scholarly journals Molecular Epidemiological Analysis of the Origin and Transmission Dynamics of the HIV-1 CRF01_AE Sub-Epidemic in Bulgaria

Viruses ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 116
Author(s):  
Ivailo Alexiev ◽  
Ellsworth M. Campbell ◽  
Sergey Knyazev ◽  
Yi Pan ◽  
Lyubomira Grigorova ◽  
...  

HIV-1 subtype CRF01_AE is the second most predominant strain in Bulgaria, yet little is known about the molecular epidemiology of its origin and transmissibility. We used a phylodynamics approach to better understand this sub-epidemic by analyzing 270 HIV-1 polymerase (pol) sequences collected from persons diagnosed with HIV/AIDS between 1995 and 2019. Using network analyses at a 1.5% genetic distance threshold (d), we found a large 154-member outbreak cluster composed mostly of persons who inject drugs (PWID) that were predominantly men. At d = 0.5%, which was used to identify more recent transmission, the large cluster dissociated into three clusters of 18, 12, and 7 members, respectively, five dyads, and 107 singletons. Phylogenetic analysis of the Bulgarian sequences with publicly available global sequences showed that CRF01_AE likely originated from multiple Asian countries, with Vietnam as the likely source of the outbreak cluster between 1988 and 1990. Our findings indicate that CRF01_AE was introduced into Bulgaria multiple times since 1988, and infections then rapidly spread among PWID locally with bridging to other risk groups and countries. CRF01_AE continues to spread in Bulgaria as evidenced by the more recent large clusters identified at d = 0.5%, highlighting the importance of public health prevention efforts in the PWID communities.

Viruses ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 441
Author(s):  
Ivailo Alexiev ◽  
Ellsworth M. Campbell ◽  
Sergey Knyazev ◽  
Yi Pan ◽  
Lyubomira Grigorova ◽  
...  

HIV-1 subtype B is the predominant strain in Bulgaria, yet little is known about the molecular epidemiology of these infections, including its origin and transmissibility. We used a phylodynamics approach by combining and analyzing 663 HIV-1 polymerase (pol) sequences collected from persons diagnosed with HIV/AIDS between 1988–2018 and associated epidemiologic data to better understand this sub-epidemic in Bulgaria. Using network analyses at a 1.5% genetic distance threshold (d) we found several large phylogenetic clusters composed mostly of men who have sex with men (MSM) and male heterosexuals (HET). However, at d = 0.5%, used to identify more recent transmission, the largest clusters dissociated to become smaller in size. The majority of female HET and persons with other transmission risks were singletons or pairs in the network. Phylogenetic analysis of the Bulgarian pol sequences with publicly available global sequences showed that subtype B was likely introduced into Bulgaria from multiple countries, including Israel and several European countries. Our findings indicate that subtype B was introduced into Bulgaria multiple times since 1988 and then infections rapidly spread among MSM and non-disclosed MSM. These high-risk behaviors continue to spread subtype B infection in Bulgaria as evidenced by the large clusters at d = 0.5%. Relatively low levels of antiretroviral drug resistance were observed in our study. Prevention strategies should continue to include increased testing and linkage to care and treatment, as well as expanded outreach to the MSM communities.


2020 ◽  
Vol 12 (2) ◽  
pp. 79-88
Author(s):  
E. N. Ozhmegova ◽  
A. A. Antonova ◽  
A. V. Lebedev ◽  
T. N. Melnikova ◽  
Т. V. Krylova ◽  
...  

The work was carried out molecular-epidemiological analysis of HIV-1 in the cities of the North-West Federal District — Vologda and Cherepovets. The study used a collection of peripheral blood mononuclear cells (PBMC) obtained from 80 HIVinfected patients: 52 samples were obtained from patients living in Cherepovets, and 28 samples — from Vologda. The distribution of the HIV-1 genetic variants in the studied cities was as follows: sub-subtype A6 — 51,25%; subtype B — 6,25%; the recombinant form of CRF_03AB — 32,5%; unique recombinant forms (URFs) — 6,25%, and 3,75% were represented by other subtypes: G and CRF63_02A1. A phylogenetic analysis confirmed the relationship of the sub-subtype A6 viruses with the A6 (IDU-A) variant predominating in Ukraine, Russia and other former Soviet Union (FSU) countries; the sequences of subtype B formed a common branch on the phylogram with reference strains characteristic of men who have sex with men; 32,5% of the nucleotide sequences formed a single cluster with the reference strain CRF03_AB. In addition to these subtypes, the presence of unique recombinant forms of HIV-1 containing segments of the sub-subtype A6 and IDU-B viruses were also found. The results of the molecular epidemiological analysis in the Vologda Oblast also showed significant differences in the genetic profile of HIV-1 in two nearby cities — Vologda and Cherepovets. Thus, the evolution of HIV-1 in the Vologda Oblast continues, with the main source of variability being the mutual penetration of viruses between risk groups and recombination processes.


