Participant-reported Outcomes from the CAPELLA Clinical Trial of Lenacapavir-based Regimens in Heavily Treatment-experienced Adults with HIV

Abstract

Lenacapavir, a first-in-class inhibitor of HIV-1 capsid function, can be administered twice yearly subcutaneously (SC). In the ongoing Phase 2/3 CAPELLA study (NCT04150068), the addition of SC lenacapavir to an optimized background regimen led to high rates of virologic suppression and was generally well tolerated. We describe participant-reported, health-related quality-of-life (HRQoL) outcomes with lenacapavir among heavily treatment-experienced people with HIV (PWH) from CAPELLA. Scores from EQ-5D-5L index and visual analogue scale (VAS), Short Form 36 (SF-36), HIV-Symptom Index (HIV-SI), and Numeric Pain Rating Scale (NPRS) at injection were collected. Mean baseline and week (W) 52 scores were: EQ-5D-5L index, 0.87 and 0.83; EQ-5D-5L VAS, 81 and 86; SF-36 physical component, 48.5 and 49.9; SF-36 mental component, 48.4 and 48.0. Scores remained stable over time (< 7% change), with values near US norms. For 15 of 20 HIV-SI symptoms, fewer participants reported them as bothersome at W52 than at baseline. Mean NPRS scores on injection were 3.9, 5.1, and 4.4 at first (W0), second (W26), and third injection (W52). Participants on lenacapavir-based regimens demonstrated stability or improvement in HRQoL and other outcomes, with fewer participants reporting bothersome HIV symptoms. These data can help clinicians address individuals’ needs and medication preferences while achieving sustained virologic suppression in heavily treatment-experienced PWH.

Supplementary Information

The online version contains supplementary material available at 10.1007/s10461-025-04625-x.

Introduction

HIV afflicts approximately 421 people per 100,000 in the US [1]. The standard of care for most people with HIV (PWH) who are initiating therapy is a once-daily (QD) integrase strand transfer inhibitor–based regimen combined with 1 or 2 nucleoside(tide) reverse-transcriptase inhibitors [2, 3]. Significant advances in the potency and tolerability of antiretroviral (ARV) therapy have led to high rates of virologic success for most who remain adherent to treatment. However, there remain a small number of PWH for whom reaching and maintaining virologic suppression (VS) is a challenge.

There are limited treatment options for PWH who are heavily treatment experienced (HTE)—those who are unable to achieve VS with combination ARV therapy due to multidrug resistance, intolerance, or safety concerns. Optimized regimens for HTE PWH are complex, individualized, and based on treatment history and resistance tests [4]. Such regimens can include multiple partially efficacious drugs to maximize the probability of achieving VS, and dosing/scheduling can be inconvenient [5].

PWH who are HTE with multidrug-resistant HIV often have low cluster of differentiation (CD) 4+ T-cell counts, indicating an impaired immune system and progression toward AIDS [6]. Low CD4+ counts have a negative impact on health and health-related quality-of-life (HRQoL), increasing the risk of opportunistic infections; comorbidities, including malignancies; and death [7, 8, 9, 10, 11]. Consequently, the care of these individuals imposes a disproportionate economic burden compared with the general population of PWH [10, 11]. There is a need for novel therapeutic options for this difficult-to-treat population that are more convenient, are less frequently administered, and lack cross-resistance with other ARV drugs.

Lenacapavir is a potent, first-in-class inhibitor of HIV-1 capsid function that disrupts multiple stages of the HIV-1 lifecycle, and its activity is not affected by resistance mutations to the 4 main ARV drug classes [12]. Lenacapavir achieved high rates of VS and was well tolerated at week 52 when administered every 6 months (Q6M) subcutaneously (SC) with an optimized background regimen (OBR) in a Phase 2/3 study (CAPELLA; NCT04150068) of PWH who were HTE [13, 14, 15]. Similarly, in a randomized, open-label, Phase 2 induction-maintenance study (CALIBRATE; NCT04143594), lenacapavir given Q6M SC or orally QD as part of combination regimens in treatment-naïve PWH led to high rates of VS and was safe and well tolerated [16].

In addition to improving clinical measures of disease activity, it is important to consider HRQoL outcomes when evaluating and differentiating treatment strategies for PWH. We report on participant-reported outcomes among a population of PWH who were HTE in the CAPELLA clinical trial of SC lenacapavir–based regimens.

