1995, recibieron QP completa 64 binomios, el porcentaje de transmisión fue 31,6 por ciento, 7 (11,66 por ciento) recibieron QP completa y 22 (36 por ciento) incompleta. En 1997, en 50 binomios, el porcentaje de transmisión fue de 12 por ciento, 26 (52,9 por ciento) recibieron QP completa y 16 (31,3 por ciento) incompleta. En 1998, en 47 binomios el porcentaje de transmisión fue de 8,5 por ciento, recibieron QP completa 31 (65 por ciento) e incompleta 14 (29,78 por ciento). Analizados desde el 1 de enero de 1995, recibieron QP completa 64 binomios, el porcentaje de transmisión fue 6,25 por ciento. Recibieron QP incompleta 57 binomios, el porcentaje de transmisión fue 8,7 por ciento. El porcentaje de transmisión en los binomios que no recibieron QP fue de 43,2 por ciento...