2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S391-S392 ◽  
Author(s):  
Melanie Stecher ◽  
Martin Hoenigl ◽  
Anna-Maria Eis-Huebinger ◽  
Clara Lehmann ◽  
Gerd Fätkenheuer ◽  
...  

Abstract Background In Germany, previous reports have demonstrated transmitted HIV-1 drug resistance mutations (DRM) in 10% of newly diagnosed individuals, affecting treatment failure and the choice of antiretroviral therapy (ART). Here, we sought to understand the molecular epidemiology of HIV DRM transmission throughout the Cologne-Bonn region, an area with one of the highest rate of new HIV infections in Europe (13.7 per 100,000 habitants). Methods We analyzed 714 HIV-1 ART naïve infected individuals diagnosed at the University Hospitals Cologne and Bonn between 2001 and 2016. Screening for DRM was performed according to the Stanford University Genotypic Resistance Interpretation. Shared DRM were defined as any DRM present in genetically linked individuals (<1.5% genetic distance). Phylogenetic and network analyses were performed to infer putative relationships and shared DRMs. Results We detected 123 DRMs in our study population (17.2% of all sequences). Prevalence of any DRM was comparable among risk groups and was highest among people from an endemic area (i.e., country with HIV prevalence >1%) (11/51, 21.6%). Nucleoside-and non-nucleoside reverse transcriptase inhibitor (NRTI/NNNRTI) resistance mutations were detected in 49 (7%) and 97 (13.6%) individuals, with the E138A in 29 (4.1%) and K103N in 11 (1.5%) being the most frequent. Frequency of DRM was comparable in clustering and not clustering individuals (17.1% vs. 17.5%). Transmission network analysis indicated that the frequency of DRM in clustering individuals was the highest in PWID (3/7, 42.9%) (Figure 1A). Genetically linked individuals harboring shared DRMs were more likely to live in suburban areas than in Central Cologne (18.8% vs. 8% of clustering sequences with DRM; Figure 1B). Conclusion The rate of DRMs was exceptionally high in the Cologne/Bonn area. Network analysis elucidated frequent cases of shared DRMs among genetically linked individuals, revealing the potential spread of DRMs and the need to prevent onward transmission of DRM in the Cologne-Bonn area. Disclosures M. Hoenigl, Gilead, Basilea, Merck: Speaker’s Bureau, Research grant and Speaker honorarium.


1990 ◽  
Vol 64 (01) ◽  
pp. 108-112 ◽  
Author(s):  
S Eichinger ◽  
I Pabinger ◽  
H Hartl ◽  
C Stain ◽  
S Mayerhofer ◽  
...  

SummaryTwenty-one immunodeficiency virus 1 (HIV 1)-positive hemophilic patients were treated with Azidothymidine (AZT) for symptomatic HIV infection. The median observation period was 20.5 months.At 25 months the probability of survival was 82%, the probability of progression of disease from CDC III or IV C2 to IV C1 (AIDS) was 20% in patients on continuous AZT treatment and 50% in patients with intermption of treatment. Three patients developed severe leukopenia and 3 patients severe anemii during AZT treatment. In 1 patient a dose-dependent striking increase of transaminases during AZT treatment was observed. In 7 patients treatment was intermpted, in 1 patient because of anemia, in 1 because of pruritus and in 5 patients because of noncompliance.No signiticant changes in the consumption of clotting factor concentrates and number of bleeding episodes before and during AZT treatment were noted.We conclude, that both hematological and non-hematological side effects of AZT in HIV 1-infected hemophilic patientr ur. comparable to those seen in other risk groups . AzT does not increase the bleeding tendency in this patient group.


2018 ◽  
Vol 69 (2) ◽  
pp. 295-305 ◽  
Author(s):  
Maia Lesosky ◽  
Molebogeng X Rangaka ◽  
Cara Pienaar ◽  
Anna K Coussens ◽  
Rene Goliath ◽  
...  

