PAIRED: Quantitative and Qualitative PAtIent-Reported Experiences and perceiveD Benefit of Treatment with Dolutegravir/Lamivudine in the United States

Abstract

Background

Understanding the treatment experiences and satisfaction of people with HIV using two-drug regimens, including dolutegravir/lamivudine (DTG/3TC), is crucial to assess ongoing needs and meet Ending the HIV Epidemic goals.

Methods

PAIRED is a mixed-methods study comprising a quantitative cross-sectional survey (using validated instruments to assess treatment satisfaction, adherence, and health-related quality of life [QOL]) and qualitative interviews. Adults in the USA who switched to DTG/3TC while virologically suppressed and had been using DTG/3TC for ≥ 3 months were eligible. All participants were surveyed, and a sub-set participated in in-depth interviews. Thematic analysis was performed to discern overarching interview themes.

Results

Overall, 474 participants completed the survey (assigned female sex at birth, 31%; non-white, 48%; aged ≥ 50 years, 50%); 20 of them participated in qualitative interviews. Treatment satisfaction, adherence, and QOL scores were high. Six themes were extracted from interviews: (1) fewer drugs are important in HIV treatment because of associated reductions in long-term drug exposure and perceived risk of toxicity; (2) high DTG/3TC satisfaction is largely due to achieved expectations regarding efficacy and safety; (3) DTG/3TC simplicity and convenience enable more freedom and autonomy; (4) treatment advancements led to HIV no longer being a “death sentence”; (5) managing HIV is no longer the main concern relative to other health conditions; and (6) some HIV unmet needs remain.

Conclusions

A large representative population with HIV had primarily positive experiences and few needs after switching to DTG/3TC. These data complement clinical trial data and support DTG/3TC effectiveness and tolerability in real-world settings.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40271-025-00779-x.

Key Points for Decision Makers

People with HIV have continuous exposure to antiretrovirals and need individualized treatment regimens that accommodate personal preferences, enhance adherence, and ensure long-term treatment success; thus, it is crucial to understand their experiences and satisfaction of HIV treatment through a patient-centric lens.

PAIRED, a mixed-methods study with a quantitative cross-sectional survey and qualitative in-depth interviews of US adults who switched to dolutegravir/lamivudine (DTG/3TC), was conducted to better understand treatment experiences (including adherence, perceptions, expectations, and satisfaction) of a diverse sample of people with HIV with demographics representative of those of the real world.

Overall, a large and representative US population of adults with HIV had positive experiences and high treatment satisfaction after switching their antiretroviral therapy to DTG/3TC, which resulted in high levels of treatment adherence; findings from PAIRED illuminate important treatment perceptions among people with HIV and can help inform both clinicians and patients when deciding on the most appropriate treatment.

Introduction

A person diagnosed with HIV in their 20s today can expect more than 50 years of exposure to antiretrovirals; thus, optimal lifelong therapy options are of great importance [1]. To enhance adherence and ensure long-term treatment success, US guidelines emphasize the need for individualized treatment regimens that accommodate personal preferences (e.g., dosing frequency, number of pills) and barriers (e.g., cost) [2]. As part of a patient-centric approach, further insight is needed regarding motivations for switching treatment and treatment satisfaction.

Dolutegravir/lamivudine (DTG/3TC) is a two-drug regimen (2DR) consisting of an integrase strand transfer inhibitor and a nucleoside reverse transcriptase inhibitor and is available as a fixed-dose, single-tablet regimen. In phase III studies, DTG/3TC demonstrated high efficacy at maintaining virologic suppression in adults living with HIV through weeks 48 (SALSA) and 196 (TANGO) and demonstrated non-inferiority to three- or four-drug regimens (3DRs or 4DRs) through weeks 48 (SALSA) and 144 (TANGO) [3–5]. However, these studies did not collect details about the participant experience. To meet the ongoing needs of people with HIV using 2DRs, including DTG/3TC, information is needed on real-world treatment satisfaction and personal experiences.

The PAIRED study comprised a quantitative survey and qualitative interviews of people with HIV who switched from a stable regimen to DTG/3TC. The primary objective was to describe the perceptions (including treatment expectations, experiences, and satisfaction) of people with HIV treated with DTG/3TC in the USA.

Methods

Study Design

A cross-sectional survey and in-depth interviews of people with HIV in the USA who were receiving DTG/3TC for ≥ 3 months were performed. All participants completed a 30-minute survey between September 2022 and August 2023 and received compensation for survey completion. The survey was available in English and Spanish and assessed DTG/3TC treatment perceptions, expectations, and satisfaction through a combination of bespoke questions and validated instruments, including the 10-item HIV Treatment Satisfaction Questionnaire (HIV-TSQ) status version, with a total score ranging from 0 (indicating extreme dissatisfaction) to 60 (indicating extreme satisfaction) [6]; the Adelphi Adherence Questionnaire™ (ADAQ; Adelphi Real World, Bollington, England), with a total score ranging from 0 (indicating complete adherence) to 4 (indicating complete non-adherence) [7]; and the 13-item quality of life questionnaire (PozQoL; higher scores reflect better quality of life), with an overall total score ranging from 13 to 65 and domain scores ranging from 4 to 20 (psychological domain) or 3 to 15 (social, health concerns, and functional domains) [8].

