Dataset Information

Safety and efficacy of long-acting injectable cabotegravir as preexposure prophylaxis to prevent HIV acquisition.

ABSTRACT:

Objective

HIV remains a significant burden, despite expanding HIV prevention tools. Long-acting injectable cabotegravir (CAB-LA) is a new preexposure prophylaxis (PrEP) product. We reviewed existing evidence to determine the efficacy and safety of CAB-LA as PrEP to inform global guidelines.

Design

Systematic review and meta-analysis.

Methods

We systematically reviewed electronic databases and conference abstracts for citations on CAB-LA from January 2010 to September 2021. Outcomes included HIV infection, adverse events, drug resistance, pregnancy-related adverse events, and sexual behavior. We calculated pooled effect estimates using random-effects meta-analysis and summarized other results narratively.

Results

We identified 12 articles/abstracts representing four multisite randomized controlled trials. Study populations included cisgender men, cisgender women, and transgender women. The pooled relative risk of HIV acquisition comparing CAB-LA to oral PrEP within efficacy studies was 0.21 (95% confidence interval: 0.07-0.61), resulting in a 79% reduction in HIV risk. Rates of adverse events were similar across study groups. Of 19 HIV infections among those randomized to CAB-LA with results available, seven had integrase strand transfer inhibitor (INSTI) resistance. Data on pregnancy-related adverse events were sparse. No studies reported on sexual behavior.

Conclusions

CAB-LA is highly efficacious for HIV prevention with few safety concerns. CAB-LA may lead to an increased risk of INSTI resistance among those who have acute HIV infection at initiation or become infected while taking CAB-LA. However, results are limited to controlled studies; more research is needed on real-world implementation. Additional data are needed on the safety of CAB-LA during pregnancy (for mothers and infants) and among populations not included in the trials.

SUBMITTER: Fonner VA

PROVIDER: S-EPMC10090368 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety and efficacy of long-acting injectable cabotegravir as preexposure prophylaxis to prevent HIV acquisition.

Fonner Virginia A VA Ridgeway Kathleen K van der Straten Ariane A Lorenzetti Lara L Dinh Nhi N Rodolph Michelle M Schaefer Robin R Schmidt Heather-Marie A HA Nguyen Van Thi Thuy VTT Radebe Mopo M Peralta Hortencia H Baggaley Rachel R

AIDS (London, England) 20230125 6

<h4>Objective</h4>HIV remains a significant burden, despite expanding HIV prevention tools. Long-acting injectable cabotegravir (CAB-LA) is a new preexposure prophylaxis (PrEP) product. We reviewed existing evidence to determine the efficacy and safety of CAB-LA as PrEP to inform global guidelines.<h4>Design</h4>Systematic review and meta-analysis.<h4>Methods</h4>We systematically reviewed electronic databases and conference abstracts for citations on CAB-LA from January 2010 to September 2021. ...[more]

