scholarly journals Long-term Outcomes in a Large Randomized Trial of HIV-1 Salvage Therapy: 96-Week Results of AIDS Clinical Trials Group A5241 (OPTIONS)

2019 ◽  
Vol 221 (9) ◽  
pp. 1407-1415 ◽  
Author(s):  
Rajesh T Gandhi ◽  
Karen T Tashima ◽  
Laura M Smeaton ◽  
Vincent Vu ◽  
Justin Ritz ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Salvage Therapy ◽  
Virologic Failure ◽  
Virologic Suppression ◽  
Cumulative Activity ◽  
Antiretroviral Medications ◽  
Resistant Group ◽  
Aids Clinical Trials ◽  
Hiv 1

Abstract Background Short-term (48-week) results of the OPTIONS trial showed that nucleoside reverse transcriptase inhibitors (NRTIs) can be safely omitted from salvage therapy as long as the regimen has a cumulative activity of >2 active antiretroviral medications. The long-term durability of this approach and outcomes in persons who have more-extensive HIV-1 drug resistance are uncertain. Methods Participants with virologic failure and anticipated antiretroviral susceptibility received an optimized regimen and were randomized to omit or add NRTIs. A separate group with more resistance (cumulative activity ≤2 active agents) received an optimized regimen including NRTIs. Results At week 96, among 360 participants randomized to omit or add NRTIs, 70% and 65% had HIV-1 RNA <200 copies/mL, respectively. Virologic failure was uncommon after week 48. Younger age and starting fewer new antiretroviral medications were associated with higher odds of virologic failure. In the highly resistant group, 53% had HIV-1 RNA <200 copies/mL at week 96. Conclusions HIV-1 salvage therapy can safely omit NRTIs without compromising efficacy or durability of response as long as the new regimen has a cumulative activity of >2 active drugs. Younger people and those receiving fewer new antiretrovirals require careful monitoring. Even among individuals with more-extensive resistance, most achieve virologic suppression. Clinical Trials Registration NCT00537394.

scholarly journals Real-World Experience with Dolutegravir-Based Two-Drug Regimens

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Douglas Ward ◽  
Moti Ramgopal ◽  
David J. Riedel ◽  
Cindy Garris ◽  
Shelly Dhir ◽  
...  
Keyword(s):  
Virologic Failure ◽  
Retrospective Chart Review ◽  
Virologic Suppression ◽  
Prior Art ◽  
The Us ◽  
Drug Regimens ◽  
Hiv 1 ◽  
Treatment Simplification

Background. Dolutegravir-based 2-drug regimens (DTG 2DRs) are now accepted as alternatives to 3-drug regimens for HIV antiretroviral treatment (ART); however, literature on physician drivers for prescribing DTG 2DR is sparse. This study evaluated treatment patterns of DTG 2DR components in clinical practice in the US. Methods. This was a retrospective chart review in adult patients in care in the US with HIV-1 who received DTG 2DR prior to July 31, 2017, with follow-up until January 30, 2018. Primary objectives of the study were to determine reasons for patients initiating DTG 2DR and to describe the demographics and clinical characteristics. All analyses were descriptive. Results. Overall, 278 patients received DTG 2DR (male: 70%; mean age: 56 years). Most patients were treatment experienced (98%), with a mean 13.5 years of prior ART. DTG was most commonly paired with darunavir (55%) or rilpivirine (27%). The most common physician-reported reasons for initiating DTG 2DR were treatment simplification/streamlining (30%) and avoidance of potential long-term toxicities (20%). Before starting DTG 2DR, 42% of patients were virologically suppressed; of those, 95% maintained suppression while on DTG 2DR. Of the 50% of patients with detectable viral load before DTG 2DR, 79% achieved and maintained virologic suppression on DTG 2DR during follow-up. There were no virologic data for 8% of patients prior to starting DTG 2DR. Only 15 patients discontinued DTG 2DR, of whom 4 (27%) discontinued due to virologic failure. Conclusions. Prior to commercial availability of the single-tablet 2DRs, DTG 2DR components were primarily used in treatment-experienced patients for treatment simplification and avoidance of long-term toxicities. Many of these patients achieved and maintained virologic suppression, with low discontinuation rates.

scholarly journals Long-term safety and efficacy of rilpivirine in combination with nucleoside/nucleotide reverse transcriptase inhibitors in HIV-1 infected patients: 336-week rollover study of phase 2b and 3 clinical studies