A sub-set was invited to participate in a 1:1, semi-structured, follow-up interview. Qualitative sampling was purposive to achieve a diverse range of experiences and insights. Interviews were guided by a study team–developed discussion guide, which included quantitative survey topics (electronic supplementary material [ESM]). Interviews were conducted by a third-party, female moderator with over 20 years of experience in qualitative interviews, including academic teaching and university-level studies. The moderator had no affiliation with the clinical sites or sponsor, did not disclose any personal motivations or assumptions to participants that might influence the data collection process, and received training on the discussion guide by the lead qualitative investigator. Participants received additional compensation for interview completion.

Each interview was approximately 60 minutes, conducted via telephone in English with no other individuals present, audio recorded (with participant awareness and consent), and transcribed verbatim. Transcripts were reviewed as they were received for dependability. Repeat interviews were not conducted. No prior relationship was established between the moderator and participants, field notes were not taken, and transcripts were not returned to participants for review or comment.

A contract research organization, Adelphi Real World, was responsible for study design, execution, and analyses independent of the sponsor, ViiV Healthcare. The sponsor provided input on survey design and reviewed the final manuscript but was not involved in data collection, coding, or interpretation. At the consent stage, participants were informed that the study was conducted by Adelphi Real World on behalf of ViiV Healthcare.

Participants

Participants were recruited using site-led methods (11 clinical sites) or community outreach (local patient advocacy groups, community partners, social media channels, patient support programs, and targeted digital advertising). A matched quality-checking process used key demographics (age, sex assigned at birth, race and ethnicity, and state of residence) to confirm that no participants were duplicated between the two recruitment methods. To ensure data were representative of the real world, minimal participant recruitment criteria were used, and each clinical site was limited to ≤ 50 participants. Adults aged ≥ 18 years were eligible if they (1) switched to DTG/3TC after its US Food and Drug Administration approval on April 8, 2019, (2) previously received a different antiretroviral therapy (ART) and were virologically suppressed (HIV RNA < 50 copies/mL) for ≥ 3 months at point of DTG/3TC initiation, and (3) were currently receiving DTG/3TC for ≥ 3 months. Both quantitative and qualitative study portions had soft-quota diversity targets (assigned female sex at birth, 25%; non-white, 40%; aged > 50 years, 40%). Participants of any previous ViiV-sponsored clinical trial (SALSA, STAT, SWORD, GEMINI-1/-2, TANGO) or ACTG A5353 were excluded.

Participants recruited via community outreach who expressed interest in follow-up interviews during the survey were considered for interviews. Key demographics (age, ethnicity, sex assigned at birth, time since diagnosis, and treatment history) were reviewed. Participants were purposively invited using the same diversity targets of the quantitative survey to include a broad range of experiences in a 20-participant sample.

Ethics Approval and Informed Consent

PAIRED was conducted in accordance with legal and regulatory requirements and followed practices described in the Guidelines for Good Pharmacoepidemiology Practices (issued by International Society for Pharmacoepidemiology), Good Practices for Outcomes Research (issued by International Society for Pharmacoeconomics and Outcomes Research), and US Food and Drug Administration Guidance for Industry: Good Pharmacovigilance and Pharmacoepidemiologic Assessment. Before data collection, the lead site received ethics approval from a centralized institutional review board (Western Institutional Review Board; tracking reference, 20224682), and ethics approvals were added for each subsequent site. All participants provided signed consent to publish anonymized findings before surveys and interviews were conducted.

Objective

The primary objective of PAIRED was to understand treatment experiences of people with HIV who switched to DTG/3TC via assessing participants’ characteristics; interests, motivations, and expectations for initiating DTG/3TC; experiences relative to expectations after initiating DTG/3TC; treatment satisfaction and adherence; psychosocial benefits of less drug exposure; and concerns.

Analyses of Quantitative Data

All collected data were de-identified, anonymized, aggregated, and transferred to an electronic database. No formal hypothesis was tested, so no formal sample size calculation was performed. Descriptive analyses were based on observed data and performed using SPSS^® Data Collection Survey Reporter version 7.5 (IBM^®, Armonk, NY, USA). Participants with missing values for a variable were removed from analyses using that variable. The HIV-TSQ total, ADAQ, and PozQoL summary scores are reported among all participants and across sub-groups based on age (< 50, ≥ 50, ≥ 65 years), sex assigned at birth (male, female), race (Black, non-Black), and ethnicity (Latinx, non-Latinx).

Analyses of Qualitative Data

Thematic analytical methods were conducted on interview transcripts [9]. Pre-determined sample size (n = 20) was based on expectations of reaching conceptual saturation while allowing for sub-population explorations. Three analysts experienced in health outcomes research (GH, KM, and AM) independently reviewed transcripts to become familiar with the data and identify emergent, prominent, or frequently reported concepts. Analysts used emergent (inductive) coding with thematic analytical methods. Initial codes, which were based on topics from the discussion guide and analyst discussions, were manually applied to each transcript by one analyst using ATLAS.ti version 22.0 (ATLAS.ti Scientific Software Development GmbH, Berlin, Germany). To review coding accuracy and consistency, the three analysts discussed assigned codes at multiple meetings, and the codebook was updated as needed to include emerging codes or sub-codes. Analysts searched for themes among the data and coding, reviewed and refined themes using “mind-mapping” techniques [10], and collectively selected and extracted representative quotes to provide context for each theme. Thematic saturation was monitored during analysis and formally assessed post hoc by dividing interviews into three approximately equal chronological groups. Saturation was determined to have been reached when no new concepts or themes emerged in the third group.

