|Year : 2018 | Volume
| Issue : 4 | Page : 513-516
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
Linghua Li1, Haolan He1, Yun Lan2, Jinfeng Chen1, Huolin Zhong1, Jingmin Nie1, Xiejie Chen1, Fengyu Hu2, Xiaoping Tang2, Weiping Cai1
1 Center for Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
2 Institute of Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, Guangzhou, China
|Date of Web Publication||18-Mar-2019|
Dr. Weiping Cai
Center for Infectious Diseases, Guangzhou Eighth People's Hospital, Guangzhou Medical University, No. 627 Dongfeng Dong Road, Guangzhou
Source of Support: None, Conflict of Interest: None
Backgrounds: This randomised controlled, open-label, non-inferiority trial was conducted in antiretroviral-naïve HIV-1-infected patients to assess the efficacy and safety of 48-week dual therapy of LPV/r plus 3TC (DT group) compared with Chinese first-line triple-therapy regimen (TT group). Methods: 198 were randomised to DT (n = 100) or TT (n = 98). Results: Ninety-two DT patients (92%) and 88 TT patients (89.8%) achieved HIV-1 RNA <50 copies/ml at week 48 (P = 0.629). Moreover, the safety profile was similar between two groups, and no secondary HIV resistance was observed. Conclusion: The results suggest that dual therapy of LPV/r plus 3TC is non-inferior to the first-line triple-therapy regimen in China.
Keywords: Antiretroviral therapy, efavirenz, lopinavir/ritonavir, randomised controlled study, simplified regimen
|How to cite this article:|
Li L, He H, Lan Y, Chen J, Zhong H, Nie J, Chen X, Hu F, Tang X, Cai W. 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. Indian J Med Microbiol 2018;36:513-6
|How to cite this URL:|
Li L, He H, Lan Y, Chen J, Zhong H, Nie J, Chen X, Hu F, Tang X, Cai W. 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. Indian J Med Microbiol [serial online] 2018 [cited 2019 Nov 16];36:513-6. Available from: http://www.ijmm.org/text.asp?2018/36/4/513/254385
| ~ Introduction|| |
In China, the current preferred first-line antiretroviral-therapy (ART) regimen is tenofovir disoproxil fumarate (TDF) plus lamivudine (3TC) plus efavirenz (EFV) (triple therapy). Long-term exposure to these regimens has been associated with toxic effects and cross-resistance within nucleoside reverse-transcriptase inhibitor (NRTI) class. Dual therapy has conventionally been thought to convey inferior efficacy and a higher risk of selecting for resistance mutations than standard triple ART,, but trials have confirmed that the simplified LPV/r (a co-formulation of lopinavir and ritonavir) plus 3TC regimen can be used in some naïve patients. LPV/r plus 3TC is the only boosted PI plus 3TC regimen with published 48-week data in ART-naïve patients. Regretfully, these reports lack data from Chinese patients, and their comparisons are based on the LPV/r-based triple therapy not the EFV-based triple therapy that is adopted as the first-line therapy in China and many other resource-limited countries. Hence, a randomised controlled, open-label, non-inferiority trial was performed to assess the efficacy of dual therapy of LPV/r plus 3TC compared with the first-line triple-therapy regimen containing TDF and 3TC plus EFV in China.
| ~ Materials and Methods|| |
The study population consisted of HIV-1-infected ART-naïve patients at least 18 years old enrolled from 1 March 2015 to 30 September 2015. All patients had a plasma HIV-1 RNA levels >1000 copies/ml and CD4+ cell count over 200 cells/mm 3. Patients who were pregnant or breastfeeding, or were coinfected with HBV or HCV, or had chronic liver disease, or had active AIDS-associated opportunistic diseases within 30 days after screening or had poor adherence, were excluded from the study. The study was approved by the ethics committee of our hospital (approval no. 20142154). Written informed consent was obtained from participants.
Randomisation was stratified according to the screening level of plasma HIV-1 RNA (≤100,000 vs. >100,000 copies/ml). Patients were randomised (1:1) to receive dual (DT; lopinavir 400 mg and ritonavir 100 mg twice daily plus 3TC 300 mg once daily) or triple therapy (TT; TDF 300 mg plus 3TC 300 mg plus EFV 600 mg, all once daily). Patients were assessed at screening, day 1 (baseline) and week 12, 24 and 48, or at early termination. Subgenotype was determined.
