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Introduction: Switch to Stribild (STB) was non‐inferior to continuation of a non‐nucleoside reverse transcriptase inhibitor (NNRTI) with emtricitabine and tenofovir DF (FTC/TDF) at week 48 in virologically suppressed HIV adults [1]. We report the Week 48 efficacy and safety of STB versus nevirapine (NVP) or rilpivirine (RPV) with FTC/TDF in suppressed subjects. Materials and Methods: Virologically suppressed subjects on an NNRTI with FTC/TDF regimens for ≥6 months were randomized (2:1) to switch to STB versus continue their NNRTI regimen. Eligibility criteria included no documented resistance to FTC and TDF, no history of virologic failure and eGFR ≥70 mL/min. The primary endpoint was the proportion of subjects in the modified ITT population who maintained HIV‐1 RNA Results: The mITT population included 433 subjects who were randomized and treated. In the non‐EFV NNRTI subgroup, 59 switched to STB; 37 continued a non‐EFV NNRTI (27 NVP, 10 RPV) with FTC/TDF. At week 48, 97% STB versus 95% non‐EFV NNRTI maintained HIV‐1 RNA Conclusions: In this small group of virologically suppressed subjects, switch to STB vs continuation of NVP or RPV with FTC/TDF was safe, well‐tolerated, and associated with a high rate of virologic suppression at week 48. There was more treatment ease with STB use., Reference Pozniak A, Markowitz M, Mills A, Stellbrink HJ, Antela A, Domingo P, et al. Switching to coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir versus continuation of non‐nucleoside reverse transcriptase inhibitor [...]

배경 The 2-drug regimen of long-acting (LA) CAB and RPV dosed i.m. every 4 weeks (Q4W) was noninferior to daily oral 3-drug ART in Phase 3 studies. Long-term Phase 2 data (LATTE-2) provide the rationale for evaluation of a longer and potentially more convenient 8-week dosing interval (Q8W). 방법 ATLAS-2M is a multicenter, open-label, Phase 3b noninferiority (NI) study of CAB+RPV LA maintenance therapy administered Q8W or Q4W to treatment-experienced, HIV-infected adults. Virologically suppressed individuals on CAB+RPV LA Q4W (ATLAS study rollover) or oral ART were randomized 1:1 to receive CAB+RPV LA Q8W or Q4W. The primary endpoint at Week 48 was the proportion with plasma HIV-1 RNA ≥50 c/mL (Snapshot, ITT-exposed [ITTe]). The key secondary endpoint was the proportion with HIV-1 RNA <50 c/mL (Snapshot, ITTe). 결과 1045 participants were randomized to CAB+RPV LA Q8W (n=522) or Q4W (n=523); 27% were female; 63% were naive to CAB+RPV LA. CAB+RPV LA Q8W was noninferior to Q4W dosing in both the primary (1.7% vs 1.0%; adjusted difference [95% CI], 0.8 [−0.6, 2.2]) and secondary analysis (94.3% vs 93.5%; adjusted difference [95% CI], 0.8 [−2.1, 3.7]). There were 8 and 2 confirmed virologic failures (CVFs; 2 sequential measures ≥200 c/mL) on Q8W and Q4W dosing, respectively; 5 and 0 CVFs, respectively, had archived resistance-associated mutations (RAMs) to RPV, either alone (n=3) or with CAB RAMs (n=1) in baseline peripheral blood mononuclear cells (PBMCs). On-treatment RAMs to RPV, CAB, or both not present in baseline PBMCs were found in 6/8 Q8W CVFs and both Q4W CVFs. The safety profile was similar for Q4W and Q8W dosing, and serious adverse events were reported in 5% of participants in the Q8W group (n=26) vs 4% in the Q4W group (n=19). Injection site reactions (ISRs) were mostly mild or moderate (98% overall) with a median duration of 3 days. Discontinuation for an adverse event occurred in 2% of participants (Q8W, n=8; Q4W, n=10), with 6 (1%) and 11 (2%) in each group due to ISRs. There was 1 death (Q8W; sepsis). Of those treated Q8W in ATLAS-2M after ≥48 weeks of Q4W dosing in ATLAS, 94% (180/191) preferred Q8W dosing. 결론 Q8W dosing of CAB+RPV LA was noninferior to Q4W dosing and well tolerated. These results support the therapeutic potential of CAB+RPV LA administered every 2 months. [ABSTRACT FROM AUTHOR]