PMID: 36723489

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Project description:BackgroundLong-acting injectable cabotegravir (CAB-LA) for preexposure prophylaxis (PrEP) has proven efficacious in randomized controlled trials. Further research is critical to evaluate its effectiveness in real-world settings and identify effective implementation approaches, especially among young sexual and gender minorities (SGMs).ObjectiveImPrEP CAB Brasil is an implementation study aiming to generate critical evidence on the feasibility, acceptability, and effectiveness of incorporating CAB-LA into the existing public health oral PrEP services in 6 Brazilian cities. It will also evaluate a mobile health (mHealth) education and decision support tool, digital injection appointment reminders, and the facilitators of and barriers to integrating CAB-LA into the existing services.MethodsThis type-2 hybrid implementation-effectiveness study includes formative work, qualitative assessments, and clinical steps 1 to 4. For formative work, we will use participatory design methods to develop an initial CAB-LA implementation package and process mapping at each site to facilitate optimal client flow. SGMs aged 18 to 30 years arriving at a study clinic interested in PrEP (naive) will be invited for step 1. Individuals who tested HIV negative will receive mHealth intervention and standard of care (SOC) counseling or SOC for PrEP choice (oral or CAB-LA). Participants interested in CAB-LA will be invited for step 2, and those with undetectable HIV viral load will receive same-day CAB-LA injection and will be randomized to receive digital appointment reminders or SOC. Clinical appointments and CAB-LA injection are scheduled after 1 month and every 2 months thereafter (25-month follow-up). Participants will be invited to a 1-year follow-up to step 3 if they decide to change to oral PrEP or discontinue CAB-LA and to step 4 if diagnosed with HIV during the study. Outcomes of interest include PrEP acceptability, choice, effectiveness, implementation, and feasibility. HIV incidence in the CAB-LA cohort (n=1200) will be compared with that in a similar oral PrEP cohort from the public health system. The effectiveness of the mHealth and digital interventions will be assessed using interrupted time series analysis and logistic mixed models, respectively.ResultsDuring the third and fourth quarters of 2022, we obtained regulatory approvals; programmed data entry and management systems; trained sites; and performed community consultancy and formative work. Study enrollment is programmed for the second quarter of 2023.ConclusionsImPrEP CAB Brasil is the first study to evaluate CAB-LA PrEP implementation in Latin America, one of the regions where PrEP scale-up is most needed. This study will be fundamental to designing programmatic strategies for implementing and scaling up feasible, equitable, cost-effective, sustainable, and comprehensive alternatives for PrEP programs. It will also contribute to maximizing the impact of a public health approach to reducing HIV incidence among SGMs in Brazil and other countries in the Global South.Trial registrationClinicaltrials.gov NCT05515770; https://clinicaltrials.gov/ct2/show/NCT05515770.International registered report identifier (irrid)PRR1-10.2196/44961.

Project description:BackgroundThe HIV Prevention Trials Network (HPTN) 083 trial showed that long-acting injectable cabotegravir was more effective than tenofovir disoproxil fumarate plus emtricitabine in preventing HIV in cisgender men and transgender women who have sex with men. We aimed to characterise the cohort of transgender women included in HPTN 083.MethodsHPTN 083 is an ongoing, phase 2b/3, randomised, multicentre, double-blind, double-dummy clinical trial done at 43 sites in seven countries (Argentina, Brazil, Peru, the USA, South Africa, Thailand, and Viet Nam). HIV-negative participants were randomly assigned (1:1) to receive injectable cabotegravir or tenofovir disoproxil fumarate plus emtricitabine. The study design and primary outcomes of the blinded phase of HPTN 083 have already been reported. An enrolment minimum of 10% transgender women was set for the trial. Here we characterise the cohort of transgender women enrolled from Dec 6, 2016, to May 14, 2020, when the study was unblinded. We report sociodemographic characteristics, use of gender affirming hormone therapy, and behavioural assessments of the transgender women participants. Laboratory testing and safety evaluations are also reported. The trial is registered at ClinicalTrials.gov, NCT02720094.FindingsHPTN 083 enrolled 570 transgender women (304 tenofovir disoproxil fumarate plus emtricitabine; 266 injectable cabotegravir). Transgender women were primarily from Asia (225 [39%]) and Latin America (205 [36%]); 330 (58%) reported using gender affirming hormone therapy. Intimate partner violence was common (270 [47%] reported emotional abuse and 172 [30%] reported physical abuse) and 323 (57%) reported a history of childhood sexual abuse. 159 (28%) transgender women disagreed that they were at risk for HIV, and 142 (25%) screened positive for depressive symptoms. During study follow-up, incidence of syphilis was 16·25% (95% CI 13·28-19·69), rectal gonorrhoea was 11·66% (9·14-14·66), and chlamydia was 20·61% (17·20-24·49). Frequency of adverse events was similar between the treatment groups. Nine seroconversions occurred among transgender women during the blinded phase of the study (seven in the tenofovir disoproxil fumarate plus emtricitabine group and two in the injectable cabotegravir group); overall incidence was 1·19 per 100 person-years (95% CI 0·54-2·25): 1·80 per 100 person-years (0·73-3·72) in the tenofovir disoproxil fumarate plus emtricitabine group and 0·54 per 100 person-years (0·07-1·95) in the injectable cabotegravir group (hazard ratio 0·34 [95% CI 0·08-1·56]). Cabotegravir concentrations did not differ by gender affirming hormone therapy use.InterpretationHIV prevention strategies for transgender women cannot be addressed separately from social and structural vulnerabilities. Transgender women were well represented in HPTN 083 and should continue to be prioritised in HIV prevention studies. Our results suggest that injectable cabotegravir is a safe and effective pre-exposure prophylaxis option for transgender women.FundingNational Institute of Allergy and Infectious Diseases and ViiV Healthcare.

