Characterization of Human Immunodeficiency Virus-1 Transmission Clusters and Transmitted Drug-Resistant Mutations in Croatia from 2019 to 2022
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. RNA Extraction, Amplification, and Sequencing
2.3. Genotyping and Drug Resistance Mutations Analysis
2.4. Deep Sequencing Analysis
2.5. Phylogenetic Analysis
2.6. Statistical Analysis
3. Results
3.1. Study Population
3.2. Prevalence of TDR and SDRMs
3.3. Deep Sequencing Analysis
3.4. Phylogenetic Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Patient Characteristics | N | % |
---|---|---|
Total | 270 | 100.0 |
Men | 254 | 94.1 |
Women | 16 | 5.9 |
Age at HIV diagnosis (years) | ||
18–35 | 111 | 41.1 |
36–47 | 95 | 35.2 |
48–59 | 53 | 19.6 |
>60 | 11 | 4.1 |
Median age (Q1–Q3), years | 38.0 (29.1–46.6) | |
Reported country of infection | ||
Croatia | 256 | 94.8 |
Other | 13 | 4.8 |
Unknown | 1 | 0.4 |
Stage at HIV diagnosis | ||
Acute infection | 114 | 42.2 |
Chronic infection (late presenters) | 51 | 18.9 |
Chronic infection (very late presenters) | 104 | 38.5 |
Unknown | 1 | 0.4 |
Transmission | ||
MSM | 231 | 85.6 |
Heterosexual | 32 | 11.9 |
IDU | 1 | 0.4 |
Unknown | 6 | 2.2 |
Year of inclusion in clinical care | ||
2019 | 83 | 30.7 |
2020 | 53 | 19.6 |
2021 | 67 | 24.8 |
2022 | 67 | 24.8 |
Baseline CD4+T cells/μL * | ||
<100 | 68 | 25.2 |
101–250 | 54 | 20.0 |
251–400 | 63 | 23.3 |
401–600 | 44 | 16.3 |
>601 | 40 | 14.8 |
Baseline CD4+T cells/μL, median (Q1–Q3) | 284 (95–460) | |
Log10 baseline plasma viraemia, median (Q1–Q3) | 5.0 (4.4–5.5) |
Total, N (%) | Persons in TC | Persons Outside TC | p-Values | Persons with SDRM | Persons without SDRM | p-Values | |
---|---|---|---|---|---|---|---|
Persons, n (%) | 229 (100.0) | 173 (75.5) | 56 (24.5) | 39 (17.0) | 190 (83.0) | ||
Gender, n a (%) | 0.525 | 0.468 | |||||
Male | 216 (94.3) | 164 (94.8) | 52 (92.9) | 36 (92.3) | 180 (94.7) | ||
Female | 13 (5.7) | 9 (5.2) | 4 (7.1) | 3 (7.7) | 10 (5.3) | ||
Age at HIV diagnosis, median years (Q1–Q3) c | 38.1 (29.0–47.0) | 36.8 (28.2–46.3) | 43.4 (36.5–47.5) | <0.001 | 33.1 (27.8–49.9) | 38.9 (29.3–47.0) | 0.359 |
Stage at HIV diagnosis a | 0.333 | 0.806 | |||||
Acute infection | 98 (42.8) | 82 (47.4) | 16 (28.6) | 16 (42.1) | 82 (43.2) | ||
Chronic infection (late presenters) | 44 (19.2) | 29 (16.8) | 15 (26.8) | 6 (15.8) | 38 (20.0) | ||
Chronic infection (very late presenters) | 86 (37.6) | 61 (35.3) | 25 (44.6) | 16 (13.2) | 70 (36.8) | ||
Unknown * | 1 (0.4) | 1 (0.6) | / | 1 (2.6) | / | ||
Log10 baseline plasma viraemia, median (Q1–Q3) c | 4.9 (4.4–5.5) | 4.9 (4.4–5.5) | 5.0 (4.4–5.5) | 0.561 | 4.8 (4.4–5.4) | 5.0 (4.4–5.6) | 0.374 |
Baseline CD4+ T cells/μL, median (Q1–Q3) c | 300.5 (95.0–460.0) | 338.0 (118.5–497.5) | 243.0 (43.5–374.0) | 0.048 | 310.5 (87.0–447.0) | 296.5 (95.0–468.0) | 0.695 |
Transmission risk b | 0.756 | 0.407 | |||||
MSM | 203 (88.6) | 154 (89.0) | 49 (87.5) | 33 (84.6) | 170 (89.5) | ||
Heterosexual | 20 (8.7) | 15 (8.7) | 5 (8.9) | 5 (12.8) | 15 (7.9) | ||
IDU * | / | / | / | / | / | ||