Materials and Methods

Study Design

Full methodology describing the CAPELLA study was published elsewhere [15]. Briefly, eligible participants had ≥ 400 copies/mL of HIV-1 RNA, resistance to at least 2 agents from 3 of 4 main ARV classes, and at most 2 fully active agents in their current regimen. Before randomization, HIV-1 RNA measurements were repeated. If participants showed a decline of ≥ 0.5 log₁₀ copies/mL (vs. screening) or a viral load < 400 copies/mL, they entered Cohort 2; participants who did not achieve these thresholds entered the double-blind Cohort 1 (Supplementary Fig. 1). Participants were assigned (2:1) to add oral lenacapavir (600 mg on days 1 and 2; 300 mg on day 8) or placebo to their failing regimen. At day 15, participants on oral lenacapavir received SC lenacapavir 927 mg Q6M; those on placebo started the 2-week oral lenacapavir lead-in followed by SC lenacapavir Q6M. Participants also received an OBR at day 15 until end of study in place of the failing regimen. In the open-label Cohort 2, participants received the oral lenacapavir lead-in alongside an OBR and switched to SC lenacapavir 927 mg Q6M plus OBR at day 15. The study’s primary endpoint was the proportion of participants who had a reduction from baseline of ≥ 0.5 log₁₀ copies/mL in plasma HIV-1 RNA viral load by day 15 (end of the functional monotherapy period); VS was examined at later timepoints [15].

The trial was approved by the institutional review board or ethics committee at each site and was conducted in compliance with international laws and guidelines. All participants provided written informed consent. The CAPELLA study (GS-US-200-4625) was reviewed by Advarra, Inc., Columbia, Maryland (Protocol ID Pro00039525), and by local IRB/ethics committees as needed.

Participant-reported Outcome Measures

The EQ-5D-5L is a widely used generic questionnaire and standardized measure of HRQoL [17]. Briefly, scores for each dimension (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) are transformed into index scores (1 = best possible health, 0 = equivalent to death, negative scores imply HRQoL worse than death) via the US composite time trade-off value, which ranges from − 0.573 (55555) to 1 (11111) [18]. Additionally, a visual analogue scale (VAS) asks to indicate, “How good or bad your health is today” (100 = best, 0 = worst). EQ-5D-5L index and VAS scores were measured at baseline (day 1 of the trial) and weeks 4, 16, 26, and 52.

The Short Form 36 (SF-36) version 2 is a 36-item, self-reported, and well-validated instrument that assesses functional health and well-being across age groups and disease states [19]. The questionnaire yields an 8-domain profile of scores, psychometrically based physical and mental component summary scores, and a preference-based health utility index. Scores for each of the 8 domains and the 2 component scores range from 0 to 100, with higher scores indicating better functioning than lower scores. SF-36 scores were measured at baseline (day 1 of the trial) and weeks 4, 16, 26, and 52.

The HIV Symptom Distress Module/HIV-Symptom Index (HIV-SI) is a validated instrument that assesses 20 common symptoms associated with HIV treatment or disease [20]. Participants self-report on a 5-point Likert-type scale (0–4), with higher scores indicating more bothersome symptoms and 0 indicating the symptom is not experienced. The HIV-SI was measured at baseline (day 1 of the trial) and weeks 4, 16, 26, and 52.

The Numeric Pain Rating Scale (NPRS) statement, “Please rate your pain at the time you received your most recent injection by circling the box that best describes it,” provides insight into the pain intensity at the time of the most recent injection via a VAS. The NPRS is a validated instrument, with higher scores (0–10) indicating worse pain [21]. Pain ratings were measured at baseline (day of first injection) and weeks 26 and 52.

Statistical Analysis

The safety analysis set (SAS) was used for all analyses and included all randomized participants who received at least one dose of study drug.

EQ-5D-5L

For the descriptive scores, the number and percentage of participants in the SAS with a response on the 5 dimensions are summarized by treatment group and by baseline result for each visit. The percentages are provided for nonmissing categories, and the denominator is the number of participants with nonmissing values at both baseline and each postbaseline visit for each baseline category. No inferential statistics were performed. For the EQ-5D-5L summary index score and EQ-5D-5L VAS score, change from baseline is summarized at each visit by treatment group. Mean (95% CI) of the score and change from baseline in EQ-5D-5L index score and EQ-5D-5L VAS score are plotted by visit. The minimal important change (MIC) is the smallest change over time in a participant-reported outcome score that reflects a meaningful difference within a group of participants. For the EQ-5D-5L index and VAS scores, established MICs (0.063 and 7, respectively) were used to interpret meaningful changes [22, 23].

