Factors Associated with Health Care Providers' Preference for Forgoing an Oral Lead-In Phase When Initiating Long-Acting Injectable Cabotegravir and Rilpivirine in the SOLAR Clinical Trial

Abstract

Cabotegravir and rilpivirine long-acting (LA) antiretroviral therapy (ART) demonstrated similar safety and efficacy in maintaining viral suppression among participants switching from daily oral to LA ART in the Extension Phase of the FLAIR trial. The Phase IIIb SOLAR study comparing efficacy and safety of daily oral versus LA ART every 2 months allowed participants and health care providers (HCPs) to choose an oral lead-in (OLI) before LA initiation or proceed by immediately starting with injections (SWI). We conducted an online survey among SOLAR HCPs (n = 110) in 13 countries to assess reasons for choosing OLI versus SWI. Logistic regression was used to identify factors influencing this decision. Thirty-two percent of HCPs reported a future preference to use OLI, whereas 54% reported a future preference for SWI. HCPs had greater odds of reporting future intentions for SWI if they were from Continental Europe versus North America [adjusted odds ratio (aOR): 3.83, p < 0.05], from sites with a greater number of participants who initiated LA ART without OLI (aOR: 1.56, p < 0.01), and those who reported comfort with the medication safety profile (aOR: 6.39, p < 0.01). HCPs who participated in LA ART trials before SOLAR had decreased odds of reporting a preference for SWI compared to those with no prior LA ART trial experience (aOR: 0.11; p < 0.01). Results indicated higher intentions to SWI over OLI among HCPs initiating participants on LA ART. A major factor associated with SWI was provider comfort with safety data, reinforcing the role of continued training regarding an SWI approach.

Introduction

In 2020, a reported 37.7 million people globally were living with HIV, with a reported 1.5 million new infections and 680,000 deaths from an AIDS-related illness.¹ While access to antiretroviral therapy (ART) has expanded greatly in recent years, more than a quarter (27%) of all people living with HIV (PLHIV) were still not yet on life-saving HIV treatment in 2020.² Access to ART among PLHIV is as critical to both the health and well-being of those living with HIV and as a means to reduce ongoing transmission to uninfected persons given the important role of treatment as prevention in the community.^3
–5 The Joint United Nations Programme on HIV/AIDS (UNAIDS) has now established the 95-95-95 HIV treatment goals to be reached by 2030.⁶

However, improvements in HIV outcomes among PLHIV and the additional treatment as prevention benefits to the general population can only be achieved through improved adherence and coverage of ART. Adherence to daily oral ART continues to be suboptimal across settings^7

–11 due to a variety of reasons (e.g., social stigma, lifestyle, psychological burden) creating a major impediment to reaching the aforementioned UNAIDS goals. In addition, in 2020, disruption in HIV prevention and treatment programs due to the COVID-19 pandemic increased challenges to meet UNAIDS HIV targets as the pandemic exacerbated barriers to access HIV testing and ART adherence across settings, further cementing the need for novel strategies to enhance HIV prevention, treatment, and care strategies.¹² Novel treatment regimens such as long-acting (LA) ARTs of injectable cabotegravir (CAB) and rilpivirine (RPV) offer important additional HIV treatment options as they present an opportunity to address barriers to ART adherence.^13,14

Published Phase III (ATLAS, FLAIR)¹⁵ and IIIb (ATLAS-2M)¹⁶ clinical trials have demonstrated noninferior efficacy and safety for the use of CAB+RPV LA in virologically suppressed PLHIV compared with an orally administered standard of care regimen, and noninferior efficacy comparing monthly to every 2 months dosing of CAB+RPV LA. Overall, there was a small percentage of confirmed virologic failures (13 participants of 1039; 1.25%)¹⁷ identified within these three large registrational trials. Furthermore, compared to the use of daily oral ART, CAB+RPV LA aids in addressing individual and sociostructural barriers to adherence due to its monthly or every 2 months dosing.¹⁸ For example, compared to oral daily ART, PLHIV participating in these trials reported that CAB+RPV LA offered a more private and convenient treatment method that helped reduce experiences of internalized stigma and potential discrimination related to others discovering their HIV status.¹⁸

