Abstract
Background:
The WHO and international treatment guidelines recommend rapid initiation of antiretroviral therapy (ART) for all treatment-naive (TN) people living with human immunodeficiency virus (HIV) (PLWH). However, data on temporal trends and clinical outcomes of ART initiation and regimen selection among TN PLWH remain limited in China. This study is designed to evaluate the real-world effectiveness of contemporary treatment strategies within the Chinese context.
Methods:
We conducted a retrospective study of 1,460 TN PLWH who initiated ART between January 2021 and December 2023 at Beijing Ditan Hospital. Data on sex, age, initiation time, ART regimens, CD4 counts, and HIV viral load were collected. Initiation time was categorized based on the time from diagnosis to ART initiation: same-day initiation (0 days), rapid initiation (1 – 7 days), regular initiation (8 – 30 days), and delayed initiation (> 30 days). The main endpoint was the rate of PLWH with virological suppression (HIV-1 RNA < 40 copies/mL) during the study period. Additionally, the durability of ART regimens and the CD4 T-cell count recovery were also evaluated. Factors associated with regimen durability were assessed using univariate and multivariate Cox proportional hazards models. Generalized estimating equations (GEE) were used to identify factors associated with virological suppression among TN PLWH.
Results:
From 2021 to 2023, the proportion of patients with same-day initiation and that of patients with rapid initiation significantly increased, rising from 8.4% (55/656) to 14.0% (69/493) and from 49.5% (325/656) to 57.6% (284/493), respectively (P < 0.001). Furthermore, 32.9% (46/140) and 36.3% (269/741) of PLWH who underwent same-day and rapid initiation, respectively, chose initial regimens containing two nucleoside reverse transcriptase inhibitors plus a non-nucleoside reverse transcriptase inhibitor. A representative regimen was efavirenz, lamivudine, and tenofovir disoproxil fumarate (EFV+3TC+TDF). All patients achieved a viral suppression rate of over 95.0% at the 24- and 36-month follow-up visits. In TN PLWH who adhered to initial regimens, GEE analysis of virological suppression factors showed both bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and dolutegravir/lamivudine (DTG/3TC) were non-inferior to EFV+3TC+TDF (odds ratio [OR] = 1.34, 95% confidence interval [CI]: 0.75 – 2.39, P = 0.318; OR = 1.92, 95% CI: 0.54 – 6.80, P = 0.311, respectively). Moreover, BIC/FTC/TAF and DTG/3TC were associated with a lower likelihood of regimen switching, with hazard ratios of 0.35 (P < 0.001) and 0.39 (P = 0.004). Besides, BIC/FTC/TAF achieved CD4 T cell counts above 350 cells/μL significantly earlier (P = 0.015).
Conclusion:
Our findings revealed the positive trend in rapid initiation in China and several challenges in clinical practice. More targeted interventions are needed to promote the use of BIC/FTC/TAF and DTG/3TC, enhance the accessibility, and ultimately improve health outcomes for PLWH.
Keywords: HIV, Virological suppression, Outcomes, Initiation types, ART regimens
1. Introduction
In 2017, the WHO recommended rapid antiretroviral therapy (ART) initiation for all individuals newly diagnosed with human immunodeficiency virus (HIV).[1] Rapid initiation has been well demonstrated to play a crucial role in long-term treatment adherence, decreasing the time to achieve virological suppression and reducing the risk of HIV transmission,[2–5] which can contribute to progress toward achieving the Joint United Nations Programme on HIV 95-95-95 targets.[6]
The development of new nucleoside and non-nucleoside reverse transcriptase inhibitors (NRTIs and NNRTIs), protease and integrase inhibitors (PIs and INSTIs),[7] as well as adjustments of the National Reimbursement Drug List (NRDL) and the National Free Antiretroviral Treatment Program (NFATP), has expanded the initial regimen options available for treatment-naive people living with HIV (PLWH). There have been several regimens recommended for rapid initiation, such as bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and lamivudine and tenofovir disoproxil fumarate plus dolutegravir (3TC+TDF+DTG).[8,9] Several randomized controlled trials and observational studies have reported high efficacy and safety of BIC/FTC/TAF among PLWH with rapid initiation.[10–13] However, not all PLWH can afford these regimens. BIC/FTC/TAF is a co-paid ART regimen included in the NRDL, while DTG is not reimbursed.
