Dataset Information

Six-Year Immunologic Recovery and Virological Suppression of HIV Patients on LPV/r-Based Second-Line Antiretroviral Treatment: A Multi-Center Real-World Cohort Study in China.

ABSTRACT: The World Health Organization guidelines recommend lopinavir/ritonavir (LPV/r) as a second-line antiretroviral therapy (ART) for HIV-infected adults in middle-income and low-income countries as a protease inhibitor boost based on clinical trials; however, the real-world safety and efficacy remain unknown. Therefore, we conducted a large-scale, multicenter retrospective cohort study to evaluate the efficacy and safety of LPV/r-based ART among HIV-infected adults in China in whom first-line therapy failed. The data were obtained from a national database covering 17 clinics in China for six years of follow-up from 2009 to 2016. Failure of first-line treatment was determined according to a viral load at least 400 copies/ml at week 48, non-completers at week 48 for any reason, and those who switched ART before week 48 for any reason such as side effects. Treatment effectiveness was assessed by the rate of CD4+T cell recovery, defined as >500 cells/mm3, and the proportion of patients achieving viral suppression, defined as <400 or <50 copies/ml according to the methods used during treatment. Safety was assessed by rates of LPV/r-related adverse events (AEs), including lipid disorder, severe abnormal liver function, myelosuppression, and renal function. Between 2009 and 2016, 1196 participants (median, 36 years old; IQR, 30-43 years) were ultimately enrolled. All patients had been on LPV/r-based second-line ART treatment for more than one year after failure of any first-line ART regimen. Overall CD4+T cell counts increased from 138 cells/mm3 to 475 cells/mm3 and 37.2% of all participants reached CD4 recovery. Viral suppression rates dramatically increased at the end of the first year (<400 copies/ml, 88.8%; <50 copies/ml, 76.7%) and gradually increased during follow-up (<400 copies/ml, 95.8%; <50 copies/ml, 94.4%). The most frequently reported AEs were LPV/r-induced lipid disorders with no obvious increase on LDL-C at follow-up visits. This is the first real-world LPV/r-based second-line treatment study to cover such a large population in China. These results provide strong clinical evidence that LPV/r-based second-line ART is effective in increasing CD4+T cell counts and viral suppression rates with tolerable side effects in HIV-infected adults in China in whom first-line treatment had failed.

SUBMITTER: Huang X

PROVIDER: S-EPMC6917650 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Six-Year Immunologic Recovery and Virological Suppression of HIV Patients on LPV/r-Based Second-Line Antiretroviral Treatment: A Multi-Center Real-World Cohort Study in China.

Huang Xiaojie X Xu Liumei L Sun Lijun L Gao Guiju G Cai Weiping W Liu Yanfen Y Ding Haibo H Wei Hongxia H Ma Ping P Wang Min M Liu Shuiqing S Chen Yaokai Y Chen Xiaohong X Zhao Qingxia Q Yu Jianhua J Song Yuxia Y Chen Hui H Wu Hao H Qin Shanfang S Li Linghua L

Frontiers in pharmacology 20191211

The World Health Organization guidelines recommend lopinavir/ritonavir (LPV/r) as a second-line antiretroviral therapy (ART) for HIV-infected adults in middle-income and low-income countries as a protease inhibitor boost based on clinical trials; however, the real-world safety and efficacy remain unknown. Therefore, we conducted a large-scale, multicenter retrospective cohort study to evaluate the efficacy and safety of LPV/r-based ART among HIV-infected adults in China in whom first-line therap ...[more]