Unknown * | 6 (2.6) | 4 (2.3) | 2 (3.6) | 1 (2.6) | 5 (2.6) | ||
HIV subtype, n (%) b | 0.593 | 0.599 | |||||
B | 191 (83.4) | 143 (82.7) | 48 (85.7) | 33 (84.6) | 158 (83.2) | ||
A1 | 10 (4.4) | 8 (4.6) | 2 (3.6) | 1 (2.6) | 9 (4.7) | ||
BD | 28 (12.2) | 22 (12.7) | 6 (10.7) | 5 (12.8) | 23 (12.1) |
Cluster, Total Number of Sequences, n | Croatian Sequences, n | Bootstrap Threshold | Type of Cluster | SDRMs | Subtype |
---|---|---|---|---|---|
1 (45) | 45 | 0.92 | Expanding | T215S | B |
2 (41) | 33 | 0.97 | Expanding | B | |
3 (15) | 15 | 0.97 | Expanding | B | |
4 (36) | 32 | 0.97 | Expanding | B | |
5 (24) | 15 | 0.93 | Expanding | B | |
6 (21) | 21 | 0.98 | Expanding | B | |
7 (9) | 9 | 0.90 | Expanding | B | |
8 (13) | 13 | 0.98 | Expanding | B | |
9 (5) | 5 | 0.98 | Newly formed | K103N | B |
10 (12) | 12 | 0.96 | Expanding | B |
T215S Cluster | T215S + L210W Cluster | K101E Cluster | K103N Cluster | |
---|---|---|---|---|
Total number of individuals, n (%) | 19 (100.0) | 4 (100.0) | 9 (100.0) | 5 (100.0) |
Gender | 6 (66.7) | |||
Male | 19 (100.00) | 4 (100.0) | 3 (33.3) | 5 (100.0) |
Female | / | / | ||
Transmission risk | ||||
MSM | 18 (94.7) | 4 (100.0) | 4 (44.4) | 5 (100.0) |
Hetero | / | / | 5 (55.5) | |
Unknown | 1 (5.3) | / | / | |
Reported country of infection | ||||
Croatia | 19 (100.0) | 4 (100.0) | 9 (100.0) | 5 (100.0) |
Other | / | / | ||
Stage at HIV diagnosis | ||||
Acute infection | 7 | 1 (25.0) | / | 4 (80.0) |
Chronic infection (late presenters) | 4 | 1 (25.0) | 2 (22.2) | 1 (20.0) |
Chronic infection (very late presenters) | 7 | 2 (50.0) | 7 (77.8) | / |
Unknown | 1 | / | / | / |
Age, median (Q1–Q3), years | 32.0 (25.0–38.6) | 35.2(27.6–39.7) | 49.9 (33.0–54.4) | 50.8 (48.8–59.2) |
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Planinić, A.; Begovac, J.; Rokić, F.; Šimičić, P.; Oroz, M.; Jakovac, K.; Vugrek, O.; Zidovec-Lepej, S. Characterization of Human Immunodeficiency Virus-1 Transmission Clusters and Transmitted Drug-Resistant Mutations in Croatia from 2019 to 2022. Viruses 2023, 15, 2408. https://doi.org/10.3390/v15122408
Planinić A, Begovac J, Rokić F, Šimičić P, Oroz M, Jakovac K, Vugrek O, Zidovec-Lepej S. Characterization of Human Immunodeficiency Virus-1 Transmission Clusters and Transmitted Drug-Resistant Mutations in Croatia from 2019 to 2022. Viruses. 2023; 15(12):2408. https://doi.org/10.3390/v15122408
Chicago/Turabian StylePlaninić, Ana, Josip Begovac, Filip Rokić, Petra Šimičić, Maja Oroz, Katja Jakovac, Oliver Vugrek, and Snjezana Zidovec-Lepej. 2023. "Characterization of Human Immunodeficiency Virus-1 Transmission Clusters and Transmitted Drug-Resistant Mutations in Croatia from 2019 to 2022" Viruses 15, no. 12: 2408. https://doi.org/10.3390/v15122408
APA StylePlaninić, A., Begovac, J., Rokić, F., Šimičić, P., Oroz, M., Jakovac, K., Vugrek, O., & Zidovec-Lepej, S. (2023). Characterization of Human Immunodeficiency Virus-1 Transmission Clusters and Transmitted Drug-Resistant Mutations in Croatia from 2019 to 2022. Viruses, 15(12), 2408. https://doi.org/10.3390/v15122408