The primary endpoint was virological response rate, defined as proportion of participants with plasma HIV-1 RNA <50 copies/ml at week 48.
Efficacy was analysed in the ITT population and per-protocol population. Safety was analysed in safety population. Statistical analyses were performed using SPSS 21 and MedCalc 16. Mann–Whitney U-tests were adopted to compare between the two groups for quantitative or ordinal data and Fisher's exact tests for nominal data. P < 0.05 indicated a statistically significant difference.
| ~ Results|| |
Totally, 274 patients were screened and 198 were eligible and were randomised to either dual therapy (n = 100) or triple therapy (n = 98). The demographics and baseline characteristics of the ITT population were balanced between groups [Table 1].
|Table 1: Demographics and baseline characteristics (intention-to-treat population)|
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The proportion of patients in DT group who reached the primary efficacy endpoint was non-inferior to that in TT group: 92 DT patients (92%) and 88 TT patients (89.8%) (difference –2.2%; 95% confidence interval −6.7% to 11.2%) [Figure 1]a. At week 48, 94.0% (94/100) patients in DT group and 90.8% (89/98) patients in TT group achieved HIV-1 RNA <400 copies/ml [Figure 1]b. Mean increases in CD4+ cell count from baseline through 48 weeks were similar between both groups (+203.2 cells/mm 3 with DT and +174.8 cells/mm 3 with TT).
|Figure 1: The proportion of patients who reached the primary efficacy and secondary virological endpoint. (a) Proportion of patients with HIV-1 RNA <50 copies/ml. (b) Proportion of patients with HIV-1 RNA <400 copies/ml|
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No significant differences in the primary endpoint were observed between the subgroups with baseline HIV-1 RNA ≤100,000 versus >100,000 copies/ml or baseline CD4+ between 200 and 350 versus >350 cells/mm 3. No significant difference was observed in the primary endpoint for genotypes AE versus BC.
No severe adverse event was reported during the entire study period. No death was observed either.
| ~ Discussion|| |
The National AIDS Plan and the Spanish AIDS study group (GESIDA) panel of experts propose 'preferred regimens' of ART as initial therapy in HIV-infected patients for 2013, which are triple-therapy regimens associated with many lifelong ART problems.,, Therefore, simplification strategies should be sought. Findings from the GARDEL trial have convincingly shown that for ART-naive patients, LPV/r plus 3TC was non-inferior to a triple-drug regimen including LPV/r in achieving and maintaining virological suppression during 48 weeks of treatment, irrespective of baseline viral load. SALT trial and OLE trial also show that dual treatment is effective, safe and non-inferior to triple treatment in HIV-1-infected patients. Consistent with previous findings, our study showed that dual therapy of LPV/r plus 3TC is non-inferior to the first-line regimen containing TDF and 3TC plus EFV in China, even in patients with high baseline viremia and regardless of subgenotype.
Even though NRTIs have been the backbone of ART since the advent of ART, substantial toxic effects still cannot be ignored. TDF has been associated with proximal tubular dysfunction, nephrogenic diabetes insipidus and nephrotic syndrome and a decrease in bone mineral density and its consequent increased risk of osteoporotic fractures., EFV is also responsible for a high percentage (40%–70%) of central nervous system adverse effects, such as increase of stroke severity and induction of anxiety- or depression-like behaviour., Therefore, simplification strategies to improve the convenience of ART have been considered while maintaining effectiveness. The lower rate of side effects and discontinuation reported in DT group of the study demonstrates that dual therapy with LPV/r plus 3TC could avoid some adverse reactions related to the first-line triple-therapy regimen in China to some extent.
In general, our results further verified the non-inferior efficacy and excellent safety of the dual therapy with LPV/r plus 3TC in China, which could provide Chinese antiviral guideline with a solid foundation for the application of LPV/r plus 3TC in ART-naïve HIV-1-infected patients. However, a larger sample size is required for further verification, and future studies should extend to the aged population and those with a baseline CD4+ cell count below 200 cells/mm 3.
The authors thank the staff of the Centre for Infectious Diseases for their assistance in supplying medical records, the staff of the Institute of Infectious Diseases for their technical support, the patients who participated in the study, Hui Chen from Capital Medical University helping statistics and Pei-shan Du recording medical data.
Financial support and sponsorship
This work was supported by the grant from Chinese National 12th Five-Year Plan on Key Infectious Diseases (2012ZX10001003-003).
Conflicts of interest
There are no conflicts of interest.
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