Dual Therapy with Lopinavir/Ritonavir plus Lamivudine could be a Viable Alternative for Antiretroviral-Therapy-Naive Adults with HIV-1 Infection Regardless of HIV Viral Load or Subgenotype in Resource-Limited Settings: A Randomised, Open-Label and Non-Inferiority Study from China

Li, Linghua; He, Hong; Lan, Yun; Chen, Jinfeng; Zhong, Huolin; Nie, Jingmin; Chen, Xiejie; Hu, Fengyu; Tang, Xiaoping; Cai, Weiping

doi:10.4103/ijmm.ijmm_18_172

Cited by 4 publications

(9 citation statements)

References 12 publications

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“…In comparison with the results obtained at 48 weeks (Li et al, 2018), the long-term effectiveness reported here at 144 weeks is more convincing. To confirm that dual ART is still effective in FIGURE 3 | test.…”

Section: Discussionsupporting

confidence: 73%

“…In China, where LPV/r is the only free protease inhibitor available to HIV patients, LPV/r is widely used (as it is in other countries with limited resources). We previously reported that DT with LPV/r plus 3TC was non-inferior to the first-line triple-therapy regimen at week 48 (Li et al, 2018). The study (ALTERLL) was continued using the same cohort, and we report here the antiretroviral long-term efficacy and safety of these regimens up to 144 weeks.…”

Section: Introductionmentioning

confidence: 75%

“…Our research was divided into two phases, up to 48 weeks and 48-144 weeks. The results obtained at 48 weeks have previously been published (Li et al, 2018). Here, the time window for this study was extended to 144 weeks.…”

Section: Methodsmentioning

confidence: 99%

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Antiretroviral Long-Term Efficacy and Resistance of Lopinavir/Ritonavir Plus Lamivudine in HIV-1-Infected Treatment-Naïve Patients (ALTERLL): 144-Week Results of a Randomized, Open-Label, Non-Inferiority Study From Guangdong, China

Guo

Chen

et al. 2021

Front. Pharmacol.

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Dual therapy with lopinavir/ritonavir (LPV/r) plus lamivudine (3TC) has been demonstrated to be non-inferior to the triple drug regimen including LPV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) in 48-week studies. However, little is known about the long-term efficacy and drug resistance of this simplified strategy. A randomized, controlled, open-label, non-inferiority trial (ALTERLL) was conducted to assess the efficacy, drug resistance, and safety of dual therapy with LPV/r plus 3TC (DT group), compared with the first-line triple-therapy regimen containing tenofovir (TDF), 3TC plus efavirenz (EFV) (TT group) in antiretroviral therapy (ART)-naïve HIV-1–infected adults in Guangdong, China. The primary endpoint was the proportion of patients with plasma HIV-1 RNA < 50 copies/ml at week 144. Between March 1 and December 31, 2015, a total of 196 patients (from 274 patients screened) were included and randomly assigned to either the DT group (n = 99) or the TT group (n = 97). In the primary intention-to-treat (ITT) analysis at week 144, 95 patients (96%) in the DT group and 93 patients (95.9%) in the TT group achieved virological inhibition with plasma HIV-1 RNA <50 copies/ml (difference: 0.1%; 95% CI, –4.6–4.7%), meeting the criteria for non-inferiority. The DT group did not show significant differences in the mean increase in CD4+ cell count (247.0 vs. 204.5 cells/mm3; p = 0.074) or the CD4/CD8 ratio (0.47 vs. 0.49; p = 0.947) from baseline, or the inflammatory biomarker levels through week 144 compared with the TT group. For the subgroup analysis, baseline high viremia (HIV-1 RNA > 100,000 copies/ml) and genotype BC did not affect the primary endpoint or the mean increase in CD4+ cell count or CD4/CD8 ratio from baseline at week 144. However, in patients with genotype AE, the DT group showed a higher mean increase in CD4+ cell count from baseline through 144 weeks than the TT group (308.7 vs. 209.4 cells/mm3; p = 0.038). No secondary HIV resistance was observed in either group. Moreover, no severe adverse event (SAE) or death was observed in any group. Nonetheless, more patients in the TT group (6.1%) discontinued the assigned regimen than those in the DT group (1%) due to adverse events. Dual therapy with LPV/r plus 3TC manifests long-term non-inferior therapeutic efficacy, low drug resistance, good safety, and tolerability compared with the first-line triple-therapy regimen in Guangdong, China, indicating dual therapy is a viable alternative in resource-limited areas.Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR1900024611].

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Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 75%

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Antiretroviral Long-Term Efficacy and Resistance of Lopinavir/Ritonavir Plus Lamivudine in HIV-1-Infected Treatment-Naïve Patients (ALTERLL): 144-Week Results of a Randomized, Open-Label, Non-Inferiority Study From Guangdong, China

Guo

Chen

et al. 2021

Front. Pharmacol.