Results

Participants

A total of 474 participants were recruited: 51% (n = 241) via 11 clinical sites and 49% (n = 233) via community outreach. Overall, the mean age was 48 (range 21–90) years, 31% (n = 145) were assigned female sex at birth, 48% (n = 226) were non-white, and 50% (n = 238) were aged ≥ 50 years (Fig. 1). Geographically, participants resided across 31 US states (99% [n = 468]), the District of Columbia (1% [n = 4]), or other US territories (< 1% [n = 2]); most (57% [n = 272]) resided in the South. Clinic-recruited participants resided across eight states, and community-recruited participants resided across all 31 states and other US territories (Fig. 1). For the interview sub-population (n = 20), the mean age was 53 years (range 33–70) years, 50% (n = 10) were assigned female sex at birth, 45% (n = 9) were non-White, and 70% (n = 14) were aged ≥ 50 years (Fig. 1).

Fig. 1.

Participant demographics of the overall (quantitative) population (N = 474) and the interview (qualitative) sub-population (n = 20). ^aParticipants of Hispanic, Latin American, or Spanish ethnicity could identify as any race; ^bIncludes working part-time, not working (seeking employment), not working (not seeking employment), homemaker, on long-term sick leave, and other (not specified). ^cGeographic regions align with the US Census Bureau’s grouping of US states. West includes Alaska, Arizona, California, Colorado, Hawaii, Idaho, Montana, Nevada, New Mexico, Oregon, Utah, Washington, and Wyoming; Midwest includes Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, Ohio, South Dakota, and Wisconsin; Northeast includes Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Vermont; and South includes Alabama, Arkansas, Delaware, District of Columbia, Florida, Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, Oklahoma, South Carolina, Tennessee, Texas, Virginia, and West Virginia. Clinic sites were located in Florida (n = 3), Connecticut (n = 2), and New Jersey, North Carolina, Texas, Michigan, California, and Colorado (n = 1 each)

General health and HIV-related characteristics are summarized in Table 1. In the overall population, 62% (293/474) of participants were on DTG/3TC for > 1 year, and 73% (348/474) had been on their previous regimen for > 1 year. Most participants (≥ 80%) switched from a 3DR or 4DR; of note, a minority switched from a different 2DR (e.g., 2% [9/474] of participants switched from cabotegravir + rilpivirine [CAB + RPV]). In both the overall population and the interview sub-population, the most common previous regimens were bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and abacavir (ABC)/DTG/3TC. In the overall population, 74% (352/474) of participants had two or more prior regimens before switching to DTG/3TC; in the interview sub-population, 90% (18/20) of participants had two or more prior regimens.

Table 1.

Baseline characteristics of PAIRED participants by population

Characteristic	Population
	Overall (n = 474)	Interview (n = 20)
Age at HIV diagnosis, ya	33 (0–66)	–
Years since HIV diagnosisa	15 (0–66)	22 (8-34)
Insurance coverage for DTG/3TC	433 (91)	–
Insurance type (multi-select options)b
Medicare	112 (26)	–
Medicaid	122 (28)	–
AIDS Drug Assistance Program	131 (30)	–
Employer-provided	140 (32)	–
Private	46 (11)	–
Other/don’t know	77 (18)	–
Support from a patient assistance program
Yes	194 (41)	–
No	229 (48)	–
Don’t know	51 (11)	–
Most common (> 10%) concomitant conditions
None	160 (34)	3 (15)
Hypertension	171 (36)	10 (50)
Depression	144 (30)	8 (40)
Neuropathy	64 (14)	7 (35)
Diabetes (type 1 or 2)	62 (13)	–
Current non-HIV medicationsc
None	79 (17)	–
1–2	148 (31)	–
3–4	125 (26)	–
≥ 5	121 (26)	–
Number of ART regimens before switchd
1	122 (26)	2 (10)
2	129 (27)	2 (10)
≥ 3	223 (47)	16 (80)
ART regimen before switch
BIC/FTC/TAF	132 (28)	6 (30)
ABC/DTG/3TC	131 (28)	7 (35)
EFV/FTC/TDF	36 (8)	0
EVG/c/FTC/TAF	26 (5)	2 (10)
Othere	95 (20)	1 (5)
Don’t know or unknown	54 (11)	4 (20)
Months on previous ART before switch
< 3–6	58 (12)	–
7–12	68 (14)	–
13–24	114 (24)	–
> 24	234 (49)	–
Months taking DTG/3TC
3–6	80 (17)	–
7–12	101 (21)	–
13–24	118 (25)	–
> 24	175 (37)	–

Data are presented as mean (range) or n (%)

ABC abacavir, ART antiretroviral therapy, BIC bictegravir, c cobicistat, CAB cabotegravir, DOR doravirine, DRV darunavir, DTG dolutegravir, EFV efavirenz, EVG elvitegravir, FTC emtricitabine, RPV rilpivirine, TAF tenofovir alafenamide, 3TC lamivudine, TDF tenofovir disoproxil fumarate

^an = 461 for overall population

^bPercentages calculated using denominator n = 433 for overall population

^cIncludes prescribed, non-prescribed, and herbal medications. One participant responded “Don’t know” in overall population

^dExcludes pre- and post-exposure prophylaxis

^eFor the overall population, other includes but is not limited to FTC/RPV/TAF, DRV/c/FTC/TAF, FTC/RPV/TDF, EVG/c/FTC/TDF, CAB + RPV, DOR/3TC/TDF, and EFV/3TC/TDF (≤ 3% each). For the interview sub-population, other is FTC/RPV/TAF

Quantitative Survey Results

The median survey completion time was 22 minutes (interquartile range 17–30) for online surveys. Timing was not recorded for pen-and-paper surveys (n = 9).

