Real-world implementation of dolutegravir plus lamivudine in people living with HIV in Southwest China

ABSTRACT

Background

Long-term outcome data from real-world studies on the implementation of a two-drug dolutegravir plus lamivudine (DTG+3TC) regimen for the treatment of human immunodeficiency virus (HIV) infection remain limited. This study evaluated the real-world effectiveness and safety of DTG+3TC in people living with HIV (PLHIV) in Southwestern China.

Methods

This was an observational, single-center, retrospective study that enrolled antiretroviral therapy (ART)-naïve (n = 36) and ART-experienced patients with HIV (n = 86) between January 2019 and April 2021. The virological response to therapy and adverse events were documented. The primary endpoint was an HIV viral load (VL) <50 copies/mL at week 48.

Results

The proportion of treatment-naïve and ART-experienced PLHIV with a VL <50 copies/mL at 48 weeks was 97.2% and 97.7%, respectively. The CD4 count increased significantly by 80.2 cells/μL (P = 0.012) and 79.0 cells/μL (P = 0.021) in the ART-naïve and ART-experienced patients, respectively. No patients discontinued DTG+3TC by week 48 due to adverse events.

Conclusion

Virologic suppression may be achieved with DTG+3TC, in ART-naïve patients with a high VL, and in ART-experienced patients with residual viremia. This study also demonstrated a low prevalence of drug-related side effects.

KEYWORDS:

• Adverse events
• dolutegravir plus lamivudine
• HIV infection
• real-world retrospective study
• virological suppression
• antiretroviral therapy

1. Introduction

With the widespread use of classical antiretroviral therapy (ART) combined with three-drug regimens, HIV infection has changed from fatal disease to a manageable chronic infectious disease [1]. The mortality rate of people living with human immunodeficiency virus (PLWHIV) has greatly reduced, and the life expectancy of patients who are HIV-positive is comparable to that of the general population [2].

Given the need to maintain treatment throughout life to prevent disease progression and reduce the risk of morbidity and mortality, researchers have studied simplification options with new antiretrovirals to minimize toxicity and support the sustained administration and effectiveness of ART [3]. During the last decade, less-drug regimens, mainly two-drug regimens (2DR) have been widely regarded a plausible alternative to the ‘standard’ three-drug regimens in virologically suppressed PLWHIV. The rationale for 2DR strategies lies in the expected improvement in the tolerability and safety profile without sacrificing virological efficacy.

Dolutegravir is a potent integrase inhibitor with a high genetic barrier to resistance, and is well-tolerated, administered once daily, with or without food, and has few known drug-drug interactions [4]. Dolutegravir plus lamivudine (DTG+3TC) has been evaluated in both ART-naïve and treated virologically suppressed patients. For example, the A5353 study [5], which restricted baseline HIV-1 RNA to <500,000 copies/mL, provided preliminary evidence for the efficacy of DTG+3TC over a 48-week course of treatment. In the GEMINI trials, the antiviral activity of DTG+3TC was comparable to that of DTG/tenofovir/emtricitabine in ART-naïve individuals with a baseline viral load <500,000 copies/mL, and no resistance was reported after 144 weeks [6]. The TANGO clinical trial showed that DTG+3TC was non-inferior in maintaining virological suppression compared to that with a tenofovir alafenamide-based three-drug regimen [7]. The International and Chinese Medical Association guidelines recommend DTG+3TC as the first-line regimen for ART-naïve individuals with HIV-1 infection and a viral load <500,000 copies/mL [1,8,9].

A plethora of real-world cohort, case-control, and case series studies have been conducted to investigate DTG 2DR in routine clinical practice [10]. Real-world evidence can provide data in populations that may be underrepresented in clinical trials, including women, older patients, and patients with multiple comorbidities. The use of real-world data can also assist in understanding the generalizability of randomized clinical trial findings to a more diverse population representative of those treated in routine clinical practice [11]. In addition, data are limited on the implementation of DTG+3TC in China. To address this knowledge gap, the present study evaluated real-world effectiveness and safety of DTG+3TC in PLHIV residing in Southwest China.