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“…The main characteristics of the 14 studies included in the metaanalysis are summarized in Table 1. The studies were published from 2008 to 2020; all but one [32] were randomized controlled trials (RCTs); all but 4 [23,28,30,32] were multinational studies. The number of patients per study ranged from 82 to 1433 subjects.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Overall, the studies included a total of 5205 HIV-naïve subjects, considering the GEMINI 1-2 studies [25,26] as a single study with the same population: 2471 in dual therapy and 2734 in triple therapy. As dual therapy, atazanavir/r plus maraviroc were used in two studies [29,32], lopinavir/r plus lamivudine in two [24,28], raltegravir plus darunavir/r in two [23,33], lopinavir/r plus tenofovir [31] or raltegravir [34] or efavirenz [35] or maraviroc [30] in one, respectively, and finally, atazanavir/r plus raltegravir [28] and darunavir/r plus maraviroc in one [36] and dolutegravir plus lamivudine in two [25,26]. Considering dolutegravir and darunavir (without maraviroc) as new antiretroviral drugs, since included in the international guidelines with a rating of recommendation and evidence of A1 [37], four studies [23,25,26,33] used, in dual regimens, new drug-based regimens and 10 old drug-based regimens [24,27e32,34e36].…”

Section: Study Characteristicsmentioning

confidence: 99%

Risk of failure in dual therapy versus triple therapy in naïve HIV patients: a systematic review and meta-analysis

Pisaturo

Onorato

Russo

et al. 2021

Clinical Microbiology and Infection

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Objectives: Several attempts have been made to test different drug-sparing strategies to reduce the drugburden and drug-related toxicities. The objective of this meta-analysis was to evaluate the relative risk (RR) of failure of dual therapies compared to triple therapies in HIV-naïve patients. Methods: We searched MEDLINE, Google Scholar and the Cochrane Library. The following criteria were used: present data from original articles comparing the two treatment regimens; published from January 2007 up to January, 2020. No language or study design restriction was applied. Subjects were HIVpositive naïve patients treated with dual or triple antiretroviral therapy (ART). A systematic review and meta-analysis was performed. Treatment failure (TF) was the primary outcome evaluated; heterogeneity was assessed using the Q statistic and I 2 . Results: Fourteen studies were included, allowing a meta-analysis on 5205 patients. The meta-analysis performed on studies that presented data at 48 weeks showed that the RR of TF (RR > 1 favouring triple therapy) in 10 studies was 1.20 (95% confidence interval (CI): 0.91e1.59, I 2 : 49.2%); the RR of virological failure (VF) in eight studies was 1.54 (95% CI: 0.84e2.86, I 2 : 54%); the RR of adverse drug reaction leading to discontinuation of the regimen at 48 weeks in eight studies was 0.76 (95% CI: 0.43e1.33, I 2 : 17.7%). In patients with less than 200 CD4þ, the RR of TF in two studies without maraviroc was 2.09 (95% CI: 1.05e4.17, I 2 : 0.0%). Regarding the studies at 96 weeks there was no difference except in rate of development of resistance, RR 1.94 (95% CI: 1.06e3.53, I 2 : 6.2%). Conclusion: Dual therapies are as effective as those with three drugs, showing no difference according to the different dual therapies, except in patients with less than 200 CD4; however, they are associated with a higher selection of resistance-associated mutations at 96 weeks of therapy.

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Characteristics and clinical significance of plasma IL‐18, sCD14, and sCD163 levels in patients with HIV‐1 infection

Cai

Guo

et al. 2022

Journal of Medical Virology

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Biomarkers of monocyte‐macrophages activation and inflammation in plasma such as interleukin‐18 (IL‐18), soluble leukocyte differentiation antigen 14 (sCD14), and sCD163 are associated with disease severity and prognosis in HIV‐1 infected patients, however, their relationships with efficacy of antiretroviral therapy (ART) need further investigation. We aimed to characterize and explore the clinical significance of plasma IL‐18, sCD14, and sCD163 in this population. This was a retrospective cohort study consisting of HIV‐1 infected patients enrolled in a randomized, controlled, open‐label, noninferiority trial (ALTERLL study), with follow‐up time points including initiation of ART (baseline), 12‐, 24‐ and 48‐weeks of treatment. Plasma levels of IL‐18, sCD14, and sCD163 were measured using the enzyme‐linked immunosorbent assay method. Viral suppression was defined as HIV‐1 RNA < 20 copies/ml. Among the 193 studied patients (median age of 29.0 years, 180 males), IL‐18 and sCD163 had U‐shaped regression curves and sCD14 had an inverted U‐shaped regression curve while the virus was decreased and immune function recovered. Patients with higher levels of IL‐18 or lower levels of sCD163 at baseline were less likely to achieve viral suppression at Week 12 or Week 24 of treatment, respectively. In multivariate analysis, baseline sCD163 ≤ 500 pg/ml (adjusted odds ratio 0.33, 95% confidence interval 0.16–0.68) was independently associated with a lower rate of viral suppression at Week 24 of treatment. In conclusion, we demonstrated different dynamic changes among IL‐18, sCD14, and sCD163 after ART. Baseline sCD163 level could be a potential predictor of early virological response to ART. Further validation and mechanistic research are needed.

show abstract

Dual Therapy with Lopinavir/Ritonavir plus Lamivudine could be a Viable Alternative for Antiretroviral-Therapy-Naive Adults with HIV-1 Infection Regardless of HIV Viral Load or Subgenotype in Resource-Limited Settings: A Randomised, Open-Label and Non-Inferiority Study from China

Cited by 4 publications

References 12 publications

Antiretroviral Long-Term Efficacy and Resistance of Lopinavir/Ritonavir Plus Lamivudine in HIV-1-Infected Treatment-Naïve Patients (ALTERLL): 144-Week Results of a Randomized, Open-Label, Non-Inferiority Study From Guangdong, China

Antiretroviral Long-Term Efficacy and Resistance of Lopinavir/Ritonavir Plus Lamivudine in HIV-1-Infected Treatment-Naïve Patients (ALTERLL): 144-Week Results of a Randomized, Open-Label, Non-Inferiority Study From Guangdong, China

Risk of failure in dual therapy versus triple therapy in naïve HIV patients: a systematic review and meta-analysis

Characteristics and clinical significance of plasma IL‐18, sCD14, and sCD163 levels in patients with HIV‐1 infection

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