2021 ◽  
pp. 135965352110623
Author(s):  
Jean Michel Molina ◽  
Luminita Ene ◽  
Pedro Cahn ◽  
Gerd Fätkenheuer ◽  
Eric Van Wijngaerden ◽  
...  
Keyword(s):  
Reverse Transcriptase ◽  
Cell Count ◽  
Virologic Failure ◽  
Transcriptase Inhibitor ◽  
Virologic Suppression ◽  
Reverse Transcriptase Inhibitors ◽  
Open Label ◽  
Safety And Efficacy ◽  
Hiv 1

Background To evaluate the long-term safety and efficacy of rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), in combination with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) in human immunodeficiency virus (HIV)–infected patients. Methods RPV-treated HIV-infected patients from phase 2b or 3 studies rolled-over into this phase 3, open-label study and received RPV 25 mg once daily (QD) with choice of two NRTIs. Adverse events (AEs), plasma viral load, CD4+ cell count, and antiviral resistance were evaluated. Results Of the 482 patients treated, 437 (>90%) patients discontinued study treatment; 371 (77%) had switched to commercially available RPV, 14 (2.9%) discontinued due to AEs, and 6 (1.2%) had virologic failure. In this rollover study, patients were followed up to week 336, although data was limited beyond 288 weeks. Forty-five (9.3%) patients were still undergoing treatment at the time of data cut-off for the current analysis (8 February 2018). The most frequently reported AEs were pregnancy in 7 (1.5%) patients and syphilis in 5 (1.0%) patients. Grade 3–4 AEs were reported in 17 (3.5%) patients, and AEs possibly related to RPV in 23 (4.8%) patients. Over 288 weeks of treatment, 80.1% (95% CI: 74.9%; 84.3%) of patients maintained virologic suppression (HIV-1 RNA <50 copies/mL). The absolute CD4+ cell count increased over time until week 192 and remained constant thereafter. Conclusions RPV 25 mg QD in combination with an investigator-selected background regimen of two NRTIs demonstrated sustained long-term virologic suppression. The treatment was well-tolerated with no new safety findings.

SENSITIVITY, SPECIFICITY, AND PREDICTIVE VALUE OF PHYSICAL EXAMINATION, CULTURE, AND OTHER LABORATORY STUDIES IN THE DIAGNOSIS DURING EARLY INFANCY OF VERTICALLY ACQUIRED HUMAN IMMUNODEFICIENCY VIRUS INFECTION

PEDIATRICS ◽  
1994 ◽  
Vol 94 (2) ◽  
pp. 274-275
Author(s):  
Susan E. Pacheco ◽  
William T. Shearer
Keyword(s):  
Clinical Trials ◽  
Physical Examination ◽  
Hiv Infection ◽  
Laboratory Studies ◽  
Diagnostic Laboratory ◽  
Predictive Values ◽  
P24 Antigen ◽  
Aids Clinical Trials ◽  
Sensitivity Specificity ◽  
Hiv 1

Purpose of the Study. To determine the HIV vertical transmission rate in an unselected group of infants born to HIV-infected mothers, and to examine the sensitivity, specificity, and positive and negative predictive values of physical examination and diagnostic laboratory studies (HIV culture, serum quantitative immunoglobulins and HIV-1 p24 antigen) in the diagnosis of HIV infection. Study Population. A group of 142 infants referred solely because they were born to HIV-infected mothers were selected for this study. Methods. Epidemiological and clinical data were obtained retrospectively from the Baylor Pediatric AIDS Clinical Trials Group HIV Infection Registry and medical records. The information recorded included results of physical examination and diagnostic laboratory tests (HIV culture, serum quantitative immunoglobulins, and HIV-1 p24 antigen). HIV cultures were performed according to a consensus protocol developed for the National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. Results. Of 142 infants whose HIV infection status was known at the time of the study, 17 (20%) had confirmed infection, and 68 (80%) had seroreverted with no evidence of infection. All HIV-infected infants were at least 3 months old when abnormal physical exam findings became apparent (lymphadenopathy and hepatosplenomegaly), but similar findings were noted in an equal number of HIV-uninfected infants. All infected infants available were HIV culture positive by 6 months of age (16/16). There was no positive cultures reported in the infants who seroreverted (32/32). Elevated immunoglobulins (IgG, IgA, IgM) were present by 6 months of age in a high percentage of infected infants. Nearly one-half of the uninfected infants had elevated immunoglobulin levels during the first 6 months of life, but in 50% of the cases it was IgG alone.