SF-36

Eight domain scores were calculated from reported scores for 35 of 36 individual items: Physical Functioning, Role Physical, Bodily Pain, General Health Perceptions, Vitality, Social Functioning, Role Emotional, and Mental Health. The unused item, Item 2, is normally used as the Health Transition score indicating participants’ general health status at a given timepoint compared to before that timepoint. The 2 summary scores, the physical component summary score and mental component summary score, were generated from the aggregate information of the 8 SF-36 domains. The change from baseline in transformed scores for the 8 domains and 2 component summary scores of the SF-36 are summarized at each visit by treatment group. No inferential statistics were performed. Mean (95% CI) of the score and change from baseline in the 8 domains and 2 component summary scores of the SF-36 are plotted by visit. For SF-36 physical component and mental component scores, established MICs (2 and 3, respectively) were used to interpret meaningful changes [24].

HIV-SI

For each question, the numeric responses are summarized by treatment group at baseline using descriptive statistics. The number and percentage of participants with no symptom (i.e., response = 0: “I don’t have this symptom”) and with symptoms (i.e., response = 1: “I have this symptom, and it doesn’t bother me,” 2: “I have this symptom, and it bothers me a little,” 3: “I have this symptom, and it bothers me,” or 4: “I have this symptom, and it bothers me a lot”) are summarized by treatment group and visit. Consistent with prior analyses, responses were dichotomized to 0 or 1 (not bothersome) and 2, 3, or 4 (bothersome) and identify and describe specific symptoms that may reflect underlying clinical phenomena for the purposes of targeted intervention [20, 25].

NPRS

The change from baseline in NPRS score is summarized by treatment group and visit using descriptive statistics. Mean (95% CI) of the score and change from baseline in NPRS score are plotted by visit. An established MIC of 2 points was used to interpret significant changes in NPRS score [21].

Results

Baseline Demographics and Clinical Characteristics

Full demographics for the CAPELLA study are published [15]. A total of 72 participants were enrolled, with each cohort consisting of 36 participants. Treatment arms in Cohort 1 were well balanced, with the exception of a numerically greater median CD4+ count at baseline in participants who received lenacapavir vs. placebo (Table 1). Median age (range) of lenacapavir-treated vs. placebo-treated participants was 55 (24–71) years vs. 54 (27–59) years. The most common ongoing medical conditions at baseline were hypertension (36%), depression (25%), and diarrhea (25%) for Cohort 1, and hypertension (33%), hypercholesterolemia (17%), and herpes simplex (14%) for Cohort 2 (Supplementary Table 1). Overall, the characteristics of the participants in Cohort 1 were similar to those in Cohort 2.

Table 1.

Baseline demographics and clinical characteristics of participants in CAPELLA [15]

Characteristic	Cohort 1		Cohort 2	All
	Lenacapavir (n = 24)	Placebo (n = 12)	Lenacapavir (n = 36)	Participants (N = 72)
Age, years, median (range)	55 (24–71)	54 (27–59)	49 (23–78)	52 (23–78)
Sex, female	7 (29)	3 (25)	8 (22)	18 (25)
Race
Black	10 (42)	6 (55)	11 (31)	27 (38)
White	12 (50)	4 (36)	13 (36)	29 (41)
Asian	2 (8)	1 (9)	12 (33)	15 (21)
Data could not be collected	0	1 (9)	0	1 (1)
Viral loada, log10 copies/mL, median (range)	4.2 (2.3–5.4)	4.9 (4.3–5.3)	4.5 (1.3–5.7)	4.5 (1.3–5.7)
CD4+ count, cells/mm3, median (range)	172 (16–827)	85 (6–237)	195 (3–1296)	150 (3–1296)
< 200 cells/mm3	16 (67)	11 (91)	19 (53)	46 (64)
Resistance to ≥ 2 drugs in major class
NRTI	23 (96)	12 (100)	36 (100)	71 (99)
NNRTI	22 (92)	12 (100)	36 (100)	70 (97)
Protease inhibitor	20 (83)	8 (67)	30 (83)	58 (81)
INSTI	20 (83)	7 (58)	23 (64)	50 (69)
All 4 major classes	14 (58)	3 (25)	16 (44)	33 (46)
Resistance to entry inhibitor
Enfuvirtide	2/23 (9)	3/10 (30)	0/25 (0)	5/58 (9)
Fostemsavir	5/23 (22)	5/10 (50)	7/21 (33)	17/54 (31)
Ibalizumab	8/23 (35)	3/10 (30)	6/25 (24)	17/58 (29)
Maravirocb	19/24 (79)	8/11 (73)	14/26 (54)	41/61 (67)
Composition of OBR
NRTI	23 (96)	9 (75)	29 (81)	61 (85)
INSTIc	16 (67)	9 (75)	22 (61)	47 (65)
Protease inhibitorc	12 (50)	9 (75)	24 (67)	45 (62)
NNRTI	6 (25)	4 (33)	14 (39)	24 (33)
Ibalizumab	9 (38)	3 (25)	5 (14)	17 (24)
Maraviroc	2 (8)	4 (33)	4 (11)	10 (14)
Fostemsavir	3 (12)	0	5 (14)	8 (11)
Enfuvirtide	1 (4)	2 (17)	2 (6)	5 (7)
Median overall susceptibility score of OBR d	2.0	1.3	2.0	2.0
Number of fully active agents in the OBR
0	4 (17)	2 (17)	6 (17)	12 (17)
1	7 (29)	7 (58)	13 (36)	27 (38)
≥ 2	13 (54)	3 (25)	17 (47)	33 (46)