In real-world settings, the initial regimen options may be influenced by various factors, such as economic considerations, which render the process inherently complex. The NFATP fully covers the cost of efavirenz plus lamivudine/tenofovir disoproxil fumarate (EFV+3TC+TDF), making it the most widely prescribed initial regimen in China despite its association with neuropsychiatric adverse effects.[11,14,15] Nationwide, 80%–90% of TN (treatment-naive) PLWH initiate ART with EFV+3TC+TDF.[16]
Although recent randomized controlled trials have focused on the efficacy of various regimens,[11,13,17] real-world studies can provide complementary insights and contribute to the understanding of the genuine use and clinical outcomes.[18] Herein, we aimed to evaluate temporal trends in ART initiation timing (same-day, rapid, regular, and delayed initiation) and compare clinical outcomes (virological suppression rates, regimen durability, and CD4 recovery) across different ART regimens among treatment-naive PLWH at a tertiary specialist hospital in Beijing, China. Our study could provide some insight into the real-world effectiveness of current treatment strategies in China.
2. Methods
2.1. Ethical approval
The study adhered to the Declaration of Helsinki and was approved by the Ethics Committee of Beijing Ditan Hospital (NO.DTEC-KY2025-122-01). The requirement for informed consent was waived by the Ethics Committee of Beijing Ditan Hospital because of the retrospective nature of the study.
2.2. Research design and population
This single-center retrospective study was conducted at Beijing Ditan Hospital in China, including TN PLWH who initiated ART from January 2021 to December 2023. The inclusion criteria were as follows: 1) individuals with confirmed HIV infection; 2) TN before ART initiation; 3) initiated ART at Beijing Ditan Hospital during the study period; and 4) had available baseline demographic and HIV-related clinical data. TN PLWH who were diagnosed with HIV at other institutions and subsequently transferred to Beijing Ditan Hospital were excluded, because their exact date of HIV diagnosis could not be reliably confirmed. A total of 1,460 TN PLWH were included in the final analysis. Demographic data and HIV-related characteristics were collected. The primary objective was to evaluate the viral suppression outcomes during the study period, while the secondary objective was to assess the regimens switch rates and CD4 recovery. The data cutoff date was June 30, 2024. The detailed study design could be found in Figure 1. Seventeen PLWH were lost to follow-up in our cohort. As each of these individuals had at least two documented medical encounters, their data were included in the subsequent analyses.
Figure 1.
The design of this study. Variables including age, sex, baseline HIV ribonucleic acid (HIV-RNA), nadir CD4 count, pre-ART CD4/CD8 ratio, treatment regimens, and initiation time types were included in the Cox proportional-hazards model and generalized estimating equations (GEE) models. Seventeen people living with HIV (PLWH) were lost to follow-up in this cohort; however, as each had at least two documented medical encounters, they were included in the subsequent analysis. ART: Antiretroviral therapy; CD: Cluster of differentiation; HIV: Human immunodeficiency virus; TN: Treatment-naive.
2.3. Data collection
Demographic data included sex, age, and time to ART initiation. HIV-related clinical characteristics, including ART regimens, HIV viral load, CD4 counts, and CD4/CD8 ratio, were collected from the medical records. The follow-up time was calculated in months from ART initiation until the loss to follow-up or the end of the study period, whichever occurred first.
All data mentioned above were extracted from both the China Disease Prevention and Control Information System and DongHua Medical Information System of Beijing Ditan Hospital, followed by a deterministic matching to ensure the accuracy and reliability of the data collected.
2.4. Definitions
Virological suppression was defined as HIV-RNA <40 copies/mL. Initiation types were categorized into four groups based on the time from diagnosis to treatment initiation: same-day initiation (0 days), rapid initiation (1–7 days), regular initiation (8–30 days), and delayed initiation (>30 days). Regimen switch involved changing to any new regimen with a different specific drug combination than the original, such as switching from elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF, one type of 2 NRTIs + INSTI) to BIC/FTC/TAF (another type of 2 NRTIs + INSTI). The regimen maintenance rate was defined as the proportion of PLWH who continued using their initial regimen without switching. Loss to follow-up was defined as having no documented medical encounter for more than 6 months.
