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HIV Treatment And Long-Acting Therapy Preferences

HIV Treatment And Long-Acting Therapy Preferences


Recent developments in long-acting antiretroviral therapy (LA-ART) offer promising prospects for enhancing HIV treatment by addressing adherence challenges. However, the success of these regimens depends on their acceptance among people living with HIV (PWH). To investigate patient preferences regarding LA-ART options, we conducted a discrete choice experiment involving PWH in the United States. This study focused on four treatment modes (oral tablets, subcutaneous injections, intramuscular injections, and implants), as well as product characteristics and administration locations.



In 2020, the Centers for Disease Control and Prevention (CDC) estimated that out of every 100 individuals diagnosed with HIV, only 74 had received proper HIV care, and 65 had achieved viral suppression, as indicated by their most recent viral load tests. Disparities in HIV care cascade outcomes were noted among various demographic groups in the United States, including adolescents, young adults, Black and Hispanic individuals, injection drug users, women, heterosexual men, foreign-born individuals, and those with lower socioeconomic status. These disparities highlight the need for innovative approaches to enhance antiretroviral therapy (ART) uptake, adherence, and retention, addressing challenges such as HIV-related stigma, treatment fatigue, missed appointments or medication refills, forgetfulness, and side effects.

Recent advancements in long-acting antiretroviral therapy (LA-ART) offer potential solutions to these challenges by providing alternative HIV treatment options that may reduce adherence barriers. Early results from the LATTE-2 randomized, open-label phase 2b trial showed promise in this regard. Participants in the trial received intramuscular injections of long-acting cabotegravir plus rilpivirine at either 4- or 8-week intervals, or a daily pill-based regimen. Both injection frequencies were as effective as the daily oral therapy in maintaining HIV viral suppression over 96 weeks. Importantly, the injectable regimen was well-received, with high levels of treatment satisfaction among participants.

Qualitative interviews associated with the trial revealed that despite experiencing some injection site reactions, participants generally found the regimen convenient and appreciated the reduced need for daily medication reminders. As a result of the success of the cabotegravir/rilpivirine regimen, research has increasingly focused on patient acceptance and preferences for injectable regimens.

Survey data indicated that a significant proportion of adults on daily ART would be willing to try long-acting injectable (LAI) ART, even if it incurred higher costs. A survey conducted by an Italian patient advocacy group found that many respondents were aware of LAI ART and expressed a preference for not taking daily pills. Furthermore, some were open to hospital-based injections at monthly or bi-monthly intervals.

While the cabotegravir/rilpivirine regimen was the first LA-ART product on the market, several promising LA-ART products are in development, potentially offering regimens with less frequent administration, fewer injections, or other advantages. Experts in HIV drug development and clinical trials have suggested that implants, subcutaneous injections, and long-acting oral tablets may become available for HIV treatment in the near future.

However, data on patient preferences for this wider range of LA-ART modalities are limited. To address this gap, discrete choice experiments (DCEs) were conducted to measure and quantify patient preferences regarding these emerging long-acting treatment options. DCEs involve participants choosing between hypothetical alternatives defined by various attributes with varying levels, helping to identify attribute influences, relative importance, and trade-offs. These experiments can be particularly valuable in early product development stages, informing developers about features that enhance acceptability.

In preparation for the DCE, key informant interviews were conducted to identify treatment modalities most likely to become available in the next 5–10 years. Based on this qualitative work and prior research on LAI ART acceptability, a DCE was developed and pilot-tested. The results from this pilot informed the design of a fully deployed DCE at research sites in Seattle, Washington, and Atlanta, Georgia.

The primary objective of this analysis is to present the results of the fully deployed DCE, which sought to understand patient preferences related to four different treatment modalities (oral tablets, subcutaneous injections, intramuscular injections, and implants) and their associated characteristics, in comparison to patients’ current daily oral HIV regimens. This research aims to contribute valuable insights into the evolving landscape of HIV treatment options and patient preferences.


Participants for the Discrete Choice Experiment (DCE) were recruited from multiple University of Washington HIV clinics in Washington (Bremerton, Everett, Federal Way, Olympia, and Seattle) and from Emory University’s Infectious Diseases Program in Atlanta, Georgia. The recruitment process took place between March 2021 and June 2022 and involved contacting patients through email, telephone, or in-person appointments at their regular clinic visits. The study aimed to enroll 350 participants from each site, totaling 700 participants. Eligibility criteria included being HIV-positive, aged 18 or older, receiving care at one of the research sites, fluency in English, and the ability to provide informed consent. Exclusions applied to individuals currently on long-acting injectable (LAI) regimens and “elite controllers” with very low viral loads not requiring antiretroviral therapy. Additionally, those found to be cognitively impaired or under the influence of drugs or alcohol during in-person screenings were excluded.

The study protocol and informed consent documents were reviewed and approved by both the University of Washington (UW) and Emory University, with UW serving as the single institutional review board overseeing the study (STUDY00007390). Informed consent was gotten electronically from all participants.

The DCE was developed based on feedback from key informants regarding potential treatment modes and their expected frequency of administration. This report led to the selection of four LA-ART treatment modalities (subcutaneous injections, implants, intramuscular injections, and long-acting oral tablets) and six additional attributes, including dosing frequency, location of treatment administration, pain during administration, pre-treatment time with an undetectable viral load, pre-treatment negative reaction testing, and “late-dose leeway” (flexibility in dosing timing). These concepts were clearly explained to participants in the survey introduction.

Attribute levels were restricted based on key informants’ input. For each mode, attributes were limited to specific levels, considering factors like pain, location, and dosing frequency. For example, long-acting oral medications were restricted to options with no pain, administration at home, and frequencies of 1 or 4 weeks.