DTG/3TC Switch

Conversations that led to a DTG/3TC switch were most often driven by specialists or other healthcare professionals (Fig. 2a). Regarding whether participants had pre-awareness before switching that DTG/3TC would reduce the number of drugs in their regimen, 71% (337/474) were informed by their doctor, whereas 4% (21/474) were unaware. Reducing the number of drugs became “extremely” or “very” important to participants (Fig. 2b) and was one of the top three reported reasons for switching (Fig. 2c). The other top reasons for switching included avoiding side effects (64% [294/462]) and minimizing long-term impacts of HIV (52% [242/462]). Overall, 87% (413/474) “agreed” or “strongly agreed” that less drug exposure with DTG/3TC is better for them in the long haul.

Fig. 2.

Participant perceptions and experiences before switching to dolutegravir (DTG)/lamivudine (3TC), including a primary driver of conversations leading to DTG/3TC switch, b importance of reducing drugs in HIV treatment, and c top three ranked factors influencing the switch to DTG/3TC. HCP healthcare professional

Treatment Satisfaction

The percentage of surveyed participants who reported being “very satisfied” (i.e., scored 6/6) with their previous ART was 31% (149/474), whereas 68% (324/474) reported being “very satisfied” with DTG/3TC (Fig. 3a); likewise, 18% (86/474) reported being “dissatisfied” (i.e., scored 0–2, where 0 indicates “very dissatisfied”) with their previous ART, compared with 3% (14/474) for DTG/3TC. Compared with their previous ART, 80% (379/474) reported that DTG/3TC was better, with 53% (252/474) reporting that DTG/3TC was “significantly better.” Most participants “agreed” or “strongly agreed” that DTG/3TC had a better impact on their overall health than 3DRs (83% [392/474]) and helped control HIV better than their previous regimen with fewer medicines (80% [380/474]; Fig. 3b). Overall, the reduced number of medicines improved treatment satisfaction to some extent (“slight” to an “extreme” extent) for 94% (447/474) of participants (“extreme” extent for 47% [221/474]).

Fig. 3.

Participant perceptions and experiences after switching to dolutegravir (DTG)/lamivudine (3TC), including a level of satisfaction with previous (left) and current (right) antiretroviral therapy (ART), where current ART scoring is the first HIV Treatment Satisfaction Questionnaire (HIV-TSQ) item; b level of agreement with statements related to previous ART; and c level of satisfaction across HIV-TSQ general, clinical, and lifestyle topics. 3DR 3-drug regimen, HIV-TSQ HIV Treatment Satisfaction Questionnaire

When treatment satisfaction was assessed using the 10-item HIV-TSQ, mean ± standard deviation (SD) total HIV-TSQ score was 54.5 ± 8.4 of 60 points (median 57.0 [interquartile range 52–60]), and ≥ 91% of participants were satisfied (i.e., scored 4–6, where 6 indicates “very satisfied”) for all 10 items. Mean total satisfaction scores were similar across sub-groups based on age, sex assigned at birth, race, and ethnicity (ranging from 53.2 ± 10.3 to 55.8 ± 5.7). The HIV-TSQ items with the highest percentage of participants scoring 4 to 6 were feeling that their HIV was well controlled (97% [460/474]), how satisfied they would be to continue receiving DTG/3TC (96% [456/474]), and how well treatment fits into their lifestyle (96% [454/474]). For the other HIV-TSQ items, 95% (449/474) found treatment to be convenient, 95% (448/474) were satisfied with DTG/3TC treatment demands, 93% (440/474) were satisfied with side effects, and 91% (433/474) found treatment to be flexible (Fig. 3c).

Overall, 3% (14/474) of participants scored HIV-TSQ treatment satisfaction as 0 to 2 (where 0 indicates “very dissatisfied”). Among these 14 participants, the most common reasons for DTG/3TC dissatisfaction were worrying about unintended disclosure of HIV status, worrying about effects on appearance, and disliking having to take a pill every day (Fig. 4).

Fig. 4.

Reasons (multi-selective) for treatment dissatisfaction among the 14 participants from the overall population who scored overall treatment satisfaction between 0 and 2 out of 6, where 0 is very dissatisfied and 6 is very satisfied, on the HIV Treatment Satisfaction Questionnaire (HIV-TSQ) (N = 474). DTG dolutegravir, 2DR 2-drug regimen, 3TC lamivudine

Adherence

Self-reported treatment adherence was high before and after the switch. In a typical 2-month period before switching, participants missed a mean of 1.8 ± 2.9 doses of previous ART (i.e., received 58.2/60 doses), and 43% (182/474) of participants recalled having complete adherence (i.e., missed no doses); in the past 2 months after switching, 1.7 ± 2.9 doses of DTG/3TC were missed (i.e., participants received 58.3/60 doses), and 47% (221/474) had complete adherence. The mean ADAQ score after DTG/3TC switch was 0.39 ± 0.37 on a scale of 0 (complete adherence) to 4 (complete non-adherence). Mean ADAQ scores were similar across sub-groups based on age, sex assigned at birth, race, and ethnicity (ranging from 0.32 ± 0.29 to 0.46 ± 0.42).

