Study Population
Overall, 33 patients were recruited in this study who switched from their conventional ART to DTG plus 3TC. The baseline characteristics are summarized in Table 1. 87.9% (29/33) of the patients were male, with a median age of 42 years (IQR: 37–55). Comorbid conditions included hyperlipidemia (40%), hypertension (35%), diabetes mellitus (9%), and cardiovascular disease (6%). The median duration of HIV infection was 3.08 years (IQR: 2.35–4.87), and the median of 2.13 years under ART (IQR: 1.05–4.23). 28 patients (84.8%) had baseline VL < 50 copies/ml, while median time of virological suppression was 21.0 months (IQR 15.3–35.7). 5 (15.2%) had experienced virological failure prior to drug switch.
Table 1
Baseline characteristics of the 33 patients enrolled in the study.
Characteristic | Value |
Male, n (%) | 29 (87.9) |
Age (years), median (IQR) | 42 (37–55) |
Mode of HIV transmission, n(%) | |
heterosexual | 2(6.1) |
MSM | 30(90.9) |
IVDU | 1(3.0) |
Duration of HIV infection (years) | 3.08(2.35–4.87) |
Nadir CD4 + cell count (cells/mm3) | |
Baseline CD4 + cell count (cells/mm3) | 515(363–595) |
Duration of ART (years) | 2.13(1.05–4.23) |
Duration of plasma HIV RNA < 50 copies/ml (months) | 21.0(15.3–35.7) |
Duration of current ARV therapy (months) | 7.9(5.7–17.2) |
Pre-switch therapy, n (%) | |
2 NRTIs + PI/r | 3(9.1) |
2 NRTIs + NNRTI | 7(21.2) |
2 NRTIs + INI | 14(42.4) |
NRTI + PI/r | 8(24.2) |
INI + PI/r | 1(3.0) |
Reasons for drug switch | |
Treatment simplification | 10(30.3) |
Virological failure | 5(15.2) |
Toxicity | |
Renal toxicity | 7(21.2) |
Liver toxicity | 0(0) |
Dyslipidemia | 7(21.2) |
Gastrointestinal toxicity | 4(12.1) |
Osteoporosis | 1(3.0) |
Other | 1(3.0) |
Most patients (24/33) were taking a standard triple-drug regimen at the time of switching as the following: 7 patients with 2NRTIs + NNRTI (21.2%), 14 with 2NRTIs + INSTI (42.4%), and 3 with 2NRTIs + PI (9.1%). The most frequent combination of NRTI was tenofovir plus 3TC (16/33), and the third drug was mainly DTG (12/33), followed by efavirenz (6/33). Nine patients were already treated on a dual ART with 3TC + lopinavir/ritonavir (LPV/r) (8/33, 24.2%) and LPV/r + raltegravir (1/33, 3.0%). Previous exposure to INSTI was documented in 15(45.5%) of individuals.
The main reasons for changing to DTG + 3TC regimen were treatment failure for 5 patients (15.2%), simplification for 10 patients (30.3%), and drug toxicity of the previous regimen for 18 patients (54.5%). These drug toxicity with current ART included 6 patients with dyslipidemia, 1 patient with decreased bone density, 6 patients with renal toxicity, 4 patients with gastrointestinal toxicity, and 1 patient with other toxicities.
Drug Resistance
Historical genotypes were assessed from 78.8% (26/33) of the participants, and proviral genotypes using baseline HIV proviral DNA were obtained from 54.5% (18/33) of the enrolled patients. 42.4% (14/33) of the participants had both historical and proviral genotypes. Altogether, cumulative baseline resistance data (historical and/or proviral) were available for 90.9% (30/33) of the patients.
According to the accumulated drug-resistant mutations analysis, pre-existing primary NRTI resistance (-R), NNRTI-R, and PI-R mutations were observed in 18.2% (6/33), 36.4% (12/33), and 3.0% (1/33), respectively. Of note, the M184V/I resistance mutation to lamivudine was present in 18.2% (6/33) participants. 2 of the 6 patients didn’t have virological suppression at baseline.
Efficacy In Virological Suppression
For the 5 patients without virologic suppression at baseline, the VL was undetectable at 12 weeks after switching for 4 patients and at 24 weeks for 1 patient, and the VL remained undetectable until the end of the follow-up period after 48 weeks. For the 28 virologically suppressed patients who changed medication for adverse drug reaction or drug simplification, viral suppression was well maintained below 50 copies/ml during follow-up. The proportion of suppressed patients who maintained undetectable VL at week 48 was 28/28 (100%; 95% CI = 88.4–100.0).
The median CD4 + count was 543 cells/µL (IQR 363–595) at baseline, and it significantly increased to 625 cells/µL (IQR 455–651) at 48 weeks from baseline (p = 0.0017). For the 6 patients with M184V/I resistance at baseline, the VL maintained suppressed at 48 weeks.
