Objectives: Long-acting formulations of cabotegravir (CAB) and rilpivirine (RPV) have demonstrated efficacy in Phase 3 studies. POLAR (NCT03639311) assessed antiviral activity and safety of CAB+RPV long-acting administered every 2 months (Q2M) in adults living with HIV-1 who previously received daily oral CAB+RPV in LATTE (NCT01641809). Design: A Phase 2b, multicenter, open-label, rollover study. Methods: LATTE participants with plasma HIV-1 RNA less than 50 copies/ml who completed at least 300 weeks on study were eligible. Participants elected to switch to either CAB+RPV long-acting Q2M or daily oral dolutegravir/RPV for maintenance of virologic suppression. The primary endpoint was the proportion of participants with HIV-1 RNA greater than or equal to 50 copies/ml at Month 12 (M12) per the Food and Drug Administration Snapshot algorithm. The incidence of confirmed virologic failure (CVF, two consecutive HIV-1 RNA measurements greater than or equal to 200 copies/ml), as well as safety, laboratory, and patient-reported outcomes (HIV Treatment Satisfaction and preference questionnaires) were also assessed. Results: Of 97 participants enrolled, 90 chose to receive CAB+RPV long-acting and seven chose dolutegravir/RPV. At M12, no participant had HIV-1 RNA greater than or equal to 50 copies/ml or met the CVF criterion in either treatment group. No new safety signals were identified. Total treatment satisfaction was high at Baseline and remained stable through M12 across both treatment groups. Overall, 88% ( n = 77/88) of long-acting arm participants preferred CAB+RPV long-acting to oral CAB+RPV. Conclusion: CAB+RPV long-acting maintained virologic suppression in participants who had previously received daily oral CAB+RPV for at least 5 years in LATTE, with a favorable safety profile. Most participants preferred CAB+RPV long-acting to their prior oral CAB+RPV regimen at M12.
The CAP is the most important policy of the European Union in terms of budget, because during long periods of time most of the EU budget was expended in this policy. Currently the CAP receives nearly half of the EU budget. So, the money spend in this policy is huge in European Union terms.
(2010). Simplified Maintenance Therapy With Abacavir/Lamivudine and Atazanavir After Discontinuation of Ritonavir. HIV Clinical Trials: Vol. 11, No. 3, pp. 170-173.
Abstract Background Cabotegravir (CAB) + rilpivirine (RPV) dosed intramuscularly monthly or every 2 months is a complete, long-acting (LA) regimen for the maintenance of HIV-1 virologic suppression. Here, we report the antiretroviral therapy as long acting suppression (ATLAS)-2M study week 152 results. Methods ATLAS-2M is a phase 3b, randomized, multicenter study assessing the efficacy and safety of CAB+RPV LA every 8 weeks (Q8W) versus every 4 weeks (Q4W). Virologically suppressed (HIV-1 RNA <50 copies/mL) individuals were randomized to receive CAB+RPV LA Q8W or Q4W. Endpoints included the proportion of participants with plasma HIV-1 RNA ≥50 copies/mL and <50 copies/mL, incidence of confirmed virologic failure (CVF; 2 consecutive measurements ≥200 copies/mL), safety, and tolerability. Results A total of 1045 participants received CAB+RPV LA (Q8W, n = 522; Q4W, n = 523). CAB+RPV LA Q8W demonstrated noninferior efficacy versus Q4W dosing, with 2.7% (n = 14) and 1.0% (n = 5) of participants having HIV-1 RNA ≥50 copies/mL, respectively, with adjusted treatment difference being 1.7% (95% CI: 0.1–3.3%), meeting the 4% noninferiority threshold. At week 152, 87% of participants maintained HIV-1 RNA <50 copies/mL (Q8W, 87% [n = 456]; Q4W, 86% [n = 449]). Overall, 12 (2.3%) participants in the Q8W arm and 2 (0.4%) in the Q4W arm had CVF. Eight and 10 participants with CVF had treatment-emergent, resistance-associated mutations to RPV and integrase inhibitors, respectively. Safety profiles were comparable, with no new safety signals observed since week 48. Conclusions These data demonstrate virologic suppression durability with CAB+RPV LA Q8W or Q4W for ∼3 years and confirm long-term efficacy, safety, and tolerability of CAB+RPV LA as a complete regimen to maintain HIV-1 virologic suppression.