scholarly journals Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort

2019 ◽  
Author(s):  
Tong Zhang ◽  
Haibo Ding ◽  
Minghui An ◽  
Xiaonan Wang ◽  
Wen Tian ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
High Risk ◽  
Virologic Failure ◽  
Baseline Viral Load ◽  
Factors Associated ◽  
Low Level ◽  
Subtype B ◽  
High Level ◽  
Hiv 1

Abstract Background: Low level viremia (LLV) often occurs during antiretroviral therapy (ART) against HIV-1. However, its impact on virologic failure (VF) is controversial because of non-uniform definitions of LLV and VF. Methods: A long-term first line regimen ART cohort from 2002–2018 from Shenyang, northeast China, was retrospectively studied. All participants were followed up every 3 to 6 months to evaluate the treatment effect. The high-risk LLV subgroups leading to VF (with strict standards) were explored with Cox proportional hazards model and linear mixed-effect model. The association factors of high-risk LLV were further explored using multivariate logistic regression analyses. Results: A total of 2155 HIV-1 infected participants were included; of these, 38.8% showed LLV. Both high level LLV (HLLV) and any other level LLV coupled with high level blip (HBL) showed higher risk of VF (hazards ratios, HRHLLV=5.93, and HRHBL=2.84, p<0.01 respectively). Moreover, HR increased with prolonged duration of LLV. Independent factors associated with high-risk LLV included the zenith baseline viral load (VL) above 6 log copies/ml (aOR=3.49, p=0.002), nadir baseline CD4+T cell counts below 200 cells/ml (aOR=1.78, p=0.011), Manchu (aOR=2.03, p=0.003), ART over 60 months (aOR=1.81, p=0.004), AZT+3TC+NVP (aOR=2.26, p<0.001) or DDI-based regimen (aOR=9.96, p<0.001), and subtype B’ infection (aOR=8.22, p=0.001). Conclusions: In case of VF with strict standards, high-risk LLV leading to VF includes VL above 400 copies/ml, occurring at least once. Serious laboratory indicators or advanced stage of infection, long term ART and subtype B’ infection might also predict the occurrence of high-risk LLV.

scholarly journals 833. Efficacy and Safety of Long-Acting Cabotegravir + Rilpivirine in Participants with HIV/HCV Co-infection: ATLAS-2M 48-Week Results

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S508-S509
Author(s):  
Ronald D’Amico ◽  
Paul Benn ◽  
Shanker Thiagarajah ◽  
Susan L Ford ◽  
Eileen Birmingham ◽  
...  
Keyword(s):  
Research And Development ◽  
Injection Site ◽  
Virologic Failure ◽  
Hcv Rna ◽  
Virologic Suppression ◽  
Efficacy And Safety ◽  
Modes Of Transmission ◽  
Long Acting ◽  
Chronic Hcv ◽  
Hiv 1