2.5. Statistical analyses
Continuous numerical variables are described as median (Q1, Q3). For the normality test, Shapiro-Wilk test was used for small samples (n < 50) and Kolmogorov-Smirnov test was used for large samples (n ≥ 50). The Kruskal-Wallis test is used for comparing non-normally distributed continuous variables. Percentages and frequencies were used to describe categorical data. The comparison was performed with the chi-squared test or Fisher’s exact test for categorical variables. Univariate and multivariate Cox analyses were conducted to evaluate factors associated with the switching of regimens/specific drug combinations. Age, sex, baseline HIV-1 RNA, nadir CD4 counts, pre-ART CD4/CD8 ratio, initial regimens/specific drug combinations and initiation types are included in Cox analyzes. The generalized estimating equation (GEE) analysis was used to assess the association between virological suppression and various variables that were included in Cox analyzes, as well as their relationship with changes in the CD4/CD8 ratio. For the Kaplan-Meier (KM) curves, the survival package was used to test the proportional hazards assumption, with results visualized using the ggplot2 packages to create curves. Since the proportional hazards assumption was violated, a Log-rank test was employed. Statistical significance was set at P < 0.05. R stats package, survival package and gee package (4.4.2) were utilized for the comparison of continuous numerical and categorical variables, Cox and GEE analyses, respectively.
As this was a retrospective, real-world cohort study, no formal sample size calculation was performed. Instead, we included all TN PLWH who initiated ART at Beijing Ditan Hospital between January 2021 and December 2023 and met the eligibility criteria. The final sample size was thus determined by the number of eligible individuals during the study period.
3. Result
3.1. Baseline characteristics of the cohort
There were 17 PLWH lost to follow-up data in our cohort. As each of these individuals had at least two documented medical encounters, they were included in the subsequent analyses. The characteristics of participants are presented in Table 1. Compared to the regular and delayed initiation, the same-day and rapid initiation demonstrated a preference for using 2 NRTIs + INSTI as the initial regimen (42.4% (205/484), 38.9% (37/95), 57.9% (81/140) and 50.9% (377/741), respectively; P = 0.012). There were no significant differences found in other indicators.
Table 1.
Demographics and baseline characteristics of study population
| Characteristics | Same-day initiation (n = 140) | Rapid inititation (n = 741) | Regular initiation (n = 484) | Delayed initiation (n = 95) | P value |
|---|---|---|---|---|---|
| Sex, n (%) | 0.300 | ||||
| Male | 138 (98.6) | 710 (95.8) | 460 (95.0) | 92 (96.8) | |
| Female | 2 (1.4) | 31 (4.2) | 24 (5.0) | 3 (3.2) | |
| Age (years), median (Q1, Q3) | 33 (29, 38) | 33 (29, 42) | 34 (28, 43) | 34 (28, 42) | 0.803 |
| Nadir CD4 counts (cells/μL), n (%) | 0.480 | ||||
| <200 | 39 (27.9) | 178 (24.0) | 109 (22.5) | 19 (20.0) | |
| ≥200 | 101 (72.1) | 563 (76.0) | 375 (77.5) | 76 (80.0) | |
| Pre-ART CD4/CD8 ratio, n (%) | 0.961 | ||||
| <0.4 | 90 (64.3) | 485 (65.5) | 309 (63.8) | 64 (67.4) | |
| 0.4–0.7 | 37 (26.4) | 192 (25.9) | 127 (26.2) | 21 (22.1) | |
| ≥7 | 13 (9.3) | 64 (8.6) | 48 (9.9) | 10 (10.5) | |
| Baseline HIV-1 RNA (log10 copies/mL), median (Q1, Q3) | 4.3 (3.7, 4.8) | 4.2 (3.4, 4.9) | 4.3 (3.4, 4.9) | 4.1 (2.9, 4.7) | 0.672 |
| Initial cART regimen, n (%) | 0.012 | ||||
| 2 NRTIs + NNRTI | 46 (32.9) | 269 (36.3) | 218 (45.0) | 42 (44.2) | |
| 2 NRTIs + INSTI | 81 (57.9) | 377 (50.9) | 205 (42.4) | 37 (38.9) | |
| 2 NRTIs + PI/r | 3 (2.1) | 33 (4.5) | 26 (5.4) | 6 (6.3) | |
| Dual therapies | 10 (7.1) | 62 (8.4) | 35 (7.2) | 10 (10.5) |
The Kruskal-Wallis test is used for comparing continuous variables and the Chi-Squared test or Fisher’s exact test for categorical variables. cART: Combination antiretroviral therapy; Q1, Q3: 25th percentile, 75th percentile; INSTI: Integrase strand transfer inhibitor; NNRTI: non-nucleoside reverse transcriptase inhibitor; PI/r: Protease inhibitor boosted with ritonavir; HIV: Human immunodeficiency virus.
