NPs safely prescribing long-acting HIV medications : The Nurse Practitioner

Secondary Logo

Journal Logo

Department: Short Communications

NPs safely prescribing long-acting HIV medications

Cadet, Myriam Jean PhD, MSN, APRN, FNP-C; Egbuna, Francisca-lenae DNP, RNC, FNP-BC; Fergus, Silorna DNP, RN

Author Information
The Nurse Practitioner 48(1):p 5-7, January 2023. | DOI: 10.1097/01.NPR.0000903000.62077.09
  • Free

In late 2021, 38.4 million people were living with HIV worldwide.1 The highest rate of diagnosis of HIV infection in the US as of 2019 was among Black adults and adolescents.2 Half of the 1.1 million people infected with HIV in the US are not receiving treatment.3 Antiretroviral therapy (ART) has been highly effective in improving life expectancy for patients. However, poor adherence to treatment can cause viral rebound, drug resistance, and HIV treatment failure.4 Inaccessibility and insufficient commitment to oral combination ART caused 10 in 100,000 HIV-related deaths worldwide.4 People living with HIV who adhere to their prescribed ART may be able to reach and maintain viral suppression to reduce the risk of secondary transmission and increase their CD4 T cell count.5-7 Individuals with medium and high levels of adherence to ART were more likely to report achieving viral suppression than those with low adherence.5

Medication adherence for chronic diseases can improve health outcomes and reduce mortality of chronic conditions.8 Ongoing research has focused on reducing adverse reactions and increasing medication adherence and treatment simplicity of HIV medications.4

The FDA approved the first extended-release [ER] injectable medication for HIV-1 in January 2021—Cabenuva (cabotegravir [CAB] ER injectable suspension; rilpivirine [RPV] ER injectable suspension), copackaged for I.M. use.9 Cabenuva will hereafter be referred to as injectable ER CAB;RPV in this article. This article emphasizes how NPs can safely and effectively prescribe the new injectable regimen.


Injectable ER CAB;RPV was found to be noninferior to standard oral therapy in maintaining virologic suppression in HIV-1.10-12 It includes copackaged CAB ER injectable suspension and RPV ER injectable suspension, each in a single-dose vial.13 CAB belongs to the integrase strand transfer inhibitor antiretroviral medication class; it inhibits HIV integrase by binding to the integrase active site and blocks DNA integration, which is essential for HIV replication.11,13 RPV is in the nonnucleoside reverse transcriptase inhibitor class; it inhibits HIV-1 replication by inhibition of HIV-1 reverse transcriptase, preventing the conversion of HIV RNA to DNA.13

Hepatic enzymes metabolize CAB and RPV primarily by UGT1A1, UGT1A9, and cytochrome P450 (CYP) 3A pathways.14 Drug excretion is via urine and feces. When administered I.M., CAB and RPV have elimination half-lives of about 5.6 to 11.5 weeks and 13 to 28 weeks, respectively.14 In comparison, the half-lives of oral CAB and RPV are 41 and 45 hours, respectively.14

Evaluation, dosing recommendations, and management

Injectable ER CAB;RPV is indicated for treatment of HIV-1 for adults and adolescents 12 years of age and older who weigh at least 35 kg, are virologically suppressed (HIV-1 RNA less than 50 copies/mL) on a stable antiretroviral regimen, and have no known or suspected drug resistance to either CAB or RPV and no history of treatment failure.13,14 It is indicated as a complete regimen.

Prior to prescribing injectable ER CAB; RPV, a history of the patient's previous ART medications, lab test results, treatment responses, hospitalizations, chronic conditions, and opportunistic infections should be obtained. Providers should refer to HIV treatment guidelines for information on required lab tests when modifying an ART regimen.15 The patient's sexual health history and mental health should also be assessed. As hepatotoxicity is a possible adverse reaction of injectable ER CAB;RPV, providers must check liver function prior to and during treatment.13,16,17

Injectable ER CAB;RPV may be initiated with an oral lead-in (oral CAB and oral RPV) for one month to assess tolerability, or without it.13,14 The optional oral lead-in doses should be taken with a meal. The injectable regimen may be administered on a monthly or every-two-month schedule and must be administered I.M. in the gluteal muscle by a healthcare provider, with the two injections given at least 2 cm apart or on opposite sides.13,14 The package insert contains detailed instructions on dosing and on appropriate management of missed injections.