2. Patients and methods

2.1. Study design and setting

We conducted a single-center, observational, retrospective study that enrolled naïve (n = 36) and ART-exposed (n = 86) PLWHIV with HIV infection who were treated with DTG (50 mg) plus 3TC for any reason from January 2019 to April 2021. Data were collected up to 31 May 2022. The standard dose of 3TC was 300 mg, and patients with renal impairment at baseline received a reduced dose (150 mg or 100 mg).

2.2. Ethics approval and informed consent

The study was performed according to the principles of the Declaration of Helsinki, and prior approval was obtained from the institutional review board of research center. The institutional review board waived the requirement for written informed consent because this was a retrospective study and all patient data were analyzed anonymously.

2.3. Inclusion criteria

The inclusion criteria were HIV infection, age ≥18 years, using DTG+3TC for any reason between January 2019 and April 2021, data on the CD4 count and VL at baseline and 48 weeks, and followed up for at least 48 weeks. As this was a retrospective study and we included all eligible patients, we did not perform any sample size calculations.

2.4. Exclusion criteria

Patients were excluded if they had active hepatitis B virus infection, pregnancy, loss of follow-up or death, or if VL, CD4 count, and blood biochemistry data were not available at baseline and 48 ± 4 weeks.

2.5. Variables and data sources

Routine follow-up in the clinic were scheduled at weeks 2, 4, 8 or 12, 24, 36, and 48. Doctors scheduled the visits according to patients’ personal conditions. The routine standard of care were as follows: Once initiated on ART, patients had their VL, CD4 count, hematology, urinalysis, blood biochemistry, electrocardiogram, chest X-ray, ultrasound, and other relevant tests at the baseline visit. At weeks 2, 4 and 36, patients had their hematology, urine, and blood biochemistry tested. At week 8 or 12, patients had their VL, CD4 count, hematology, urine, and blood biochemistry tested. At weeks 24 and 48, patients had their VL, CD4 count, hematology, urinalysis, blood biochemistry tested.

The data were abstracted and collected from case report form and hospital laboratory system. Body weight, immunological response, and blood biochemistry were assessed at baseline and week 48. The clinical effectiveness of DTG+3TC was evaluated based on virological suppression and increases in the CD4 count at week 48. Safety was assessed throughout the study, including adverse events, drug-related adverse events, serious adverse events (SAEs), adverse events leading to discontinuation of DTG+3TC, and laboratory indicators. The primary endpoint was the proportion of patients with an HIV VL of <50 copies/mL at week 48. The secondary endpoints included the changes in body weight, CD4 count, and blood biochemistry; and adverse events of patients at week 48. Dyslipidemia was defined as a high total cholesterol (TC ≥5.2 mmol/L), triglyceride (TG ≥1.7 mmol/L), low high-density lipoprotein cholesterol (HDL-C < 1.0 mmol/L) or high low-density lipoprotein cholesterol (LDL-C ≥ 3.4 mmol/L). Dyslipidemia was present if any one of these four lipid parameters was abnormal [12]. Osteopenia was defined as a T value of less than or equal to −1 on dual energy X-ray bone mineral density examination [13].

2.6. Statistical analysis

Qualitative variables were reported as frequency distributions, whereas quantitative variables were described as the median with interquartile ranges (IQR) or the mean with standard deviation (SD). The Kolmogorov–Smirnov test was used to determine whether numerical variables fit the assumptions for normality of distribution. A Students t-test was used to compare normally distributed independent variables between baseline and week 48, while the Mann–Whitney U test was used for continuous numerical variables that followed a non-normal distribution. Statistical significance was set at p < 0.05. Statistical analyses were performed using SPSS version 23.0 (IBM, Armonk, NY, USA).

3. Results

3.1. Patient characteristics

The patient selection process is shown in Figure 1. A total of 140 patients received DTG+3TC for any reason between January 2019 to April 2021. One ART-naïve patient discontinued DTG + 3TC due to economic difficulties and three patients did not complete 48 weeks follow-up. Seven ART-experienced patients had missing baseline data, two patients discontinued DTG + 3TC, and an additional five patients did not complete 48 weeks follow-up. The study sample (n = 122) comprised 36 ART-naïve and 86 ART-exposed patients. The baseline characteristics of the patients are described in Table 1.

