Molecular Epidemiological Analysis of the Origin and Transmission Dynamics of the HIV-1 CRF01_AE Sub-Epidemic in Bulgaria
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Patient Samples
2.2. Dataset and Sequence Analyses
2.3. Statistical Analysis
3. Results
3.1. Characteristics of the HIV-1 CRF01_AE Infections in Bulgaria
3.2. Identification and Characterization of HIV-1 Subtype CRF01_AE Transmission Clusters in Bulgaria
3.3. Assortative Mixing of Pairs, Sex, Similar Ages, Transmission Category, and Geographic Location in the HIV-1 CRF01_AE Transmission Networks
3.4. Origin of HIV-1 CRF01_AE Infections in Bulgaria
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Characteristic | Subtype CRF01_AE n (%) | Other Subtypes n (%) | p Value |
---|---|---|---|
Total | 270 | 1413 | |
Sex | <0.0001 | ||
Men | 187 (69.3) | 1195 (84.6) | |
Women | 83 (30.7) | 218 (15.4) | |
Age (years) | 0.001 | ||
≤19 | 28 (10.4) | 68 (4.8) | |
20–29 | 108 (40.0) | 538 (38.1) | |
30–39 | 90 (33.3) | 493 (34.9) | |
40–49 | 35 (13.0) | 204 (14.4) | |
≥50 | 9 (3.3) | 110 (7.8) | |
Country of Birth | 0.0018 | ||
Bulgaria | 269 (99.6) | 1361 (96.3) | |
Other country | 1 (0.4) | 52 (3.7) | |
Likely Country of Infection | <0.0001 | ||
Bulgaria | 251 (93.0) | 1176 (83.2) | |
Other country 2 | 19 (7.0) | 237 (16.8) | |
Region in Bulgaria | <0.0001 | ||
Sofia | 164 (60.7) | 625 (44.2) | |
Other regions | 106 (39.3) | 788 (55.8) | |
Transmission category 3 | <0.0001 | ||
HET | 101 (37.4) | 592 (41.9) | |
MSM | 13 (4.8) | 630 (44.6) | |
PWID | 141 (52.2) | 158 (11.2) | |
Other | 15 (5.6) | 33 (2.3) |
Characteristic | Odds Ratio | 95% CI | p Value | |
---|---|---|---|---|
Sex (Women vs. Men) | 2.14 | 1.48 | 3.08 | <0.0001 |
Age at diagnosis (in years) | 1.00 | 0.99 | 1.02 | 0.73 |
Likely country of infection (Bulgaria vs. Other) | 1.90 | 1.11 | 3.27 | 0.02 |
Region in Bulgaria (Sofia vs. Other) | 2.98 | 2.19 | 4.05 | <0.0001 |
Transmission category | <0.0001 | |||
MSM vs. HET | 0.13 | 0.07 | 0.24 | <0.0001 |
PWID vs. HET | 6.40 | 4.41 | 9.28 | <0.0001 |
Other vs. HET | 3.44 | 1.64 | 7.23 | 0.001 |
Cluster Sizes at 1.5% | Male | Female | HET | MSM | MSM/PWID | PWID | Vertical | Mean/Median Age at Diagnosis | Diagnosis Date Range | Likely Country of Infection (Bulgaria) | Likely Country of Infection (Other) 2 | |
154 | 116 | 38 | 30 | 5 | 8 | 108 | 3 | 28.4/29.0 | 2002–2019 | 143 | 11 | |
7 | 5 | 2 | 2 | 0 | 0 | 5 | 0 | 38.9/39.0 | 2018–2019 | 6 | 1 | |
5 | 5 | 0 | 1 | 0 | 0 | 4 | 0 | 33.0/32.0 | 2010–2019 | 5 | 0 | |
Three dyads (6 total) | 4 | 2 | 4 | 0 | 0 | 2 | 0 | 38.8/32.5 | 1999–2019 | 5 | 1 | |
Singletons (98 total) | 57 | 41 | 64 | 8 | 1 | 22 | 3 | 31.2/31.0 | 1995–2019 | 92 | 6 | |
Totals | 270 | 187 | 83 | 101 | 13 | 9 | 141 | 6 | 30.0/29.0 | 1995–2019 | 251 | 19 |
Cluster Sizes at 0.5% | Male | Female | HET | MSM | MSM/PWID | PWID | Vertical | Mean/Median Age at Diagnosis | Diagnosis Date Range | Likely Country of Infection (Bulgaria) | Likely Country of Infection (Other) 2 | |
18 | 10 | 8 | 0 | 0 | 0 | 18 | 0 | 22.5/20.5 | 2009–2018 | 17 | 1 | |
12 | 9 | 3 | 2 | 1 | 0 | 9 | 0 | 30.3/31.0 | 2009–2015 | 10 | 2 | |