The oral lead-in (OLI) phase for CAB+RPV LA entails a 4-week period of oral therapy with the same regimen CAB (30 mg by mouth daily) and RPV (25 mg by mouth daily) before initiating injections of CAB+RPV LA. The purpose of this OLI phase is to assess tolerability before injection dosing.¹⁹ However, a recent study (FLAIR week 124 extension) found that CAB+RPV LA has an acceptable safety profile and is effective when initiation occurs by starting with injections (SWI) without an OLI phase.²⁰ In this study initiation of CAB+RPV LA by omitting the OLI phase presented no elevated safety concerns.²⁰ Based on the conclusions of this study, several regulators, including the US Food and Drug Administration (FDA)²¹ and the European Union's (EU's) European Medicines Agency (EMA),^22,23 have approved a 4-week OLI phase as optional when initiating CAB+RPV LA. Initiating CAB+RPV LA by SWI is potentially more convenient for people who choose this treatment modality,^19,20,24,25 and would not disadvantage groups that may have difficulty adhering to daily oral ART.^24,25 Furthermore, at the clinic level, the OLI phase could impose undue strains associated with staffing and resources needed for the management of the OLI requirement.²⁵ Prior research suggests that there are ongoing questions and concerns among health care providers (HCPs) regarding LA ART's introduction into routine clinical care, including those related to SWI.²⁴

As roll-out of LA ART continues to expand across different settings, it is essential to further understand clinicians' perspectives and experiences regarding how to optimize its introduction among PLHIV. This study sought to understand the perceptions of HCPs participating in a Phase IIIb study of CAB+RPV LA around use of OLI versus SWI and how they translate to clinical practice when initiating LA ART treatment.

Methods

SOLAR study

The Phase IIIb SOLAR study aims to assess the virologic efficacy and safety of switching subjects with HIV-1 who are virologically suppressed with undetectable plasma viremia on bictegravir/emtricitabine/tenofovir alafenamide to CAB+RPV LA administered every 2 months compared with maintenance of the daily oral medication. The study's primary endpoint is the proportion of participants with HIV-1 RNA ≥50 c/mL at month 12. In the SOLAR study, participants and HCPs were given the option of selecting an OLI phase before CAB+RPV LA initiation or SWI. We surveyed HCPs from the SOLAR study to explore the factors that drove the decision to use an OLI phase before transitioning to every 2-month intramuscular injections compared to SWI.

The SOLAR study was conducted in 117 clinical sites across 14 countries. These countries and sites had the study target population, as well as a history of participation in HIV clinical trials and medication efficacy assessments, and were in turn engaged in the broader SOLAR protocol.

Provider survey

We conducted a cross-sectional online survey among HCPs in 13 countries participating in the SOLAR study. Eligible HCPs were involved in the decision-making process regarding the use of an OLI phase among participants. A total of 128 HCPs were eligible to participate in the survey, including physicians, nurse practitioners, nurses, physician assistants, and other key medical/research personnel, meeting the eligibility criteria. The survey was administered online between September 2021 and January 2022 utilizing the Qualtrics survey online platform.²⁶ The survey was offered in five different languages: English, French, Japanese, Spanish, and German. Eligible HCPs were sent an invitation to participate in the survey via e-mail announcements, which included the survey link, sent by the study sponsor (ViiV Healthcare) making them aware of the online survey, including its objective, content, and length. The survey took ∼15 min to complete; no financial compensation was provided for survey completion.

Measures

The survey included 21 questions, including 2 open-ended questions, and explored HCP characteristics and their perspectives and experiences with the OLI phase. Variables collected related to HCPs' background included country of clinic site, clinical role, experience participating in other CAB+RPV LA studies, number of SOLAR participants that have started CAB+RPV LA, and number of SOLAR participants who started CAB+RPV LA using a SWI approach (without an OLI phase). The survey evaluated HCPs' perspectives and experiences with the OLI phase, including (1) future intentions to use OLI versus SWI, (2) participant–provider dynamics that influenced a provider's decision to use OLI before LA dosing, (3) perspectives of the need to use OLI versus SWI, and (4) concerns about using a SWI approach when initiating a participant on a CAB+RPV LA regimen.

