Biktarvy® (BIC/FTC/TAF)

Viral Blips

This document is in response to your request for a summary of key data regarding the frequency and impact of viral blips in virologically suppressed participants treated with Biktarvy® (bictegravir/emtricitabine/tenofovir alafenamide [BIC/FTC/TAF]).

This document includes content from, or references to, clinical practice guidelines, and inclusion should not be interpreted as a treatment recommendation or an endorsement of the guidelines by Gilead Sciences, Inc.

Some data may be outside of the US FDA-approved prescribing information. In providing this data, Gilead Sciences, Inc. is not making any representation as to its clinical relevance or to the use of any Gilead product(s). For information about the approved conditions of use of any Gilead drug product, please consult the FDA-approved prescribing information.

The full indication, important safety information, and boxed warnings are available at:
www.gilead.com/-/media/files/pdfs/medicines/hiv/biktarvy/biktarvy_pi.

Summary

Clinical Data on Viral Blips in Participants Treated With BIC/FTC/TAF

Analyses from several phase 3 clinical studies in participants who were ARV naive and virologically suppressed showed that rates of viral blips were low, were similar between BIC/FTC/TAF and comparator arms, and did not clinically affect virologic outcomes.1-6

Viral Load Assays

PWH with undetectable viral loads can have incidents of detectable viral loads due to intrinsic viral load assay variability.7

Clinical Data on Viral Blips in Participants Treated With BIC/FTC/TAF

Studies GS-US-380-1489 and GS‑US‑380‑1490

Study designs and demographics

Study 1489 and 1490 were phase 3, randomized, double-blind, active-controlled, non‑inferiority clinical studies that compared BIC/FTC/TAF (Study 1489, n=314; Study 1490, n=320) with DTG/ABC/3TC (Study 1489, n=315) or DTG + FTC/TAF (Study 1490, n=325) in adult PWH who were ARV naive (Figure 1).8,9

Figure 1. Studies 1489 and 1490: Study Designs8-11

Abbreviations: HLA=human leukocyte antigen; TFV=tenofovir.

Table 1. Studies 1489 and 1490: Baseline Demographics and Disease Characteristics8,12-14

Viral blip analysis1

All participants with ≥1 on-treatment post-baseline HIV-1 RNA value were included in a viral blip analysis through Week 144 (N=1240). Viral blips were defined as a single HIV-1 RNA ≥50 c/mL, preceded and followed by HIV-1 RNA <50 c/mL, after achievement of confirmed virologic suppression (defined as two consecutive HIV-1 RNA values of <50 c/mL). The proportion of participants who experienced viral blips in this analysis was similar across treatment groups. Furthermore, the proportion of participants who experienced low-level (HIV-1 RNA <200 c/mL) or high-level (HIV-1 RNA ≥200 c/mL) viral blips was similar between treatment groups (Table 2).

Table 2. Studies 1489 and 1490: Occurrence of Viral Blips Through Week 1441

aP=0.3. bP=0.2. cP=0.53. dP=0.55.

In the BIC/FTC/TAF treatment groups, there was no significant difference in efficacy between participants who did and did not experience viral blips. Among participants who received DTG-containing regimens, efficacy was significantly lower in those who experienced viral blips than in those who did not. Overall, at Week 144, the percentage of participants who were virologically suppressed was lower among those who experienced viral blips, including high-level viral blips (≥200 c/mL), than among those who did not
(Figure 2).

Figure 2. Studies 1489 and 1490: Virologic Outcomes of Participants With Viral Blips vs No Viral Blips at Week 144 Using LOCF1

Abbreviation: NS=not significant.

aNo viral blips. bViral blips <200 c/mL. cViral blips ≥200 c/mL.

Note: The “+” symbol denotes the presence of viral blips; the “-“ symbol denotes the absence of viral blips.