The most common (≥ 20%) reasons why 253 participants missed one or more doses of DTG/3TC within the past 2 months included forgetting (64% [161/253]), not having DTG/3TC with them at the time (34% [85/253]), and being too busy (30% [75/253]). Although 39% (99/253) of these participants had no suggestions for how adherence could be improved, others most frequently indicated (among multi-select options) that dosing reminders (30% [77/253]) and reduced dosing frequency (29% [73/253]) could improve adherence. From other survey questions among the overall population, 73% (348/474) of participants expressed “slight” to “extreme” fear of being rejected when someone learns about their HIV status, and 16% (75/474) had skipped a dose to avoid other people seeing.

Health-Related Quality of Life

Quality of life was generally high, with mean PozQoL summary scores of 46.5 ± 10.5 out of 65 overall, 15.7 ± 3.3 out of 20 on the psychological domain, 10.3 ± 3.5 out of 15 on the social domain, 8.8 ± 3.4 out of 15 on the health concerns domain, and 11.7 ± 3.5 out of 15 on the functional domain (n = 474 for all except overall summary score and social domain [n = 473 for both]). Mean PozQoL summary scores were similar across sub-groups based on age, sex assigned at birth, race, and ethnicity (ranging from 44.8 ± 10.5 to 48.2 ± 10.5), with most indicative of high quality of life (46–53) [8, 11]; however, moderate quality-of-life scores (37–45) [8, 11] were observed among participants aged < 50 years (44.8 ± 10.5) or who reported ethnicity as Latinx (45.4 ± 10.7).

After DTG/3TC switch, 76% (360/474) of participants agreed they had less interference with daily life/everyday activities. Moreover, most participants reported feeling “not at all” or “slightly” (69% [327/474]) worn out from managing their HIV, and 64% (302/474) were “very” or “extremely” optimistic about their future. However, concerns about general health varied, with 31% (145/474) indicating they were “not at all” or “slightly” worried about their health and 37% (174/474) indicating they were “very” or “extremely” worried. Others had monetary concerns; for instance, 18% (86/474) of participants reported “always” being worried about the cost of HIV treatment, and 14% (68/474) found living on total household income to be “very difficult” due to financial burden.

Qualitative Thematic Analysis

Interview durations ranged from approximately 40 to 75 minutes. Six distinct themes were identified via thematic analysis of the 20 in-depth interview transcripts (Fig. 5; ESM). Characteristics of this sub-population are in Table 1 and Fig. 1.

Fig. 5.

Thematic analysis methodology used to identify overarching themes and sub-themes from transcripts of in-depth qualitative interviews

Theme 1: Having a reduced number of medicines in HIV treatment is important to people with HIV because of the associated reduction in long-term drug exposure and the perception of lower risk of toxicities

In most cases, doctors instigated the discussion about DTG/3TC switch. A minority of participants were satisfied with their previous regimen and slightly hesitant to switch (“if it’s not broke, don’t fix it” [US05, US06]), but most would agree with their doctor’s rationale and make the decision to switch together. Other participants wanted to switch to a 2DR for the sake of longevity: “…I figured that it would be a little kinder to my kidneys and/or my liver, whichever one processes the medications. I’m going to be taking medications for the rest of my life. As I age, I’ll probably be taking other medications for this or that or whatever you take as you age. So, I figure the less medication I need to put into my system, probably the better” (US10).

Nearly all interviewed participants knew that DTG/3TC had fewer drugs than their previous regimen. Whereas most knew this from discussions with their doctor, others learned via magazine articles, sponsored presentations, television advertisements, friends, and seminars: “[The doctor] let me know what was in it. But [as] far as the other medications and stuff like that, I used to go to… I don’t want to call it a seminar. But little get togethers where they all sit down and talk to us about, educate us on what’s going on, medications and stuff. I honestly paid attention. I learned a lot. And I noticed where they have different medications just in that one pill” (US01).

Participants felt it was important to reduce cumulative exposure to drugs and lessen the accompanying burden on their body from perceived toxicities. The number of drugs was viewed in the context of HIV being a lifelong treatment, with participants proactively thinking about how age-related comorbidities may require them to take additional drugs in the future:

“I would say at one point, it didn’t matter. But now that I’m getting older and I have a brand-new primary care provider, the first thing she said when she met me was… ‘You’re on a lot of medications. Let’s try to reduce this.’ So that emphasized to me the importance of lowering my number of medications” (US17).

“…the more drugs you take, the more you have to worry about internal functions like your liver or your kidneys, your heart, your cholesterol, just other stuff. That’s really important to me” (US19).

Other reasons for switching to a 2DR included wanting to avoid toxicities from either a previous regimen or a developing or worsening concomitant condition, especially regarding vital organ function: “I was on a medication, [BIC/FTC/TAF]. I gained a lot of weight. There were some irregularities in my labs with regards to my kidneys. My physician suggested that I change. She said it was more important to be on a drug that had less impact on my kidneys. I also am a diabetic. She suggested that we change, and I did” (US12).

When prompted, almost all participants stated they would be happy to remain on DTG/3TC long-term. However, two participants perceived that the effectiveness of regimens is reduced over time and preferred to switch regimens every so often.

Theme 2: Overall, there was very high satisfaction with DTG/3TC, largely due to expectations being met regarding efficacy and safety

Participants from the interview sub-population were largely satisfied with DTG/3TC. A common area of satisfaction was treatment efficacy. All participants self-reported undetectable viral loads (“numbers are good”), and CD4+ T-cell counts were perceived to fluctuate less often:

“The experience is better. I’ve been undetected. I don’t have any side effects, no stomach issues, none of that other stuff. I don’t have [any] problems with it” (US01).

