Artículos de revista (Inst. Salud Tropical)
Permanent URI for this collectionhttps://hdl.handle.net/10171/52056
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- Current and historic HIV‑1 molecular epidemiology in paediatric and adult population from Kinshasa in the Democratic Republic of Congo(2020) Carlos-Chillerón, S. (Silvia); Holguín, Á. (África); Galán, J.C.; Rubio-Garrido, M. (Marina); González‑Alba, J.M. (José María); Barquín, D. (David); Reina, G. (Gabriel); Ndarabu, A. (Adolphe)HIV-1 diversity may impact monitoring and vaccine development. We describe the most recent data of HIV-1 variants and their temporal trends in the Democratic Republic of Congo (DRC) from 1976 to 2018 and in Kinshasa from 1983–2018. HIV-1 pol sequencing from dried blood collected in Kinshasa during 2016–2018 was done in 340 HIV-infected children/adolescents/adults to identify HIV-1 variants by phylogenetic reconstructions. Recombination events and transmission clusters were also analyzed. Variant distribution and genetic diversity were compared to historical available pol sequences from the DRC in Los Alamos Database (LANL). We characterized 165 HIV-1 pol variants circulating in Kinshasa (2016–2018) and compared them with 2641 LANL sequences from the DRC (1976–2012) and Kinshasa (1983–2008). During 2016–2018 the main subtypes were A (26.7%), G (9.7%) and C (7.3%). Recombinants accounted for a third of infections (12.7%/23.6% Circulant/Unique Recombinant Forms). We identifed the frst CRF47_BF reported in Africa and four transmission clusters. A signifcant increase of subtype A and sub-subtype F1 and a signifcant reduction of sub-subtype A1 and subtype D were observed in Kinshasa during 2016–2018 compared to variants circulating in the city from 1983 to 2008. We provide unique and updated information related to HIV-1 variants currently circulating in Kinshasa, reporting the temporal trends of subtypes/CRF/URF during 43 years in the DRC, and providing the most extensive data on children/adolescents.
- The BRCT domain from the homologue of the oncogene PES1 in Leishmania major (LmjPES) promotes malignancy and drug resistance in mammalian cells(2022) Peña-Guerrero, J. (José); Larrea, E. (Esther); Guruceaga, E. (Elizabeth); Fernández-Rubio, C. (Celia); Nguewa, P.A. (Paul Alain)Around 15% of cancer cases are attributable to infectious agents. Epidemiological studies suggest that an association between leishmaniasis and cancer does exist. Recently, the homologue of PES1 in Leishmania major (LmjPES) was described to be involved in parasite infectivity. Mammalian PES1 protein has been implicated in cellular processes like cell cycle regulation. Its BRCT domain has been identified as a key factor in DNA damage-responsive checkpoints. This work aimed to elucidate the hypothetical oncogenic implication of BRCT domain from LmjPES in host cells. We generated a lentivirus carrying this BRCT domain sequence (lentiBRCT) and a lentivirus expressing the luciferase protein (lentiLuc), as control. Then, HEK293T and NIH/3T3 mammalian cells were infected with these lentiviruses. We observed that the expression of BRCT domain from LmjPES conferred to mammal cells in vitro a greater replication rate and higher survival. In in vivo experiments, we observed faster tumor growth in mice inoculated with lentiBRCT respect to lentiLuc HEK293T infected cells. Moreover, the lentiBRCT infected cells were less sensitive to the genotoxic drugs. Accordingly, gene expression profiling analysis revealed that BRCT domain from LmjPES protein altered the expression of proliferation- (DTX3L, CPA4, BHLHE41, BMP2, DHRS2, S100A1 and PARP9), survival- (BMP2 and CARD9) and chemoresistance-related genes (DPYD, Dok3, DTX3L, PARP9 and DHRS2). Altogether, our results reinforced the idea ...
- HIV-1 diagnosis using dried blood spots from patients in Kinshasa, DRC: a tool to detect misdiagnosis and achieve World Health Organization 2030 targets(Elsevier, 2021) Carlos-Chillerón, S. (Silvia); Makonda, B. (Benit); Holguín, Á. (África); Fernández-Alonso, M. (Miriam); Rubio-Garrido, M. (Marina); Barquín, D. (David); Reina, G. (Gabriel); Ndarabu, A. (Adolphe)Introduction: Currently, only 54% of the population of the Democratic Republic of the Congo (DRC) know their HIV status. The aim of this study was to detect HIV misdiagnosis from rapid diagnostic tests (RDT) and to evaluate serological immunoassays using dried blood spots (DBS) from patients in Kinshasa, DRC. Methods: Between 2016 and 2018, 365 DBS samples were collected from 363 individuals and shipped to Spain. The samples were from people with a new HIV positive (n = 123) or indeterminate (n = 23) result, known HIV-positive patients (n = 157), and a negative control group (n = 62). HIV serology was performed using Elecsys HIV combi PT (Roche), VIDAS HIV Duo Quick (BioMérieux), and Geenius (Bio- Rad). In addition, HIV RNA detection was performed in all samples using the COBAS AmpliPrep/COBAS Taqman HIV-1 Test 2.0 (Roche). Results: Overall, 272 samples were found to be positive and 93 to be negative for HIV serology. The sensitivity was 100% for both Elecsys and VIDAS techniques, but specificity was slightly higher for the VIDAS test: 100% (96.1–100%) vs 98.9% (94.1–99.9%). Of the 23 indeterminate cases using RDT, only three cases were true-positives with a detectable viral load. Eleven samples out of the 280 classified as positive by RDT corresponded to nine patients who had received a false diagnosis of HIV through RDT (3.9%); six of them had been on antiretroviral therapy for at least 2 years. Conclusions: Elecsys HIV combi PT and VIDAS HIV Duo Quick immunoassays showed high sensitivity and specificity when using DBS. RDT-based serological diagnosis can lead to HIV misdiagnosis with personal and social consequences in sub-Saharan Africa.