Primary outcome

Future intentions to SWI versus use of OLI

We explored the primary outcome of interest of the present study via a survey item assessing HCPs' future intention to use or not use an OLI phase when transitioning a patient to CAB+RPV LA based on their experience to date. Responses for this question included five possible choices: (a) strong preference to use OLI; (b) some preference to use OLI; (c) no preference; (d) some preference not to use OLI; and (e) strong preference not to use OLI. HCPs who responded as having some or a strong preference not to use an OLI were coded as preferring to SWI, while participants who responded some or a strong preference for OLI were coded as preferring OLI.

Statistical analyses

We began by exploring the survey through descriptive analysis. We examined the frequencies and proportions of categorical variables and assessed the distribution of continuous variables noting key parameters, including mean, median, standard deviation (SD), interquartile range, and range. We conducted bivariate analyses, including chi-squares and two sample t-tests of the data, to examine the factors associated with the main outcome of interest regarding their preference for SWI compared to initiating LA ART using OLI. Single variable logistic regressions were further used to explore the association of different background perspectives and experiences with CAB+RPV LA initiation measures with the outcome of interest. Regarding final model selection, items that showed a trend toward significance (p < 0.10) in the single variable logistic regression analyses were retained and included in the final multivariable logistic regression analysis. All models controlled for HCPs' geographical region and clinical role. Multivariable logistic regression results are expressed as adjusted odds ratio (aOR) and 95% confidence intervals (CIs). Stata SE version 15.1²⁷ was used to conduct all quantitative analyses.

Results

Providers' characteristics

Table 1 presents the provider's background characteristics. A total of 111 HCPs responded to the survey. Among these HCPs, 36% were from North America (United States and Canada), 27% were from Continental Europe (Belgium, France, Netherlands, Switzerland, and Germany), 18.9% were from Southern Europe (Italy and Spain), 9.9% were from Northern Europe (United Kingdom and Ireland), and 8.1% were from Asia-Pacific (Japan and Australia). The majority of HCPs were physicians (82.9%). In addition, for most HCPs, the SOLAR study was their first experience participating in a CAB+RPV LA study (65.8%).

Table 1.

Sample Characteristics of SOLAR Study Health Care Providers (n = 111)

	n	%
Region
North America	40	36.0
Northern Europe	11	9.9
Continental Europe	30	27.0
Southern Europe	21	18.9
Asia-Pacific	9	8.1
Provider role
Physician	92	82.9
Nurse, nurse practitioner, or doctor of nursing practice	10	9.0
Other research staff	9	8.1
Prior experience with CAB LA + RPV LA
First time participating in CAB LA + RPV LA study	73	65.8
Has participated in 1 or more CAB LA + RPV LA studies	38	34.2

CAB, cabotegravir; LA, long-acting; RPV, rilpivirine.

Experience related to the use of OLI versus SWI

For most HCPs, nearly half of their participants had initiated CAB+RPV LA using a SWI approach compared to an OLI approach (Table 2). The mean number of SOLAR participants that have started CAB+RPV LA per site was 4.5 (SD, 3.7; range, 0–27), with a mean number of participants SWI of 2.2 (SD, 2.7; range, 0–15). Over half of HCPs indicated using the scientific literature to assess the need for an OLI phase (68.4%). Regarding the level of influence that a participant's preference has on whether to use OLI, nearly half of HCPs indicated that a participant's preference was very influential (49.5%); 23.2% indicated that it was somewhat influential.

Table 2.

Health Care Providers' Experience and Perspectives Related to with Oral Lead-In Versus Starting with Injection (n = 111)