“I think [my numbers] aren’t bouncing around. Not just the CD4 but the percentage, which, I’ve been told, is more important than the actual number” (US17).

Another common area of satisfaction was the reduction of perceived toxicities and side effects with DTG/3TC. Specifically, improvements in weight maintenance and stomach/gastrointestinal, bone, and kidney issues were noted:

“[Fewer] side effects as far as the stomach issues. No nightmares has made my life better. You know what I mean? I don’t dread taking the medication, so it does make a difference” (US02).

“…I’ve been excellent in that regard. It went from one extreme…3 different side effects for one medicine, on to [DTG/3TC] and to have them all erased. You know what I mean? It’s like I have a clean slate here” (US20).

The convenience and flexibility of DTG/3TC dosing was another area of satisfaction that improved quality of life for interviewed participants, who no longer had to worry about taking their pill at a certain time or with a meal. Furthermore, the smaller pill size of DTG/3TC relative to ABC/DTG/3TC and cobicistat-boosted elvitegravir (EVG/c)/FTC/TAF was appreciated:

"There is life with HIV. And [DTG/3TC] is assisting to help with the quality of life. [Laughter] If it wouldn’t be for [DTG/3TC], where would I be?” (US11).

“The pill wasn’t huge. It was smaller in size …That’s not [something] that everyone thinks about. When you live with a medication, it’s part of your life. You look at all these things” (US13).

When prompted to provide negative aspects of their experience with DTG/3TC, one participant felt that the once-daily dosing frequency could be improved; one participant reported a reduction in CD4+ T-cell count (by 200–250 cells/mm³) and side effects (fatigue, headaches); and one participant indicated that DTG/3TC did not meet expectations because, although their viral load remained undetectable, their CD4+ T-cell percentage plateaued at 25% after an initial increase. Several participants who were satisfied with DTG/3TC noticed few or no differences from their previous ART.

Theme 3: DTG/3TC offers simplicity and is a convenient treatment; this has enabled people with HIV to have more freedom and autonomy in their daily life compared with prior ART

Greater convenience with DTG/3TC was attributed to factors such as not having to take the pill with a heavy meal, treatment “forgiveness” or flexibility to catch up on missed or late doses, pill storage, and once-daily single-tablet dosing:

“You don’t have to…you could take it with or without food, which is a very big plus. That’s an important factor … I just get up every morning and just pop my pill with a glass of water and I’m good to go. Not worrying that I have to eat breakfast … not having to eat at 6:00 in the morning” (US23).

“Say I’m going away for a while. I could just put it in my pocket and know that, hey, it’s right there and it’s not a big bottle like some of my old medicines I used to take. I don’t have to refrigerate it. That’s a good thing” (US03).

“[It’s] easy to take. If I do miss a dose or if I miss the time I usually take it, there’s not a problem with me taking it later that day… If I missed within 3 or 4 hours, or even later, it has no problem. I can get right back on the cycle the next day” (US11).

Participants felt they could tailor their medication to their lifestyle, with more autonomy and freedom over when and how to take their medication. Once-daily dosing was “easy,” “simple,” and “manageable,” and they could focus on other aspects of life after taking their pill for the day:

“Easy, one pill a day, and no issues… [It’s] very important. Life’s busy and crazy enough” (US05).

“It's been simplified, and I appreciate how simple it is to take my medicine every day. I’m really grateful for that because it makes it easier for me” (US06).

Theme 4: Advancement in treatment (including DTG/3TC) has led to HIV no longer being a “death sentence,” which, for many people, gives them peace of mind when managing their HIV

Participants felt that DTG/3TC met all their expectations, even among those who were satisfied with their previous ART and hesitant to switch. They expressed gratitude for the reduced numbers of drugs and pills in HIV treatments available today (described as a “blessing” and having “come a long way”) and could do more with friends and family because DTG/3TC reduced side effects experienced with prior ARTs: "Okay, number one, that I’m grateful to, first to God, and then the people who make [DTG/3TC]. It can make me do whatever I want to do. I can live a normal life. I can take it with food, and not with food. I can do things with everyone in the family. It made my life easy […and I can] do what I want to do. It’s one of the best” (US16).

A minority mentioned harsh side effects they experienced from older therapies (e.g., azidothymidine [AZT]) or family or friends who passed away from AIDS in the 1980s and 1990s, which are experiences that may be exclusive to older individuals:

“What I don’t appreciate is how difficult it was in the beginning and how terrible side effects were. I wasn’t in the early, early years of AIDS when people only had AZT. But I still had a few very bad [sic], with lipodystrophy, lipoatrophy, exhaustion, headache, etc. So, I appreciate how far it has come” (US17).

“I can’t think of any negatives currently. I had so many friends die in the '90s that I feel blessed that I’m where I am and can live almost a normal life with this disease at this point” (US04).

HIV was no longer perceived as a “death sentence,” and HIV control was no longer a frequent cause of worry (“no news is good news”): “I appreciate the fact that there is medication that is effective. Because I remember when there wasn’t. Back in the day, you were here today and gone tomorrow, literally” (US02). However, some participants expressed concerns about whether newly diagnosed individuals would take medication compliance seriously or become complacent with the advanced treatments available today.