Across all treatment arms, high-level viral blips were observed more often in participants with a cumulative adherence rate ≤95% than in participants with a cumulative adherence rate >95%. In the overall population, low-level viral blips (<200 c/mL) were observed more frequently in participants with a cumulative adherence rate >95% than in participants with ≤95% adherence; study authors suggested this may be due in part to assay variation. Very low‑level blips (20–50 c/mL) were observed in comparable proportions across all treatment arms and did not impact virologic outcomes.

Safety14

In Study 1489, participants treated with BIC/FTC/TAF reported fewer drug-related AEs than did those taking DTG/ABC/3TC (30% vs 42%, respectively; P=0.0021). SAEs occurred in 13% of participants in the BIC/FTC/TAF arm and in 17% of participants in the DTG/ABC/3TC arm. Drug-related nausea occurred in significantly fewer participants in the BIC/FTC/TAF arm than in the DTG/ABC/3TC arm (6% vs 18%, respectively; P<0.0001). AEs led to DTG/ABC/3TC discontinuation in 2% of participants; no AEs led to discontinuation in the BIC/FTC/TAF arm. Three deaths were documented, none of which were considered treatment‑related.

In Study 1490, participants treated with BIC/FTC/TAF reported similar rates of drug-related AEs compared to those taking DTG + FTC/TAF (22% vs 29%, respectively). SAEs occurred in 20% of participants in the BIC/FTC/TAF arm and in 12% of participants in the DTG + FTC/TAF arm. Nausea was the most common drug-related AE: BIC/FTC/TAF, 3%; DTG + FTC/TAF, 5%. AEs that led to drug discontinuation occurred in 6% of participants in each arm. Three and 4 deaths were documented in the BIC/FTC/TAF and DTG + FTC/TAF arms, respectively; none of which were considered treatment-related.

SOLAR Study2

A phase 3b, randomized (ratio of 2:1), open-label, multicenter, noninferiority study assessed the efficacy and safety of switching to CAB + RPV IM Q8W compared with continuing BIC/FTC/TAF in virologically suppressed PWH. An exploratory analysis assessed HIV-1 RNA samples to evaluate the effect of viral blips (single HIV-1 RNA value of 50–200 c/mL with values of HIV-1 RNA <50 c/mL before and after) on CVF (two consecutive HIV-1 RNA values ≥200 c/mL) from baseline through Month 12. Of the 670 participants included in the mITT-E analysis, 447 participants (67%) switched to CAB + RPV IM Q8W, and 223 participants (33%) continued to receive BIC/FTC/TAF. Baseline characteristics were similar between arms.

From baseline through Month 12, viral blips were reported in 4% of participants in both the CAB + RPV IM Q8W group (n/N=19/447) and the BIC/FTC/TAF group (n/N=9/223); of the participants with viral blips, 5% (1/19) and 11% (1/9), respectively, had HIV-1 RNA ≥50 c/mL at Month 12. Neither of the 2 participants in the CAB + RPV IM Q8W group who had CVF had viral blips through Month 12.

Study GS-US-380-1878

Study design and demographics

A phase 3, prospective, randomized, open-label clinical study was conducted to compare switching to BIC/FTC/TAF 50/200/25 mg STR (n=290) with staying on a baseline regimen of boosted DRV or ATV + 2 NRTIs (FTC/TDF or ABC/3TC; n=288) in virologically suppressed adult PWH (Figure 3).3,15 Viral loads were obtained at Weeks 4, 8, and 12 and then every 12 weeks through Week 48.16

Figure 3. Study 1878: Study Design3,15

Table 3. Study 1878: Baseline Demographics and Disease Characteristics3,15

Safety15

Both regimens were well tolerated. Any-grade AEs that occurred in ≥5% of participants in either the BIC/FTC/TAF or boosted DRV or ATV + 2 NRTIs treatment groups were headache (12% vs 4%, respectively), diarrhea (8% vs 6%), nasopharyngitis (7% vs 12%), URTI (7% vs 8%), back pain (4% vs 6%), and arthralgia (4% vs 5%).The most common drug-related AEs (≥2%) for BIC/FTC/TAF were headache (5%) and flatulence, nausea, and diarrhea (2% each).