Background: Phase 3 clinical studies showed non-inferiority of long-acting intramuscular cabotegravir and rilpivirine dosed every 4 weeks to oral antiretroviral therapy. Important phase 2 results of every 8 weeks dosing, and supportive modelling, underpin further evaluation of every 8 weeks dosing in this trial, which has the potential to offer greater convenience. Our objective was to compare the week 48 antiviral efficacy of cabotegravir plus rilpivirine long-acting dosed every 8 weeks with that of every 4 weeks dosing., Methods: ATLAS-2M is an ongoing, randomised, multicentre (13 countries; Australia, Argentina, Canada, France, Germany, Italy, Mexico, Russia, South Africa, South Korea, Spain, Sweden, and the USA), open-label, phase 3b, non-inferiority study of cabotegravir plus rilpivirine long-acting maintenance therapy administered intramuscularly every 8 weeks (cabotegravir 600 mg plus rilpivirine 900 mg) or every 4 weeks (cabotegravir 400 mg plus rilpivirine 600 mg) to treatment-experienced adults living with HIV-1. Eligible newly recruited individuals must have received an uninterrupted first or second oral standard-of-care regimen for at least 6 months without virological failure and be aged 18 years or older. Eligible participants from the ATLAS trial, from both the oral standard-of-care and long-acting groups, must have completed the 52-week comparative phase with an ATLAS-2M screening plasma HIV-1 RNA less than 50 copies per mL. Participants were randomly assigned 1:1 to receive cabotegravir plus rilpivirine long-acting every 8 weeks or every 4 weeks. The randomisation schedule was generated by means of the GlaxoSmithKline validated randomisation software RANDALL NG. The primary endpoint at week 48 was HIV-1 RNA ≥50 copies per mL (Snapshot, intention-to-treat exposed), with a non-inferiority margin of 4%. The trial is registered at ClinicalTrials.gov, NCT03299049 and is ongoing., Findings: Screening occurred between Oct 27, 2017, and May 31, 2018. Of 1149 individuals screened, 1045 participants were randomised to the every 8 weeks (n=522) or every 4 weeks (n=523) groups; 37% (n=391) transitioned from every 4 weeks cabotegravir plus rilpivirine long-acting in ATLAS. Median participant age was 42 years (IQR 34-50); 27% (n=280) female at birth; 73% (n=763) white race. Cabotegravir plus rilpivirine long-acting every 8 weeks was non-inferior to dosing every 4 weeks (HIV-1 RNA ≥50 copies per mL; 2% vs 1%) with an adjusted treatment difference of 0·8 (95% CI -0·6-2·2). There were eight (2%, every 8 weeks group) and two (<1%, every 4 weeks group) confirmed virological failures (two sequential measures ≥200 copies per mL). For the every 8 weeks group, five (63%) of eight had archived non-nucleoside reverse transcriptase inhibitor resistance-associated mutations to rilpivirine at baseline. The safety profile was similar between dosing groups, with 844 (81%) of 1045 participants having adverse events (excluding injection site reactions); no treatment-related deaths occurred., Interpretation: The efficacy and safety profiles of dosing every 8 weeks and dosing every 4 weeks were similar. These results support the use of cabotegravir plus rilpivirine long-acting administered every 2 months as a therapeutic option for people living with HIV-1., Funding: ViiV Healthcare and Janssen., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: GB Virus C (GBV-C) has been associated with a better prognosis of HIV-1 disease in adults. Little is known about prevalence and interaction between GBV-C, HIV-1, and/or hepatitis C virus (HCV) in hemophiliac children and adolescents., Methods: A well-characterized cohort of HIV-1-infected and HIV-1-uninfected hemophiliac children and adolescents followed in the Hemophilia Growth and Development Study (HGDS) were evaluated using quantitative reverse transcription polymerase chain reaction to detect GBV-C RNA in samples from baseline and last follow-up visit., Results: HIV-1-infected (n = 202) and HIV-1-uninfected (n = 119) patients had a low prevalence of GBV-C infection at baseline (0.9 and 0%), which increased at time of last follow-up visit to 25.2% and 26.3%, respectively. In addition, at the time of the follow-up GBV-C measurement, those GBV-C infected had been followed longer and had higher CD4(+) cell counts and lower HIV-1 viral loads than those GBV-C uninfected. These beneficial effects of GBV-C were no longer significant after controlling for CD4(+) cell count and HIV-1 RNA at baseline. HCV RNA clearance was more common amongst those who were not GBV-C infected than those who became GBV-C viremic., Conclusions: This study confirms a positive association of GBV-C with milder course of HIV-1 infection. GBV-C infection was associated with a higher likelihood of persistent HCV infection.