Data are n (%) unless otherwise specified

^aTwo participants in Cohort 2 had a viral load of more than 400 copies/mL at screening but less than 50 copies/mL at enrollment. ^bSusceptibility to maraviroc was assessed by means of the profile coreceptor tropism assay (Monogram Biosciences), which indicates whether the activity of maraviroc is anticipated on the basis of coreceptor use (CCR5, CXCR4, or dual mix). Of the 72 participants in this category, 24 (33%) received dolutegravir twice a day and 22 (31%) received darunavir twice a day. ^dThe drug susceptibility score to an individual antiretroviral medication was deemed according to a proprietary algorithm, with 1.0 = full susceptibility, 0.5 = partial susceptibility, and 0 = no susceptibility. The overall susceptibility score of the optimized background therapy was the sum of the individual scores. For historical resistance reports, the scores were derived from data provided by the investigators

CD, cluster of differentiation; CCR5, C-C chemokine receptor type 5; CXCR4, C-X-C chemokine receptor type 4; INSTI, integrase strand transfer inhibitor; NNRTI, non-nucleoside reverse-transcriptase inhibitor; NRTI, nucleoside reverse-transcriptase inhibitor; OBR, optimized background regimen

From New England Journal of Medicine, Segal-Maurer S, et al., for the CAPELLA Study Investigators; Capsid Inhibition with Lenacapavir in Multidrug-Resistant HIV-1 Infection, Volume 386, Page 1793–1803. Copyright © 2022 Massachusetts Medical Society. Reprinted with permission

EQ-5D-5L

Among all participants, the mean EQ-5D-5L index score was 0.870 (compared with the US norm of 0.851) [26], and the mean VAS score was 81.0 (compared with the US norm of 80.4) [26] at baseline (Fig. 1). The mean change from baseline values for the EQ-5D-5L index and VAS scores were − 0.06 and 3, respectively, at week 52. Both mean scores remained stable; no group mean changes represented meaningful change, as mean scores stayed within the MIC thresholds for improving or worsening.

Fig. 1.

Mean EQ-5D-5L index scores (A) and VAS scores (B) by visit (SAS). BL refers to day 1 of the trial. Higher EQ-5D-5L scores indicate better quality of life. BL, baseline; SAS, statistical analysis set; VAS, visual analogue scale

SF-36

At baseline, the mean SF-36 physical component summary score was 48.5, and the mean SF-36 mental component summary score was 48.4 (compared with US norms of 50 for both component scores) [19] (Fig. 2). Both component summary scores remained stable over time, with the week 52 change from baseline values being 1.0 and − 0.9 for the physical and mental component scores, respectively.

Fig. 2.