Abstract Background The phase IIIb ATLAS-2M study demonstrated non-inferiority of long-acting (LA) cabotegravir (CAB) + rilpivirine (RPV) dosed every 8 weeks (Q8W) compared with every 4 weeks (Q4W) for maintenance of virologic suppression. Hepatitis C virus (HCV) co-infection occurs in ~6% of people with HIV due to shared modes of transmission. We report efficacy and safety of CAB + RPV LA in participants with HIV/HCV co-infection in ATLAS-2M. Methods Participants with HIV-1 RNA &lt; 50 c/mL receiving CAB + RPV LA Q4W (transitioned from ATLAS [NCT02951052]) or oral comparator ART were randomized 1:1 to receive CAB + RPV LA Q4W or Q8W. Baseline HCV RNA was assessed by polymerase chain reaction. Participants with symptomatic chronic HCV infection requiring treatment within 12 months or liver enzymes not meeting entry criteria were excluded. Week 48 assessments included proportion with HIV-1 RNA ≥50 and &lt; 50 c/mL (Snapshot algorithm), general and hepatic safety, and pharmacokinetics. Results HIV/HCV co-infection was present in 10 (1%) of 1045 participants, 60% of whom were female at birth. At Week 48, 9/10 (90%) and 972/1035 (94%) participants with HIV/HCV co-infection and HIV mono-infection, respectively, had HIV-1 RNA &lt; 50 c/mL (adjusted difference, 4.1; 95% CI, −14.5 to 22.6). No participants with HIV/HCV co-infection had HIV-1 RNA ≥50 c/mL (vs 14/1035 [1%] with HIV mono-infection) or confirmed virologic failure through Week 48 (vs 10 [1%] with HIV mono-infection); 1/10 (10%) discontinued for reasons other than adverse events (AEs). Excluding injection site reactions (ISRs), AEs and serious AEs were reported in 4 (40%) and 0 participants with HIV/HCV co-infection, respectively; the only AE reported in &gt;1 participant was injection site pain (n=5; 50%). In participants with HIV/HCV co-infection, all ISRs were grade 1/2; none led to withdrawal. No hepatic laboratory abnormalities were reported in participants with HIV/HCV co-infection through Week 48; rates were low in those with HIV mono-infection (Table). Plasma CAB and RPV concentrations were similar between groups. Conclusion CAB + RPV LA was effective and well tolerated in this small cohort of participants with HIV and asymptomatic HCV co-infection. Disclosures Ronald D’Amico, DO, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Paul Benn, MB ChB FRCP, ViiV Healthcare (Employee) Shanker Thiagarajah, MB ChB, GlaxoSmithKline (Employee, Shareholder) Susan L. Ford, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Eileen Birmingham, MD, MPH, Janssen Research and Development (Employee, Shareholder) Ojesh R. Upadhyay, MPH, MBA, GlaxoSmithKline (Employee) Louise Garside, PhD, GlaxoSmithKline (Employee) Rodica Van Solingen-Ristea, MD, Janssen Research and Development (Employee)ViiV Healthcare (Employee) Kati Vandermeulen, M.SC., Janssen Research and Development (Employee) William Spreen, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

scholarly journals 877. North American Phase 3/3b Experience with Long-Acting Cabotegravir and Rilpivirine: Efficacy, Safety, and Virologic Outcomes

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S530-S531
Author(s):  
Babafemi O Taiwo ◽  
Darrell Tan ◽  
Parul Patel ◽  
Paula Teichner ◽  
Joseph Polli ◽  
...  
Keyword(s):  
Treatment Guidelines ◽  
Virologic Failure ◽  
Descriptive Analysis ◽  
Injection Site Reaction ◽  
Treatment Preference ◽  
Virologic Suppression ◽  
Research Support ◽  
Phase 3 ◽  
Long Acting ◽  
Hiv 1