7 | 6 | 1 | 1 | 0 | 0 | 6 | 0 | 27.9/29.0 | 2011–2015 | 7 | 0 | |
3 | 2 | 1 | 0 | 0 | 0 | 3 | 0 | 38.0/38.0 | 2018–2019 | 2 | 1 | |
Six dyads (12 total) | 9 | 3 | 0 | 0 | 2 | 9 | 1 | 29.2/29.5 | 2009–2019 | 12 | 0 | |
Singletons (218 total) | 151 | 67 | 98 | 12 | 7 | 96 | 5 | 30.7/30.0 | 1995–2019 | 203 | 15 | |
Totals | 270 | 187 | 83 | 101 | 13 | 9 | 141 | 6 | 30.0/29.0 | 1995–2019 | 251 | 19 |
Cluster Sizes at 3.5% | Male | Female | HET | MSM | MSM/PWID | PWID | Vertical | Mean/Median Age at Diagnosis | Diagnosis Date Range | Likely Country of Infection (Bulgaria) | Likely Country of Infection (Other) 2 | |
249 | 176 | 73 | 83 | 12 | 9 | 141 | 4 | 30.0/29.0 | 1995–2019 | 234 | 15 | |
Three dyads (6 total) | 3 | 3 | 6 | 0 | 0 | 0 | 0 | 30.3/30.0 | 2006–2019 | 4 | 2 | |
Singletons (15 total) | 8 | 7 | 12 | 1 | 0 | 0 | 2 | 29.5/29.0 | 1998–2018 | 13 | 2 | |
Totals | 270 | 187 | 83 | 101 | 13 | 9 | 141 | 6 | 30.0/29.0 | 1995–2019 | 251 | 19 |
Cluster Size, Genetic Distance (d) Threshold, Total Persons | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Size | d 2 | Total 3 | Size | d | Total | Size | d | Total | Size | d | Total | Size | d | Total | Size | d | Total | Size | d | Total | Size | d | Total | |
Cluster Characteristic | dyad | 0.5 | 12 | dyad | 1.5 | 6 | 3–9 | 0.5 | 10 | 3–9 | 1.5 | 12 | ≥10 | 0.5 | 30 | ≥10 | 1.5 | 154 | All | 0.5 | 52 | All | 1.5 | 172 |
Region | 0.05 | 1 | 0.41 | −0.07 | 0.72 | 0.29 | 0.66 | 0.28 | ||||||||||||||||
Sex | −0.33 | −0.5 | −0.24 | −0.07 | −0.03 | 0.01 | −0.05 | 0 | ||||||||||||||||
Transmission category | −0.24 | 1 | −0.3 | −0.2 | −0.04 | 0.03 | −0.06 | 0.03 |
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Alexiev, I.; Campbell, E.M.; Knyazev, S.; Pan, Y.; Grigorova, L.; Dimitrova, R.; Partsuneva, A.; Gancheva, A.; Kostadinova, A.; Seguin-Devaux, C.; et al. Molecular Epidemiological Analysis of the Origin and Transmission Dynamics of the HIV-1 CRF01_AE Sub-Epidemic in Bulgaria. Viruses 2021, 13, 116. https://doi.org/10.3390/v13010116
Alexiev I, Campbell EM, Knyazev S, Pan Y, Grigorova L, Dimitrova R, Partsuneva A, Gancheva A, Kostadinova A, Seguin-Devaux C, et al. Molecular Epidemiological Analysis of the Origin and Transmission Dynamics of the HIV-1 CRF01_AE Sub-Epidemic in Bulgaria. Viruses. 2021; 13(1):116. https://doi.org/10.3390/v13010116
Chicago/Turabian StyleAlexiev, Ivailo, Ellsworth M. Campbell, Sergey Knyazev, Yi Pan, Lyubomira Grigorova, Reneta Dimitrova, Aleksandra Partsuneva, Anna Gancheva, Asya Kostadinova, Carole Seguin-Devaux, and et al. 2021. "Molecular Epidemiological Analysis of the Origin and Transmission Dynamics of the HIV-1 CRF01_AE Sub-Epidemic in Bulgaria" Viruses 13, no. 1: 116. https://doi.org/10.3390/v13010116
APA StyleAlexiev, I., Campbell, E. M., Knyazev, S., Pan, Y., Grigorova, L., Dimitrova, R., Partsuneva, A., Gancheva, A., Kostadinova, A., Seguin-Devaux, C., Elenkov, I., Yancheva, N., & Switzer, W. M. (2021). Molecular Epidemiological Analysis of the Origin and Transmission Dynamics of the HIV-1 CRF01_AE Sub-Epidemic in Bulgaria. Viruses, 13(1), 116. https://doi.org/10.3390/v13010116