Cabotegravir 600mg/3ml prolonged-release suspension for injection vials

Abstract Background In 2023, there were 39.9 million people living with HIV (PLWH) worldwide and 630 000 deaths related to HIV. New strategies are needed, and long-acting antiretrovirals (LAAs) are now widely considered to have great potential to help end the HIV epidemic. This systematic review and meta-analysis compare the safety and efficacy of LAA versus standard oral treatment (SOT) for HIV. Methods PubMed and Embase databases, supplemented by ClinicalTrials.gov and grey literature, were searched. Randomized controlled trials (RCTs) reporting efficacy and/or safety of LAA versus SOT for PLWH until June 2024 were included. Efficacy (HIV RNA < 50 copies/mL) and HIV RNA ≥ 50 copies/mL, adverse events (AEs), treatment discontinuation, CD4 count, metabolic parameters and drug resistance were assessed. Prespecified subgroup analyses were conducted. The risk of bias was assessed with Cochrane RoB 2.0. Certainty of evidence was assessed using GRADE. Results Six RCTs were eligible for inclusion, involving 2829 participants. LAA was non-inferior to SOT in suppressing HIV RNA < 50 copies/mL [Risk Difference (RD), −0.00; 95% CI, −0.03–0.02; P = 0.83; I2 = 51%; high quality of evidence (QoE)]. LAA was associated with higher drug resistance (percentage pooled estimate, 57%; 95% CI, 33%–78% versus 9%; 95% CI, 2%–30%; moderate QoE) and risk of grade 1–4 AEs than SOT [Risk Ratio (RR), 1.22; 95% CI, 1.12–1.33; P < 0.001; I2 = 62%; moderate QoE]. Conclusions LAA has non-inferior efficacy compared to SOT. However, participants receiving LAA were at a higher risk of developing drug resistance, cross-resistance and AEs.

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Randomized controlled trial evidence suggests that long‐acting injectable (LA‐I) cabotegravir and rilpivirine (CAB+RPV) has similar virological failure (VF) rates to daily oral therapy, but clinical practice evidence is lacking. Integrase inhibitor (INI) resistance may limit future therapy. The optimal regimen is uncertain.

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Abstract Background The long-acting injectable regimen of cabotegravir plus rilpivirine (CAB/RPV) emerged as an alternative to oral standard-of-care integrase strand transfer inhibitor (INSTI)–based regimens for individuals with adherence challenges or preference for reduced dosing schedules. Although oral INSTI regimens have a high barrier to emergent resistance, less is known about the potency and durability of CAB/RPV. Methods We reviewed clinical trial registries, PubMed, EMBASE, and conference abstract databases to identify reports of CAB/RPV for HIV therapy. We abstracted data on virologic failure (VF) and treatment-emergent INSTI resistance at 48 weeks (range: 24–52). We used single-proportion meta-analysis to summarize outcomes in 3 populations: antiretroviral therapy (ART)–naive individuals initiating CAB/RPV following suppression on oral ART, ART-experienced individuals switched to CAB/RPV with virologic suppression, and ART-experienced individuals switched to CAB/RPV with detectable viremia. Cochrane's RoB 2.0 and ROBINS-1 tools assessed risk of bias. Results Thirty-three studies (N = 9224) reported VF prevalence. Nineteen studies (N = 5662) reported resistance data. VF prevalence was 1% (95% CI: 1%–3%) in induction-maintenance studies, 1% (1%–2%) in switch-suppressed studies, and 5% (3%–10%) in switch-viremic studies. INSTI resistance prevalence among successfully genotyped participants at failure was 71% (25%–95%), 61% (44%–75%), and 41% (20%–65%) respectively. Dolutegravir cross-resistance was common (64% of those with emergent resistance). Conclusions Although VF rates with CAB/RPV were low, INSTI resistance emerged in approximately 40%–70% of individuals experiencing VF. These rates are significantly higher than those for oral INSTI-based regimens. Both individual-level and broader resistance surveillance may be warranted in populations with expanding CAB/RPV use. Clinical Trials Registration. PROSPERO registration CRD42024543919.