Mean SF-36 physical component summary scores (A) and mental component summary scores (B) by visit (SAS). BL refers to day 1 of the trial. Higher SF-36 scores indicate better functioning than lower scores. BL, baseline; SAS, statistical analysis set; SF-36, Short Form 36

HIV Symptom Distress Module/HIV-SI

The proportion of participants who reported symptoms as bothersome decreased over time (Fig. 3). For 15 of 20 HIV-related symptoms assessed via the HIV-SI, fewer participants reported bothersome symptoms at week 52 than at baseline. For 10 of 20 symptoms—fatigue or loss of energy; feeling dizzy or lightheaded; diarrhea/loose bowels; feeling sad, down, or depressed; feeling nervous or anxious; cough or trouble catching breath; muscle aches or joint pain; changes in body shape or weight; problems with weight loss; and hair loss—the proportion of participants reporting those symptoms as bothersome was decreased by ≥ 5% at week 52 vs. baseline. In contrast, for only 2 symptoms—pain, numbness, or tingling in hands or feet (21% increase) and headache (5% increase)—did the proportion of participants reporting them as bothersome increase ≥ 5% from baseline to week 52. The greatest decrease in the proportion of participants who reported symptoms as bothersome occurred with fatigue or loss of energy (− 15%), feeling nervous or anxious (− 14%), and muscle aches or joint pain (− 10%). The 8 remaining symptoms—fevers, chills, or sweats; trouble remembering; nausea or vomiting; difficulty falling asleep; skin problems; loss of appetite; bloating/pain in stomach; and problems with having sex—did not have an increase or decrease of ≥ 5% in the proportion of participants reporting those symptoms as bothersome.

Fig. 3.

The proportion of individuals who reported each symptom as at least a little bothersome (HIV-SI ≥ 2) among all participants. ^* ≥ 5% decrease at week 52 vs. baseline. ^† ≥ 5% increase at week 52 vs. baseline. Baseline refers to day 1 of the trial. Percentages in the plot are based on participants responding with 2 (“it bothers me a little”), 3 (“it bothers me”), and 4 (“it bothers me a lot”) on the HIV-SI response scale. HIV-SI, HIV-Symptom Index

NPRS

Mean ± SD NPRS scores were stable over time and ranged from 3.9 ± 3.4 to 5.1 ± 3.2 through week 52 (Fig. 4); individual scores were highly variable (data not shown). Based on the MIC threshold, mean changes from baseline in NPRS score did not represent meaningful change.

Fig. 4.

Mean NPRS scores. BL refers to day 1 of the first SC injection. Higher NPRS scores indicate worse pain. BL, baseline; NPRS, Numeric Pain Rating Scale; SC, subcutaneous

Discussion

In this trial of lenacapavir as treatment for HIV-1 infection, HTE participants demonstrated high, stable HRQoL over time, supporting the tolerability of SC lenacapavir plus OBR. HIV-SI scores showed that most participants found a majority of symptoms to be less than a little bothersome, and participants’ experience of their symptoms mainly improved from baseline to week 52. It is possible symptoms reported as bothersome, or showed increases in being bothersome, were influenced by other ongoing medical conditions, which were present in most participants, and by their associated treatments, including agents in the OBR (Supplementary Table 1). The minimal changes observed in NPRS scores are consistent with the mild injection-site reactions (ISRs) reported among trial participants [15]. Swelling, erythema, pain, nodules, and induration, mostly Grade 1 or 2, were the most commonly reported ISRs through week 52; however, the majority of participants (74–90%) did not report these ISRs during the study [27, 28]. By week 52, 47 participants (65%) had at least 1 ISR related to lenacapavir, which were mostly mild (94%; n = 44 of 47) and generally resolved within 1 to 8 days [14]. 22% of participants experienced an ISR related to pain after the first injection, and only 1 participant discontinued SC lenacapavir due to an injection-site nodule by week 52 [14]. At week 52 in this study, there was an increase in bothersomeness in the HIV-SI item, “pain, numbness, tingling in the hands and feet,” which is likely unrelated to injection-site pain, as injections were administered in the abdomen. Additionally, the prevalence of this symptom should be considered in light of the notable number of participants with peripheral neuropathy (17% [12/72]) and/or pain (7% [5/72]) at study baseline (Supplementary Table 1).