	Mean	SD
Number of SOLAR participants at your site in total that have started CAB LA + RPV LA	4.5	3.7
Number of SOLAR participants that have initiated CAB LA + RPV LA SWI	2.2	2.7
	n	%
Utilizes scientific literature to assess need for OLI phase^a	65	68.4
Level of influence of participant's preferences in decision to use or not OLI^a
Very influential	47	49.5
Somewhat influential	22	23.2
Not very influential	10	10.5
Not at all influential	16	16.8
Most important factor driving decisions to SWI^a
Participant request	34	35.8
Provider comfort with the safety data	27	28.4
Provider comfort with the pharmacokinetic data	5	5.3
Ease of implementing the change from previous regimen	3	3.2
Participant already on an alternative INSTI-based regimen	6	6.3
Prior clinical experience with RPV and its safety profile	4	4.2
Drug–drug interaction with other oral meds	1	1.1
Need for OLI phase before transitioning a participant to CAB LA + RPV LA^b
Absolutely necessary	11	11.8
Helpful but not necessary	52	55.9
Not necessary at all	27	29.0
No opinion	3	3.2
Level of concern about SWI when initiating a CAB LA + RPV LA regimen for a participant^b
Very concerned	5	5.4
Somewhat concerned	19	20.4
Not very concerned	45	48.4
Not at all concerned	24	25.8
Intentions to use OLI vs. SWI in the future^b
Preference to use OLI (n = 30)	30	32.3
No preference (n = 14)	14	15.1
Preference to SWI (n = 49)	49	52.7

n = 95.

n = 93.

CAB, cabotegravir; INSTI, integrase strand transfer inhibitor; LA, long-acting; OLI, oral lead-in; RPV, rilpivirine; SD, standard deviation; SWI, starting with injection.

When HCPs were asked to choose the most important factor in driving their decision to SWI when initiating a participant on CAB+RPV LA, 35.8% indicated that the most important factor was a participant's request, while 28.4% indicated that the most important factor was their comfort with the medication safety data. Other reasons provided as most important factors driving the decision to SWI were participant already on an alternative integrase strand transfer inhibitor-based regimen (6.3%), comfort with the pharmacokinetic data (5.3%), prior clinical experience with RPV and its safety profile (4.2%), ease of implementing the change from previous regimen (3.2%), and drug-drug interaction with other oral medications (1.1%).

Perspectives related to the need for OLI versus SWI

HCPs were asked their perspectives on the need for an OLI phase before transitioning a participant to CAB+RPV LA. Over half of HCPs reported that an OLI phase is helpful but not necessary (55.9%) and 29.0% indicated that an OLI phase is not necessary at all (Table 2). Only 11.8% of HCPs indicated that an OLI phase is absolutely necessary. 3.2% of HCPs indicated not having an opinion about the need for an OLI phase. Related to the level of concern about SWI when initiating a CAB+RPV LA regimen for a participant, most HCPs indicated being not very concerned or not at all concerned (48.4% and 25.8%, respectively). In contrast, 20.4% of HCPs indicated being somewhat concerned and 5.4% indicated being very concerned about SWI and not using an OLI phase when initiating participants on a CAB+RPV LA regimen.

HCPs were asked to expand on their greatest concerns related to not using an OLI phase and SWI in an open-ended question. Over half of HCPs (58.1%) continued to indicate that they had no concerns over SWI (“none”). However, among HCPs who elaborated on their concerns, most HCPs reported concerns related to tolerance to treatment, adverse effects or adverse drug reactions, and hypersensitivity to the medication. One HCP expressed the following:

“Though the data for safety and tolerability of direct to injections exists, [the Doctor] has proceeded with caution using the OLI for all patients as the injectable therapy is still novel. [It is] deemed better to approach with caution and allow for monitoring of side effects on the OLI as the tablets can be easily stopped.” (Other research staff, North American region)

Another HCP reported:

“Oral lead-in provides reassurance of tolerability to patients who find this important in their decision making about switching therapy.” (Physician, Asia-Pacific region)

Furthermore, when HCPs were asked (in a second open-ended question) what would be helpful to providers in terms of making future decisions regarding whether to use an OLI phase and in addressing any concerns about SWI, most participants (65.8%) indicated a desire to see “more data” on the safety, tolerability, and pharmacokinetics of the medication. One HCP elaborated on this point:

“Duration of undesirable side effects after receiving injections (i.e., how long patients can expect adverse events to last should they opt for direct to injection and experience adverse effects), more data collected on the safety and tolerability of direct to injections.” (Other research staff, North American region)