Abstract licence: CC BY-NC-ND

BackgroundHIV remains an important global public health crisis. Antiretroviral treatment has been essential to suppress viral replication, and in at-risk individuals, antiretroviral pre-exposure prophylaxis drugs (PrEP) lower transmission rates. Unfortunately, current oral regimens require stringent daily adherence to be effective. Long-acting intra-muscular cabotegravir potentially averts the issue of poor patient adherence. This formulation has the potential to cause a breakthrough in mitigating the spread of HIV; however, safety in pregnancy is still to be established. This systematic review aimed to assess the data relating to the safety and prevalence of adverse effects of cabotegravir in pregnancy.Methods and analysisThe research followed the PRISMA guidelines and Cochrane Handbook. Keyword and MeSH term combinations were utilised. Studies matching the inclusion criteria published between 2016 and 2023 through EMBASE, PubMed, Scopus, Science Direct, Cochrane Library, Medline, and Web of Science were reviewed. Studies were screened by title and abstract, followed by full-text screening by two independent investigators. Duplicate studies were removed. Relevant data was extracted from the selected studies. Critical appraisal and the risk of bias were evaluated using the Joanna Briggs Institute (JBI) SUMARI program. The I2 test was used to assess statistical heterogeneity.Results and outcomesOf the 12,357 studies identified, 6 articles were included in the review. This review investigated 41 known pregnancies in females on cabotegravir, of which 25 live babies were born, 8 were not born due to spontaneous/elective abortion, and 8 were lost to follow-up. No congenital abnormalities, birth defects, or foetal adverse effects were reported.ConclusionThe small sample size currently precludes a definitive conclusion on the safety profile of cabotegravir use during pregnancy. More research in this area is required to assess this drug's role in utero.Systematic review registrationThis systematic review and meta-analysis protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) with the registration number CRD42023449146.

Abstract licence: CC BY-NC-ND 4.0

Abstract Background The HIV epidemic continues to grow with 1.5 million new infections globally in 2021. In 2019, 62% of new infections were amongst key at-risk populations. HPTN 083 and 084 trials showed up to 88% increased efficacy of long-acting cabotegravir (CAB-LA) compared to continuous oral tenofovir/emtricitabine (TDF/FTC). However, the expense of CAB-LA ($22,200 per person per year (pppy)) limits its availability to populations who need it most. In most countries, HIV prevention budgets are highly limited, with TDF/FTC available as a low-cost generic. Methods We conducted a systematic review of studies on global HIV incidence in at-risk populations. The weighted incidence was calculated for each population, blood donors, and the general population. We evaluated potential HIV infection rates for 4 prevention strategies: no PrEP, continuous CAB-LA (annual cost $22,200 per person (pp)), continuous TDF/FTC (annual cost $48pp), and event-driven TDF/FTC (annual cost $12pp). For each PrEP strategy we assumed an additional $4 pppy for HIV testing, and $14 pppy for education and service access. Assumed efficacy was 90% for continuous CAB-LA, 60% for continuous TDF/FTC, and 30% for event-driven TDF/FTC. Using weighted HIV incidence rates and an assumed $1million fixed budget for HIV prevention, annual HIV infection rates for each target population were calculated for each PrEP strategy. Results The database searches identified 98 studies in 5,230,189 individuals. Incidence per 100 person-years (pys) ranged from 0.03 in blood donors to 3.82 in people who inject drugs (Table 1). Within the fixed $1 million budget, annual HIV infections in commercial sex workers (incidence of 3.1/100pys) would be 1,033 for no PrEP, 1,032 for continuous CAB-LA, 752 for continuous TDF/FTC, and 723 for event-driven TDF/FTC. The same trends were seen across all populations: use of event-driven PrEP prevented the largest number of HIV infections for fixed budgets. Table 1 A table showing the number of studies, total sample size, and average incidence of HIV infection in key populations, blood donors and the general population. Conclusion CAB-LA is the most efficacious form of PrEP, but high prices limit numbers who can be treated. More HIV infections can be prevented using low-cost event-driven TDF/FTC as PrEP: far more people can be treated for fixed budgets. This result is consistent across a range of at-risk populations in different countries. Disclosures All Authors: No reported disclosures

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