Basic characteristics of the participants
We collected a total of 468 ART-failure individuals who met the inclusion criteria through routine reporting, and the pol gene sequence in the plasma sample of 256 participants were successfully amplified and analyzed. Of these, 166 were considered drug resistant and 90 were drug sensitive
(Table 1). Of these,91.41% were men; the median age was 35.61 years (IQR:28.73-48.67); and more than half of the participants (55.86%) were unmarried, 28.13% were married or cohabiting, and 16.02% were divorce or separation; the most common infection routes were mainly homosexual contact (56.25%) and heterosexual contact (30.86%).
Of 256 participants experiencing treatment failure, 46.88% were WHO stage I patients, followed by WHO stage IV patients (20.31%), WHO stage II patients (18.36%), and WHO stage III patients (14.45%); the median time of ART was 33.15 months (IQR:25.41-49.83); the initial ART regimen for most patients was 3TC+TDF+EFV (82.03%); the current ART regimen with a large proportion were LPV/r+3TC+AZT (33.98%), EFV+3TC+TDF (29.69%) and LPV/r+3TC+TDF (23.44%), respectively. The median viral load was 36205 copies/ml (IQR:11234-96047).
Genetic subtypes
Among the 256 successfully amplified samples, CRF01_AE (77.73%) was the predominant genotype, followed by subtype B (9.77%), unique recombinant forms (URFs) (5.08%), CRF07_BC (3.52%), subtype A (1.95%), subtype C (1.56%), and CRF08_BC (0.39%) (Figure 1). In addition, the two URFs recombination patterns were CRF01_AE/B and BC. The most common subtype for these infected by MSM was CRF01_AE, followed by subtype B, and for those infected by heterosexual contact, the most common subtype was also CRF01_AE, followed by URFs (Table 2).
Table 2 Prevalence of genotypes among ART-failure patients infected by different route of transmissions
Routes of infection
|
CRF01_AE
|
B
|
CRF07_BC
|
A
|
C
|
CRF08_BC
|
URFs
|
Total
|
MSM
|
114(79.17)
|
15(10.42)
|
5(3.47)
|
1(0.69)
|
3(2.08)
|
0(0.00)
|
6(4.16)
|
144
|
Heterosexual
|
61(77.22)
|
5(6.33)
|
2(2.53)
|
3(3.80)
|
1(1.27)
|
1(1.27)
|
6(7.59)
|
79
|
Others
|
24(72.73)
|
5(15.15)
|
2(6.06)
|
1(3.03)
|
0(0.00)
|
0(0.00)
|
1(3.03)
|
33
|
Total
|
199(77.73)
|
25(9.77)
|
9(3.52)
|
5(1.95)
|
4()1.56
|
1(0.39)
|
13(5.08)
|
256
|
HIV-1 drug resistance analysis
Of the 256 ART-failure cases, 64.84% had drug resistance to any of the three classes of antiretroviral drugs; 50.39% were dual resistant to NRTIs and NNRTIs; and the percentages of resistance to NNRTIs, NRTIs, and PIs was 62.89%,50.39% and 3.13%, respectively (Figure 2). The percentages of resistance to ABC, 3TC, FTC, ddI, d4T, and TDF drugs were 50.39%, 49.22%, 49.22%, 43.36%, 37.11%, and 36.33%, respectively. Only 0.39% showed drug resistance to AZT. The percentage of resistance to NNRTIs was high. 62.89% of participants showed resistance to EFV and NVP;50.00% showed resistance to RPV; and 38.28% showed resistance to ETR. The resistance rate to the only PIs drug (NFV) was 3.13% (Figure 3).
The percentage of drug resistance associated mutations in NNRTIs, NRTIs, and PIs among 256 ART-failure patients are listed as follows (Table 3). The most common mutations associated with drug resistance to NNRTIs were G190S (31.25%), Y181C (25.78%), K101E (17.19%), V179D (15.23%), and K103N (12.89%). As well, K65R (29.69%), M184V (28.52%), and Y115F (10.55%) were found as the most frequent mutations to NRTIs. There were only three drug resistance associated mutations to PIs, which were M46I (3.52%), L33F (1.95%) and K20KT (0.39%), respectively.
Factors Associated with Drug Resistance
Ten potential risk factors were considered in the univariate logistic regression analysis (Table 4). Of these factors, duration of ART, current ART regimen, viral load, gene subtype, and WHO clinical stages significantly were correlated with drug resistance (p<0.05). To identify the risk factors associated with HIV-1 drug resistance, these five statistically significant factors were included in the multivariate logistic regression model. Two factors were found to be significantly associated with the developing of HIV-1 DR in ART-failure participants: current ART regimen
(compared to 3TC +TDF+ EFV regimen: the other regimen AOR 0.99,95% CI 0.40-2.45; LPV/r+3TC+TDF regimen AOR 0.17,95% CI 0.07 -0.40; EFV+3TC+TDF regimen AOR 0.50,95% CI 0.18-1.37;), and viral load (compared to VL>80000:VL 0-40000 AOR 18.34, 95% CI 3.42- 98.40; VL 40001-80000 AOR 2.09, 95% CI 0.57-7.68).