OLE analysis

An analysis of participants who switched to BIC/FTC/TAF in the OLE phase of Study 1878 was conducted to measure the frequency of viral blips, preexisting resistance, and virologic outcomes. To be included, participants were required to have no documented or suspected resistance to FTC or TAF and no prior virologic failure. Historical genotyping was collected if available but was not required for study entry. Efficacy was analyzed in participants who switched to BIC/FTC/TAF in the OLE phase and had ≥1 HIV-1 RNA measurement during the OLE while they were receiving treatment with the study drug. Virologic outcomes based on the last available on-treatment HIV-1 RNA were classified as either success (HIV‑1 RNA <50 c/mL) or failure (HIV-1 RNA ≥50 c/mL). Resistance testing was attempted for all participants in the resistance analysis population (CVF with HIV-1 RNA ≥200 c/mL at the confirmation visit or HIV-1 RNA ≥200 c/mL at Week 48 or last visit on study drug). A viral blip was defined as a single HIV-1 RNA ≥50 c/mL after the baseline visit, preceded and followed by HIV-1 RNA <50 c/mL.3,17

Efficacy and safety

Efficacy was high in the OLE phases, and no treatment-emergent resistance developed. HIV-1 RNA was <50 c/mL in 99% of participants who were receiving BIC/FTC/TAF at their last study visit (BIC/FTC/TAF median treatment duration: 101 weeks; maximum duration: 181 weeks; Table 4).3,11 No safety data were available for the OLE phase.

Table 4. Study 1878 OLE: Virologic Outcomes11a

aHIV-1 RNA values corrected per author communication.

Viral blip analysis3

The occurrence of viral blips was infrequent, and the rate was similar between treatment groups in the OLE (BIC/FTC/TAF, 4% and boosted DRV or ATV + 2 NRTIs  BIC/FTC/TAF, 6%). The majority of participants with viral blips had virologic suppression at the last study visit (Table 5).

Table 5. Study 1878 OLE: Viral Blip Occurrence Overview3

aParticipants had viral blips at Week 48 but were later resuppressed to HIV-1 RNA <50 c/mL at end of study.

bThis participant had HIV-1 RNA ≥50 c/mL at the last study visit but was later resuppressed to <50 c/mL on commercial BIC/FTC/TAF.

No significant differences were observed in baseline characteristics, preexisting resistance, or adherence between participants with ≥1 viral blip and those with no viral blips (Table 6). Lower adherence (<95% by pill count) was significantly associated with high-level viral blips (HIV-1 RNA ≥200 c/mL; Figure 4).

Table 6. Study 1878 OLE: Viral Blip Status According to Select Baseline Characteristics and Adherence for All Participants Who Received BIC/FTC/TAF3

aExcluded 4 participants due to lack adherence data.

bExcluded 34 participants due to lack of baseline genotype data.

dAt last study visit, all participants had HIV-1 RNA <50 c/mL.

Figure 4. Study 1878 OLE: Adherence <95% by Viral Blip HIV-1 RNA Category for All Participants Who Received BIC/FTC/TAF (n=532)3

aExcluded 4 participants due to lack of adherence data.

bOne participant experienced viral blips with HIV-1 RNA of <200 c/mL and HIV-1 RNA of ≥200 c/mL, which was counted in both treatment groups.

Study GS-US-380-1844

Study design

A phase 3, randomized, double-blind study evaluated the safety and efficacy of switching to BIC/FTC/TAF (n=282) compared with staying on a baseline regimen of DTG + ABC/3TC or DTG/ABC/3TC STR (n=281) in virologically suppressed adult PWH.16 An analysis measured the frequency of viral blips, preexisting resistance, and virologic outcomes through Week 168, including the OLE phase after Week 48 (Figure 5). Historical genotyping was collected if available but was not required for study entry. Efficacy was analyzed in all participants with ≥1 on‑treatment HIV-1 RNA measurement. Virologic outcomes were determined for all participants who switched to BIC/FTC/TAF, based on the last available on-treatment HIV-1 RNA, and were classified as either success (HIV-1 RNA <50 c/mL) or failure (≥50 c/mL). Resistance testing was attempted for all participants in the resistance analysis population (HIV-1 RNA ≥200 c/mL at the confirmation visit, Week 48, or last visit on study drugs). Resistance data were available through historical genotype or retrospective baseline proviral genotype. A viral blip was defined as a single HIV-1 RNA ≥50 c/mL after the baseline visit, preceded and followed by HIV-1 RNA <50 c/mL.4

Figure 5. Study 1844: Study Design4

aCould include components of an STR.