Abstract Background The risk of individuals infected with human immunodeficiency virus (HIV)-1 developing tuberculosis (TB) is high, while both prognostic and diagnostic tools remain insensitive. The potential for plasma biomarkers to predict which HIV-1–infected individuals are likely to progress to active disease is unknown. Methods Thirteen analytes were measured from QuantiFERON Gold in-tube (QFT) plasma samples in 421 HIV-1–infected persons recruited within the screening and enrollment phases of a randomized, controlled trial of isoniazid preventive therapy. Blood for QFT was obtained pre-randomization. Individuals were classified into prevalent TB, incident TB, and control groups. Comparisons between groups, supervised learning methods, and weighted correlation network analyses were applied utilizing the unstimulated and background-corrected plasma analyte concentrations. Results Unstimulated samples showed higher analyte concentrations in the prevalent and incident TB groups compared to the control group. The largest differences were seen for C-X-C motif chemokine 10 (CXCL10), interleukin-2 (IL-2), IL-1α, transforming growth factor-α (TGF-α). A predictive model analysis using unstimulated analytes discriminated best between the control and prevalent TB groups (area under the curve [AUC] = 0.9), reasonably well between the incident and prevalent TB groups (AUC > 0.8), and poorly between the control and incident TB groups. Unstimulated IL-2 and IFN-γ were ranked at or near the top for all comparisons, except the comparison between the control vs incident TB groups. Models using background-adjusted values performed poorly. Conclusions Single plasma biomarkers are unlikely to distinguish between disease states in HIV-1 co-infected individuals, and combinations of biomarkers are required. The ability to detect prevalent TB is potentially important, as no blood test hitherto has been suggested as having the utility to detect prevalent TB amongst HIV-1 co-infected persons.


2017 ◽  
Vol 89 (11) ◽  
pp. 44-49 ◽  
Author(s):  
I A Lapovok ◽  
A E Lopatukhin ◽  
D E Kireev ◽  
E V Kazennova ◽  
A V Lebedev ◽  
...  

Aim. To simultaneously analyze HIV-1 samples from all Russian regions to characterize the epidemiology of HIV infection in the country as a whole. Subjects and methods. The most extensive study was conducted to examine nucleotide sequences of the pol gene of HIV-1 samples isolated from HIV-positive persons in different regions of Russia, with the diagnosis date being fixed during 1987—2015. The nucleotide sequences of the HIV-1 genome were analyzed using computer programs and on-line applications to identify a virus subtype and new recombinant forms. Results. The nucleotide sequences of the pol gene were analyzed in 1697 HIV-1 samples and the findings were that the genetic variant subtype A1 (IDU-A) was dominant throughout the entire territory of Russia (in more than 80% of all infection cases). Other virus variants circulating in Russia were analyzed; the phenomenon of the higher distribution of the recombinant form CRF63/02A in Siberia, which had been previously described in the literature, was also confirmed. Four new recombinant forms generated by the virus subtype A1 (IDU-A) and B and two AG recombinant forms were found. There was a larger genetic distance between the viruses of IDU-A variant circulating among the injecting drug users and those infected through heterosexual contact, as well as a change in the viruses of subtype G that caused the outbreak in the south of the country over time in 1988—1989. Conclusion. The findings demonstrate continuous HIV-1 genetic variability and recombination over time in Russia, as well as increased genetic diversity with higher HIV infection rates in the population.


2001 ◽  
Vol 356 (1410) ◽  
pp. 815-823 ◽  
Author(s):  
Stanley A. Plotkin

A book published in 1999 hypothesized that the scientists who worked with the CHAT type 1 attenuated polio strain tested in the former Belgian Congo in the late 1950s had covertly prepared the vaccine in chimpanzee kidney cells contaminated with a simian immunodeficiency virus, which evolved into HIV–1 group M. This paper summarizes the results of the investigation conducted by the author to determine the legitimacy of the accusation. Testimony by eyewitnesses, documents of the time, epidemiological analysis, and ancillary phylogenetic, virologic and PCR data all concur to reject the hypothesis as false and without factual foundation.


