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Background: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells. Methods: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4+T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens. Results: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4+T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4+T cell count: 45 vs. -5 cells/µL, p<0.001). After ABT discontinuation, CD4+T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p=0.012). In laboratory analysis, naïve CD4+ T cell amountswere lowest among participants with unsatisfactory immune response (uIR) to ABT (p=0.001). The proportion of caspase 3+CD45RA+CD31+CD4+ T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT (p<0.05). Conclusion: Significant CD4+T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis. [ABSTRACT FROM AUTHOR]

Albuvirtide (ABT) is the first long-acting HIV fusion inhibitor developed in China, blocking the invasion of HIV-1 virus into target cells. This study aimed to compare the pharmacokinetics (PK), tolerability, and safety of ABT following a single intravenous (IV) bolus injection or intravenous drip in healthy Chinese subjects. A single-center, randomized, open-label, single-period, parallel phase I clinical trial was conducted. Thirty subjects were randomly divided into three groups in a ratio of 1:1:1. After an overnight fast, all subjects received a single dose of 320 mg ABT either by intravenous drip for 45 min (group A) or bolus injection for 0.5 min (group B), or bolus injection for 3 min (group C). ABT plasma concentrations were analyzed using a validated enzyme-linked immunosorbent assay (ELISA). Non-compartmental analysis was used to evaluate PK parameters. The median time to reach maximum concentration was 0.75 h in group A and 0.16 h in both groups B and C. Elimination half-life, mean residence time, apparent clearance, and apparent volume of distribution were similar among the three groups. The 90% confidence intervals (CI) of geometric mean ratios of PK parameters for groups B and C relative to group C were within 85–120%. All adverse events (AEs) reported in this study were mild, according to the CTCAE guidelines and the study investigator's judgement. ABT bolus injections for 0.5 min and 3 min are expected to be well tolerated and to exhibit similar PK characteristics as IV drip for 45 min, offering potential clinical benefits. [ABSTRACT FROM AUTHOR]

Abstract Background Managing multidrug-resistant (MDR) HIV infections in children is particularly challenging due to the lack of experience with new drugs in the pediatric setting. Second-line albuvirtide (ABT) with an optimized antiretroviral background therapy was approved for adults and adolescents after first-line treatment failure. This paper describes the treatment outcomes and adverse effects of an ABT-based dual-active antiretroviral treatment regimen in a child with MDR HIV strains. Case presentation A 13 year-old Chinese female patient infected with MDR HIV strains showed a decrease in viral load (from 4.48 log10 to 1.73 log10) and an increase in CD4 + T cells (from 15 to 308 cells/µl) after 12 months of treatment with an ABT-based antiretroviral regimen. The child showed no relevant drug-related adverse reactions. Conclusions The case reported here could suggest that an ABT-based antiretroviral therapy might be beneficial and without relevant toxicity in children with MDR HIV. Infectiologists specializing in managing HIV should be prepared to manage an increasing number of children with MDR HIV. ABT might be a new treatment option for MDR HIV infection in children.

Background: Managing multidrug-resistant (MDR) HIV infections in children is particularly challenging due to the lack of experience with new drugs in the pediatric setting. Second-line albuvirtide (ABT) with an optimized antiretroviral background therapy was approved for adults and adolescents after first-line treatment failure. This paper describes the treatment outcomes and adverse effects of an ABT-based dual-active antiretroviral treatment regimen in a child with MDR HIV strains. Case presentation: A 13 year-old Chinese female patient infected with MDR HIV strains showed a decrease in viral load (from 4.48 log10 to 1.73 log10) and an increase in CD4 + T cells (from 15 to 308 cells/µl) after 12 months of treatment with an ABT-based antiretroviral regimen. The child showed no relevant drug-related adverse reactions. Conclusions: The case reported here could suggest that an ABT-based antiretroviral therapy might be beneficial and without relevant toxicity in children with MDR HIV. Infectiologists specializing in managing HIV should be prepared to manage an increasing number of children with MDR HIV. ABT might be a new treatment option for MDR HIV infection in children. [ABSTRACT FROM AUTHOR]

• Albuvirtide (ABT) is a novel long-acting HIV fusion inhibitor. • ABT combined with LPV/r was non-inferior to LPV/r based three-drug regimen. • ABT combined with LPV/r showed a good safety profile. • ABT combined with LPV/r showed a trend of improvement in renal function. • ABT might be an interesting alternative option for HIV treatment and prevention. [ABSTRACT FROM AUTHOR]