Efficacy4

Efficacy was high in both the randomized and OLE phases, and no treatment‑emergent resistance developed. HIV-1 RNA was <50 c/mL in 98% of participants who were receiving BIC/FTC/TAF at their last study visit (BIC/FTC/TAF median treatment duration: 96 weeks; maximum duration: 168 weeks; Table 7).

Table 7. Study 1844: Virologic Outcomes4

Viral blip analysis4

Viral blips were experienced by 0.3% to 0.6% of participants who received BIC/FTC/TAF per study visit (Table 8). Eighty-three percent of participants (19/23) who experienced viral blips with BIC/FTC/TAF in the randomized and OLE phases had HIV‑1 RNA <200 c/mL.

Table 8. Study 1844: Viral Blip Occurrence Overview4

aDiscontinued study with HIV-1 RNA 499 c/mL and resistance test assay failure.

bExperienced 4 viral blips during the study between 50 and 200 c/mL.

No significant differences were observed in baseline characteristics, preexisting resistance, or adherence between participants with ≥1 viral blip and those with no viral blips (Table 9). Adherence was not significantly lower in participants with viral blips with HIV-1 RNA >200 c/mL than in participants without viral blips.

Table 9. Study 1844: Blip Status According to Select Baseline Characteristics and Adherence for All Participants Who Received BIC/FTC/TAF4

aFour participants without adherence data were excluded.

bParticipants were excluded if they did not have baseline genotype data: ≥1 blip (n=22) and no viral blips (n=1).

cThis participant also had K103N mutation.

Safety16,18

At Week 168, the most common any-grade AEs reported in ≥5% of participants in the BIC/FTC/TAF arm were URTI, nasopharyngitis, diarrhea, arthralgia, back pain, headache, sinusitis, bronchitis, and syphilis. TRAEs were reported in 39 participants (7%), and most were Grade 1. Headache was the most commonly reported TRAE (2%). In participants treated with BIC/FTC/TAF, a total of 7 AEs (1%) led to study discontinuation: headache (n=3), vomiting (n=1), cerebrovascular accident (n=1), abnormal dreams (n=1), and suicidal ideation (n=1, not considered related to study treatment by investigator).

Study GS-US-380-4030

Study design

A phase 3, randomized, double-blind, multicenter, active-controlled study evaluated the efficacy of BIC/FTC/TAF (n=284) vs DTG + FTC/TAF (n=281) in virologically suppressed PWH, including those with known baseline resistance mutations (Figure 6). The final analysis included additional baseline resistance data obtained through proviral DNA testing, which provided genotypic resistance data for 83% of participants. Population genotyping and phenotyping for RT, PR, and IN were conducted at CVF, Week 48, or at the last visit.5,19  

Figure 6. Study 4030: Study Design5,19

Viral blip analysis

A viral blip analysis was conducted and included all participants who had ≥1 on‑treatment post‑baseline HIV-1 RNA value through Week 48. Any post-baseline HIV-1 RNA ≥50 c/mL preceded and followed by an HIV-1 RNA <50 c/mL was considered a viral blip.5

Fifteen participants (2.7%) experienced viral blips in this study, and the incidence was similar between treatment groups (Table 10; P=1). One participant experienced >1 viral blip. Most of the viral blips that occurred in participants treated with BIC/FTC/TAF were <200 c/mL, and all participants with viral blips ≥200 c/mL were virologically suppressed at Week 48. Baseline NRTI-R was not associated with an increased occurrence of viral blips (Table 10). Virologic suppression at Week 48 was not affected by the occurrence of viral blips (Figure 7).5

