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