Safety And Tolerability
The laboratory parameters were analyzed for lipid profile, renal function, liver function, and complete blood cell counts before and after the regimen change. The impact of DTG plus 3TC in laboratory parameters at 48 weeks is shown in Table 2. During the 48-week follow-up, an increase in median LDL-cholesterol levels (+ 0.77 mg/dL, p < 0.0001) and a slight decrease in median triglyceride levels (-0.6 mg/dL, p = 0.0179) and the total cholesterol/HDL-cholesterol ratio (-0.327, p = 0.0366) were observed in the lipid profile, but the median changes in serum concentration of total cholesterol and HDL-cholesterol were not statistically significant (Table 2). For the patients who switched to DTG plus 3TC because of dyslipidemia (n = 7), a significant decrease in total cholesterol and total triglycerides were observed at 48 weeks of -1.6 and − 1.3 mg/dL, respectively (p = 0.0039; p = 0.0040) (Table 3).
Table 2
Analytical changes between baseline and 48 weeks of all patients.
Parameter | Baseline | IQR | 48 weeks after | IQR | P value |
Lipid profile | | | | | |
Cholesterol (mg/dL) | 4.6 | 4.073–6.775 | 4.74 | 3.865–5.308 | 0.1987 |
HDL-C (mg/dL) | 0.96 | 0.89–1.19 | 1.06 | 0.9–1.19 | 0.3333 |
LDL-C (mg/dL) | 2.35 | 1.8–3.08 | 3.12 | 2.74–3.87 | < 0.0001 |
Triglycerides (mg/dL) | 2.21 | 1.27–4.37 | 1.61 | 1.2–2.22 | 0.0179 |
TC: HDL-C | 5.022 | 4.133–6.395 | 4.695 | 3.55–5.35 | 0.0366 |
Renal profile | | | | | |
Creatinine (mg/dL) | 71.6 | 60.2–77.3 | 86.8 | 75–97 | 0.0034 |
eGFR (mL/min/1.73 m2) | 106.4 | 78.16–118.2 | 88.6 | 75.71–107.9 | 0.0047 |
Liver function | | | | | |
ALT, UI/L | 20.4 | 13.9–34.1 | 21.7 | 14.9–37.4 | 0.5607 |
AST, UI/L | 22 | 16.5–26.9 | 20.7 | 18.4–24.7 | 0.6889 |
Bilirubin, mg/dL | 14.7 | 10.9–20.2 | 13.2 | 10.7–16.6 | 0.5503 |
Other tests | | | | | |
Body weight (kg) | 69.2 | 62.5–75.3 | 70.5 | 65.0-78.8 | 0.3214 |
Glucose, mg/dL | 5.3 | 4.98–6.18 | 4.95 | 4.69–5.52 | 0.1888 |
Platelet count (*103/mL) | 230 | 193-269.5 | 216 | 194.5-260.5 | 0.7141 |
Table 3
Analytical changes between baseline and 48 weeks of patients with drug toxicity at baseline.
Patients with laboratory abnormality | Parameter | Baseline | IQR | Week 48 | IQR | P value |
Renal toxicity | Creatinine (mg/dL) | 113.2 | 106.5-122.6 | 96.1 | 94.3-117.1 | 0.013 |
| eGFR (mL/min/1.73 m2) | 77.4 | 67.8–83.3 | 87.1 | 84.2–90.9 | 0.039 |
Dyslipidemia | TC (mg/dL) | 6.8 | 6.3–8.2 | 5.2 | 4.6–5.9 | 0.003 |
| HDL-C (mg/dL) | 1.3 | 1.2–1.6 | 1.2 | 0.9–1.5 | 0.734 |
| LDL-C (mg/dL) | 3.7 | 3.4–4.2 | 3.9 | 3.1–4.6 | 0.438 |
| TG (mg/dL) | 3.4 | 2.4–13.8 | 2.1 | 1.5–3.3 | 0.004 |
The change to dual therapy also resulted in a significant increase in the median value of serum creatinine (+ 15.2 mg/dL, p = 0.0034), and a significant decrease in the mean eGFR value (-17.8 mL/min/1.73 m2, p = 0.0047) (Table 2). The analysis of patients who switched to DTG plus 3TC because of renal toxicity (n = 7) showed a trend toward a decrease in creatine (-17.1 mg/dL, p = 0.013) and an increase in eGFR (+ 9.7 mL/min/1.73 m2, p = 0.039) at 48 weeks.(Table 3)
As shown in Table 2, no significant change was found in body weight before and after drug change. Regarding liver function tests, no significant changes were observed in ALT, AST, and total bilirubin levels. There was also no significant adverse reaction observed when comparing the complete blood count and serum glucose at the time of drug change and the last follow-up after the drug change. No patient experienced serious adverse effects, AIDS-related events or died during the follow-up period. None of the enrolled participants discontinued study treatment due to adverse events.