Future intentions to SWI versus using an OLI phase

Fifty-four percent of HCPs reported a future preference for SWI, while 32% reported a future preference to use OLI. 15.1% indicated having no preference for either SWI or OLI. Across regions, with the exception of North America, most HCPs report a preference for SWI (Fig. 1). Table 3 presents the multivariable results assessing provider future preference for SWI. HCPs had greater odds of reporting future intentions for SWI if they were from Continental Europe compared to North America (aOR: 3.83, 95% CI: 1.01–14.57); from sites with a greater number of participants who initiated CAB+RPV LA without an OLI phase (odds increase with every additional participant; aOR: 1.56, 95% CI: 1.21–2.02); and if they reported that the main reason for SWI was their level of comfort with the medication safety profile (aOR: 6.39, 95% CI: 1.78–22.91). In contrast, HCPs with previous experience in CAB+RPV LA studies, before SOLAR, had decreased odds of reporting a preference for SWI compared to those with no prior CAB+RPV LA trial experience (aOR 0.11; 95% CI: 0.03–0.47).

FIG. 1.

Health care providers' future intentions to use OLI versus SWI when initiating participants on LA ART. ART, antiretroviral therapy; LA, long-acting; OLI, oral lead-in; SWI, starting with injection.

Table 3.

Single Variable and Multivariable Results Assessing Health Care Providers' Future Preference for Starting with Injection (n = 93)

	OR	95% CI	aOR	95% CI
Region (reference: North America)
Northern Europe	9.333^**	1.022–85.21	6.971^*	0.691–70.33
Continental Europe	2.167	0.712–6.589	3.833^**	1.008–14.57
Southern Europe	1.333	0.440–4.041	0.273	0.0542–1.375
Asia-Pacific	1.067	0.242–4.702	1.613	0.192–13.58
Provider role: physician	2.108	0.692–6.419	3.301	0.788–13.84
Prior experience with CAB LA + RPV LA	0.289^***	0.118–0.711	0.112^***	0.0266–0.473
Utilize scientific literature to assess need for OLI phase	1.941	0.793–4.751
Number of patients who started on CAB LA + RPV LA without OLI phase	1.359^**	1.024–1.804	1.564^***	1.211–2.020
Participant's preferences in decision to use or not OLI phase is very influential	1.773	0.775–4.057
Most important factor for decision not to use OLI: participant request	1.839	0.763–4.430
Most important factor for decision not to use OLI: provider comfort with the safety data	2.850^**	1.088–7.465	6.387^***	1.781–22.91

CI based on robust standard errors.

***

p < 0.01, ^** p < 0.05, ^* p < 0.1.

aOR, adjusted odds ratio; CAB, cabotegravir; CI, confidence interval; LA, long-acting; OLI, oral lead-in; OR, odds ratio; RPV, rilpivirine.

Discussion

This is the first study to explore clinicians' experiences, perspectives, and preferences related to how to optimize the initiation of an LA ART regimen with the goal of addressing barriers or delays to starting LA among PLHIV. In this survey of HCPs participating in a LA ART clinical trial, providers reported a stronger preference for initiating CAB+RPV LA directly by SWI compared to using an OLI phase and is consistent with the recent supplementary approvals by regulators on an optional approach to the OLI phase.^21
–23 Findings from open-ended questions also highlighted important areas for training, communication, and support for providers as access to these novel methods of ART treatment expand across the globe.²⁸

In our study, more than three-quarters of providers indicated that having an OLI phase was not necessary when transitioning participants to CAB+RPV LA. This is an important finding as removal of the OLI phase may decrease barrier to access and uptake of LA ART, especially across more vulnerable population groups due to the strict requirement of daily pill adherence during the OLI phase before LA ART.^24,25 Furthermore, most providers also indicated not being concerned with a decision to initiate patients by directly SWI in the future compared to using an OLI phase. These findings are consistent with research from a recent phase III trial that found at week 124, CAB+RPV ART had an acceptable safety profile and noninferior efficacy irrespective of use of OLI or SWI.²⁰

Among the contributing factors motivating providers' future preference for LA ART initiation by SWI was providers' prior clinical experience initiating participants on CAB+RPV LA without the use of an OLI phase. In contrast, providers with prior experience in CAB+RPV clinical trials had decreased odds of future preference to initiate participants on LA ART using an SWI approach. This is potentially related to these trials requiring an OLI phase as part of the study protocol.