No dosage adjustment is needed for patients with mild or moderate renal or hepatic impairment. Increased monitoring for adverse reactions is recommended for patients with severe renal impairment or end-stage renal disease receiving injectable ER CAB;RPV. The medication has not been studied in patients with severe hepatic impairment and therefore should be used with caution in this population.13,14 There is not enough data on the use of injectable ER CAB;RPV in pregnant people to assess for risk of birth defects, including neural tube defects, or miscarriage; however, it is important to note that CAB is a structural analogue of dolutegravir, which has been associated with neural tube defects.13,14

Adverse reactions

The most common adverse reaction to injectable ER CAB;RPV was local injection site reactions, such as edema, formation of a nodule at the site, and pain.18 Additional adverse reactions can include pyrexia, fatigue, headache, and elevated lipase, among others. Hypersensitivity reactions and serious postinjection reactions have been reported.13 Elevation of liver chemistries and hepatotoxicity are potential adverse reactions.16,17 The drug should be discontinued if hepatotoxicity is suspected. The drug also carries a warning for depressive disorders, which may include signs or symptoms such as depression, mood changes, suicidal ideation or attempt, and negative thoughts.13

Drug interactions

I.M. drug administration allows for bypassing of the gastrointestinal (GI) tract, avoiding drug-drug interactions (DDIs) at that level.14 Therefore, certain interactions exist for CAB and RPV when taken orally but not when administered I.M. CAB and RPV, when taken orally, can cause DDIs. For example, use of oral RPV with a proton pump inhibitor is contraindicated because increased gastric pH can lead to decreased RPV concentration, thus potentially resulting in loss of virologic response and development of resistance.14,15 Similarly, H2-receptor antagonists should be administered at least 12 hours before or 4 hours after oral RPV.15 Chelation is a concern when oral CAB is administered with antacids containing calcium, magnesium, iron, or zinc, and it is therefore recommended that these antacids only be administered at least 2 hours before or 4 hours after oral CAB.14

Drug interactions for both oral and I.M. formulations can result from concomitant use of drugs that are inducers of enzymes that metabolize CAB (UGT1A1 and UGT1A9) or inducers or inhibitors of enzymes that metabolize RPV (CYP3A).13 For example, certain antiepileptic and antimycobacterial drugs and the herbal product St. John's wort can decrease the concentration of CAB and/or RPV. Additionally, RPV has been associated with QTc prolongation.14 Injectable ER CAB;RPV should be used with caution in combination with drugs with a known risk of torsades de pointes.13 NPs should refer to the drug package insert for a complete list of drug interactions.

Barriers to ART adherence

NPs should assess for barriers to ART, including drug resistance, comorbidities, mental health and substance use disorders, DDIs, presence of drug toxicities or adverse reactions, difficulty accessing medications, high costs, stigma, low health literacy, competing priorities related to life events, caregiving demands, and unstable housing as well as for discrepancies in self-reported medication adherence and viral load results. In discussing options for ART, NPs should employ shared decision making to learn about and respect patients' values and preferences and provide potential alternatives to the route of medication administration where appropriate.19,20


Advantages of prescribing an ER injectable ART over oral includes a less frequent dosing schedule, decreased pill burden, convenience, and avoidance of DDIs at the level of the GI tract.14,20 Additionally, injectable ART administered in a clinic can provide privacy in that patients do not need to store HIV medications at home.21 A study on patient perception found that 57% of participants were likely to accept long-acting injectable ART.22

Ethical issues

Kates notes several ethical considerations in use of clinician-administered long-acting injectable ART: the clinician's authority may cause anxiety for some patients, and the associated adherence monitoring may be considered intrusive; in addition, patients may have concerns about being unable to stop therapy quickly due to the long-acting nature of the drug.21

Justification of potential administration of long-acting ART to those who lack decision-making capacity and cannot provide informed consent presents another ethical issue.21 Creation of policies regarding involuntary treatment may be needed.


NPs are uniquely positioned to prescribe effective HIV treatments. ART efficacy and tolerability have transformed HIV into a manageable chronic condition. Use of long-acting injectable ART can help prevent social stigma, improve patient privacy, decrease pill burden, offer convenience, and help maintain confidentiality.23 Research on acceptability, implementation, and uptake of long-acting ART regimens for HIV-1 is needed.22

HIV disproportionally affects people of color with limited access to comprehensive healthcare services.24 Therefore, it is crucial that options such as long-acting injectable ART are accessible and affordable to all patients. Additionally, it is important for providers to understand the ethical issues specific to this form of ART. Providers should refer to the drug package insert and HIV guidelines for complete prescribing details.13,15