Table 10. Study 4030: Viral Blips According to Baseline Resistance Category5,19

aTwenty participants were stratified to Categories 1 or 2 based on investigator-suspected NRTI-R that was not confirmed by genotyping: 1 participant in the BIC/FTC/TAF treatment group and 2 participants in the DTG + FTC/TAF treatment group were not included in the viral blip analysis; thus, for the viral blip analysis, BIC/FTC/TAF, n=283 and DTG + FTC/TAF, n=279.

bOne participant without known preexisting NRTI-R experienced 2 viral blips.

cK65R/E/N, ≥3 TAMs, including M41L or L210W, or T69 insertions.

dM184V/I, K70E/G/M/Q/S/T, L74V/I, V75A/S/M/T, Y115F, T69D, Q151M, M41L, D67N, K70R, L210W, T215F/Y, or K219Q/E/R/N mutations.

eNo NRTI-R–associated mutations.

Figure 7. Study 4030: Efficacy Outcomes at Week 48 for Participants With and Without Viral Blips Using LOCF5

aOne participant in the BIC/FTC/TAF treatment group with no preexisting NRTI-R had HIV-1 RNA of 2340 c/mL at Week 48 but was resuppressed at the next visit.

Safety20

The most commonly reported AEs (≥10%) in either group were nasopharyngitis, diarrhea, and URTI. Drug-related AEs occurring in ≥2% in either group were diarrhea and headache. Six participants (2%) in each arm discontinued the study because of AEs. There was 1 death documented in each arm; the death in the BIC/FTC/TAF arm was considered unrelated to study drug by the investigator.

BRAAVE 2020

Study design

The BRAAVE 2020 study was a phase 3, randomized, open-label, multicenter study that evaluated the efficacy and safety of switching to BIC/FTC/TAF vs continuing with a baseline regimen of 2 NRTIs plus a third agent in virologically suppressed PWH who self-identified as African American, Black, or mixed race, including Black (Figure 8).6

Baseline resistance was analyzed with historical genotypes, if available, and HIV-1 proviral DNA genotype testing was retrospectively performed on baseline samples. Participants with preexisting resistance detected after enrollment were permitted to continue in the study. The resistance analysis population included any participant with CVF (HIV‑1 RNA ≥50 c/mL at two consecutive visits) and HIV-1 RNA ≥200 c/mL at the confirmation visit or with HIV‑1 RNA ≥200 c/mL at Weeks 24, 48, or 72, or last visit, with no resuppression of HIV-1 RNA to <50 c/mL while on study treatment.21,22 Secondary INSTI‑R was the most frequently observed preexisting resistance substitution (Table 11).6 

Figure 8. BRAAVE 2020: Study Design6,21

aThe allowed third agents included any INSTI except BIC, any PI, maraviroc, or any NNRTI except etravirine.

bExcept K65R/E/N, T69 insertions, or ≥3 TAMs.

Table 11. BRAAVE 2020: Resistance Substitutions at Baseline6

Results through Week 726 

By the last visit, virologic suppression was achieved by 99% of participants (486/489) overall and by 100% of participants (22/22) who had ≥1 viral blip. Viral blips occurred at a mean frequency of 0.9% of study visits (Figure 9); 21 participants experienced 1 blip, and 1 participant experienced 2 blips at 4 and 12 weeks after switching to BIC/FTC/TAF. Fifty‑seven percent of viral blips (13/23) were HIV‑1 RNA <200 c/mL. No treatment‑emergent resistance was observed during the study through Week 72.

Figure 9. BRAAVE 2020: Frequency of Viral Blips Through Week 60 After Switch to BIC/FTC/TAF6 

High adherence (≥95%) to BIC/FTC/TAF was reported in 74% of participants (363/489) and in 19/22 participants with viral blips. There were no significant differences in adherence between treatment groups (P=0.91) or between participants who experienced viral blips and those who did not (P=0.24).  