Overall, the proportion of PLWH initiating ART with same-day and rapid initiation increased (from 8.4% (55/656) to 14.0% (69/493) and 49.5% (325/656) to 57.6% (284/493), respectively; P < 0.001), as detailed in Figure 2A. Figure 2B shows an increasing percentage of PLWH starting ART on 2 NRTIs + INSTI (from 37.2% (244/656) to 58.4% (288/493); P < 0.001). Meanwhile, the use of 2 NRTIs + NNRTI decreased (from 56.1% (368/656) to 23.5% (116/493); P < 0.001). Similar trends were also observed in the use of initial ART specific drug combinations (Figure 2C). As shown in Figure 2D, the primary regimens representing different classes demonstrated high maintenance rates. Specifically, the proportions for EFV+3TC+TDF (2 NRTIs + NNRTI), BIC/FTC/TAF (2 NRTIs + INSTI), lopinavir/ritonavir (LPV/r)+3TC+TDF (2 NRTIs + PI/r), and DTG/3TC (dual therapy) were 560/575, 507/700, 57/68, and 114/117, respectively. Besides, 32.9% (46/140) and 36.3% (269/741) of PLWH with same-day and rapid initiation, respectively, opted for 2 NRTIs + NNRTIs (represented by EFV+3TC+TDF) as an initial regimen (Table 1).
Figure 2.
Trends in ART initiation types and regimens over three consecutive periods. (A) Distribution of initiation time types (Delayed, Regular, Rapid, and Same-day initiation) across three periods. (B) Proportion of different initial ART regimens: Dual therapies, 2 NRTIs + PI/r, 2 NRTIs + INSTI, and 2 NRTIs + NNRTI. (C) Specific drug combinations within each period, including DTG/3TC, LPV/r+3TC+TDF, BIC/FTC/TAF, and EFV+3TC+TDF. (D) Overall proportions of ART regimens with corresponding specific drug combinations across all periods. ART: Antiretroviral therapy; NRTIs: Nucleoside reverse transcriptase inhibitors; PI/r: Protease inhibitor boosted with ritonavir; NNRTIs: Non-nucleoside reverse transcriptase inhibitors; INSTIs: Integrase inhibitors; DTG: Dolutegravir; 3TC: Lamivudine; BIC: Bictegravir; FTC: Emtricitabine; TAF: Tenofovir alafenamide; TDF: Tenofovir disoproxil fumarate; LPV/r: Lopinavir/ritonavir; EFV: Efavirenz.
3.2. The retention rate of antiretroviral therapy regimens
A higher percentage of PLWH with DTG/3TC maintained their regimen compared to EFV+3TC+TDF (93.9% (107/114) vs. 67.0% (375/560), P < 0.001; Figure 3B). The KM curves (Figure 3C and D) showed the maintenance rate changes over 36 months for each initial ART regimen. Of note, the discrepancy in the KM curves and bar plots for 2 NRTIs + INSTI and BIC/FTC/TAF (Figure 3C and D) could be attributed to a subset of PLWH who initiated with E/C/F/TAF. All these PLWH switched to other regimens over the three-year period (Figure S1A, http://links.lww.com/IDI/A72), which significantly contributed to the discrepancy.
Figure 3.
ART regimen continuation rates and time to switch among different regimens. (A) Proportion of ART regimen continuation versus switching by initial ART regimen type. (B) Proportion of ART regimen continuation versus switching by specific drug combination. (C) Kaplan-Meier curve of time to regimen switch by ART regimen type (2 NRTIs + NNRTI, 2 NRTIs + INSTI, 2 NRTIs + PI/r, and Dual therapies). (D) Kaplan-Meier curve of time to regimen switch by specific drug combination (EFV+3TC+TDF, BIC/FTC/TAF, LPV/r+3TC+TDF, and DTG/3TC). ART: Antiretroviral therapy; NRTIs: Nucleoside reverse transcriptase inhibitors; PI/r: Protease inhibitor boosted with ritonavir; NNRTIs: Non-nucleoside reverse transcriptase inhibitors; INSTIs: Integrase inhibitors; DTG: dolutegravir; 3TC: Lamivudine; BIC: Bictegravir; FTC: Emtricitabine; TAF: Tenofovir alafenamide; TDF: tenofovir disoproxil fumarate; LPV/r: lopinavir/ritonavir; EFV: efavirenz.
