Cell-Mediated Immune Predictors of Vaccine Effect on Viral Load and CD4 Count in a Phase 2 Therapeutic HIV-1 Vaccine Clinical Trial

Abstract Background Ibalizumab-uiyk (IBA) was recently approved for the treatment of multi-drug-resistant HIV-1 infection in patients (pts) failing other antiretroviral regimens. Clinical trial data demonstrated a decrease in HIV-1 viral load in 83% and 43% of patients (n = 40) receiving IBA for 2 and 25 weeks (weeks), respectively. Real-world post marketing data are needed. This pilot study reports the experience of IBA utilization in POICs. Methods Medical records of patients receiving intravenous IBA from approval through April 2019 were reviewed. Data collected include demographics, infection and treatment history, IBA regimen and adverse events. Plasma HIV-1 RNA viral load (log10 copies/mL) and CD4 count (cells/µL) were collected at baseline and as available during therapy. Based on available follow-up (FU) labs, response was assessed at 4–10 weeks (FU 1), 14–22 weeks (FU 2), and 24–37 weeks (FU 3). Results Nine patients (mean age: 48 ± 11 years, 67% male) from 7 POICs received IBA for a median duration of 33 weeks (range 4–43). Median length of HIV-1 diagnosis was 22 years (range 8–25). Resistance to ≥1 drug in at least 3 drug classes was reported in 56%. All patients received at least one concurrent anti-retroviral agent. IBA was initiated at 2000 mg followed by 800 mg every 2 weeks. All patients received infusions as scheduled (151 total infusions) except for one requiring a second loading dose. Baseline mean CD4 count and viral load were 49 cells/µL and 4.9 log10 copies/mL, respectively. Labs obtained at FU 1 indicated a decrease in viral load of at least 0.5 log10 copies/mL in 6/8 patients (75%); a mean reduction of 2.1 ± 1.8 log10 copies/mL (Table 1). Mean HIV-1 titers available for patients at FU 2 (n = 6) and FU 3 (n = 7) were 3.1 ± 2.0 and 3.2 ± 2.6 log10 copies/mL, respectively. Mean CD4 counts were 65 ± 57 cells/µL at FU 1, 96 ± 61 cells/µL at FU 2 and 88 ± 82 cells/µL at FU 3. Adverse events were reported in 8 patients (89%), most common itching/rash, diarrhea and abdominal pain. None resulted in discontinuation of IBA. Conclusion This study confirms the antiviral activity of IBA in patients with advanced HIV-1 infection in the real-world setting. We observed well-tolerated therapy with an early reduction in HIV-1 viral load of 75%, followed by a 43% reduction ≥24 weeks, consistent with the clinical trial. Disclosures All authors: No reported disclosures.

Download Full-text

P067 HLA-B*57 Carriage in a post-treatment viral load controller from an hiv-1 therapeutic vaccine clinical trial

Human Immunology ◽

10.1016/j.humimm.2019.07.120 ◽

2019 ◽

Vol 80 ◽

pp. 102

Author(s):

Jinatanat Ananworanich ◽

Aviva Geretz ◽

Donn Colby ◽

Michal Sarnecki ◽

Philip K. Ehrenberg ◽

...

Keyword(s):

Clinical Trial ◽

Viral Load ◽

Therapeutic Vaccine ◽

Post Treatment ◽

Vaccine Clinical Trial ◽

Hiv 1

Download Full-text

Frequency of Cytomegalovirus Viral Load in Iranian Human Immunodeficiency Virus-1-Infected Patients with CD4+ Counts <100 Cells/mm3

Intervirology ◽

10.1159/000514385 ◽

2021 ◽

pp. 1-5

Author(s):

Mohammad Reza Jabbari ◽

Hoorieh Soleimanjahi ◽

Somayeh Shatizadeh Malekshahi ◽

Mohammad Gholami ◽

Leila Sadeghi ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Viral Load ◽

Cell Count ◽

Previous History ◽

Cd4 Count ◽

Cd4 Cell Count ◽

Cell Counts ◽

Immunodeficiency Virus ◽

Cd4 Cell ◽

Hiv 1

Objectives: The aim of present work was to assess cytomegalovirus (CMV) viremia in Iranian human immunodeficiency virus (HIV)-1-infected patients with a CD4+ count <100 cells/mm3 and to explore whether CMV DNA loads correlate with CD4+ cell counts or associated retinitis. Methods: This study was conducted at the AIDS research center in Iran on HIV-1-infected patients with CD4+ count <100 cells/mm3, antiretroviral therapy-naive, aged ≥18 years with no previous history of CMV end-organ disease (CMV-EOD). Results: Thirty-nine of 82 patients (47.56%) had detectable CMV viral load ranging from 66 to 485,500 IU/mL. CMV viral load in patients with retinitis ranges from 352 to 2,720 IU/mL, and it was undetectable in 2 patients. No significant associations between CMV viremia and CD4+ cell count was found (p value = 0.31), whereas significant association of CMV viremia in HIV-infected patients with retinitis was found (p < 0.02). Conclusions: We estimated the frequency of CMV viral load infection in Iranian HIV-1-infected patients with a CD4+ cell count <100 mm3/mL in the largest national referral center for HIV-1 infection in Iran. Further research is required on the relevance of CMV viral load in diagnostic and prognostic value of CMV-EOD.