Figure 1. Flowchart of patients with dolutegravir plus lamivudine.

Table 1. Baseline characteristics of study patients (n = 122).

Characteristic	ART-naïve (N = 36)	ART-experienced (N = 86)
Sex, n(%)
Male	29 (80.6)	72 (83.7)
Female	7 (19.4)	14 (16.3)
Age median (IQR), year	76.0 (71.3–78.8)	59.0 (37.0–70.3)
Age ≥60 years, n (%)	32 (88.9)	42 (48.8)
CD4 count
Median (IQR), cells/μL	205.0 (123.3–310.3)	269.5 (186.3–444.5)
<200 cells/µL, n (%)	17 (47.2)	25 (29.1)
≥200 cells/µL, n (%)	19 (52.8)	61 (71.9)
HIV viral load, copies/mL, n (%)
<50	0 (0)	74 (86.0)
50–499,999	28 (77.8)	12 (14.0)
≥500,000	8 (22.2)	0 (0)
CKD-EPI Scr ≤60 mL/min, n (%)	21 (58.3)	34 (39.5)
Comorbidities, n (%)
Cardiovascular disease	19 (52.7)	17 (19.8)
Diabetes	9 (25.0)	8 (9.3)
Renal impairment	21 (58.3)	34 (39.5)
AIDS-related opportunistic infections, n (%)	11 (30.5)	21 (37.5)
Primary reasons for use of DTG+3TC, n (%)
Low potential for interaction	16 (44.4)	4 (4.7)
Renal impairment	10 (27.8)	18 (20.9)
Easy to take	6 (16.7)	6 (7.0)
Reduce drug burden	3 (8.3)	4 (4.7)
Dyslipidemia	1 (2.8)	9 (10.5)
Osteopenia	0 (0)	12 (14.0)
Simplification/Optimization	0 (0)	9 (10.5)
Side effects of previous ART	0 (0)	14 (16.2)
Others	0 (0)	10 (11.6)
Previous ART, n (%)
2NRTIs+NNRTIs	NA	37 (43.0)
2NRTIs+INSTIs	NA	34 (39.5)
Other	NA	15 (17.5)
Previous TDF-based regimen, n (%)	NA	50 (58.1)

Abbreviations: 3TC, lamivudine; AIDS, acquired immunodeficiency syndrome; ART, antiretroviral treatment; CKD-EPI Scr, Chronic Kidney Disease Epidemiology Collaboration base Serum creatinine; DTG, dolutegravir; INSTIs, integrase inhibitors; IQR, interquartile range; NA, not applicable; NNRTIs, non-nucleoside reverse transcriptase inhibitors; NRTIs, nucleoside reverse transcriptase inhibitors; TDF, tenofovir disoproxil fumarate.

The ART-naïve group was predominantly male (80.6%), with a median age of 76.0 years (IQR, 71.3–78.8 years), with 32 (88.9%) patients aged ≥60 years. In this group, eight patients (22.2%) had a baseline HIV VL >500,000 copies/mL, and 17 patients (47.2%) had a baseline CD4 count of <200 cells/μL. The prevalence of cardiovascular disease was 52.7%. The main reasons for choosing DTG+3TC included a low potential for drug-drug interactions (44.4%) and renal impairment (27.8%) (Table 1).

The ART-experienced group also consisted primarily of male patients (83.7%), with a median age of 59.0 years (IQR, 37.0–70.3 years), and 48.8% of patients were ≥60 years old. At baseline, 74 (86.0%) patients had virological suppression (HIV VL <50 copies/mL), with a median CD4+ count of 269.5 cells/μL (range, 186.3–444.5 cells/μL). The reasons for using DTG+3TC in this group included renal impairment (20.9%) and osteopenia (14.0%). Prior to switching to DTG+3TC, 50 (58.1%) patients had received tenofovir disoproxil fumarate (TDF), and 12 (14.0%) patients had detectable VL levels (≥50 copies/mL) (Table 1).