1. World Health Organization (WHO). 2021.
2. Centers for Disease Control and Prevention (CDC). Diagnoses of HIV infection in the United States and dependent areas. 2019: national profile. 2021.
3. Goldschmidt R, Chu C. HIV infection in adults: initial management. Am Fam Physician. 2021;103(7):407–416.
4. Rasaq Kayode O, Afeez Babatunde O. Cabenuva®: differentiated service delivery and the community pharmacists' roles in achieving UNAIDS 2030 target in Nigeria. Saudi Pharm J. 2021;29(8):815–819. doi:10.1016/j.jsps.2021.06.003.
5. Haider MR, Brown MJ, Harrison S, et al. Sociodemographic factors affecting viral load suppression among people living with HIV in South Carolina. AIDS Care. 2021;33(3):290–298. doi:10.1080/09540121.2019.1703892.
6. Imahashi M, Ode H, Kobayashi A, et al. Impact of long-term antiretroviral therapy on gut and oral microbiotas in HIV-1-infected patients. Sci Rep. 2021;11(1):1–10.
7. Nachman S, Townsend CL, Abrams EJ, et al. Long-acting or extended-release antiretroviral products for HIV treatment and prevention in infants, children, adolescents, and pregnant and breastfeeding women: knowledge gaps and research priorities. Lancet HIV. 2019;6(8):e552–e558. doi:10.1016/S2352–3018(19)30147-X.
8. Neiman AB, Ruppar T, Ho M, et al. CDC grand rounds: improving medication adherence for chronic disease management—innovations and opportunities. MMWR Morb Mortal Wkly Rep. 2017;66(45):1248–1251.
9. FDA. FDA approves cabenuva and vocabria for the treatment of HIV-1 infection. 2021.
10. Currier JS. Monthly injectable antiretroviral therapy—version 1.0 of a new treatment approach. N Engl J Med. 2020;382(12):1164–1165. doi:10.1056/NEJMe2002199.
11. Swindells S, Andrade-Villanueva J-F, Richmond GJ, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med. 2020;382(12):1112–1123. doi:10.1056/NEJMoa1904398.
12. Rizzardini G, Overton ET, Orkin C, et al. Long-acting injectable cabotegravir + rilpivirine for HIV maintenance therapy: week 48 pooled analysis of phase 3 ATLAS and FLAIR trials. J Acquir Immune Defic Syndr. 2020;85(4):498–506. doi:10.1097/QAI.0000000000002466.
13. Cabenuva [package insert]. ViiV Healthcare Company.
14. Hodge D, Back DJ, Gibbons S, Khoo SH, Marzolini C. Pharmacokinetics and drug-drug interactions of long-acting intramuscular cabotegravir and rilpivirine. Clin Pharmacokinet. 2021;60(7):835–853. doi:10.1007/s40262-021-01005-1.
15. U.S. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV.
16. CATIE. Cabenuva (injectable cabotegravir + rilpivirine) fact sheet. 2020.
17. Cunha RF, Simões S, Carvalheiro M, Pereira JM, Costa Q, Ascenso A. Novel antiretroviral therapeutic strategies for HIV. Molecules. 2021;26(17):5305. doi:10.3390/molecules26175305.
18. Swindells S, Andrade-Villanueva J-F, Richmond GJ, et al. Long-acting cabotegravir and rilpivirine for maintenance of HIV-1 suppression. N Engl J Med. 2020;382(12):1112–1123. doi:10.1056/NEJMoa1904398.
19. Scarsi KK, Swindells S. The promise of improved adherence with long-acting antiretroviral therapy: what are the data? J Int Assoc Provid AIDS Care. 2021;20. doi:10.1177/23259582211009011.
20. Bares SH, Scarsi KK. A new paradigm for antiretroviral delivery: long-acting cabotegravir and rilpivirine for the treatment and prevention of HIV. Curr Opin HIV AIDS. 2022;17(1):22–31. doi:10.1097/coh.0000000000000708.
21. Kates OS. What we know about long-acting injectable antipsychotics can help innovate HIV care. AMA J Ethics. 2021;23(5):E405–E409. doi:10.1001/amajethics.2021.405.
22. Koren 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;19. doi:10.1177/2325958220981265.
23. Thoueille P, Choong E, Cavassini M, Buclin T, Decosterd LA. Long-acting antiretrovirals: a new era for the management and prevention of HIV infection. J Antimicrob Chemother. 2022;77(2):290–302. doi:10.1093/jac/dkab324.
24. Chapin-Bardales J, Rosenberg ES, Sullivan PS. Trends in racial/ethnic disparities of new AIDS diagnoses in the United States, 1984–2013. Ann Epidemiol. 2017;27(5):329–334. doi:10.1016/j.annepidem.2017.04.002.
Wolters Kluwer Health, Inc. All rights reserved.