Another significant finding from the current study is that providers had increased odds to prefer future initiation of CAB+RPV LA by SWI if they indicated comfort with the medication safety data. Providers' concerns related to omitting an OLI phase during initiation was attributed to the need to assess individual participants' tolerance to the treatment and any possible adverse reactions. However, prior phase II, III, and IIIb clinical trials, conducted with nearly 1500 participants, have found no major drug safety signals or hypersensitivity reactions during the OLI phase.^{16,19,20,29,30} In addition, published results from the phase III FLAIR clinical trial expanded this evidence by indicating that CAB+RPV LA has an acceptable safety profile when initiating directly with injections.²⁰ As a result, use of CAB+RPV without OLI is now approved by the US FDA²¹ and the EU's EMA.^22,23

Despite the majority of providers indicating utilizing scientific literature to assess the need for an OLI phase, our findings suggest that there is still a need for continued training and education among HCPs on the safety and tolerability of CAB+RPV LA using a SWI approach. This aligns with providers' calls for greater data generation and dissemination on the safety, tolerability, and pharmacokinetics of the medication to support an SWI approach in the context of LA ART.

In addition, in open-ended questions, participating providers from the current study indicated that patient requests to initiate LA ART via SWI were a critical factor in motivating their decisions. This finding is important in terms of the need to further assess and support patient preferences and literacy in future research and intervention work. The broader literature suggestions that a significant proportion of patients across settings are interested in LA ART,^31,32 and that there may be specific subgroups of patients who prefer LA over oral ART given their lifestyles. In turn, further research regarding patient–provider communication³¹ and shared decision-making will be important as LA ART access expands across geographic contexts.

While this is the first study to examine providers' experience, perspective, and preference for an OLI phase versus an SWI approach when initiating participants on LA ART, there are some limitations that warrant consideration. First, this is a cross-sectional study of providers currently participating in a Phase IIIb clinical trial. As such, their perspective and opinions may vary from the real-world experiences of providers implementing LA ART regimens. Second, the limited sample size did not allow us to explore more in-depth within countries or regional factors influencing the use of OLI versus SWI. Our findings are also limited to the experiences of providers in North America, Northern Europe, Continental Europe, Southern Europe, and Asia-Pacific, and as such, results may not be generalizable to other regions that are not represented in the study. In addition, this study focused specifically on HCP perspectives, whereas future research should further integrate patients' views and experiences regarding SWI versus OLI. Finally, this study was limited to understanding the use of OLI versus SWI for the CAB+RPV LA regimen, and as such findings from this study cannot be generalized to other LA ART regimens as other active pharmaceutical ingredients may exhibit other safety and efficacy profiles.

Findings from this study highlight providers' preference to initiate patients on LA ART starting with injections and forgoing the OLI phase aligning with current evidence demonstrating the safety and efficacy of CAB+RPV LA ART initiation without the use of an OLI phase. It is also consistent with the recent approval by many regulatory agencies of an optional approach to the OLI phase before the CAB+RPV LA ART. Providers' preference for starting with injections was driven by prior experience not using an OLI during CAB+RPV LA ART initiation and their level of comfort with the medication safety profile. Continued provider education and training related to CAB+RPV LA, including SWI, should focus on medication safety and tolerability as part of efforts to ensure equitable access to CAB+RPV LA ART among PLHIV.

Footnotes

Acknowledgments

We want to acknowledge ViiV Healthcare and GSK, including their central and in-country teams for their contributions and assistance in identifying eligible sites and providers, to participate in the study survey. In addition, we thank all participating providers for their contributions to this work. Finally, we want to acknowledge that results from this article were presented in the 24th International AIDS Conference (AIDS 2022).

Authors' Contributions

D.K., T.S.K., M.P.B., and A.B. helped conceptualize the study; D.K., T.S.K., M.P.B., A.B., and A.H. assisted with study implementation; D.K., T.S.K., M.P.B., and A.B. led the instrument development; T.S.K. and D.K. led the data analysis. T.S.K. led the article writing and all authors contributed to article development and review. All authors have read and approved the final version of the article.

