Long-Acting Cabotegravir and Rilpivirine for HIV-1 Suppression

Switch to 2-Monthly Dosing After 5 Years of Daily Oral Therapy

Anthony Mills; Gary J. Richmond; Cheryl Newman; Olayemi Osiyemi; Jerry Cade; Cynthia Brinson; Jerome De Vente; David A. Margolis; Kenneth C. Sutton; Viviana Wilches; Sarah Hatch; Jeremy Roberts; Cynthia McCoig; Cindy Garris; Kati Vandermeulen; William R. Spreen

Disclosures

AIDS. 2022;36(2):195-203. 

In This Article

Results

Participants

Of the 98 participants from the LATTE study who were screened for eligibility, 97 entered the Maintenance Phase of POLAR [intention-to-treat exposed (ITT-E) population]. One participant failed screening due to abnormal electrocardiogram results (prolonged QTc interval). Participant disposition is shown in Figure 1b. Of those enrolled, 90 of 97 participants (93%) elected to receive CAB+RPV long-acting therapy, while the remaining seven of 97 (7%) chose to receive daily oral DTG/RPV. Baseline participant characteristics are summarized in Table 1.

Efficacy

In the ITT-E population, no participant in either treatment arm had HIV-1 RNA greater than or equal to 50 copies/ml at Month 12, as per the FDA Snapshot algorithm (Figure 2 and Supplemental Digital Content, Table S1, http://links.lww.com/QAD/C328, Efficacy outcomes at Month 12). Overall, 88 of 90 (98%) and seven of seven (100%) participants in the CAB+RPV long-acting and DTG/RPV arms, respectively, maintained virologic suppression at Month 12. The remaining two (2%) participants in the CAB+RPV long-acting arm had no virologic data at Month 12; one discontinued treatment due to an adverse event and the other was lost to follow-up. Through Month 12, no participants met the CVF criterion in either treatment arm. Consequently, no resistance data were generated. At Month 12, following at least 6 years of CAB+RPV therapy (including ~300 weeks of oral CAB+RPV in LATTE), the median [interquartile range (IQR)] CD4+ cell count change from Baseline in POLAR was –12.5 (–138.0, 71.0) cells/μl in the CAB+RPV long-acting arm and –68.0 (–152.0, 152.0) cells/μl in the DTG/RPV arm. CD4+ cell counts prior to initiating oral CAB+RPV are detailed in the primary publication of the LATTE study.[20]

Figure 2.

Efficacy outcomes at Month 12. aTwo (2%) participants in the LA arm had no virologic data at Month 12; one discontinued treatment due to an AE and the other was lost to follow-up. Figure 2 was presented previously at IDWeek; October 21–25, 2020; Virtual; Oral. AE, adverse event; CAB, cabotegravir; DTG, dolutegravir; LA, long-acting; Q2M, every 2 months; RPV, rilpivirine.

Safety and Tolerability

Through Month 12, 86 of 90 (96%) participants in the CAB+RPV long-acting arm and three of seven (43%) in the DTG/RPV arm reported adverse events (Table 2). All reported drug-related adverse events were of mild (Grade 1) or moderate (Grade 2) severity, most of which were injection site reactions (ISRs) in the CAB+RPV long-acting arm. The most frequently reported non-ISR drug-related adverse events in the CAB+RPV long-acting arm were pyrexia (8%, n = 7/90) and fatigue (4%, n = 4/90). One participant experienced a drug-related adverse event in the DTG/RPV arm (headache). There was one withdrawal due to an adverse event (CAB+RPV long-acting arm; drug-related adverse event of depression) and one drug-related serious adverse event (CAB+RPV long-acting arm; injection site extravasation) that resolved by drainage on the same day and did not lead to study discontinuation. No clinically relevant patterns of adverse events over the 12-month period were observed.

Injection Site Reactions. In total, 70 of 90 (78%) participants in the CAB+RPV long-acting arm reported at least one ISR, for a total of 463 ISR events (Supplemental Digital Content, Table S2, http://links.lww.com/QAD/C328, ISR overview). All ISR events were either mild (Grade 1; 84%, n = 389/463) or moderate (Grade 2; 16%, n = 74/463) in severity, and most (92%, n = 424/463) resolved within 7 days, with a median (IQR) duration of 3 (2, 4) days. The incidence of ISRs decreased over the study period (Supplemental Digital Content, Figure S1, http://links.lww.com/QAD/C328, ISR incidence over time through Month 12), with 67% (n = 60/90) of participants reporting ISRs on Day 1 compared with 26% (n = 23/88) at the Month 12 visit. The most commonly reported ISRs in the CAB+RPV long-acting arm (≥5% of participants) were injection site pain (74%, n = 67), injection site discomfort (11%, n = 10), injection site swelling (6%, n = 5), and injection site nodule (6%, n = 5). No participants withdrew from the study due to an ISR or injection intolerability.

Weight Change. At Baseline, the median (range) weight was 85.6 kg (56.3, 177.3 kg) in the CAB+RPV long-acting arm and 82.0 kg (65.0, 98.3 kg) in the DTG/RPV arm. At Month 12, there was a median weight increase of 1.6 kg (–4.5, 10.5 kg) from Baseline in the DTG/RPV arm, while no change from Baseline in median weight was observed in the CAB+RPV long-acting arm (–22.2, 16.8 kg). A decrease in weight was classified as an adverse event for one participant in the CAB+RPV long-acting arm but was deemed unrelated to treatment.

Patient-reported Outcomes

HIVTSQs mean [standard deviation (SD)] total scores were high at Baseline [CAB+RPV long-acting arm, 62.83 (4.88); DTG/RPV, 63.71 (3.68)] and remained stable at Months 6 [CAB+RPV long-acting arm, 62.60 (5.61); DTG/RPV, 64.43 (3.05)] and 12 [CAB+RPV long-acting arm, 62.38 (6.46); DTG/RPV, 63.86 (4.49)] across both treatment groups. At Month 12, mean (SD) total HIVTSQc scores, representing changes in satisfaction from prior therapy, were high in both treatment groups [CAB+RPV long-acting arm, 28.0 (6.78); DTG/RPV arm, 27.7 (6.97)], with positive mean change scores observed for all individual items for both arms (Supplemental Digital Content, Figure S2, http://links.lww.com/QAD/C328, Mean HIVTSQc individual item scores at Month 12). An exploratory analysis of therapy preference at Month 12 indicated that, of the 88 participants in the CAB+RPV long-acting arm with a recorded response to the preference questionnaire, 88% (n = 77/88) preferred CAB+RPV long-acting Q2M over daily oral CAB+RPV, the regimen received in the LATTE study for at least 5 years (Figure 3). The most commonly cited reasons for preference among the 83 participants who provided responses included increased convenience (69%, n = 57/83) and the frequency of administration (57%, n = 47/83).

Figure 3.

Treatment preference at Month 12 for participants receiving CAB+RPV LA Q2M. Figure 3 was presented previously at IDWeek; October 21–25, 2020; Virtual; Oral. CAB, cabotegravir; LA, long-acting; Q2M, every 2 months; RPV, rilpivirine.

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