Introduction: There have been no prospective clinical studies investigating adherence and tolerability of HIV post-exposure prophylaxis (PEP) in China. Tolerability, adherence, and transmitted drug resistance are concerns, especially when single-tablet regimen (STR) usage is low. The present study aimed to explore the safety, tolerability, and adherence of regimens containing albuvirtide (ABT) compared with recommended non-STR antiretrovirals for HIV PEP. Methods: This was a prospective, open-label, multicenter cohort study. The subjects were stratified into 3 groups based on their preference: ABT + Dolutegravir (DTG) (Group 1), ABT + Tenofovir disoproxil fumarate (TDF) + Lamivudine (3TC) (Group 2), and DTG + TDF + 3TC (Group 3). All enrolled subjects received PEP within 72 h after exposure and continued for 28 days, and were followed-up for 12 weeks. Results: A total of 330 participants were enrolled in the three groups. Most participants were male (87.2%). Sexual contact was the most frequent mode of exposure (91.9%). The average time from exposure to treatment was 26.8 ± 19.5 h. There were no statistically significant differences between the three study groups with respect to completion of oral medication at 28 days. The 28-day completion rate was shown to be significantly higher with ABT versus oral (88.9% vs. 64.0%; p < 0.0001), and adherence with ABT was 94.4% compared to 75.7% with oral PEP (p < 0.0001). Subjects in ABT-containing Group 1 exhibited higher adherence than those in Group 3 (87.3% vs. 72.9%; p < 0.05). None of the participants reported serious adverse drug reactions which led to withdrawal from the study. All the drug regimens were found to be safe and well tolerated. No HIV incident case was observed during the study period. Conclusions: ABT-containing regimens (ABT + DTG or ABT + TDF + 3TC) offer a good option for HIV PEP due to higher completion rates and adherence than the DTG + TDF + 3TC regimen. The overall safety was comparable and acceptable among the three groups. Registration: The study was registered in Chinese Clinical Trial Registry with registration number (ChiCTR1900022881, http://www.chictr.org.cn/showprojen.aspx?proj=37395). [ABSTRACT FROM AUTHOR]

To evaluate the safety and efficacy of albuvirtide (ABT) in the treatment of patients with Coronavirus Disease 2019 (CO VID-19). The study was conducted in 22 patients with laboratory-confirmed COVID-19 infections in the Public Health Clinical Center of Chengdu from February to April, 2020. All patients intravenously received 320 mg of ABT on Day 1, 2, 3, 8 in addition to standard care. The primary endpoint was a coronavirus-negative result and the pneumonia was alleviated in patients. It showed that the average age of the patients was 48.2 ± 18.0 years old, and 10 of them (45.5%) were male. The most common symptoms were cough (81.8%), expectoration (72.7%), fever (27.3%), while no abnormal blood cell count was observed among these patients. The CT examination showed that 6 patients (27.3%) with unilateral pneumonia and 15 of them (68.2%) with bilateral pneumonia, confirmed by massive patchy shadows and ground glass opacities within patient lungs. After the ABT treatment, the cough, expectoration and fever were relieved by 33.3%, 43.8% and 100%, respectively. The mean body temperature recovery time was 2.5 days (range, 1-4 days). The alleviated pneumonia was seen in 14 patients (63.6%) by CT scanning after day 8. Based on nasopharyngeal sampling, the COVID-19 RNA was negatively detected in 14 of 22 patients after 8 days of ABT treatment. Meanwhile, no obvious adverse events occurred during and after treatment. The results showed that ABT presents a favorable clinical response in patients infected with COVID19. [ABSTRACT FROM AUTHOR]

Background: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells., Methods: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4 + T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4 + T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens., Results: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4 + T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4 + T cell count: 45 vs. -5 cells/µL, p <0.001). After ABT discontinuation, CD4 + T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p =0.012). In laboratory analysis, naïve CD4 + T cell amounts were lowest among participants with unsatisfactory immune response (uIR) to ABT ( p =0.001). The proportion of caspase 3 + CD45RA + CD31 + CD4 + T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT ( p <0.05)., Conclusion: Significant CD4 + T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis., Competing Interests: The authors SY, YuL, DX, MH was/were employed by Frontier Biotechnologies Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, (Copyright © 2024 Fan, Hu, Li, Ding, Liu, Yu, Hu, Su, Li, Yu, Xie, Zhao and Ma.)

1. A clinical study to assess the interactions between albuvirtide (320 mg) and lopinavir/ritonavir (400/100 mg) was conducted in 10 HIV-1-infected subjects. Because albuvirtide requires a long period to achieve steady state, and extended monotherapy may lead to early resistance, it is unethical to take albuvirtide alone to achieve steady state. Therefore, a population pharmacokinetic model was developed to predict steady-state concentration-time curve of solely administered albuvirtide. 2. When albuvirtide and lopinavir/ritonavir were co-administered, the plasma concentration of albuvirtide when the infusion ended (Cend) increased by about 34%, but the geometric mean ratios and 90% confidence intervals (90% CIs) of AUC(0–t)[1.09 (0.96–1.24)] andCtrough[1.00 (0.83–1.20)] were within the range of 0.8–1.25. For lopinavir, the ratios (90% CIs) of AUC(0–t),CmaxandCtroughwere 0.63 (0.49–0.82), 0.67 (0.53–0.86) and 0.65 (0.46–0.91); for ritonavir, those ratios (90% CIs) were 0.62 (0.42–0.91), 0.61 (0.38–0.99) and 0.72 (0.40–1.26), respectively. 3. Co-administration of albuvirtide with lopinavir/ritonavir has little effect on albuvirtide exposure, but it decreases the plasma exposures of lopinavir/ritonavir. However, the drug–drug interactions may not reduce the effectiveness of this co-therapy, the trough concentration of lopinavir may be sufficient and this combination could achieve similar clinical efficacy with marketed drugs. So, a phase 3 clinical trial without dose adjustment is underway to validate their effectiveness and safety. [ABSTRACT FROM AUTHOR]