Ethical Approval

The study protocol was approved by the Institutional Review Board of the George Washington University Milken Institute School of Public Health.

Consent

All participants involved in the study provided informed consent.

Author Disclosure Statement

T.S.K. and D.K. received support for this study via a ViiV Healthcare contract. M.P.B., K.S., D.S.P., and R.D. are employees of ViiV Healthcare. A.H. was an employee of ViiV Healthcare at the time of the research implementation. A.B. is an employee of GlaxoSmithKline. All other authors were investigators on trials supported, in part, by ViiV Healthcare.

Funding Information

This study was funded by ViiV Healthcare.

References

UNAIDS. Global HIV & AIDS Statistics—Fact Sheet. 2022.

HIV/AIDS JUNPo. Confronting Inequalities: Lessons for Pandemic Responses from 40 Years of AIDS. Report No: UNAIDS/JC3020E Global AIDS Update. Joint United Nations Programme on HIV/AIDS (UNAIDS): Geneva, Switzerland; 2021.

Forsythe

, McGreevey

, Whiteside

, et al. Twenty years of antiretroviral therapy for people living with HIV: Global costs, health achievements, economic benefits. Health Aff (Millwood), 2019; 38(7):1163–1172; doi: 10.1377/hlthaff.2018.05391.

Delva

, Eaton

, Meng

, et al. HIV treatment as prevention: Optimising the impact of expanded HIV treatment programmes. PLoS Med, 2012; 9(7):e1001258; doi: 10.1371/journal.pmed.1001258.

Cohen

, McCauley

, Gamble

. HIV treatment as prevention and HPTN 052. Curr Opin HIV AIDS, 2012; 7(2):99–105; doi: 10.1097/COH.0b013e32834f5cf2.

UNAIDS. Understanding Fast-Track: Accelerating Action to End the AIDS Epidemic by 2030. UNAIDS: Geneva, Switzerland; 2015.

Heylen

, Chandy

, Shamsundar

, et al. Correlates of and barriers to ART adherence among adherence-challenged people living with HIV in southern India. AIDS Care, 2021; 33(4):486–493; doi: 10.1080/09540121.2020.1742862.

Akinwunmi

, Buchenberger

, Scherzer

, et al. Dose-related and contextual aspects of suboptimal adherence to antiretroviral therapy among persons living with HIV in Western Europe. Eur J Public Health, 2021; 31(3):567–575; doi: 10.1093/eurpub/ckaa229.

Edmonds

, Aspiras

, Rose

, et al. Cross-sectional evaluation of perceived health care provider engagement, self-efficacy, and ART adherence in people living with HIV/AIDS. AIDS Care, 2021; 33(2):154–158; doi: 10.1080/09540121.2019.1703889.

10.

Quinn

, Voisin

. ART adherence among men who have sex with men living with HIV: Key challenges and opportunities. Curr HIV/AIDS Rep, 2020; 17(4):290–300; doi: 10.1007/s11904-020-00510-5.

11.

Glick

, Russo

, Huang

, et al. ART uptake and adherence among female sex workers (FSW) globally: A scoping review. Glob Public Health, 2022; 17(2):254–284; doi: 10.1080/17441692.2020.1858137.

12.

Laurence

. Intersecting pandemics of epidemiology, inequality, genetics, and immunology: COVID-19 and AIDS. AIDS Patient Care STDS, 2022; 36(5):169–171; doi: 10.1089/apc.2022.29008.com.

13.

Mills

, Richmond

, Newman

, et al. Long-acting cabotegravir and rilpivirine for HIV-1 suppression: Switch to 2-monthly dosing after 5 years of daily oral therapy. AIDS, 2022; 36(2):195–203; doi: 10.1097/qad.0000000000003085.

14.

Dandachi

, Dang

, Lucari

, et al. Acceptability and preferences for long-acting antiretroviral formulations among people with HIV infection. AIDS Care, 2021; 33(6):801–809; doi: 10.1080/09540121.2020.1764906.

15.

Rizzardini

, Overton

, Orkin

, 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.

16.

