A total of 346 patients were screened. We included 222 patients for analysis. The inclusion process of the study was detailed in Fig. 1. Baseline characteristics of the patients included in the study were displayed in Table 1.
Table 1
Baseline characteristics of study population
Baseline Characteristic
|
|
Age (years), median (IQR)
|
47 (35–57)
|
Male, n (%)
|
205 (92.3)
|
Race, n (%)
|
|
Chinese
|
176 (79.3)
|
Malay
|
32 (14.4)
|
Indian
|
12 (5.4)
|
Others
|
2 (0.9)
|
HIV Risk Group, n (%)
|
|
Heterosexual Contact Only
|
96 (43.2)
|
Homosexual Contact Only
|
93 (41.9)
|
Others
|
28 (12.6)
|
Unknown
|
5 (2.3)
|
Previous ART, n (%)
|
|
Backbone
|
Tenofovir/Lamivudine or Tenofovir/Emtricitabine
|
135 (60.8)
|
Abacavir/Lamivudine
|
60 (27.0)
|
Zidovudine/Lamivudine
|
23 (10.3)
|
Stavudine/Lamivudine
|
4 (1.9)
|
Third Agent
|
Efavirenz
|
94 (42.3)
|
Rilpivirine
|
52 (23.4)
|
Atazanavir/ritonavir
|
30 (13.5)
|
Nevirapine
|
20 (9.0)
|
Raltegravir
|
15 (6.8)
|
Darunavir/ritonavir
|
5 (2.3)
|
Dolutegravir
|
4 (1.8)
|
Lopinavir/ritonavir
|
2 (0.9)
|
Reasons for switching to ABC/3TC + RPV, n (%)
|
|
Intolerance
|
117 (52.7)
|
Cost reduction
|
66 (29.7)
|
Simplification of regimen
|
52 (23.4)
|
Drug-drug interaction
|
5 (2.3)
|
Others
|
3 (1.4)
|
Unknown
|
31 (14.0)
|
Comorbidities, n (%)
|
|
Myocardial infarction
|
4 (1.8)
|
Ischemic heart disease
|
5 (2.3)
|
Other cardiovascular pathologies
|
7 (3.2)
|
Hypertension
|
39 (17.6)
|
Diabetes mellitus
|
18 (8.1)
|
Dyslipidemia
|
67 (30.2)
|
Kidney disease
|
15 (6.8)
|
Hepatitis B
|
7 (3.2)
|
Hepatitis C
|
16 (7.2)
|
No. of patients with 5 or more medications (polypharmacy), n (%)
|
63 (28.4)
|
Current smokers, n (%)
|
41 (18.5)
|
IQR, interquartile range |
The median age was 47 years (interquartile range [IQR]:35–57). Majority of the patients were male (92.3%). The composition of pre-switch NRTI backbone (in combination with either 3TC or FTC) was as follows: TDF (60.8%), ABC (27.0%) zidovudine (10.3%), and stavudine (1.9%). The most common pre-switch third agents were efavirenz (42.3%) among the NNRTI, atazanavir/ritonavir (13.5%) among the PI, and raltegravir (6.8%) among the INSTI. Fifty-two (23.4%) patients already had RPV as their third agent prior to switch. The most common pre-switch combination was TDF + 3TC + RPV, which accounted for 45/222 (20.3%) of all pre-switch regimens. Intolerance (52.7%), cost (29.7%), and simplification of regimen (23.4%) were the most common reasons cited for switching regimen. Thirty-one patients (14.0%) had no documented reason for switch.
The primary outcome was achieved in 197 out of 222 patients [88.8%, 95% confidence interval (CI): 83.7%-92.4%]. Four patients (1.8%) had virologic failure (Supplementary Table 1), while 21 patients (9.5%) discontinued treatment for non-virologic reasons before 48 ± 12 weeks (Supplementary Table 2). Among those who achieved the primary outcome, 7 patients had viral blips during the 48 ± 12 weeks follow-up period.
Of the 4 patients who experienced virologic failure, 3 patients had HIV-1 RNA > 500 copies/ml at the end of the study period and developed emergent antiretroviral resistance. The first patient experienced virologic failure on the 52th week of switching regimen. Resistance testing showed M184MIV, V108VI, E138EK, K238KN mutations. This patient reported no missed doses, but administered ART at irregular timings with inconsistent caloric intake. The second patient failed on the 45th week of ABC/3TC + RPV and had M184I, E138K, H221HY mutations. He estimated missing doses once a week, and having erratic meal consumption. The third patient experienced virologic failure within 17 weeks of switching regimen, with emerging resistance mutations consisting of L74LV, M184I, E138EG, Y181YCF, M230L. This patient claimed full adherence to his ART, including administration with meals. The last patient had 3 consecutive readings of low-level viremia (HIV-1 RNA > 50 copies/ml but < 200 copies/ml). This patient later achieved virologic suppression without the need to change regimen after the study period.
Among the 21 patients who discontinued treatment for non-virologic reasons, 13/21 (61.9%) were due to AEs attributed to ABC/3TC + RPV. The details of these AEs that led to discontinuation are reported in Supplementary Table 2. Of the remaining 8/21 (38.1%) patients that discontinued treatment for non-virologic reasons, half were to avoid drug-drug interactions with other concomitant medications, and one-quarter were due to personal financial issues. A total of 49 AEs were observed in 31 out of 222 patients (14.0%) during the follow-up period (Table 2). All the AEs resolved spontaneously or upon therapy discontinuation. The most common type of AE was neuro-psychiatric (i.e. forgetfulness, insomnia, mood changes, vivid dreams), comprising 28/49 (57.1%) of all AEs reported.