3.2. Dolutegravir and lamivudine effectiveness

The virologic suppression rate was 97.2% (35/36) in the ART-naïve group at week 48. The virological inhibition rates at week 48 for baseline CD4 count < 200 cells/μL and ≥200 cells/μL were 94.1% and 100%, respectively (Figure 2). Of the eight ART-naïve patients with an HIV VL ≥500,000 copies/mL, seven (88.8%) had HIV VL <50 copies/mL after 48 weeks of treatment (Table 2). One ART-naïve patient achieved virological inhibition at 24 weeks and then HIV VL had increased to 42,400 copies/mL at 48 weeks, due to skipping pills for 75 days during the follow-up (Table 2).

Figure 2. Analysis of patients with an HIV viral load <50 copies/ml at week 48. At week 48, 97.2% of ART-naïve and 97.7% of ART-experienced patients had a viral load <50 copies/mL. Among patients with baseline CD4 count <200 cells/µL, 94.1% of ART-naïve and 95.8% of ART-experienced patients had a viral load <50 copies/mL. Abbreviation: ART, antiretroviral therapy.

Table 2. Follow-up data of ART-naïve PLHIV with an HIV viral load ≥500,000 copies/mL.

Number	Age (year)	Sex	HIV viral load (copies/mL)				CD4 count (cells/μL)		Side effects of ART	Skipping pills (days)
			Baseline	8 w	24 w	48 w	Baseline	48 w
1	82	Male	1,000,000	122	69.3	< 20	147	245	Rash	0
2	90	Male	839,000	99.4	< 20	45.4	53	333	No	0
3	77	Male	771,000	NA	29	TND	168	346	No	0
4	76	Male	698,000	96.6	TND	TND	106	133	No	0
5	78	Male	568,000	170	< 20	34	106	234	No	0
6	79	Male	552,000	< 20	TND	TND	24	136	No	0
7	20	Male	557,000	60.4	TND	TND	161	328	No	0
8	75	Male	545,000	951	TND	42400	44	222	No	75

Abbreviations: ART, antiretroviral treatment; NA, not applicable; TND, not detected.

Of the 86 ART-experienced patients, 84 (97.7%) had a VL <50 copies/mL at week 48. The virological inhibition rates at week 48 for baseline CD4 count <200 cells/μL and ≥200 cells/μL were 95.8% and 98.4%, respectively (Figure 2). Among the 12 ART-experienced patients with an HIV VL ≥50 copies/mL, 11 of them with combined diseases and 91.7% (11/12) had an HIV VL <50 copies/mL at week 48 (Table 3). Of the two patients with an HIV VL ≥50 copies/mL at week 48, one patient experienced persistent low-level viremia on ART, but no information was available regarding drug resistance. The other patient had a VL >50 copies/mL at 48 weeks due to discontinuing DTG+3TC for 30 days during the follow-up.

Table 3. Details of antiretroviral therapy-experienced patients with an HIV viral load more than 50 copies/mL at baseline.

Number	Age (years)	Comorbidities	Main reason for use of DTG+3TC	HIV VL (copies/mL)		CD4 count (cells/μL)
				Baseline	48 w	Baseline	48 w
1	60	TB, CM, syphilis	Reduce drug burden	635	TND	196	190
2	84	TB, herpes zoster	Reduce drug burden	473	TND	419	217
3	74	PJP, renal impairment, TM	Low potential for interaction	404	TND	28	145
4	78	CVD, thrombocytopenia	Intolerable dizziness	23,900	TND	157	310
5	38	syphilis, dyslipidemia	Dyslipidemia	69.2	TND	388	503
6	88	CVD, COPD, renal impairment	Reduce nephrotoxicity	189	TND	183	340
7	82	Hypertension, renal impairment	Reduce nephrotoxicity	60.3	TND	218	243
8	68	Renal impairment, fungal infection	Reduce nephrotoxicity	649	74	69	538
9	72	CVD, renal impairment	Gasrointenstinal side effects	118	TND	184	346
10	36	NA	ABC/3TC/DTG regimen not available	61.9	TND	166	246
11	79	Renal impairment	Reduce nephrotoxicity	233	TND	198	300
12	69	Renal impairment, syphilis	Reduce nephrotoxicity	216,000	TND	110	378