The covariate-adjusted Cox regression analysis (Table 2) suggested that BIC/FTC/TAF and DTG/3TC were independent factors for lower risk of regimen switching (HR: 0.35, 95% CI: 0.25 – 0.50, P < 0.001; HR: 0.39, 95% CI: 0.21 – 0.74, P = 0.004).
Table 2.
Univariate and multivariate Cox regression analysis of factors associated with regimen switching among PLWH (n = 1,460)
| Characteristics | Univariate analysis | Multivariate analysis | ||
|---|---|---|---|---|
| HR (95% CI) | P value | HR (95% CI) | P value | |
| Age | ||||
| <50 years | Reference | / | / | |
| ≥50 years | 1.12 (0.77 – 1.61) | 0.560 | / | / |
| Sex | ||||
| Male | Reference | / | / | |
| Female | 1.06 (0.56 – 2.00) | 0.869 | / | / |
| Baseline HIV-RNA (log10 copies/mL) | ||||
| ≤5 | Reference | / | / | |
| >5 | 1.23 (0.9 – 1.68) | 0.195 | / | / |
| Nadir CD4 counts (cells/μL) | ||||
| ≤200 | Reference | / | / | |
| >200 | 0.94 (0.69 – 1.27) | 0.669 | / | / |
| Initial specific drug combinationa | ||||
| EFV+3TC+TDF | Reference | Reference | ||
| BIC/FTC/TAF | 0.35 (0.24 – 0.50) | <0.001 | 0.35 (0.25 – 0.50) | <0.001 |
| LPV/r+3TC+TDF | 1.14 (0.70 – 1.86) | 0.598 | 1.24 (0.77 – 1.99) | 0.371 |
| DTG/3TC | 0.38 (0.20 – 0.73) | 0.003 | 0.39 (0.21 – 0.74) | 0.004 |
| Initiation type | ||||
| Rapid inititation | Reference | Reference | ||
| Same-day initiation | 0.87 (0.54 – 1.41) | 0.579 | 0.90 (0.56 – 1.45) | 0.674 |
| Regular initiation | 0.81 (0.61 – 1.06) | 0.120 | 0.81 (0.62 – 1.06) | 0.100 |
| Delayed initiation | 0.58 (0.33 – 1.02) | 0.061 | 0.57 (0.32 – 1.01) | 0.056 |
Only factors with a P–value < 0.1 in the univariable analysis were included in the multivariate analysis.
aExcept for EFV+3TC+TDF, BIC/FTC/TAF, LPV/r+3TC+TDF, and DTG/3TC, there were a small proportion of other specific drug combinations in each regimen. To enhance the stability and robustness of the Cox regression analysis, we extracted 1,238 teatment naive PLWH with these four regimens from the total population to conduct this analysis. DTG: Dolutegravir; 3TC: Lamivudine; BIC: Bictegravir; FTC: Emtricitabine; TAF: Tenofovir alafenamide; TDF: Tenofovir disoproxil fumarate; LPV/r: Lopinavir/ritonavir; EFV: Efavirenz; HR: Hhazard ratio; CI: Confidence interval; HIV: Human immunodeficiency virus; PLWH: People living with HIV; /: Not applicable.
3.3. Virological outcome
3.3.1. Overall suppression rates among study population
Out of the 1,460 individuals, 1,034 maintained their initial regimens and 426 switched to other regimens (all switch types are shown in Figure S1A, http://links.lww.com/IDI/A72). The switch from 2 NRTIs + NNRTI to 2 NRTIs + INSTI predominantly occurred in 2022, while a gradual increase in the proportion of switching from 2 NRTIs + NNRTI to dual therapies was observed.
The suppression rates for four initiation types were relatively similar over observation period, and all groups achieved a viral suppression rate of over 95.0% at the 24- and 36-month follow-up visits (Figure S1B, http://links.lww.com/IDI/A72). Compared to other initial regimens, the 2 NRTIs + PI/r showed a consistently poorer viral suppression rate, despite some improvement over time (Figure S1C, http://links.lww.com/IDI/A72). Similar results could be found in specific drug combinations (Figure S1D, http://links.lww.com/IDI/A72).