In the Long-Acting Antiretroviral Treatment Enabling Trial 2 (LATTE-2) phase 2b study, long-acting (LA) injectable cabotegravir + rilpivirine dosed every 8 weeks (Q8W) or every 4 weeks (Q4W) demonstrated comparable efficacy with daily oral antiretroviral therapy (ART) through 96 weeks in ART-naive adults with human immunodeficiency virus type 1 (HIV-1). Here we report efficacy, tolerability, and safety of cabotegravir + rilpivirine LA over approximately 5 years.After 20 weeks of oral cabotegravir + abacavir/lamivudine, participants were randomized to cabotegravir + rilpivirine LA Q8W or Q4W or continue oral ART through the 96-week maintenance period. In the extension period through week 256, participants continued their current LA regimen (randomized Q8W/Q4W groups) or switched from oral ART to Q8W or Q4W LA therapy (extension-switch groups). Endpoints assessed included proportion of participants with HIV-1 RNA <50 copies/mL (Snapshot algorithm) and adverse events (AEs).At week 256, 186 of 230 (81%) participants in randomized Q8W/Q4W groups and 41 of 44 (93%) participants in extension-switch groups had HIV-1 RNA <50 copies/mL. No protocol-defined virologic failures occurred after week 48. Injection wsite reactions infrequently resulted in discontinuation (4 [2%] and 1 [2%] participants in randomized Q8W/Q4W and extension-switch groups, respectively). Three participants in randomized Q8W/Q4W groups experienced drug-related serious AEs, including 1 fatal serious AE (Q4W group); none occurred in extension-switch groups. Of 25 participants with AEs leading to withdrawal, 20 were in the randomized Q4W group; no AE leading to withdrawal occurred in >1 participant.Cabotegravir + rilpivirine LA exhibited long-term efficacy and tolerability, demonstrating its durability as maintenance therapy for HIV-1 infection.Clinical Trials Registration. NCT02120352.
Objective: Treatment of HIV patients with daily tesamorelin, a growth hormone-releasing factor analogue, for 26 weeks resulted in a significant decrease in visceral adipose tissue (VAT) and improvement in lipids. The objective of the 26-week extension phase was to evaluate long-term safety and effects of tesamorelin. Design: HIV patients with central fat accumulation in the context of antiretroviral therapy were randomized to tesamorelin 2 mg (n = 273) or placebo (n = 137) s.c. daily for 26 weeks. At week 26, patients originally on tesamorelin were rerandomized to 2 mg tesamorelin (T–T group, n = 154) or placebo (T–P group, n = 50), whereas patients originally on placebo were switched to tesamorelin (P–T group, n = 111). Methods: Safety included adverse events and glucose parameters. Results: Tesamorelin was generally well tolerated. The prevalence of adverse events and serious adverse events during the extension phase was comparable with the initial phase. Changes in glucose parameters over 52 weeks were not clinically significant and similar to those after 26 weeks. The change in VAT was sustained at −18% over 52 weeks of treatment (P < 0.001 versus baseline) as was the change in triglycerides (−51 mg/dl, P < 0.001 versus baseline). Similar sustained beneficial effects were seen for total cholesterol, but high-density lipoprotein decreased minimally over 52 weeks. Upon discontinuation of tesamorelin, VAT reaccumulated. Conclusion: Treatment with tesamorelin was generally well tolerated and resulted in sustained decreases in VAT and triglycerides over 52 weeks without aggravating glucose. Though effects on VAT are sustained during treatment for 52 weeks, these effects do not last beyond the duration of treatment.
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