PMID: 31920648

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Project description:BackgroundAntiretroviral Therapy (ART) in children remains challenging due to resource-constrained settings. We conducted a 13-year, prospective, multicenter cohort study on the effectiveness and safety of LPV/r-based regimens in ART-naive and ART-experienced children.MethodsFrom January 2008 to May 2021, children living with HIV-1 were recruited with LPV/r-based regimens from 8 clinical research sites in 6 provinces in China. Effectiveness outcomes were virologic failure (defined as at least two consecutive measurements of VL > 200 copies/mL after 6 months of ART) and immune response (defined as CD4% recovered to more than 25% after 12 months of treatment). The safety outcomes were treatment-related grade 2-4 adverse events and abnormal laboratory test results.ResultsA total of 345 ART-naïve children and 113 ART-experienced children were included in this cohort study. The median follow-up time was 7.3 (IQR 5.5-10.5) years. The incidence density of virologic failure was 4.1 (95% CI 3.3-4.9) per 100 person-years in ART-naïve children and 5.0 (95% CI 3.5-6.5) per 100 person-years in ART-experienced children. Kaplan Meyer (KM) curve analysis showed children with ART experience were at a higher risk of virologic failure (p < 0.05). The risk factors of virologic failure in ART-naïve children were clinic setting in rural hospitals (aHR = 2.251, 1.108-4.575), annual missed dose times >5 days of LPV intake (aHR = 1.889, 1.004-3.554); The risk factor of virologic failure in ART-experienced children was missed dose times >5 days (aHR = 2.689, 1.299-5.604) and mother as caregivers for ART administration (aHR = 0.475, 0.238-0.948). However, during long-term treatment, viral suppression rates between ART-naïve and ART-experienced children remained similar. No significant differences were observed in the immune response, treatment-related grade 2-4 events, and abnormal laboratory test results between ART-naïve children and ART-experienced children.ConclusionOur research underscores that with consistent, long-term treatment of LPV/r-based regimens, ART-experienced children can achieve therapeutic outcomes comparable to ART-naïve children. It provides crucial insights on LPV/r-based regimens in pediatric HIV treatment, especially in resource-limited settings where high-cost Integrase Strand Transfer Inhibitors (INSTs) are inaccessible. This evidence-based understanding provides an essential addition to the global therapeutic strategies for pediatric HIV treatment.

Project description:ObjectiveTo compare changes over 48 weeks in body fat, lipids, Metabolic Syndrome and cardiovascular disease risk between patients randomised 1:1 to lopinavir/ritonavir (r/LPV) plus raltegravir (RAL) compared to r/LPV plus 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second-line therapy.MethodsParticipants were HIV-1 positive (>16 years) failing first-line treatment (2 consecutive HIV RNA >500 copies/mL) of NNRTI +2N(t)RTI. Whole body dual energy x-ray absorptiometry was performed at baseline and week 48. Data were obtained to calculate the Metabolic Syndrome and Framingham cardiovascular disease (CVD) risk score. Linear regression was used to compare mean differences between arms. Logistic regression compared incidence of metabolic syndrome. Associations between percent limb fat changes at 48 weeks with baseline variables were assessed by backward stepwise multivariate linear regression. Analyses were adjusted for gender, body mass index and smoking status.Results210 participants were randomised. The mean (95% CI) increase in limb fat over 48 weeks was 15.7% (5.3, 25.9) or 0.9 kg (0.2, 1.5) in the r/LPV+N(t)RTI arm and 21.1% (11.1, 31,1) or 1.3 kg (0.7, 1.9) in the r/LPV+RAL arm, with no significant difference between treatment arms (-5.4% [-0.4 kg], p>0.1). Increases in total body fat mass (kg) and trunk fat mass (kg) were also similar between groups. Total:HDL cholesterol ratio was significantly higher in the RAL arm (mean difference -0.4 (1.4); p = 0.03), there were no other differences in lipid parameters between treatment arms. There were no statistically significant differences in CVD risk or incidence of Metabolic Syndrome between the two treatment arms. The baseline predictors of increased limb fat were high viral load, high insulin and participant's not taking lipid lowering treatment.ConclusionIn patients switching to second line therapy, r/LPV combined with RAL demonstrated similar improvements in limb fat as an N(t)RTI + r/LPV regimen, but a worse total:HDL cholesterol ratio over 48 weeks.Trial registrationThis clinical trial is registered on Clinicaltrials.gov, registry number NCT00931463 http://clinicaltrials.gov/ ct2/show/NCT00931463?term = NCT00931463&rank = 1.