Abbreviations: 3TC, lamivudine; ABC, abacavir; ART, antiretroviral therapy; CM, cryptococcal meningitis; COPD, chronic obstructive pulmonary disease; CVD, cardiovascular disease; DTG, dolutegravir; NA, not applicable; PJP, Pneumocystis jiroveci pneumonia; TB, tuberculosis; TM, Talaromyces marneffei; TND, not detected; VL, viral load.

Among 36 naïve patients, the 3TC dose was adjusted to 150 mg in 8 patients, and 100 mg in one patient at baseline due to renal impairment (Table 4).

Table 4. Follow-up data of ART-naïve patients with 3TC dose adjusted at baseline.

Number	Age (years)	3TC dose (mg)	Viral load (copies/mL)		CD4 count (cells/μL)		Scr (µmol/L)		CKD-EPI Scr (mL/min)
			Baseline	48 wk	Baseline	48 wk	baseline	48 wk	baseline	48 wk
1	76	100	46,100	TND	648	337	199.6	225.1	21.17	18.82
2	77	150	24,600	TND	123	438	92.1	91.5	38.47	40.59
3	74	150	345,000	TND	376	644	106.0	115.4	38.06	37.87
4	78	150	93,300	TND	134	89	114.8	80.8	28.39	38.76
5	72	150	136,000	TND	209	152	101.6	144.7	27.12	21.65
6	71	150	119,000	TND	180	208	154.5	91.1	40.95	68.44
7	82	150	110,000	TND	205	238	87.0	97.0	46.45	39.51
8	80	150	3110	TND	337	310	107.4	106.1	40.98	39.09

Abbreviations: 3TC, lamivudine; ART, antiretroviral therapy; CKD-EPI Scr, Chronic Kidney Disease Epidemiology Collaboration-based serum creatinine; NA, not applicable; TND, not detected.

3.3. Immunological response and biological outcomes

Body weight, immunological response, and biochemical indices of the patients after using the DTG+3TC regimen for 48 weeks are summarized in Figure 3.

Figure 3. Changes in biochemical indices between baseline and week 48. (a) Body weight, immunological response, and biochemical indices of ART-naïve patients after using the DTG+3TC regimen. (b) Body weight, immunological response, and biochemical indices of ART-experienced patients after using the DTG+3TC regimen. Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; CKD-EPI Scr, Chronic Kidney Disease Epidemiology Collaboration-based serum creatinine; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-dendensity lipoprotein cholesterol; Scr, serum creatinine; TC, total cholesterol; TG, triglyceride. *, expressed as mean ± standard deviation.

Among the 36 ART-naïve patients, the CD4 count significantly increased by 80.2 cells/μL (P = 0.012), and the CD4+/CD8+ ratio increased by 0.29 (P < 0.001). Serum creatinine (Scr), TC, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) increased significantly (p = 0.017, p = 0.004, p = 0.026, and p = 0.003, respectively). There were no significant changes in body weight, alanine aminotransferase, aspartate aminotransferase, chronic kidney disease epidemiology collaboration-based serum creatinine (CKD-EPI Scr), and triglyceride (TG) from baseline to week 48 (P > 0.05, Figure 3a).

Among the 86 ART-experienced patients, the CD4 count increased significantly by 79 cells/μL (P = 0.021), and the triglyceride decreased significantly by 0.37 mmol/L (P = 0.008). The Scr increased significantly (P = 0.030). There were no significant changes in body weight, CD4+/CD8+ ratio, alanine aminotransferase, aspartate aminotransferase, CKD-EPI Scr, TC, or HDL-C (P > 0.05, Figure 3b).