Download Full-text

834. Characterization of Heavily Treatment Experienced HIV-1 Infected Clinical Trial Participants Infected with SARS-CoV-2 COVID 19: Fostemsavir BRIGHTE Phase 3 Clinical Trial

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.1030 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S509-S509

Author(s):

Shiven Chabria ◽

Stephane De Wit ◽

Amy Pierce ◽

Bronagh M Shepherd ◽

Michael Warwick-Sanders ◽

...

Keyword(s):

Clinical Trial ◽

Supplemental Oxygen ◽

Multidrug Resistant ◽

Cd4 Count ◽

People Living With Hiv ◽

Research Support ◽

Increased Risk ◽

Living With Hiv ◽

Hiv 1

Abstract Background BRIGHTE is an ongoing global study evaluating the gp120 attachment inhibitor fostemsavir (FTR) in heavily treatment-experienced (HTE) adults with multidrug resistant (MDR) HIV-1 unable to form a viable antiretroviral (ARV) regimen. An estimated 2 million people living with HIV-1 have been infected with SARS-CoV-2. Those with HIV viremia and/or low CD4+ counts are at increased risk of serious adverse outcome. We describe the reported COVID cases in a clinical trial population of people living with MDR HIV and immune suppression. Methods At the start of the COVID pandemic, all ongoing BRIGHTE subjects had achieved ≥ 192 weeks on FTR and optimized background ARVs; results through Week 96 were presented previously. Investigators used WHO guidelines for COVID diagnosis and reported exposure, testing results and symptom presence. Figure 1. BRIGHTE Study Design Results 371 subjects [272 Randomized Cohort (RC), 99 Non-Randomized Cohort (NC)] were enrolled; 44% were ≥ 50 years of age and 86% had an AIDS history. Median CD4+ count at study start of was 80 cells/mm3 (IQR 11–202); 30% with ≤ 20 cells/mm3. 250 subjects remained in BRIGHTE at pandemic start. By April 2021, 17 subjects (14 RC, 3 NC) had confirmed COVID infection (positive PCR test). Severity was Grade 1-3, all cases resolved with no deaths. Six subjects were hospitalized (Table 1); most recent CD4+ count prior to COVID were 293-1641 cells/mm3 and 5/6 subjects were virologically suppressed. Treatments often included prophylactic anticoagulants and supplemental oxygen; no cART changes were made. The remaining 11/17 confirmed cases were managed outpatient. Five more subjects had suspect COVID not confirmed by PCR and 2 subjects had negative PCR tests. Table 1. Characterization of Participants with Serious AEs of Confirmed COVID-19 Infections – All Hospitalizations Conclusion A total of 22/250 COVID-19 cases (17 confirmed, 5 unconfirmed) have been reported in BRIGHTE. Outcomes were reassuring with no deaths or known persistent sequelae, despite having advanced HIV and comorbid diseases at baseline associated with poorer COVID outcomes. Outcomes may have benefitted from immunologic improvement during the trial. Disclosures Shiven Chabria, MD, Viiv Healthcare (Employee) Stephane De Wit, MD, Gilead (Grant/Research Support)Janssen (Grant/Research Support)Merck Sharpe & Dohme (Grant/Research Support)ViiV Healthcare (Grant/Research Support) Amy Pierce, BS, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Bronagh M. Shepherd, PhD, GlaxoSmithKline (Employee, Shareholder) Michael Warwick-Sanders, BM BSc DPM MFPM, GSK (Employee) Marcia Wang, PhD, GlaxoSmithKline (Employee, Shareholder) Andrew Clark, MD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Peter Ackerman, MD, GSK/ViiV Healthcare (Employee, Shareholder)

Download Full-text

EBV AND HHV-6 CIRCULATING SUBTYPES IN PEOPLE LIVING WITH HIV IN BURKINA FASO, IMPACT ON CD4 T CELL COUNT AND HIV VIRAL LOAD

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2017.049 ◽

2017 ◽

Vol 9 (1) ◽

pp. 2017049 ◽

Cited By ~ 2

Author(s):

Lassina TRAORE ◽

Ouéogo NIKIEMA ◽

Abdoul Karim OUATTARA ◽

Tegwindé Rébéca COMPAORE ◽

Serge Théophile SOUBEIGA ◽

...