This analysis has several limitations. While the number of study participants was relatively small (N = 72), the proportion of PWH in the general population who are HTE is relatively low (2–10%) [29]. Additionally, general inherent limitations of patient-reported outcome instruments apply. For example, interpretation of scales may differ from participant to participant (i.e., an HRQoL score signifying to some as poor health may be considered as the best possible health for others). Further, a variety of factors, such as preexisting conditions or concomitant injectable medications (e.g., enfuvirtide), may influence participants’ responses to these instruments. An ad hoc analysis of data from CAPELLA showed that participants who received SC lenacapavir with other injectable agents had lower median NPRS scores vs. those who received SC lenacapavir without other injectable agents (data not shown). In the ad hoc analysis, ongoing medical conditions thought to influence pain did not appear to substantially influence baseline NPRS scores. However, interpretation is limited by the small subgroup of participants who did not have a qualifying medical condition.

The EQ-5D-5L instrument—a general measure of health—may not be specific or sensitive enough to detect differences between subgroups. Qualitative patient follow-up interviews and future studies evaluating HRQoL and participant-reported outcomes when lenacapavir is paired with other long-acting agents in synchronous and fixed-dose combinations would be valuable. Finally, the MICs referenced in this study were not HIV specific, as none were found for these instruments in published literature.

Despite these limitations, this analysis has several strengths. There was a low level of missing data in CAPELLA. While other injectable ARVs with different modes of administration and frequencies are available, literature describing patient-reported outcome data with long-acting ARV medications is sparse, particularly among HTE populations [30, 31, 32]. Our report provides insight into HRQoL among HTE PWH over a full year. Some PWH may not want to add to their pill burden, especially considering that high pill burden is associated with significantly lower adherence [33]. As long-acting ARVs have recently been introduced, patient-reported HRQoL data are valuable for clinicians to consider when tailoring therapy for their patients. Lenacapavir is being developed as a potential foundation for future long-acting oral and injectable therapies, offering a diverse range of options to make sustained VS accessible to a greater number of PWH while addressing individual needs and preferences. Additionally, ongoing research may indicate lenacapavir could be a meaningful option to other populations, such as people who would benefit from pre-exposure prophylaxis, and may thus help address unmet public health needs.

Conclusions

Treatment of an HTE population of PWH using SC lenacapavir–based regimens in CAPELLA was largely well tolerated, and participant-reported outcomes demonstrated high, stable HRQoL over time, thus suggesting a favorable safety profile consistent with low discontinuation rates. NPRS findings aligned with previous clinical trial outcomes in which ISRs were primarily Grade 1 in nature, and no participants discontinued due to pain. These data highlight the potential for lenacapavir with OBR to decrease most HIV symptoms without compromising HRQoL for HTE PWH.

Electronic Supplementary Material

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Author Contributions

Moti Ramgopal provided clinical insight and supported data interpretation and review of the manuscript. Dylan J. Mezzio provided project oversight and supported the development of the statistical analysis plan, data interpretation and visualization, and review and editing of the manuscript. Keith Dunn supported data interpretation and visualization and review and editing of the manuscript. Shan-Yu Lin developed the statistical analysis plan and supported data interpretation, generation of tables and figures, and review of the manuscript. Damemarie Paul supported the development of the statistical analysis plan, data interpretation and visualization, and review of the manuscript. Martin S. Rhee provided oversight of the trial design and supported review of the data and manuscript. All authors have met ICMJE requirements for authors and provided approval of this version of the manuscript.

Funding

This work was funded by Gilead Sciences, Inc.; CAPELLA Clinical Trials.gov number, NCT04150068, first submitted October 28, 2019.

Data Availability

Gilead Sciences shares anonymized individual patient data upon request or as required by law or regulation with qualified external researchers based on submitted curriculum vitae and reflecting non conflict of interest. The request proposal must also include a statistician. Approval of such requests is at Gilead Science’s discretion and is dependent on the nature of the request, the merit of the research proposed, the availability of the data, and the intended use of the data. Data requests should be sent to datarequest@gilead.com.

Declarations

Author Information

Moti Ramgopal has served as a consultant for Merck; ViiV Healthcare; and Gilead Sciences, Inc.; and has been a member of the speakers bureau for AbbVie; Gilead Sciences, Inc.; ViiV Healthcare; and Janssen.

Dylan J. Mezzio, Keith Dunn, Shan-Yu Liu, and Martin S. Rhee are employees of Gilead Sciences, Inc., and may hold stock options.

Damemarie Paul was an employee of Gilead Sciences, Inc., at the time this work was done and may hold Gilead stock.

Antonella Castagna reports funding, participation in advisory boards and speaker panels, and preparation of educational materials from ViiV Healthcare; Gilead Sciences, Inc.; Merck Sharp and Dohme; Janssen; and Cilag.