3.3.2. Suppression rates in PLWH who persistently received initial regimens
A GEE model with an exchangeable correlation structure was employed to investigate the association between various factors and viral suppression (Table 3). The GEE analysis suggested that baseline HIV-RNA levels >5 log10 copies/mL could impair the post-treatment viral suppression (OR: 0.54, 95% CI: 0.29–0.98, P = 0.041). LPV/r+3TC+TDF was less effective in achieving viral suppression compared to the reference regimen (OR: 0.35, 95% CI: 0.13–0.94, P = 0.044). No interaction effect between the regimens/specific drug combinations and other covariates was found.
Table 3.
GEE analysis of associations between virological suppression and estimated factors among PLWH who persistently used initial regimens
| Characteristics | OR (95% CI) | P value |
|---|---|---|
| Age | ||
| Young (<50 years) | Reference | |
| Old (≥50 years) | 0.74 (0.33 – 1.67) | 0.466 |
| Sex | ||
| Male | Reference | |
| Female | 0.41 (0.13 – 1.29 ) | 0.126 |
| Baseline HIV-RNA (log10 copies/mL) | ||
| ≤5 | Reference | |
| >5 | 0.54 (0.29 – 0.98) | 0.041 |
| Nadir CD4 counts (cells/μL) | ||
| ≤200 | Reference | |
| >200 | 0.68 (0.38 – 1.22) | 0.187 |
| Specific drug combination | ||
| EFV+3TC+TDF | Reference | |
| BIC/TAF/FTC | 1.34 (0.75 – 2.39) | 0.318 |
| LPV/r+3TC+TDF | 0.35 (0.13 – 0.94) | 0.044 |
| DTG/3TC | 1.92 (0.54 – 6.80) | 0.311 |
| Initiation type | ||
| Rapid inititation | Reference | |
| Same-day initiation | 1.50 (0.45 – 5.05) | 0.513 |
| Regular initiation | 0.70 (0.40 – 1.26) | 0.241 |
| Delayed initiation | 0.60 (0.25 – 1.39) | 0.244 |
| Time point | ||
| 6 months | Reference | |
| 12 months | 1.71 (0.97 – 3.00) | 0.061 |
| 24 months | 5.73 (2.13 – 15.41) | <0.001 |
This GEE model included 986 PLWH who persistently used EFV+3TC+TDF, BIC/FTC/TAF, LPV/r+3TC+TDF, or DTG/3TC. DTG: dolutegravir; 3TC: Lamivudine; BIC: Bictegravir; FTC: Emtricitabine; TAF: Tenofovir alafenamide; TDF: Tenofovir disoproxil fumarate; LPV/r: Lopinavir/ritonavir; EFV: Efavirenz; OR: Odds ratio; CI: Confidence interval; GEE: Generalized estimating equation; HIV: Human immunodeficiency virus; PLWH: People living with HIV.
3.3.3. Suppression rates in PLWH who switched regimens
Participants with single regimen switch (n = 372) were included in the second GEE analysis. The result (Table 4) show the suppression rate increased after switch (OR = 9.39, 95% CI: 3.95–22.30, P < 0.001). Higher baseline HIV-RNA levels and lower nadir CD4 counts were associated with a reduced likelihood of achieving viral suppression (OR = 0.38, 95% CI: 0.18–0.80, P = 0.011; OR = 0.44, 95% CI: 0.21–0.94, P = 0.034). In terms of switch types, switching from 2 NRTIs + INSTI to 2 NRTIs + NNRTI was significantly associated with low odds of achieving viral suppression, with an OR of 0.19 (95% CI: 0.04–0.87, P = 0.032). There was no interaction effect observed between switch types and other covariates.
Table 4.