Safety

The rates of AEs reported through Week 24 were comparable between participants who switched to BIC/FTC/TAF and those who continued their baseline regimen. AEs that led to discontinuation of study drug were reported in 7 participants who switched to BIC/FTC/TAF and in none of the participants who continued with the baseline regimen through Week 24. The following AEs led to study drug discontinuation and were considered treatment‑related by study investigators: abdominal distension and flatulence (n=1); diarrhea, dry mouth, psychomotor hyperactivity, agitation, anxiety, and insomnia (n=1); diarrhea (n=1); headache (n=1); migraine (n=1); and nightmare (n=1). Acute kidney injury led to study drug discontinuation in 1 participant but was not considered treatment related by study investigators.23 In each arm, Grade 3 to 4 AEs and SAEs occurred in 5% and 4% of participants, respectively. TRAEs occurred in 11% of participants in the BIC/FTC/TAF arm and in none who continued their baseline regimen.23,24

Six additional AEs that led to study drug discontinuation between Weeks 24 and 72 and included hemorrhage of intracranial aneurysm with multiple sequelae (n=1), headache and hyperhidrosis (n=1, headache was treatment-related); abdominal distension and flatulence (n=1; both were treatment-related); COVID-19 (n=2); and change in bowel consistency and flatulence (n=1, both were treatment related).24 No treatment‑related deaths were reported through Week 48.25

Retrospective Chart Review26

A retrospective chart review compared HIV viral blips (low-level blip: HIV-1 RNA 51–‍200 c/mL; high-level blip: 201–‍1000 c/mL) in patients who received BIC/FTC/TAF (n=138), DTG/ABC/3TC (n=95), or FTC/RPV/TAF (n=91) between March 2017 and October 2021. Key demographics and disease characteristics for the BIC/FTC/TAF, DTG/ABC/3TC, and FTC/RPV/TAF groups were as follows: mean age, 50.9, 52.6, and 52.7 years, respectively; 77%, 75%, and 67% were male; 63%, 56%, and 63% were Black or African American; 42%, 24.2%, and 51.6% had a BMI >30 kg/m2; and the average duration of ARV therapy was 16, 17, and 3.37 years.

There was no significant difference in the incidence of viral blips in the BIC/FTC/TAF and FTC/RPV/TAF groups: 16% vs 14%, respectively (P=0.73); however, significantly more patients had viral blips in the DTG/ABC/3TC group than in the BIC/FTC/TAF group (36% vs 16%, respectively; P=0.0003). Overall, 15 high-level viral blips occurred; the incidence by group was as follows (differences were not statistically significant): BIC/FTC/TAF, 3.6%; DTG/ABC/3TC, 6.3%; and FTC/RPV/TAF, 4.4%. Study authors noted that viral load testing was performed annually in some patients, which limited the interpretation of results as viral blips vs low‑level viremia.

Viral Load Assays

Systematic Review

Current HIV-1 viral load assays can have lower limits of detection (HIV‑1 RNA 20 c/mL). A systematic review of viral load assays showed that sources of variability between assays include differences in technology platform, plasma input volume, and ability to detect HIV‑1 subtypes. Ideally, repeated monitoring of PWH should be performed on the same platform consistently to enable appropriate interpretation of viral load changes. PWH with undetectable viral loads can have incidents of detectable viral loads due to intrinsic viral load assay variability.7 Previous work has shown that when switching from the older Amplicor viral load assay to the TaqMan viral load assay, there was an increase in the frequency of detectable plasma HIV-1 RNA at the 50 c/mL threshold.27

Recent data have further described the effect of intrinsic viral load assay variability when monitoring HIV-1 viral load at the lower end of the detectable range. This latter work has implications for monitoring of patients who are virologically suppressed and experience transient viral blips.28