- High drug resistance levels could compromise the control of HIV infection in paediatric and adolescent population in Kinshasa, the Democratic Republic of Congo.(2021) Carlos-Chillerón, S. (Silvia); Holguín, Á. (África); Rubio-Garrido, M. (Marina); Rodríguez-Galet, A. (Ana); Barquín, D. (David); Reina, G. (Gabriel); Ndarabu, A. (Adolphe); Valadés-Alcaraz, A. (Ana)Background The inadequacy of HIV viraemia and resistance monitoring in Africa leads to uncontrolled circulation of HIV strains with drug resistance mutations (DRM), compromising antiretroviral therapy (ART) effectiveness. This study describes the DRM prevalence and its therapeutic impact in HIV-infected pediatric patients from Kinshasa (Democratic Republic of Congo, DRC). Methods From 2016-2018, dried blood were collected from 71 HIV-infected children and adolescents under ART in two hospitals in Kinshasa for HIV-1 DRM pol analysis, predicted ARV-susceptibility by Stanford and phylogenetic characterization. Results HIV-1 sequences were recovered from 55 children/adolescents with 14 years of median-age. All had received nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTI, NNRTI), 9.1% protease inhibitors (PI) and only one integrase inhibitor (INI). Despite the use of ART, 89.1% showed virological failure and 67.3% carried viruses with major-DRM to one (12.7%), two (47.3%), or three (5.5%) ARV-families. Most children/adolescents harbored DRM to NNRTI (73.5%) or NRTI (61.2%). Major-DRM to PI was present in 8.3% and minor-DRM to INI in 15%. Dual-class-NRTI+NNRTI resistance appeared in 53.1% of patients. Viruses presented high/intermediate resistance to nevirapine (72.9% patients), efavirenz (70.9%), emtricitabine/lamivudine (47.9%), rilpivirine (41.7%), etravirine (39.6%), doravidine (33.3%), zidovudine (22.9%), among others. Most participants were susceptible to INI and PI. Great diversity of variants was found, with a high rate (40%) of unique recombinants. Conclusion The high DRM prevalence observed among HIV-infected children and adolescents in Kinshasa could compromise the 95-95-95-UNAIDS targets in the DRC. It also reinforces the need for routine resistance monitoring for optimal rescue therapy election in this vulnerable population to control the spread of resistant HIV in the country.
- Utility Of POC Xpert HIV-1 Tests For Detection-Quantifcation Of Complex HIV Recombinants Using Dried Blood Spots From Kinshasa, D. R. Congo(Springer Science and Business Media LLC, 2019) Carlos-Chillerón, S. (Silvia); Holguín, Á. (África); Fernández-Alonso, M. (Miriam); Rubio-Garrido, M. (Marina); Barquín, D. (David); Reina, G. (Gabriel); Ndarabu, A. (Adolphe)Point-of-Care (POC) molecular assays improve HIV infant diagnosis and viral load (VL) quantification in resource-limited settings. We evaluated POC performance in Kinshasa (Democratic Republic of Congo), with high diversity of HIV-1 recombinants. In 2016, 160 dried blood samples (DBS) were collected from 85 children (60 HIV-, 18 HIV+, 7 HIV-exposed) and 75 HIV+ adults (65 treated, 10 naive) at Monkole Hospital (Kinshasa). We compared viraemia with Cepheid-POC-Xpert-HIV-1VL and the non-POC-COBAS®AmpliPrep/COBAS®TaqMan®HIV-1-Testv2 in all HIV+, carrying 72.4%/7.2% HIV-1 unique/complex recombinant forms (URF/CRF). HIV-1 infection was confirmed in 14 HIV+ children by Cepheid-POC-Xpert-HIV-1Qual and in 70 HIV+ adults by both Xpert-VL and Roche-VL, identifying 8 false HIV+ diagnosis performed in DRC (4 adults, 4 children). HIV-1 was detected in 95.2% and 97.6% of 84 HIV+ samples by Xpert-VL and Roche-VL, respectively. Most (92.9%) HIV+ children presented detectable viraemia by both VL assays and 74.3% or 72.8% of 70 HIV+ adults by Xpert or Roche, respectively. Both VL assays presented high correlation (R2 = 0.89), but showing clinical relevant ≥0.5 log VL differences in 15.4% of 78 cases with VL within quantification range by both assays. This is the first study confirming the utility of Xpert HIV-1 tests for detection-quantification of complex recombinants currently circulating in Kinshasa.