Table 2
Summary of adverse events
Summary of adverse effects
|
n
|
Total number of adverse effects
|
49
|
Patients with ≥ 1 adverse effects
|
31
|
Patients who discontinued therapy due to adverse effects
|
13
|
Types of adverse effects
|
n
|
Neuro-psychiatric (i.e. forgetfulness, insomnia, mood changes, vivid dreams)
|
28
|
Digestive (i.e. abdominal pain, stomach-ache)
|
11
|
Dermatological (i.e. rash)
|
4
|
Others (e.g. fatigue, lipodystrophy, gynecomastia)
|
6
|
Data obtained on changes in the selected laboratory values over the study duration are summarized in Table 3. A statistically significant increase in CD4 was observed (p < 0.01), with a median absolute change of 31 cells/uL (IQR: -31.50 to + 140.75). There were no significant changes in fasting blood glucose and HbA1c after switching regimen, based on the small number of patients analysed (11 patients for fasting blood glucose and 8 patients for HbA1c). There was a statistically significant change observed for eGFR (p < 0.01), with a median absolute change of -4.24 ml/min/1.73 m2 (IQR: -14.06 to + 5.27), while no significant change was detected for eCrCl (p = 0.463), with a median absolute change of -0.79 ml/min (IQR: -8.81 to + 7.97). No significant changes in lipid profiles were detected. A statistically significant decrease of -6 U/L (IQR: -11 to 0) was seen for ALT.
Table 3
Laboratory values at baseline and at end of follow-up period
Laboratory parameter
|
Median (IQR)
|
p-value
|
Absolute CD4 Count (n = 38)
|
Baseline (cells/uL)
|
323 (220 to 519)
|
|
Follow up (cells/uL)
|
397 (252 to 603)
|
|
Follow up Duration (Weeks)
|
49 (44 to 52)
|
|
Change (cells/uL)
|
31 (-32 to + 141)
|
< 0.01b
|
Glucose Monitoring
|
|
|
Fasting blood glucose (n = 11)
|
Baseline (mmol/L)
|
5.1 (4.9 to 5.7)
|
|
Follow Up (mmol/L)
|
5.2 (4.7 to 5.5)
|
|
Follow up Duration (Weeks)
|
50 (46 to 52)
|
|
Change (mmol/L)
|
0.3 (-0.5 to + 0.4)
|
0.654b
|
HbA1c (n = 8)
|
Baseline (%)
|
5.75 (5.55 to 6.5)
|
|
Follow Up (%)
|
5.85 (5.5 to 6.78)
|
|
Follow up Duration (Weeks)
|
50 (40 to 58)
|
|
Absolute Change (%)
|
0.05 (-0.08 to + 0.2)
|
0.288a
|
Renal
|
|
|
eGFR (n = 139)
|
Baseline (ml/min/1.73 m2)
|
90 (78 to 104)
|
|
Follow Up (ml/min/1.73 m2)
|
87 (76 to 99)
|
|
Follow up Duration (Weeks)
|
49 (40 to 54)
|
|
Change (ml/min/1.73 m2)
|
-4 (-14 to 5)
|
< 0.01b
|
eCrCl (n = 139)
|
Baseline (ml/min)
|
91 (76 to 106)
|
|
Follow Up (ml/min)
|
90 (76 to 106)
|
|
Follow up Duration (Weeks)
|
49 (40 to 54)
|
|
Change (ml/min)
|
-1 (-9 to + 8)
|
0.423a
|
Lipids
|
|
|
TC (n = 38)
|
Baseline (mmol/L)
|
5.1 (4.6 to 6.0)
|
|
Follow Up (mmol/L)
|
5.2 (4.4 to 5.8)
|
|
Follow up Duration (Weeks)
|
51 (45 to 54)
|
|
Change (mmol/L)
|
0.1 (-1.1 to + 0.8)
|
0.778b
|
HDL-C (n = 38)
|
Baseline (mmol/L)
|
1.0 (0.9 to 1.4)
|
|
Follow Up (mmol/L)
|
1.2 (0.9 to 1.3)
|
|
Follow up Duration (Weeks)
|
50 (45 to 54)
|
|
Change (mmol/L)
|
0 (-0.2 to + 0.2)
|
0.762b
|
dC LDL-C (n = 38)
|
Baseline (mmol/L)
|
2.9 (2.6 to 3.6)
|
|
Follow Up (mmol/L)
|
2.8 (2.4 to 3.5)
|
|
Follow up Duration (Weeks)
|
51 (45 to 54)
|
|
Change (mmol/L)
|
-0.1 (-0.5 to + 0.5)
|
0.817b
|
LDL-C (n = 35)
|
Baseline (mmol/L)
|
3.1 (2.6 to 3.7)
|
|
Follow Up (mmol/L)
|
3.1 (2.7 to 3.7)
|
|
Follow up Duration (Weeks)
|
51 (45 to 54)
|
|
Change (mmol/L)
|
0.1 (-0.6 to + 0.7)
|
0.972b
|
Liver
|
|
|
ALT (n = 117)
|
Baseline (U/L)
|
28 (21 to 44.5)
|
|
Follow Up (U/L)
|
22 (16 to 30)
|
|
Follow up Duration (Weeks)
|
48 (41 to 52)
|
|
Change (U/L)
|
-6 (-11 to + 0)
|
< 0.001a
|
a Wilcoxon signed rank test
b Paired samples t-test
eGFR – Estimated glomerular filtration rate
eCrCl – Estimated creatinine clearance
TC – Total cholesterol
HDL-C – High density lipoprotein cholesterol
dC LDL-C – Low density lipoprotein cholesterol estimated with the de Cordova Eq.19
LDL-C – Low density lipoprotein cholesterol
ALT – Alanine transaminase
|