In an analysis of viral load assay variability, 50 aliquots of diluted WHO HIV-1RNA standards at viral loads <200 c/mL, and multiple aliquots of plasma samples from 4 patients who experienced viral blips that ranged from 50 to 200 c/mL after having had HIV-1 RNA <50 c/mL, were quantified using the Cobas AmpliPrep/Cobas TaqMan v2.0 HIV-1 assay (Roche). The investigators found that, in WHO standard samples with HIV-1 RNA of 36 c/mL and 18 c/mL, HIV-1 viral load was quantified as being ≥50 c/mL in 66% and 18% of assay replicates, respectively. Retesting stored plasma samples from previously virologically suppressed patients who experienced low‑level viremia resulted in HIV-1 RNA <50 c/mL in 14/15 (93%) of these samples. The authors recommended that, in cases of unexpected low‑level viremia, retesting the same HIV RNA sample (a stored aliquot) and reconfirming undetectable viral load may prevent additional clinical visits, blood draws, laboratory tests, and patient anxiety. Conversely, confirmation of the detectable viral load on the original plasma sample would then trigger an additional laboratory visit and repeat plasma sample draw to confirm potential virologic failure.28

Clinical Guidelines Regarding Virologic Failure

Recommendations from the US Department of Health and Human Services (DHHS) regarding virologic failure, including viral blips, in treatment-experienced patients can be accessed using the following link: https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/virologic-failure.

References

1. Acosta RK, Andreatta K, D'Antoni ML, Collins S, Martin H, White KL. HIV Viral Blips in Adults Treated with INSTI-Based Regimens Through 144 Weeks [Poster 0540]. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); 08-11 March, 2020; Boston, MA.

2. Latham C, Urbaityte R, Sutton K, Sutherland-Phillips D, Spreen W, D’Amico R. HIV-1 RNA Blips and Low-Level Viral Replication: SOLAR (CAB + RPV LA vs. BIC/FTC/TAF) [Poster 627]. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); March 03-06, 2024; Denver, CO.

3. Andreatta K, Chang S, Delaney M, et al. Long-term Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide After Switch From Boosted Protease Inhibitor-Based Regimens Including in Those With Preexisting Resistance and Viral Blips [Poster PE1/19]. Paper presented at: 18th European AIDS Conference; October 27-30, 2021; London, United Kingdom.

4. Andreatta K, Chang S, Delaney M, et al. Long-term Efficacy Among Participants Switched to Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) from Dolutegravir/Abacavir/Lamivudine (DTG/ABC/3TC) with Preexisting Resistance and Viral Blips [Presentation]. Paper presented at: 11th International AIDS Society (IAS) Conference on HIV Science Virtual; 18-21 July, 2021.

5. Acosta RK, Liu H, Collins SE, Martin H, White KL. Baseline NRTI Resistance in Suppressed Participants Did Not Lead to Viral Blips on Bictegravir/Emtricitabine/Tenofovir Alafenamide B/F/TAF or Dolutegravir DTG + F AF Through eek 48 in Study 380-4030 [Poster PEB0257]. Paper presented at: AIDS 2020: 23rd International AIDS Conference Virtual; 06-10 July, 2020.

6. Andreatta K, D'Antoni ML, Chang S, et al. High efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in Black adults in the United States, including those with pre-existing HIV resistance and suboptimal adherence. J Med Virol. 2024;96(10):e29899.

7. Department of Health and Human Services (DHHS). Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection. Last updated: 31 January. 2024.

8. Wohl DA, Yazdanpanah Y, Baumgarten A, et al. Bictegravir Combined with Emtricitabine and Tenofovir Alafenamide Versus Dolutegravir, Abacavir, and Lamivudine for Initial Treatment of HIV-1 Infection: Week 96 Results from a Randomised, Double-Blind, Multicentre, Phase 3, Non-Inferiority Trial. The Lancet HIV. 2019;6(6):e355-e363.

9. Stellbrink HJ, Arribas JR, Stephens JL, et al. Co-Formulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide Versus Dolutegravir with Emtricitabine and Tenofovir Alafenamide for Initial Treatment of HIV-1 Infection: Week 96 Results from a Randomised, Double-Blind, Multicentre, Phase 3, Non-Inferiority Trial. The Lancet HIV. 2019;6(6):e364-e372.

