Use of Long-Acting Injectable Cabotegravir and Rilpivirine in HIV Maintenance Therapy
Faculty Advisor Name
Abby Massey
Department
Department of Health Professions
Description
Abstract: To determine if long acting injectables cabotegravir and rilpivirine are non-inferior to oral antiretroviral therapy at maintaining viral load suppression below 50 copies per milliliter of serum. Design: Systematic literature review. Methods: A search was done in PubMed using the terms “HIV + cabotegravir” or “HIV + cabotegravir, rilpivirine drug combination.” Limitations included non-randomized control trials, comparison of injectable regimens directly or injectables to placebo, studies that evaluate compliance or side effects only, and studies with small sample sizes. Results: Meta-analysis revealed that continued use of injectables was sufficient in maintaining viral suppression at 93.6%, 92.5%, and 94% in each of the respective studies. This demonstrated non-inferiority to oral therapy. Conclusion: Overall, the three studies randomized participants in oral or long acting therapies after an oral induction period. Long-acting injectable formulations were proven to be non-inferior in the maintenance of viral load suppression. Use of monthly injectable antiretrovirals offers an alternative for increased compliance to many people living with HIV. Efficacy of long-acting injectables as initial therapy and their use in the pediatric population need further study.
Introduction:
Human Immunodeficiency virus (HIV) remains a global health concern with an estimated 37.7 million people living with HIV.1 HIV is an RNA virus that enters primarily through anogenital mucosa and then acts by targeting dendritic cells, macrophages, and CD4+ T cells. Risk factors for transmission include men who have sex with men, IV drug users, blood product recipients, and needle-stick exposure among healthcare workers. The natural course if the disease progresses to a chronic infection characterized by a depletion of CD4+ T cells; this results in an inability to mount an immune response to pathogens.
Prior to the introduction of antiretroviral therapy, HIV was a death sentence due to the acquisition of opportunistic infections that are terminal. However, improvements in therapy have drastically improved the life expectancy and quality of life for those living with HIV, allowing these individuals to achieve a lifespan approaching that of the general population. Despite the advancements made in treatment, typical regimens involve daily intake of two to three orally administered drugs requiring a high degree of medication adherence in order to sustain suppression of the virus. Elements including dosing frequently, food considerations, other drug-drug interactions, as well as the emotional burden of taking multiple pills each day have precipitated the issue of non-compliance and viral resistance to the therapy. Alternate methods to combat these obstacles have started the pursuit for more acceptable and appealing options.
Long-acting injectable antiviral therapy has shown to be a promising alternative to the daily oral antiviral regimen. Injectable therapy lessens the concern of dietary modifications as well as the stringent compliance required to follow a daily oral medication regimen. The integrase inhibitor cabotegravir and the non-nucleoside reverse-transcriptase inhibitor rilpivirine both have long-acting injectable formulations that have recently been released onto the market. Cabotegravir and Rilpivirine already have shown long-standing success in their oral formulations for HIV infection and their use as injectables is currently under evaluation.
Use of Long-Acting Injectable Cabotegravir and Rilpivirine in HIV Maintenance Therapy
Abstract: To determine if long acting injectables cabotegravir and rilpivirine are non-inferior to oral antiretroviral therapy at maintaining viral load suppression below 50 copies per milliliter of serum. Design: Systematic literature review. Methods: A search was done in PubMed using the terms “HIV + cabotegravir” or “HIV + cabotegravir, rilpivirine drug combination.” Limitations included non-randomized control trials, comparison of injectable regimens directly or injectables to placebo, studies that evaluate compliance or side effects only, and studies with small sample sizes. Results: Meta-analysis revealed that continued use of injectables was sufficient in maintaining viral suppression at 93.6%, 92.5%, and 94% in each of the respective studies. This demonstrated non-inferiority to oral therapy. Conclusion: Overall, the three studies randomized participants in oral or long acting therapies after an oral induction period. Long-acting injectable formulations were proven to be non-inferior in the maintenance of viral load suppression. Use of monthly injectable antiretrovirals offers an alternative for increased compliance to many people living with HIV. Efficacy of long-acting injectables as initial therapy and their use in the pediatric population need further study.
Introduction:
Human Immunodeficiency virus (HIV) remains a global health concern with an estimated 37.7 million people living with HIV.1 HIV is an RNA virus that enters primarily through anogenital mucosa and then acts by targeting dendritic cells, macrophages, and CD4+ T cells. Risk factors for transmission include men who have sex with men, IV drug users, blood product recipients, and needle-stick exposure among healthcare workers. The natural course if the disease progresses to a chronic infection characterized by a depletion of CD4+ T cells; this results in an inability to mount an immune response to pathogens.
Prior to the introduction of antiretroviral therapy, HIV was a death sentence due to the acquisition of opportunistic infections that are terminal. However, improvements in therapy have drastically improved the life expectancy and quality of life for those living with HIV, allowing these individuals to achieve a lifespan approaching that of the general population. Despite the advancements made in treatment, typical regimens involve daily intake of two to three orally administered drugs requiring a high degree of medication adherence in order to sustain suppression of the virus. Elements including dosing frequently, food considerations, other drug-drug interactions, as well as the emotional burden of taking multiple pills each day have precipitated the issue of non-compliance and viral resistance to the therapy. Alternate methods to combat these obstacles have started the pursuit for more acceptable and appealing options.
Long-acting injectable antiviral therapy has shown to be a promising alternative to the daily oral antiviral regimen. Injectable therapy lessens the concern of dietary modifications as well as the stringent compliance required to follow a daily oral medication regimen. The integrase inhibitor cabotegravir and the non-nucleoside reverse-transcriptase inhibitor rilpivirine both have long-acting injectable formulations that have recently been released onto the market. Cabotegravir and Rilpivirine already have shown long-standing success in their oral formulations for HIV infection and their use as injectables is currently under evaluation.