The DCE survey underwent pilot testing with 50 participants, leading to iterative improvements. The survey introduced each treatment mode or “option,” along with visual images and explanations, and participants were instructed that each hypothetical LA-ART regimen would require two products administered through the same mode. Assumptions were made that all options would work equally well, costs would be comparable to participants’ current regimens, and the safety of treatment locations would not be affected by COVID-19.

The DCE consisted of 17 choice scenarios, each offering three options: two systematically generated hypothetical LA-ART regimens and a constant choice to continue their current daily oral treatment. Participants were randomized into one of four blocks, each with 16 choice scenarios presented in random order. The DCE was designed using Ngene software, with the experimental design being unlabelled.

Participants could access the survey at home through an emailed link or in a private area within the clinic. Eligibility and consent were assessed using a questionnaire in REDCap, followed by the administration of the DCE survey in SurveyEngine, an online platform designed for preference research. Various questions about HIV history, current and past ART regimens, experience with injections, pill storage, and clinic visits were asked. Additional data were collected on quality of life, provider support, social support, socio-demographic characteristics, and preferences for reminders about clinic visits or treatment administration. Clinical data were also abstracted from medical records if participants consented.

Descriptive statistics were used to summarize participant characteristics, and conditional logistic regression was employed to analyze participants’ choices across all tasks. Attribute-level preference weights were the primary endpoints, with model fit assessed using log likelihood ratio tests and Akaike’s Information Criterion. An interaction between treatment mode and pain was included due to attribute restrictions.

Stratified analyses were performed to explore differences in preference weights between participants in Georgia and those in Washington State. Mean preference-weight estimates for each attribute were graphed relative to the mean attribute effect.

The data analyses were conducted using Stata version 17.0 or R version 4.2.2.


The study enrolled a total of 700 participants, with 350 individuals at each of the two research sites. The characteristics of this participant population are presented, both as an overall summary and separately by site. The median age of the participants was 51 years, with a range spanning from 18 to 73 years. Regarding gender identification, 70% of participants identified as cisgender males, 24% as cisgender females, and 6% as non-binary, transgender, or falling into other gender categories.

Significant differences were observed between participants at the two research sites. In Atlanta, participants were less likely to identify as of Hispanic ethnicity and more likely to be Black, female, heterosexual, unemployed, or uninsured. They had a longer history of living with HIV, had been on antiretroviral therapy (ART) for a more extended period, had lower recent CD4 counts, were more likely to have been diagnosed with AIDS, and were less likely to have an undetectable viral load. Despite these differences, Atlanta participants were more likely to take only one HIV pill per day. Moreover, they were more inclined to choose their current daily oral regimen over the long-acting antiretroviral therapy (LA-ART) options presented. Atlanta participants also tended to complete the DCE survey in the clinic with assistance from research staff.

In terms of preference weights for LA-ART attributes across the entire study population, LA oral tablets were the only mode that received strong preference over the current daily oral treatment. The preference weight for LA oral tablets was notably higher at 0.89 (95% CI 0.75, 1.04), while the preference weight for the current treatment was much lower at 0.03 (95% CI -0.11, 0.18). Annual implants and injections with no pain were the next preferred LA-ART options, although their preference weights had overlapping confidence intervals with the current treatment.

Participants displayed a preference for longer time intervals between doses, with clear distinctions among dosing frequencies such as 3 months, 2 months, monthly, and weekly. Administration at home was preferred over clinics, which, in turn, were preferred over pharmacies.

Attributes with less impact on preferences included oral lead-in treatment for viral suppression or negative reaction testing, as well as late-dose leeway. However, in each case, a preference was discernible, favoring no pre-treatment requirements and longer late-dose leeway, indicated by non-overlapping 95% confidence intervals.

Seattle participants exhibited stronger preferences for LA-ART regimens than their Atlanta counterparts. Seattle participants showed a clear preference for long-acting oral treatment, while implants and injectable regimens had overlapping confidence intervals with the current therapy, suggesting similar utility. Furthermore, dosing frequency had a pronounced effect on preferences for Seattle participants, with a preference for longer dosing intervals.

In Atlanta, the 95% confidence intervals for long-acting oral treatment overlapped with those of the current therapy, and implants were less preferred, with 95% confidence intervals falling below those of the current therapy for all implant options. Injection options also had overlapping 95% confidence intervals with the current therapy, indicating similar utility.

While longer dosing intervals were preferred in Atlanta, there was an overlap between 95% confidence intervals for 2 and 3 months, as well as between 95% confidence intervals for 1 week and 1 month. Clinic and home preferences were clear in Atlanta, but the 95% confidence intervals for clinic and home overlapped.

Lastly, participants at the Atlanta site had a preference for longer late-dose leeway, but they did not exhibit a clear preference regarding pre-treatment time undetectable and pre-treatment negative reaction testing.


In summary, individuals living with HIV in the United States are on the verge of having multiple choices when it comes to long-acting antiretroviral therapy (LA-ART). Our research findings indicate that LA oral tablets are likely to be favored by a significant portion of patients over their current treatment regimens. Additionally, implants and injections with longer durations between administrations may find acceptance among some patients.

To further enhance our understanding of patient preferences, it is imperative to explore the sources of variation in preferences among individuals. Additionally, future research should closely examine the actual adoption rates and patient retention on these LA-ART products once they become available in clinical practice. This valuable information will help guide healthcare providers and policymakers in offering the most suitable treatment options and improving the overall quality of care for people living with HIV.

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