GEE analysis of associations between virological suppression and factors among PLWH who had experienced single regimen switched (n = 372)
| Characteristics | OR (95% CI) | P value |
|---|---|---|
| Baseline HIV-RNA (log10 copies/mL) | ||
| ≤5 | Reference | |
| >5 | 0.38 (0.18 – 0.80) | 0.011 |
| Nadir CD4 counts (cells/μL) | ||
| ≥200 | Reference | |
| <200 | 0.44 (0.21 – 0.94) | 0.034 |
| Switch typea | ||
| 2 NRTIs + NNRTI → 2 NRTIs + INSTI | Reference | |
| 2 NRTIs + INSTI → 2 NRTIs + INSTI | 0.56 (0.22 – 1.44) | 0.228 |
| 2 NRTIs + INSTI → 2 NRTIs + NNRTI | 0.19 (0.04 – 0.87) | 0.032 |
| 2 NRTIs + INSTI → Dual therapies | 1.04 (0.28 – 3.82) | 0.956 |
| 2 NRTIs + NNRTI → 2 NRTIs + NNRTI | 0.10 (0.01 – 1.19) | 0.069 |
| 2 NRTIs + NNRTI → Dual therapies | 1.20 (0.30 – 4.71) | 0.797 |
| 2 NRTIs + PI/r or PI/c → 2 NRTIs + INSTI | 0.30 (0.07 – 1.21) | 0.089 |
| 2 NRTIs + PI/r or PI/c → Dual therapies | 0.34 (0.07 – 1.68) | 0.184 |
| Dual therapies → 2 NRTIs + INSTI | 0.26 (0.05 – 1.30) | 0.100 |
| Time point | ||
| Pre-regimen switch | Reference | |
| At the time of regimen switch | 1.63 (0.92 – 2.88) | 0.092 |
| Post-regimen switch | 9.39 (3.95 – 22.30) | <0.001 |
aThe insufficient sample size of some switch types contributed to perfect separation in the GEE model, we excluded these categories when the model was constructed. Only factors with a P value < 0.05 in were presented in the table. NRTIs: Nucleoside reverse transcriptase inhibitors; PI/r: Protease inhibitor boosted with ritonavir; NNRTIs: Non-nucleoside reverse transcriptase inhibitors; INSTIs: Integrase inhibitors; PI/c: Protease inhibitor boosted with cobicistat; OR: Odds ratio; CI: Confidence interval; GEE: Generalized estimating equation; HIV: Human immunodeficiency virus; PLWH: People living with HIV.
3.4. CD4 cell counts recovery
KM curves were generated to show the cumulative probability of immune reconstitution for each initiation type and regimens (Figure 4A–C). Compared to initiating with EFV+3TC+TDF (median 7.0 months, Q1–Q3: 6.8–8.5), PLWH who started with BIC/FTC/TAF (median 6.7 months, Q1–Q3: 6.4–7.0) achieved CD4 cell counts above 350 cells/μL earlier (P = 0.015). Compared to other regimens, PLWH with 2 NRTIs + PI/r or LPV/r+3TC+TDF had poorer immune reconstitution (median 12.3 and 9.1 months). No significant difference in CD4 cell recovery was observed among the different initiation types in overall TN PLWH.
Figure 4.
Time to achieve CD4 cell counts over 350 cells/μL among different initiation types and regimens. (A) Kaplan-Meier curve of regimens (2 NRTIs + NNRTI, 2 NRTIs + INSTI, 2 NRTIs + PI/r, and Dual therapies). (B) Kaplan-Meier curve of specific drug combinations (EFV+3TC+TDF, BIC/FTC/TAF, LPV/r+3TC+TDF, and DTG/3TC). (C) Kaplan-Meier curve of initiation time types (Rapid, Same-day, Regular, and Delayed initiation). ART: Antiretroviral therapy; NRTIs: Nucleoside reverse transcriptase inhibitors; PI/r: Protease inhibitor boosted with ritonavir; NNRTIs: Non-nucleoside reverse transcriptase inhibitors; INSTIs: Integrase inhibitors; DTG: Dolutegravir; 3TC: Lamivudine; BIC: Bictegravir; FTC: Emtricitabine; TAF: Tenofovir alafenamide; TDF: Tenofovir disoproxil fumarate; LPV/r: Lopinavir/ritonavir; EFV: Efavirenz.
4. Discussion
Rapid initiation in TN PLWH has been well demonstrated to enhance long-term adherence, reducing the time to achieve virological suppression and decreasing the risk of HIV transmission.[2–5] Our study showed a significant increase in same-day and rapid initiation rates observed from 2021 to 2023. Overall, TN PLWH across all initiation types achieved viral suppression rates over 95% at the 24- and 36-month follow-up.