3.4. Adverse events

The estimated rates of drug-related adverse events in the ART-naïve group and ART-experienced group were 16.7% and 4.7%, respectively (Table 5). One patient’s breast enlargement was shown by ultrasound in the external hospital at week 7 and we were not sure if it was related to DTG+3TC regimen. No adverse effects led to the discontinuation of DTG+3TC at week 48. Two (5.6%) patients had SAEs (renal impairment) that required hospitalization. Patient 1 was a 94-year-old man with a history of hypertension, type 2 diabetes, chronic bronchitis, and renal impairment (baseline CKD-EPI Scr, 32.8 mL/min). Patient 2 was a 77-year-old man with a history of renal impairment (baseline CKD-EPI Scr: 42.5 mL/min); He developed pulmonary tuberculosis, and multiple blood tests revealed hyperglycemia.

Table 5. Overview of adverse events associated with DTG+3TC in our patient sample.

Adverse events	ART-naïve N (%)	ART-experienced N (%)
Any adverse event	7 (19.4)	5 (5.8)
Lumbago	1 (2.8)	0 (0)
Headache	1 (2.8)	2 (2.3)
Fatigue	2 (5.6)	1 (1.2)
Gastrointestinal	2 (5.5)	2 (2.3)
Breast enlargement	1 (2.8)	0 (0)
Drug-related adverse event	6 (16.7)	4 (4.7)
Rash	2 (5.5)	0 (0)
Kidney abnormality	1 (2.8)	3 (3.5)
Dyslipidemia	3 (8.3)	1 (1.2)
Discontinuation due to adverse event	0 (0)	0 (0)
Serious adverse event	2 (5.6)	0 (0)

Abbreviations: 3TC, lamivudine; ART, antiretroviral therapy; DTG, dolutegravir.

4. Discussion

In this retrospective study of DTG+3TC treatment in PLHIV living in Southwest China, a high viral suppression rate was observed at week 48 in both ART-naïve and ART-experienced patients. No patients discontinued DTG+3TC due to adverse events.

Virological and immunological indicators are reliable for predicting disease progression and evaluating antiviral effectiveness. These markers can also independently predict the clinical processes and survival of patients with HIV/AIDS [1]. DTG+3TC has demonstrated non-inferiority to tenofovir-based regimens for individuals who are ART-naïve and virologically suppressed on another regimen [6,7]. In our study, one ART-naïve patient and two ART-experienced patients had virological failure at week 48, which is consistent with the findings of previous studies [2,5–7]. Eight of the 36 ART-naïve patients (22.2%) had a baseline viral load of >500,000 copies/mL, of whom seven had a VL <50 copies/mL at week 48, which is consistent with the results of the GEMINI 1 and 2 and the STAT studies [6,14]. In the GEMINI 1 and 2 studies, among 13 ART-naïve participants with a baseline VL of >500,000 copies/mL, 11 (84.6%) had a viral load of <50 copies/mL at week 48. In the STAT study, among the 19 participants with a baseline HIV VL of ≥500,000 copies/mL, the levels were suppressed to less than 50 copies/mL at week 24 in 13 (68%) of them. Among the 12 ART-experienced patients with an VL ≥50 copies/mL, only one had a VL ≥50 copies/mL after 48 weeks of DTG+3TC.

The CD4+/CD8+ ratio, which naturally decreases with age, is associated with increased mortality, and is considered a marker of both acute and chronic inflammation. After the initiation of ART, there is an increase in the CD4 count and a decrease in the CD8 count [15]. In our study, the CD4 count of the patients increased at week 48 of DTG+3TC treatment, suggesting that the immune function of the patients improved after ART with DTG+3TC, which is consistent with the results of most previous studies [3–7,16].

In patients with HIV and comorbidities, simplifying the medication regimen can reduce drug-drug interactions and reduce the risk of kidney dysfunction. In this study, 88.9% of ART-naïve patients and 48.8% of ART-experienced patients were aged ≥60 years. These patients had a high proportion of comorbidities, including cardiovascular disease, cerebrovascular diseases, and type II diabetes mellitus. The main reasons for choosing DTG+3TC included a low potential for drug-drug interactions and low risk of renal impairment, suggesting that this regimen is a good choice for older patients with comorbid chronic non-communicable diseases.