Keyword(s):

Viral Load ◽

T Cell ◽

Cell Count ◽

Cd4 Count ◽

Cd4 T Cell ◽

People Living With Hiv ◽

Study Population ◽

Living With Hiv ◽

Hiv 1 ◽

Cd4 T Cell Count

Epstein Barr Virus (EBV) and Human Herpes Virus 6 (HHV-6) are responsible for severe diseases, particularly in immunocompromised persons. There are poor data on the infection with these opportunistic viruses in Burkina Faso.The purpose of this study is to characterize EBV and HHV-6 subtypes and to assess their impact on CD4 T cell count, HIV-1 viral load and antiretroviral treatment in people living with HIV-1.The study population consisted of 238 HIV-positive patients with information on CD4 count, HIV-1 viral load and HAART. Venous blood samples collected on EDTA tubes were used for EBV and HHV-6 Real Time PCR subtyping.An infection rate of 6.7% (16/238) and 7.1% (17/238) were found respectively for EBV and HHV-6 in the present study. Among EBV infections, similar prevalences were noted for both subtypes (3.9% [9/238] for EBV-1 vs 4.6% [11/238] for EBV-2) with 2.1% (5/238) of co-infection. HHV-6A infection represented 6.3% (15/238) of the study population against 5.0% (12/238) for HHV-6B. . EBV-2 infection was significantly higher in patients with CD4 count ≥ 500 compared to those with CD4 count less than 500 cells (1.65% vs 8.56%, p = 0,011). The prevalence of EBV and HHV-6 infections were almost similar in HAART-naive and HAART-experienced patients.The present study provides information on the prevalence of EBV and HHV-6 subtypes in people living with HIV-1 in Burkina Faso. The study also suggests that HAART treatment has no effect on infection with these opportunistic viruses in people living with HIV-1.

Download Full-text

541. Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in HIV-1 Treatment Naïve Patients: Week 48 Results in Subgroups Based on Baseline Viral Load, CD4+ Count, and WHO Clinical Staging

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.550 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S201-S201 ◽

Cited By ~ 1

Author(s):

Christoph D Spinner ◽

Bruce Rashbaum ◽

Cheryl Mcdonald ◽

Cristina Mussini ◽

Donghan Luo ◽

...

Keyword(s):

Viral Load ◽

Cd4 Count ◽

Baseline Viral Load ◽

Clinical Staging ◽

Treatment Naïve ◽

Tenofovir Alafenamide ◽

Hiv 1

Download Full-text

Suboptimal Antiretroviral Drug Levels and Virologic Failures among PLHIV at a Rural Referral Hospital in South Western Uganda: A Descriptive Cross-sectional Study.

10.21203/rs.3.rs-122206/v1 ◽

2020 ◽

Author(s):

Silvano Samba Twinomujuni ◽

Patrick E. Ogwang ◽

Felicitas Roelofsen ◽

Jackson K. Mukonzo ◽

Esther Cathyln Atukunda

Keyword(s):

Clinical Trial ◽

Steady State ◽

Viral Load ◽

Cd4 Count ◽

Referral Hospital ◽

Hiv Care ◽

Drug Levels ◽

Antiretroviral Drug ◽

Persons Living With Hiv ◽

Western Uganda

Abstract Background: Achieving favorable HIV treatment outcomes is a major challenge, particularly due to non-adherence and consequent sub-therapeutic plasma antiretroviral drug levels. This is often complicated by the development of resistant strains due to mutations. Monitoring antiretroviral drug levels in the blood of patients enrolled on ART can reveal if levels are too high, enough, or too low. High levels may lead to dose-dependent side effects and sub-therapeutic levels could promote treatment failure and resistance. In Uganda, as part of routine HIV care, plasma antiretroviral drug level is estimated indirectly by clinic-based pill counts and patient self-reported adherence, which give no evidence of ingested medication. This study aimed at exploring steady-state nevirapine and efavirenz drug levels in HIV patients accessing ART at a rural referral hospital in South Western Uganda. Methods: This study was nested into a randomized clinical trial that evaluated the effect of Artemisia annua L. and Moringa oleifera on immunological response and viral load among persons living with HIV (PLHIV). In the parent study, 250 HIV-infected patients with continued immunologic suppression (CD4 count < 350cells/µL) despite a minimum of one-year on ART were enrolled. Out of 250 clinical trial participants, 95 were randomly selected for steady-state efavirenz and nevirapine plasma concentration sampling having taken the last at bedtime. Additionally, CD4 count, HIV load, liver, and renal function tests were determined. Participants were also interviewed for adherence, and factors that affect blood drug levels.Results: Of the 95 participants sampled, 67 (71%) and 28 (30%) were on efavirenz or nevirapine based ART respectively. The median viral load for participants on the efavirenz regimen was 490 copies/mL (IQR 116, 1900) while that for the participants on the nevirapine regimen was 500 copies/mL (IQR 137, 1270). The median plasma level for the participants on the nevirapine regimen (6.56 mg/L IQR 4.50, 9.80) was higher than that for the participants on the efavirenz regiment (2.54 mg/L IQR 1.47, 5.12). The prevalence of virologic failure among participants sampled on the efavirenz regimen was higher (37%) compared to that of the participants on the nevirapine regimen (21%). 30% of all plasma samples tested had sub-therapeutic levels of either efavirenz or nevirapine, including 2% in which no drugs were detected.Conclusion: Periodic therapeutic drug monitoring should be incorporated as one of the components in the monitoring of ART adherence to ensure adequate blood levels among adults accessing ART at MRRH, SW Uganda.

Download Full-text