Project description:BackgroundThe HIV Prevention Trials Network (HPTN) 083 trial demonstrated the superiority of long-acting injectable cabotegravir (CAB-LA) compared with oral emtricitabine-tenofovir disoproxil fumarate (F/TDF) for HIV preexposure prophylaxis (PrEP).ObjectiveTo identify the maximum price premium (that is, greatest possible price differential) that society should be willing to accept for the additional benefits of CAB-LA over tenofovir-based PrEP among men who have sex with men and transgender women (MSM/TGW) in the United States.DesignSimulation, cost-effectiveness analysis.Data sourcesTrial and published data, including estimated HIV incidence (5.32, 1.33, and 0.26 per 100 person-years for off PrEP, generic F/TDF and branded emtricitabine-tenofovir alafenamide (F/TAF), and CAB-LA, respectively); 28% 6-year PrEP retention. Annual base-case drug costs: $360 and $16 800 for generic F/TDF and branded F/TAF. Fewer side effects with branded F/TAF versus generic F/TDF were assumed.Target population476 700 MSM/TGW at very high risk for HIV (VHR).Time horizon10 years.PerspectiveHealth care system.InterventionCAB-LA versus generic F/TDF or branded F/TAF for HIV PrEP.Outcome measuresPrimary transmissions, quality-adjusted life-years (QALYs), costs (2020 U.S. dollars), incremental cost-effectiveness ratios (ICERs; U.S. dollars per QALY), maximum price premium for CAB-LA versus tenofovir-based PrEP.Results of base-case analysisCompared with generic F/TDF (or branded F/TAF), CAB-LA increased life expectancy by 28 000 QALYs (26 000 QALYs) among those at VHR. Branded F/TAF cost more per QALY gained than generic F/TDF compared with no PrEP. At 10 years, CAB-LA could achieve an ICER of at most $100 000 per QALY compared with generic F/TDF at a maximum price premium of $3700 per year over generic F/TDF (CAB-LA price <$4100 per year).Results of sensitivity analysisIn a PrEP-eligible population at high risk for HIV, rather than at VHR (n = 1 906 800; off PrEP incidence: 1.54 per 100 person-years), CAB-LA could achieve an ICER of at most $100 000 per QALY versus generic F/TDF at a maximum price premium of $1100 per year over generic F/TDF (CAB-LA price <$1500 per year).LimitationUncertain clinical and economic benefits of averting future transmissions.ConclusionEffective oral PrEP limits the additional price society should be willing to pay for CAB-LA.Primary funding sourceFHI 360; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Allergy and Infectious Diseases; National Heart, Lung, and Blood Institute; National Institute on Drug Abuse; the Reich HIV Scholar Award; and the Steve and Deborah Gorlin MGH Research Scholars Award.

Dataset Information

Safety and efficacy of long-acting injectable cabotegravir as preexposure prophylaxis to prevent HIV acquisition.

Objective

Design

Methods

Results

Conclusions

Publications

Safety and efficacy of long-acting injectable cabotegravir as preexposure prophylaxis to prevent HIV acquisition.

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