Medication compliance is an important factor that affects the effectiveness of ART. Poor compliance is a major risk factors for limited ART effectiveness in patients with HIV. If medication is not taken regularly, the virus cannot be easily suppressed [17]. Three patients had virologic failure at 48 weeks, of whom two patients experience virological rebound due to missing their doses of medication [18]. DTG is known to inhibit the organic cation transporter 2 on the basolateral side of the proximal tubule cells of the kidney, and leads to increased serum creatinine levels, although it does not cause a true impairment in renal functioning. There was a significant increase in Scr levels both in ART-naïve (p = 0.017) and ART-experienced (p = 0.030) patients at 48 weeks in our study, which was within the normal range. This observation was consistent with those from other switch trials [3,19,20]. Dyslipidemia, characterized by elevated LDL-C or TC levels, is an important risk factor for atherosclerosis and cardiovascular disease [12]. The prevalence of dyslipidemia in Chinese adult HIV/AIDS patients has increased up to 75.6%, and is characterized by high triglyceride and low HDL-C levels [21]. Within this cohort, we found a significant increase in TC (p = 0.004) and LDL-C (p = 0.003) after 48 weeks of treatment with 3TC+DTG in ART-naïve patients, which is consistent with the results of a pooled analysis of the ongoing fully powered phase clinical trials, GEMINI 1 and 2 [6]. In GEMINI 1 and 2 trials, TC, LDL cholesterol, and total triglycerides increased from baseline to week 48 in the DTG+3TC regimen, and a significantly greater increase was observed in these indexes than in the three-drug regimen group. The overall risk of atherosclerosis and cardiovascular disease is dependent on a complex interaction between cholesterol levels and other cardiovascular risk factors. It is suspected that the increase in blood lipids may be due to the fact that approximately half of the ART-naïve patients in this study had cardiovascular disease complications. In addition, there were no significant changes in body weight. The TG levels of ART-experienced patients decreased at week 48, which was consistent with the results of the DOLAMA study and TANGO study [3,7].

In this study, we found that no discontinuation of the DTG+3TC regimen due to adverse drug-related events at week 48. This shows that DTG+3TC is tolerable and safe, which play a very important role toward ensuring adherence to long-term treatment. The limitations of our study included its retrospective, single, small sample size, open-label, and non-comparator group design, and the restrictive exclusion criteria also limited information on the effectiveness and safety of DTG+3TC in the excluded population.

5. Conclusions

The results of this study suggest that DTG+3TC is a safe option to achieve and maintain virological suppression, in both ART-naïve patients with a high VL and ART-experienced patients with residual viremia at baseline. As this regimen has few drug-related adverse events, it ensured increased patient compliance and adherence. However, it is necessary to pay attention to the dyslipidemia in ART-naïve patients with comorbidities and intervene promptly.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

Xiaoyan Yang, Xiaoxin Xie and Yanhua Fu contributed to the conception and design of the research. The methodology and analysis plan were constructed by Hai Long and Jun Li. Hai Long and Lin Gan were responsible for the study design and analysis plan and carried out the data monitoring; Lin Gan performed the statistical analysis. Xiaoxin Xie, Yanhua Fu, Chunli Song and Yebin Song contributed to the interpretation of data. Xiaoyan Yang wrote the original draft. All authors substantially contributed to the conception and design of the article and interpreting the relevant literature and were involved in writing the article or revised it for intellectual content. All authors agreed on the submission of the manuscript to the journal and reviewed and agreed on all versions of the article before submission, during revision, the final version accepted for publication, and significant changes introduced at the proofing stage. All authors had access to the study data and take responsibility for the integrity of the data and accuracy of the data analysis.

Acknowledgment

We thank the site staff who supported the study.

Data availability statement

The datasets used or analysed during the current study available from the corresponding author on reasonable request.

Additional information

Funding

This work was supported by the Science and Technology Foundation of Guizhou Province (Qian kehe support [2021] 055).