Interestingly, though BIC/FTC/TAF and DTG/3TC have demonstrated efficacy and lower rates of discontinuation in TN PLWH,[10,11,17,19,20] EFV+3TC+TDF was non-inferior to these two regimens in PLWH who persistently received this regimen. The result of GEE analysis was consistent with the RCT findings reported by Wang R et al.,[11] as 97.9% of PLWH initiating with BIC/FTC/TAF achieved viral suppression and 93.7% with EFV+3TC+TDF (difference, 4.2%; 95% CI, –0.7% to 10.1%). Though EFV+3TC+TDF showed similar viral suppression rate with BIC/FTC/TAF and DTG/3TC, the real-life experience with BIC/FTC/TAF and DTG/3TC was different from EFV+3TC+TDF. PLWH initiating with BIC/FTC/TAF and DTG/3TC exhibited a significantly higher likelihood of continuing these regimens over time, potentially due to factors such as high tolerability and low incidence of adverse effects.[11,17,19,20] Besides, PLWH with BIC/FTC/TAF or DTG/3TC achieved CD4 T cell counts above 350 cells/μL significantly earlier compared to EFV+3TC+TDF, which might be associated with earlier viral suppression.[21] Thus, initiating with BIC/FTC/TAF or DTG/3TC might provide a more favorable experience to PLWH in real-life settings.
However, 32.9% and 36.3% of PLWH with same-day and rapid initiation, respectively, opted for 2 NRTIs + NNRTIs (represented by EFV+3TC+TDF) as an initial regimen. EFV+3TC+TDF was also commonly used in the overall TN PLWH. The observed regimen selection patterns reflect complex real-world decision-making processes. Some key factors drove the continued use of EFV+3TC+TDF despite global trends toward BIC/FTC/TAF or DTG/3TC: (1) economic considerations – EFV+3TC+TDF was fully covered by the NFATP, while BIC/FTC/TAF and DTG/3TC required co-payment; (2) guidance – EFV+3TC+TDF was still considered as a free first-line regimen in NFATP. These factors explain why 32.9%–36.3% of rapid initiators still received EFV+3TC+TDF.
There was still a small proportion of TN PLWH initiating with LPV/r+3TC+TDF. PLWH with LPV/r+3TC+TDF had poor viral suppression rates at all time points and was associated with HIV viremia, which was well confirmed in several studies.[22,23] PLWH with LPV/r+3TC+TDF also tend to have lower cumulative probability to achieve CD4 cell counts over 350 cells/μL. The low viral suppression rate, higher switch rate, and poor CD4 cell recovery might be associated with the higher pill burden, more complex dosing schedules and unwanted side-effects of LPV/r+3TC+TDF,[24] which may affect adherence and long-term outcomes.
This study had some limitations. First, given the nature of this study, the study may be subject to biases inherent in data collection and reliance on existing medical records, even though a deterministic matching among two medical records systems and multiple regression were performed to minimize bias. Besides, the superior virological efficacy observed with DTG/3TC requires cautious interpretation due to the more restrictive eligibility criteria. Second, BMI was not systematically collected in this study, which can provide additional prognostic information. Third, the short follow-up period and the single-center design may limit generalizability. Of note, while EFV+3TC+TDF demonstrated robust virological efficacy in this study, this may be because the study was conducted under standard care conditions in a metropolitan area.
In conclusion, our study showed positive trends in same-day and rapid ART initiation following the RAPID Initiative, as well as the challenges of initial regimens selection. Despite BIC/FTC/TAF and DTG/3TC providing more favorable experience, the common use of EFV+3TC+TDF among TN PLWH raises concerns about long-term adherence and treatment sustainability. More targeted interventions are needed to promote the use of BIC/FTC/TAF and DTG/3TC, enhance the accessibility and ultimately improve health outcomes for PLWH.
Author Contributions
Hongxin Zhao conceived and designed the study. Jiantao Fu, Ying Liu, Yifan Guo, and Jing Chen collected the data. Jiantao Fu and Ying Liu performed the analyses, interpreted the data, and drafted the manuscript. Jiantao Fu prepared the figures. All authors critically revised the manuscript for important intellectual content and approved the final version to be published.
Conflicts of interest
None.
Data Availability Statement
The original data in this study can be obtained from the corresponding author upon reasonable request.
Funding Statement
This work was supported by Capital’s Funds for Health Improvement and Research (CFH2024-2-2175) and Collaboration, Consistency, and Innovation Program of the National Center for Infectious Diseases (GCST20250101).
Footnotes
Jiantao Fu and Ying Liu contributed equally to this work.
How to cite this article: Fu J, Liu Y, Guo Y, et al. Temporal trends and clinical outcomes of antiretroviral therapy initiation and regimens in treatment-naive people with HIV: A real-world study at a tertiary specialist hospital in Beijing, China. Infect Dis Immun 2026;6(3):186–194. doi: 10.1097/ID9.0000000000000194
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The original data in this study can be obtained from the corresponding author upon reasonable request.