1987 ◽  
Author(s):  
J Desmyter

AIDS virus (HIV) transmission by transfusions and blood products has been essentially halted in industrialized countries which haye introduced systematic anti-HIV screening of donations in 1985. New anti-HIV screening assays, based in part on the replacement of disrupted HIV virions by defined DNA recombinant HIV antigens, have improved specificity; sensitivity has been improved as to dectect seroconversion at an earlier stage. Confirmatory assays and (self-)exclusion of risk groups from blood donation do remain mandatory. HIVAg can be detected in some infections before antibody conversion, and HIVAg is more likely to be found in those anti-HIV positives who proceed to disease. However, there is no justification so far for routine parallel HIVAg and anti-HIV screening. There is continued uncertainty how many HIV carriers have not (yet) developed antibody, but their numbers may have been overestimated. Studies to determine how many HIV transmitters have escaped blood bank detection, and why, need to be undertaken in spite of formidable logistic difficulties.The risk of developing AIDS is now estimated at 25-50 % within 10 years after the infectious contact. It is not clear whether the risk should be estimated differently in different groups or persons. In cities in Central Africa, 5-20 % of men and women are confirmed anti-HIV positives. At least 75 % of this HIV carrier rate is due to heterosexual transmission. Heterosexual transmission has been slower in Western countries, but factors precluding slow evolution to high figures by the same route outside Africa have not been identified. Therefore, countries have no choice in advocating behaviour changes in the general population, and not only in the classical risk groups. Initial hesitations toward extended voluntary and confidential screening are dwindling. Well-conceived confidential screening may be the only way to avoid strong-armed government intervention. The latter is certain to be divisive, and is likely to be counterproductive on balance.An efficacious vaccine remains remote, but an antiviral which prolongs life by at least several months in AIDS patients, but not all of them, is now available. Zidovudine (AZT), however, is toxic and mere prolongation of life without cure will impose an additional burden on AIDS economics.A novel virus (HIV-2) has been identified and is already widespread in West-Africans. It causes AIDS, but the present ratio of AIDS cases in those infected seems lower than with HIV(-l); this feature may be transient. HIV-2 antibodies are either detected or missed by anti-HIV-1 screens; if found, they can be distinguished from anti-HIV-1 only by special confirmatory technique. New screening assays showing equal sensitivity for HIV-1 and HIV-2 in a single test should be devised. At present, HIV-2 is very rare in Western countries compared to HIV-1.


2020 ◽  
Vol 96 (6) ◽  
pp. 451-456 ◽  
Author(s):  
Alessia Lai ◽  
Annalisa Bergna ◽  
Francesco Roberto Simonetti ◽  
Marco Franzetti ◽  
Giorgio Bozzi ◽  
...  

ObjectivesTransgender people are disproportionately affected by the HIV-1 epidemic. We evaluated the origin of HIV-1 variants carried by South American transgenders living in Milan by combining accurate phylogenetic methods and epidemiological data.MethodsWe collected 156 HIV-1 pol sequences obtained from transgender patients engaged in sex work (TSWs) followed between 1999 and 2015 at L. Sacco Hospital, Milan, Italy. Phylogenetic analyses were conducted by HIV-TRACE, MrBayes, MacClade and Beast programs. Reference sequences were retrieved from Los Alamos and local databases. Last negative testing or proxy data from clinical records of infected individuals were used to investigate the country of infection.ResultsAmong South American TSWs, the most represented HIV-1 subtypes were B (70.5%), F1 (12.8%) and C (4.4%). Gene flow migrations of B subtype indicated significant fluxes from TSWs to Italians (21.3%) belonging to all risk groups (26.4% to heterosexuals (HEs), 18.9% to men who have sex with men (MSM), 15.1% to injecting drug users). The largest proportion of bidirectional fluxes were observed between Italians and TSWs (24.6%). For F1 subtype, bidirectional viral fluxes involved TSWs and Italians (7.1% and 14.3%), and a similar proportion of fluxes linked TSWs and Italian HEs or MSM (both 15.8%). Significant fluxes were detected from Italians to TSWs for subtype C involving both MSM (30%) and HEs (40%). Country of HIV-1 acquisition was identified for 72 subjects; overall, the largest proportion of patients with B subtype (73.5%) acquired HIV-1 infection in South America.ConclusionsOur results indicated that South American transgenders largely contribute to the heterogeneity of HIV-1 variants in our country. The high number of clusters based on all subtypes indicated numerous transmission chains in which TSWs were constantly intermixed with HEs and MSM. Our results strongly advocate interventions to facilitate prevention, diagnosis and HIV-1 care continuum among transgender people.


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