The optimum implementation of long-acting injectable cabotegravir–rilpivirine in sub-Saharan Africa
Authors: Halima Dawood
Journal: The Lancet Global Health (2021)

The current armamentarium for the treatment of HIV infection has advanced from taking multiple pills several times a day to a single-combination tablet daily. Now people living with HIV also have the promise of long-acting injectable antiretroviral treatment, such as long-acting injectable cabotegravir, an integrase strand inhibitor, together with rilpivirine, a long-acting nucleoside reverse transcriptase inhibitor.1Swindells S Andrade-Villanueva J-F Richmond G et al.Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression.N Engl J Med. 2020; 382: 1112-1123Crossref PubMed Scopus (88) Google Scholar This advance in drug delivery is a potential game changer in the management of HIV infection. This new drug combination reduces treatment time from 365 to 12 dosing days per year,2ViiV HealthcareViiV Healthcare announces first global regulatory approval of CABENUVA; the first complete, long-acting, regimen for the treatment of HIV.https://viivhealthcare.com/en-gb/media/press-releases/2020/march/viiv-healthcare-announces-first-global-regulatory-approval-of-ca/Date: March 20, 2020Date accessed: January 26, 2021Google Scholar and from three drugs to two drugs for individuals who have no previous treatment failure and are virologically suppressed.1Swindells S Andrade-Villanueva J-F Richmond G et al.Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression.N Engl J Med. 2020; 382: 1112-1123Crossref PubMed Scopus (88) Google Scholar This regimen could address some of the previous challenges with drug adherence, such as pill fatigue and the need for constant pill refills. It is vital that new interventions are safe, tolerable, affordable, acceptable, and accessible to all people living with HIV. The long-acting cabotegravir–rilpivirine trials have reported high rates of satisfaction with this intervention, despite injection site pain as an adverse effect.3Koren DE Fedkiv V Zhao H et al.Perceptions of long-acting injectable antiretroviral treatment regimens in a United States Urban Academic Medical Center.J Int Assoc Provid AIDS Care. 2020; (published online Dec 17.)https://doi.org/10.1177/2325958220981265Crossref PubMed Scopus (1) Google Scholar In addition to cost-effectiveness, acceptability and uptake will ascertain successful implementation of this novel modality of treatment administration. Many health-care systems will need to decide on how best to translate and implement this new intervention.4Havlir D Gandhi M Implementation challenges for long-acting antivirals as treatment.Curr Opin HIV AIDS. 2015; 10: 282-289Crossref PubMed Scopus (15) Google Scholar The Article by Phillips and colleagues5Phillips AN Bansi-Matharu L Cambiano V et al.The potential role of long-acting injectable cabotegravir–rilpivirine in the treatment of HIV in sub-Saharan Africa: a modelling analysis.Lancet Glob Health. 2021; (published online March 23.)https://doi.org/10.1016/S2214-109X(21)00025-5Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar uses an existing individual-based model of HIV to predict the optimal way to introduce the long-acting cabotegravir–rilpivirine combination in three clinical scenarios in sub-Saharan Africa, to establish cost-effectiveness over 10 years from a health system perspective.6Rajoli RKR Curley P Chiong J et al.Predicting drug–drug interactions between rifampicin and long-acting cabotegravir and rilpivirine using physiologically based pharmacokinetic modeling.J Infect Dis. 2019; 219: 1735-1742Crossref PubMed Scopus (19) Google Scholar The introduction of long-acting dual treatment of cabotegravir and rilpivirine was compared with the current emerging first-line treatment of dolutegravir (oral integrase strand inhibitor) in all individuals already on antiretroviral therapy (ART), in those with a recently measured viral load of less than 1000 copies per mL, and in those with a viral load of more than 1000 copies per mL.5Phillips AN Bansi-Matharu L Cambiano V et al.The potential role of long-acting injectable cabotegravir–rilpivirine in the treatment of HIV in sub-Saharan Africa: a modelling analysis.Lancet Glob Health. 2021; (published online March 23.)https://doi.org/10.1016/S2214-109X(21)00025-5Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar All three scenarios in the model would result in an increase in the proportion of viral load suppression and a decrease in AIDS-associated mortality, but also a potential increase of integrase strand inhibitor and non-nucleotide reverse transcriptase inhibitor resistance.5Phillips AN Bansi-Matharu L Cambiano V et al.The potential role of long-acting injectable cabotegravir–rilpivirine in the treatment of HIV in sub-Saharan Africa: a modelling analysis.Lancet Glob Health. 2021; (published online March 23.)https://doi.org/10.1016/S2214-109X(21)00025-5Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar Using a cost of US$120 per year, targeting patients with a viral load of more than 1000 copies per mL yielded a median cost per disability-adjusted life-year averted of $404 across all settings. The two other approaches did not yield a cost-effective strategy at this cost per year and will only yield a benefit if the price of the drug is lowered.5Phillips AN Bansi-Matharu L Cambiano V et al.The potential role of long-acting injectable cabotegravir–rilpivirine in the treatment of HIV in sub-Saharan Africa: a modelling analysis.Lancet Glob Health. 2021; (published online March 23.)https://doi.org/10.1016/S2214-109X(21)00025-5Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar Hence, in sub-Saharan Africa, it appears that the most cost-effective approach would be to target individuals with a viral load of more than 1000 copies per mL; that is, those who are less adherent to oral therapy and might benefit from intramuscular monthly administration of ART.5Phillips AN Bansi-Matharu L Cambiano V et al.The potential role of long-acting injectable cabotegravir–rilpivirine in the treatment of HIV in sub-Saharan Africa: a modelling analysis.Lancet Glob Health. 2021; (published online March 23.)https://doi.org/10.1016/S2214-109X(21)00025-5Summary Full Text Full Text PDF PubMed Scopus (3) Google Scholar These findings highlight the challenges that implementation of new interventions present in different settings worldwide. When a new more convenient treatment option is available, it does not necessarily mean that it can be easily translated into different settings cost-effectively and equitably. The challenges with respect to implementation, such as drug interactions with treatment of opportunistic infections (eg, tuberculosis7 and hepatitis B), and the need to maintain cold chain and deliver intramuscular injections, might present unequal access to medication in different settings. Furthermore, it is worth noting that this intervention requires a lead-in phase of oral medication before transitioning to the intramuscular injection, which could be a barrier to implementation in a patient already having challenges with an oral regimen. Nevertheless, this novel mechanism of drug delivery is the first of many proposed long-acting agents in development that might be available in the future and might address the challenges associated with this novel regimen. HD reports personal fees from Sanofi, South Africa, and workshop attendance sponsorship from Biomieruex, South Africa. The potential role of long-acting injectable cabotegravir–rilpivirine in the treatment of HIV in sub-Saharan Africa: a modelling analysisOur modelling suggests that injectable cabotegravir–rilpivirine offers potential benefits; however, to be a cost-effective option, its introduction might need to be carefully targeted to individuals with HIV who might otherwise have suboptimal adherence to ART. As data accumulate from trials and implementation studies, such findings can be incorporated into the model to better inform on the full consequences of policy alternatives. Full-Text PDF Open Access