Theme 5: HIV is no longer the main health concern and DTG/3TC complements the management of other diagnosed health conditions, enabling people with HIV to better focus on their overall health

Interviewed participants were less worried about their HIV than their other health conditions, including long-COVID, osteoporosis, depression, diabetes, chronic pain, and psoriasis. With HIV being less of a burden, other health conditions and overall health could be prioritized:

“It’s allowed me to focus on my diabetes and my weight. I’ve lost 19 pounds and I’ve reduced my insulin and my other diabetes treatments… [it] makes me feel good. It makes me feel that I have a little more control going forward with my health overall” (US12).

“It’s the other issues, physical health issues that I have that’s taking its toll. It kind of supersedes the HIV. The HIV’s not the issue” (US02).

Moreover, interviewees felt it was important to reduce the number of their HIV medicines because they were already taking medicine for other comorbid conditions: “It’s important because I take more than HIV medicine. Since being positive, it has affected my blood sugar. So, I’m taking a lot of other medicine, in addition to the HIV. So, I’m ingesting a lot of toxins. I’m concerned about that …It was important for me to have [fewer] toxins going into my body” (US20).

Theme 6: There remain some unmet treatment needs, short of a cure, in the HIV space

Most unmet needs cited among the interview sub-population centered on the psychological effects of being reminded daily of their HIV status: “I feel like I’m on pill overload. It’s a constant reminder. It’s a daily reminder that I’m living with this chronic illness. So that kind of gets on my nerves” (US20).

Many participants raised the ongoing issue of stigma around HIV and were self-conscious about taking their medication in public or around others. Some indicated that treatment with a reduced frequency of dosing (e.g., monthly or every 6 months) would be appreciated, provided that efficacy and safety were not compromised: “It’s second nature, but it’s not natural. A treatment, say a pill once a month or an injection once a month or every 6 months, that would just change a little bit of the psychology around the illness for me” (US12).

Although most participants were satisfied with the DTG/3TC pill, one thought it could be smaller. Moreover, some participants suggested alternative administration routes (e.g., patches, lozenges, nasal spray). A few participants indicated they would opt for an injectable regimen with a reduced dosing frequency and were considering the long-acting injectable CAB + RPV, though others who did not like injections did not feel like it was right for them: “I couldn’t commit to [CAB + RPV], so then I went on to [DTG/3TC]” (US20).

Discussion

The PAIRED study surveyed and interviewed a representative sample of people with HIV across the USA who switched to DTG/3TC to understand their treatment experiences. Quantitative data were acquired using validated instruments [6–8]. Participants were highly satisfied with treatment, as shown by good adherence and high quality-of-life scores. Open-ended, in-depth interviews provided additional perceptiveness regarding treatment expectations and experiences of people with HIV that otherwise could not be captured through the finite topics and choices of surveys and questionnaires. These qualitative data gave a voice to participants to better understand influential factors prompting the switch to DTG/3TC, treatment satisfaction, and unmet needs.

When considering whether to switch to DTG/3TC, many participants felt it was important to reduce the number of drugs in their regimen without having to compromise on efficacy or safety (theme 1). In most cases, healthcare professionals instigated conversations about switching to DTG/3TC and educated participants that switching would reduce the number of drugs in their regimen. Once participants were informed, treatment simplification with fewer drugs became a very important treatment consideration as a means of mitigating perceived toxicities and lowering overall drug exposure. Interviewed participants considered the benefits of drug simplification in the long term and wanted to reduce their cumulative exposure to drugs, acknowledging that the need for additional non-HIV medications is likely to increase with age. Indeed, explanations from interviewed participants corroborate published findings that polypharmacy is a growing concern among people with HIV [12].

After switching to DTG/3TC, participants had high satisfaction levels regarding HIV control, side effects, and treatment fitting into their lifestyle, and improvements were noted in convenience and peace of mind (themes 2–5). The percentage of participants who reported being “very satisfied” with treatment more than doubled from 31% with previous ART to 68% after switching to DTG/3TC. Mean self-reported adherence levels were high (0.39 ± 0.37 on a scale of 0 [complete adherence] to 4 [complete non-adherence]), and the overall mean PozQoL score was 46.5 ± 10.5 out of 65, indicative of high quality of life with DTG/3TC. These results are consistent with the significant positive association between ART satisfaction and complete adherence observed in a study of people with HIV in the USA who participated in the Adelphi Real World HIV Disease Specific Programme™ [13]. In this study, participants with complete adherence had a significantly higher mean PozQoL score than did participants who were mostly adherent or less adherent, primarily driven by differences in the psychological domain (14.7 vs 11.6 and 11.1 [out of 20], respectively) and functional domain (11.9 vs 10.5 and 9.9 [out of 15], respectively). PozQoL psychological and functional domains were also high (15.7 and 11.7, respectively) in PAIRED. Thus, ART must meet the expectations and needs of people with HIV to keep treatment satisfaction high, enhance quality of life, and encourage optimal adherence.

Given the high rates of DTG/3TC satisfaction, there were few unmet needs in the overall population and interview sub-population (theme 6). Areas for improvement were the broader psychological concerns of stigma and of treatment being a daily reminder of HIV status, which were captured in qualitative interviews. Alternative methods of administration could help meet these needs, such as injectable regimens that have less frequent dosing. For example, in the phase IIIb CUSTOMIZE study, participants who switched to monthly CAB + RPV long-acting injections had mean increases from baseline (60.7 of 66 points) on the 12-item HIV-TSQ of 1.5 points after 4 months and 2.6 points after 12 months [14].