Overton

, Richmond

, Rizzardini

, et al. Long-acting cabotegravir and rilpivirine dosed every 2months in adults with HIV-1 infection (ATLAS-2M), 48-week results: A randomised, multicentre, open-label, phase 3b, non-inferiority study. Lancet, 2021; 396(10267):1994–2005; doi: 10.1016/s0140-6736(20)32666-0.

17.

Cutrell

, Schapiro

, Perno

, et al. Exploring predictors of HIV-1 virologic failure to long-acting cabotegravir and rilpivirine: A multivariable analysis. AIDS (London, England), 2021; 35(9):1333.

18.

Kerrigan

, Mantsios

, Gorgolas

, et al. Experiences with long acting injectable ART: A qualitative study among PLHIV participating in a Phase II study of cabotegravir + rilpivirine (LATTE-2) in the United States and Spain. PLoS One, 2018; 13(1):e0190487; doi: 10.1371/journal.pone.0190487.

19.

Llibre

, Sax

. Reassessing oral lead-in for injectable long-acting HIV therapy. Lancet HIV, 2021; 8(11):e660–e661; doi: 10.1016/s2352-3018(21)00269-1.

20.

Orkin

, Bernal Morell

, Tan

DHS

, et al. Initiation of long-acting cabotegravir plus rilpivirine as direct-to-injection or with an oral lead-in in adults with HIV-1 infection: Week124 results of the open-label phase 3 FLAIR study. Lancet HIV, 2021; 8(11):e668–e678; doi: 10.1016/s2352-3018(21)00184-3.

21.

U.S. Food and Drug Administration. Cabenuva: Highlights of Prescribing Information. 2022. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212888s005s006lbl.pdf [Last accessed: August 03, 2022].

22.

European Medicines Agency. Vocabria: Procedural steps taken and scientific information after the authorisation. European Medicines Agency; 2022. Available from: https://www.ema.europa.eu/en/documents/procedural-steps-after/vocabria-epar-procedural-steps-taken-scientific-information-after-authorisation_en.pdf [Last accessed: August 12, 2022].

23.

European Medicines Agency. Committee for medicinal products for human use (CHMP): Minutes for the meeting on 13–16 September 2021. European Medicines Agency; 2021. Available from: https://www.ema.europa.eu/en/documents/minutes/minutes-chmp-meeting-13-16-september-2021_en.pdf [Last accessed: August 12, 2022].

24.

Mantsios

, Murray

, Karver

, et al. Multi-level considerations for optimal implementation of long-acting injectable antiretroviral therapy to treat people living with HIV: Perspectives of health care providers participating in phase 3 trials. BMC Health Serv Res, 2021; 21(1):255–255; doi: 10.1186/s12913-021-06214-9.

25.

Hojilla

, Gandhi

, Satre

, et al. Equity in access to long-acting injectables in the USA. Lancet HIV, 2022; 9(3):e145–e147; doi: 10.1016/s2352-3018(22)00031-5.

26.

Qualtrics. Qualtrics. Qualtrics: Provo, UT, USA; 2020.

27.

StataCorp. Stata Statistical Software. 2020.

28.

Thoueille

, Choong

, Cavassini

, et al. 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.

29.

Swindells

, Andrade-Villanueva

, Richmond

, 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.

30.

Margolis

, Gonzalez-Garcia

, Stellbrink

, et al. Long-acting intramuscular cabotegravir and rilpivirine in adults with HIV-1 infection (LATTE-2): 96-week results of a randomised, open-label, phase 2b, non-inferiority trial. Lancet, 2017; 390(10101):1499–1510; doi: 10.1016/s0140-6736(17)31917-7.

31.

Philbin

, Parish

, Bergen

, et al. A qualitative exploration of women's interest in long-acting injectable antiretroviral therapy across six cities in the women's interagency HIV study: Intersections with current and past injectable medication and substance use. AIDS Patient Care STDS, 2021; 35(1):23–30; doi: 10.1089/apc.2020.0164.

32.

Massaroni

, Delle Donne

, Borghetti

, et al. Use of long-acting therapies for HIV care in Italy: Are people living with HIV prepared for change? A cross-sectional study. AIDS Patient Care STDS, 2022; 36(5):178–185; doi: 10.1089/apc.2022.0030.