Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial

TLDR: Both long-acting regimens met primary criteria for comparability in viral suppression relative to the oral comparator group and the primary analysis used a Bayesian approach to evaluate the hypothesis that the proportion with viral suppression for each long- acting regimen is not worse than the oral regimen proportion.

About: This article is published in The Lancet.The article was published on 2017-09-23 and is currently open access. It has received 376 citations till now. The article focuses on the topics: Cabotegravir & Bictegravir.

Figures

Figure 2: Proportion of patients with HIV-1 RNA concentration less than 50 copies per mL (FDA snapshot algorithm) by visit in the maintenance-exposed population and snapshot outcomes at week 96 Error bars show 95% CIs, derived using the normal approximation. FDA=US Food and Drug Administration. LA=long-acting.

Figure 4: Summary of patient-reported outcomes at (A) week 48 (maintenance treatment) and (B) week 96 The data are based on the observed case dataset of patients who completed questionnaires at week 48 and week 96 (HIV Treatment Satisfaction Questionnaire, status version). LA=long-acting.

Table 2: Summary of total adverse events and treatment-related adverse events through week 96 in the safety maintenance population

Figure 1: Trial profile LA=long-acting. *Multiple reasons for screening failure were reported for two patients. †310 patients were enrolled, but one patient withdrew consent after baseline visit procedures were done and before study treatment was initiated. ‡Two patients completed the induction period (and had day 1 assessments) but did not enter the maintenance period and were not randomly assigned (because of investigator discretion and lack of efficacy). §Patient experienced suspected protocol-defined virological failure at the time of withdrawal, which was subsequently confirmed.

Figure 3: Arithmetic mean (SD) plasma concentration–time profiles following every 4 weeks and every 8 weeks administration of (A) cabotegravir LA and (B) rilpivirine LA through week 48 Cτ=concentration at the end of dosing interval. LA=long-acting. PA-IC90=protein-adjusted 90% inhibitory concentration.

Table 1: Baseline demographics and disease characteristics (maintenance-exposed population)

Frequently asked questions

Q1. What were the primary endpoints of the study?

The primary endpoints were the proportion of patients with viral suppression at week 32 (as defined by the US Food and Drug Administration snapshot algorithm), protocol-defined virological failures, and safety events through 96 weeks. 

Q2. How long did the LATTE-2 study last?

The LATTE-2 study evaluated long-acting cabotegravir plus rilpivirine for maintenance of HIV-1 viral suppression through 96 weeks. 

Q3. How many patients were treated with oral treatment?

Injection-site reactions were mild (3648 [84%] of 4360 injections) or moderate (673 [15%] of 4360 injections) in intensity and rarely resulted in discontinuation (two [<1%] of 230 patients); injection-site pain was reported most frequently. 

Q4. How many copies of the HIV-1 RNA were used in the study?

Randomisation was computer-generated with stratification by HIV-1 RNA (<50 copies per mL, yes or no) during the first 12 weeks of the induction period. 

Q5. How many patients were randomly assigned to the maintenance period?

Among 309 enrolled patients, 286 were randomly assigned to the maintenance period (115 to each of the 4-week and 8-week groups and 56 to the oral treatment group). 

Q6. How was the treatment of the infection tolerated?

The two-drug combination of all-injectable, long-acting cabotegravir plus rilpivirine every 4 weeks or every 8 weeks was as effective as daily three-drug oral therapy at maintaining HIV-1 viral suppression through 96 weeks and was well accepted and tolerated. 

Q7. How many doses of cabotegravir were included in the primary efficacy and?

All randomly assigned patients who received at least one dose of study drug during the maintenance period were included in the primary efficacy and safety analyses. 

Q8. How many doses of cabotegravir were given to treatment-naive adults?

In this randomised, phase 2b, open-label study, treatment-naive adults infected with HIV-1 initially received oral cabotegravir 30 mg plus abacavir–lamivudine 600–300 mg once daily. 

Q9. What is the primary analysis of the study?

The primary analysis used a Bayesian approach to evaluate the hypothesis that the proportion with viral suppression for each longacting regimen is not worse than the oral regimen proportion by more than 10% (denoted comparable) according to a prespecified decision rule (ie, posterior probability for comparability >90%).