Abstract Background Cabotegravir (CAB) plus rilpivirine (RPV) is the first complete long-acting (LA) regimen recommended by treatment guidelines for the maintenance of HIV-1 virologic suppression. CAB+RPV LA dosed every 4 weeks (Q4W) or every 8 weeks (Q8W) demonstrated noninferior efficacy in multinational Phase 3/3b trials. This post hoc descriptive analysis summarizes efficacy, virologic outcomes, safety, and treatment preference for US and Canadian (CAN) participants through Week (W) 48. Methods This analysis focuses on data for US/CAN participants naive to CAB+RPV (n=376) from the larger pooled population of the ATLAS, FLAIR, and ATLAS-2M Phase 3/3b studies (N=1245). Endpoints included the proportion of participants with plasma HIV-1 RNA ≥ 50 and &lt; 50 c/mL at W48 (FDA Snapshot algorithm), incidence of confirmed virologic failure (CVF; 2 consecutive HIV-1 RNA ≥ 200 c/mL), safety, and treatment preference through W48. Results 376 US/CAN participants received CAB+RPV LA Q4W or Q8W. Median (range) age was 39y (20–74); 14.9% were female, 66.0% were White. At W48, 93.1% (350/376) maintained virologic suppression (HIV-1 RNA &lt; 50 c/mL), 1.9% (7/376) had HIV-1 RNA ≥ 50 c/mL, and 0.8% (3/376) met the CVF criterion, consistent with the overall global pooled population (Table 1). Two of the three participants with CVF had ≥ 2 of the three baseline factors (archived RPV resistance-associated mutations [RAMs], HIV subtype A6/A1, body mass index [BMI] ≥ 30 kg/m2) previously associated with CVF. Among the US/CAN participants with a single baseline factor, none met CVF. Overall, archived RPV RAMs were observed in 3.2% (12/376), HIV subtype A6/A1 in 1.1% (4/376), and BMI ≥ 30 kg/m2 in 26.3% (99/376) of participants. Safety and injection site reaction findings were similar to the overall pooled population (Table 2). Most participants (120/134, 89.6%) preferred LA over oral dosing (7/134, 5.2%). Table 1. Snapshot outcomes following CAB+RPV LA Q4W and Q8W at Week 48 in participants naive to CAB+RPV from ATLAS, FLAIR, and ATLAS-2M (ITT-E population) Table 2. Safety summary through Week 48 following CAB+RPV LA Q4W and Q8W or comparator ART in participants naive to CAB+RPV from ATLAS, FLAIR, and ATLAS-2M Conclusion In US/CAN Phase 3/3b trial participants, CAB+RPV LA was highly effective and well tolerated, with outcomes consistent with the overall pooled population. Baseline prevalence of archived RPV RAMs and subtype A6/A1 was low and aligned with regional prevalence/surveillance data. CAB+RPV LA provides a tolerable and effective injectable LA treatment option for virologically suppressed US/CAN individuals with HIV. Disclosures Babafemi O. Taiwo, MBBS, Gilead (Consultant)Merck (Consultant)ViiV Healthcare (Consultant) Darrell Tan, MD PhD, Abbvie (Grant/Research Support)Gilead (Grant/Research Support)GlaxoSmithKline (Scientific Research Study Investigator)ViiV Healthcare (Grant/Research Support) Parul Patel, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Paula Teichner, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Joseph Polli, PhD, FAAPS, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Louise Garside, PhD, GlaxoSmithKline (Employee) Ronald D’Amico, DO, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Christine L. Talarico, M.S., GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Rodica Van Solingen-Ristea, MD, Janssen Research and Development (Employee)ViiV Healthcare (Employee) Bryan Baugh, MD, Janssen, Johnson & Johnson (Employee, Shareholder) William Spreen, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Michael Aboud, MBChB, MRCP, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Matthew Bosse, DO, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

scholarly journals Factors associated with high-risk low-level viremia leading to virologic failure: 16-year retrospective study of a Chinese antiretroviral therapy cohort

2020 ◽  
Author(s):  
Tong Zhang ◽  
Haibo Ding ◽  
Minghui An ◽  
Xiaonan Wang ◽  
Wen Tian ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
High Risk ◽  
Virologic Failure ◽  
Baseline Viral Load ◽  
Factors Associated ◽  
Low Level ◽  
Subtype B ◽  
High Level ◽  
Hiv 1

Abstract Background: Low level viremia (LLV) often occurs during antiretroviral therapy (ART) against HIV-1. However, whether LLV increases the risk of virologic failure (VF) is controversial because of the non-uniform definitions of LLV and VF. Methods: A long-term first line regimen ART cohort from 2002–2018 from Shenyang, northeast China, was retrospectively studied. All participants were followed up every 3 to 6 months to evaluate the treatment effect. The high-risk LLV subgroups leading to VF (with strict standards) were explored with Cox proportional hazards model and linear mixed-effect model. The association factors of high-risk LLV were further explored using multivariate logistic regression analyses. Results: A total of 2155 HIV-1 infected participants were included; of these, 38.7% showed LLV. Both high level LLV (HLLV) and any other level LLV coupled with high level blip (HLB) showed higher risk of VF (hazards ratios, HRHLLV=5.93, and HRHLB=2.84, p<0.05 respectively). Moreover, HR increased with prolonged duration of LLV. Independent factors associated with high-risk LLV included the zenith baseline viral load (VL) above 6 log copies/ml (aOR=3.49, p=0.002), nadir baseline CD4+T cell counts below 200 cells/mm3 (aOR=1.78, p=0.011), Manchu (aOR=2.03, p=0.003), ART over 60 months (aOR=1.81, p=0.004), AZT+3TC+NVP (aOR=2.26, p<0.001) or DDI-based regimen (aOR=9.96, p=0.002), and subtype B’ infection (aOR=8.22, p=0.001). Conclusions: In case of VF with strict standards, high-risk LLV leading to VF includes VL above 400 copies/ml, occurring at least once. Serious laboratory indicators or advanced stage of infection, long term ART and subtype B’ infection might also predict the occurrence of high-risk LLV.

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