Discussions enriched quantitative survey answers with additional context and uncovered topics that were not present in quantitative data. For instance, participants could clarify why they had a high level of agreement about treatment convenience in the survey; for some, convenience meant discretionary storage or fewer dose restrictions (e.g., flexible dose timing, not having to take DTG/3TC with food). Interviews revealed that HIV was less of a burden with DTG/3TC, and participants could thus focus on treating other comorbidities or overall health. Participants who were familiar with the challenges of early ART were grateful for HIV treatment advancements but worried about whether newly diagnosed individuals would take current therapies for granted or become complacent with sub-optimal adherence.

Historically, certain demographics have been underrepresented in phase III HIV trials [15, 16]. PAIRED recruited a population representative of the demographics of the US population with HIV. Of people with HIV aged ≥ 13 years at year end of 2022 in the USA (estimated N = 1,238,000), estimated race/ethnicity was 40% Black/African American (PAIRED, 33%) and 26% Hispanic/Latin American (PAIRED, 34%); 22% were assigned female sex at birth (PAIRED, 31%); 38% were aged ≥ 55 years (PAIRED, 50% aged ≥ 50 years); and 47% resided in the South (PAIRED, 57%) [17]. In PAIRED, 49% of participants were recruited by community outreach, thus lending greater representation of non-consulting, harder-to-reach individuals (e.g., those not actively seeking treatment in a clinic at the time of the survey).

PAIRED also has limitations that should be acknowledged. First, treatment bias may limit the generalizability of results to a broader population. People living in non-US countries, receiving DTG/3TC as first-line ART, or who discontinued DTG/3TC were not included; however, the study population was representative of people with HIV in the USA, and discontinuation rates for any reason are expected to be low based on rates from the phase III SALSA (6% [14/246] through week 48) and TANGO (17% [62/369] through week 196) studies [3, 5].

Second, participants receiving DTG/3TC for > 3 months may be predisposed to report positive experiences and greater satisfaction, as treatment satisfaction significantly correlated with time on current treatment in studies of people with HIV initiating first-line ART [18] and people managing other chronic conditions [19]. Discontinuation of DTG/3TC at ≤3 months is expected to have minimal impact in PAIRED. Few participants discontinued for treatment-related reasons in SALSA (2% [4/246]) and TANGO (2% [9/369]) at or before a longer initial time period, 48 weeks (data on file), consistent with observational studies such as TANDEM (2% [3/192] of people in the suppressed-switch cohort discontinued after a median of 30 weeks) [20]. Using those proportions, an estimated 2% (10/474) of PAIRED participants would have discontinued for treatment-related reasons within 48 weeks.

Third, cross-sectional studies describe a single snapshot in time and cannot attribute cause-and-effect relationships. Fourth, qualitative research is by nature subjective (researcher bias, beliefs, and values are fundamentally intertwined with the research process); however, trustworthiness and credibility are garnered by involving multiple analysts in data interpretation, from the initial independent transcript reviews to reflexive discussions of their interpretations throughout the process [21, 22]. To further strengthen rigor, a structured codebook was applied and dual independent coding was undertaken, with consistency across coders reviewed and discussed. Finally, the HIV-TSQ and ADAQ have no standardized scoring interpretation; however, the median HIV-TSQ satisfaction score of 57 (of 60) observed in this study can be interpreted as high with relative confidence. The standardized interpretation of the PozQoL summary score was derived from a study of an Australian population primarily comprising Anglo-Celtic or European individuals (72%) and gay or bisexual men who have sex with men (88%), demographics of which may be similar to some but not all the representative demographics of the US sample in PAIRED, thus limiting generalizability [8, 11].

Conclusion

A large and representative US population of adults with HIV had overall positive experiences and high treatment satisfaction after switching their ART to DTG/3TC, which in turn is compatible with high levels of adherence. These outcomes supplement results from clinical trials and support that DTG/3TC is effective and well tolerated in real-world clinical settings, including in populations often underrepresented in clinical trials.

Supplementary Information

Below is the link to the electronic supplementary material.

Funding

This study was funded by ViiV Healthcare.

Declarations

Conflicts of Interest

JS has served as the principal investigator for clinical trials for which his institution received grants and has received honoraria from AbbVie, Gilead, Janssen, Merck, Theratechnologies, and ViiV Healthcare. APB and DM are employees of ViiV Healthcare and own stock in GSK. GH, KM, and AM are employees of Adelphi Real World, which was contracted by ViiV Healthcare for this analysis. GV is an employee of ViiV Healthcare.

Ethics Approval

Ethics approval to conduct this study was granted by Western Institutional Review Board (tracking reference, 20224682).

Consent to Participate

All participants provided informed consent to participate in surveys and interviews.

Consent for Publication

All participants provided signed consent to publish anonymized findings before surveys and interviews were conducted.

Data Availability

Anonymized individual participant data and study documents can be requested for further research from www.clinicalstudydatarequest.com.

Author Contributions

GH, KM, AM, DM, and GV contributed to the conception of the study. APB, GH, KM, AM, DM, and GV contributed to the design of the study. JS, GH, KM, AM, and DM contributed to the acquisition of data. APB, GH, KM, AM, DM, and GV contributed to the analysis of data. All authors contributed to the interpretation of data, drafting the manuscript, and critically revising the manuscript for important intellectual content. All authors approved the manuscript for publication.