Project description:IntroductionThe potential impact of socio-economic condition on virological suppression during antiretroviral treatment (ART) in sub-Saharan Africa is largely unknown. In this case-control study, we compared socio-economic factors among Ethiopian ART recipients with lack of virological suppression to those with undetectable viral load (VL).MethodsCases (VL>1000 copies/ml) and controls (VL<150 copies/ml) aged ≥15years, with ART for >6 months and with available VL results within the last 3 months, were identified from registries at public ART clinics in Central Ethiopia. Questionnaire-based interviews on socio-economic characteristics, health condition and transmission risk behavior were conducted. Univariate variables associated with VL>1000 copies/ml (p<0.25) were added to a multivariable logistic regression model.ResultsAmong 307 participants (155 cases, 152 controls), 61.2% were female, and the median age was 38 years (IQR 32-46). Median HIV-RNA load among cases was 6,904 copies/ml (IQR 2,843-26,789). Compared to controls, cases were younger (median 36 vs. 39 years; p = 0.004), more likely to be male (46.5% vs. 30.9%; p = 0.005) and had lower pre-ART CD4 cell counts (170 vs. 220 cells/μl; p = 0.009). In multivariable analysis of urban residents (94.8%), VL>1000 copies/ml was associated with lower relative wealth (adjusted odds ratio [aOR] 2.98; 95% CI 1.49-5.94; p = 0.016), geographic work mobility (aOR 6.27, 95% CI 1.82-21.6; p = 0.016), younger age (aOR 0.94 [year], 95% CI 0.91-0.98; p = 0.011), longer duration of ART (aOR 1.19 [year], 95% CI 1.07-1.33; p = 0.020), and suboptimal (aOR 3.83, 95% CI 1.33-10.2; p = 0.048) or poor self-perceived wellbeing (aOR 9.75, 95% CI 2.85-33.4; p = 0.012), after correction for multiple comparisons. High-risk sexual behavior and substance use was not associated with lack of virological suppression.ConclusionGeographic work mobility and lower relative wealth were associated with lack of virological suppression among Ethiopian ART recipients in this predominantly urban population. These characteristics indicate increased risk of treatment failure and the need for targeted interventions for persons with these risk factors.

Project description:BACKGROUND:Adequate antiretroviral exposure is crucial to virological suppression. We assessed the relationship between atazanavir hair levels with self-reported adherence, virological outcomes, and the effect of a home-based adherence intervention in HIV-infected adolescents failing second-line antiretroviral treatment in Zimbabwe. METHODS:HIV-infected adolescents on atazanavir/ritonavir-based second-line treatment for ?6 months with viral load (VL) >1000 copies/mL were randomized to either standard care (control) or standard care plus modified directly administered antiretroviral therapy (intervention). Questionnaires were administered; VL and hair samples were collected at baseline and after 90 days in each group. Viral suppression was defined as <1000 copies/mL after follow-up. RESULTS:Fifty adolescents (10-18 years) were enrolled; 23 (46%) were randomized to intervention and 27 (54%) to control. Atazanavir hair concentration <2.35 ng/mg (lower interquartile range for those with virological suppression) defined a cutoff below which most participants experienced virological failure. Male sex (P = 0.03), virological suppression at follow-up (P = 0.013), greater reduction in VL (P = 0.006), and change in average self-reported adherence over the previous month (P = 0.031) were associated with adequate (>2.35 ng/mg) hair concentrations. Participants with virological failure were more likely to have suboptimal atazanavir hair concentrations (RR = 7.2, 95% CI: 1 to 51, P = 0.049). There were no differences in atazanavir hair concentration between the arms after follow-up. CONCLUSIONS:A threshold of atazanavir concentrations in hair (2.35 ng/mg), above which virological suppression was likely, was defined for adolescents failing second-line atazanavir/ritonavir-based ART in Zimbabwe. Male sex and better self-reported adherence were associated with adequate atazanavir hair concentrations. Antiretroviral hair concentrations may serve as a useful clinical tool among adolescents.

Dataset Information

Six-Year Immunologic Recovery and Virological Suppression of HIV Patients on LPV/r-Based Second-Line Antiretroviral Treatment: A Multi-Center Real-World Cohort Study in China.

Publications

Six-Year Immunologic Recovery and Virological Suppression of HIV Patients on LPV/r-Based Second-Line Antiretroviral Treatment: A Multi-Center Real-World Cohort Study in China.

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