10. Orkin C, Sax PE, Arribas J, et al. Long-term Efficacy and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide in ART-Naïve Adults [Poster PE3/14]. Paper presented at: 17th European AIDS Conference; 06-09 November, 2019; Basel, Switzerland.

11. Gilead Sciences Inc. Data on File.

12. Sax PE, Pozniak A, Montes ML, et al. Coformulated Bictegravir, Emtricitabine, and Tenofovir Alafenamide Versus Dolutegravir With Emtricitabine and Tenofovir Alafenamide, For Initial Treatment of HIV-1 Infection (GS-US-380-1490): A Randomised, Double-Blind, Multicentre, Phase 3, Non-Inferiority Trial. Lancet. 2017;390:2073-2082.

13. Gallant J, Lazzarin A, Mills A, et al. Bictegravir, Emtricitabine, and Tenofovir Alafenamide Versus Dolutegravir, Abacavir, and Lamivudine for Initial Treatment of HIV-1 Infection (GS-US-380-1489): A Double-Blind, Multicentre, Phase 3, Randomised Controlled Non-Inferiority Trial. Lancet. 2017;390:2063-2072.

14. Orkin C, DeJesus E, Sax PE, et al. Three-Year Outcomes of the Fixed-Dose Combination Bictegravir, Emtricitabine, and Tenofovir Alafenamide vs Dolutegravir-Containing Regimens for Initial Treatment of HIV-1 Infection: Week 144 Results from Two Randomised, Double-Blind, Multicentre, Phase 3, Non-Inferiority Trials. The Lancet HIV. 2020;7:e389–400.

15. Daar ES, DeJesus E, Ruane P, et al. Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial. The Lancet HIV. 2018;5(7):e347-e356.

16. Molina JM, Ward D, Brar I, et al. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. The Lancet HIV. 2018;5(7):e357-365.

17. Andreatta K, Martin R, Chang S, et al. Previously Undocumented Pre-existing Resistance and Maintenance of Virologic Suppression in HIV-1 RNA-Suppressed Patients Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) [Poster MOPEB243]. Paper presented at: 10th IAS Conference on HIV Science (IAS 2019); 21-24 July, 2019; Mexico City, Mexico.

18. Brar I, Ruane P, Ward D, et al. Long-term Follow-up After a Switch to Bictegravir, Emtricitabine, and Tenofovir Alafenamide From Dolutegravir, Abacavir, and Lamivudine [Poster 1028]. Paper presented at: IDWeek Virtual; 21-25 October, 2020.

19. Acosta R, Willkom M, Andreatta K, et al. Keeping the Pressure on Archived NRTI Resistance: Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF) Triple Therapy in Study 4030 [Poster MOPEB241]. Paper presented at: 10th IAS Conference on HIV Science (IAS 2019); 21-24 July, 2019; Mexico City, Mexico.

20. Sax PE, Rockstroh JK, Luetkemeyer AF, et al. Switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with Human Immunodeficiency Virus. Clin Infect Dis. 2020:1-9.

21. Andreatta K, D'Antoni ML, Chang S, et al. High Efficacy of Bictegravir/Emtricitabine/Tenofovir Alafenamide in African-American Adults With HIV Including Those with Preexisting Resistance, Viral Blips, and Suboptimal Adherence [Poster 629]. Paper presented at: IDWeek Virtual; 29 Sept-03 Oct, 2021.

22. Andreatta K, D'Antoni ML, Chang S, et al. Preexisting Resistance and B/F/TAF Switch Efficacy in African Americans [Poster 509]. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); 08-11 March, 2020; Boston, MA.

23. Hagins D, Kumar P, Saag M, et al. Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study. J Acquir Immune Defic Syndr. 2021;88(1):86-95.

24. Kumar P, Stephens JL, Wurapa AK, et al. Week 72 Outcomes and COVID-19 Impact From the BRAAVE 2020 Study: a Randomized Switch to B/F/TAF in Black American Adults With HIV [Poster 802]. Paper presented at: 11th International AIDS Society (IAS) Conference on HIV Science Virtual; 18-21 July, 2021.

25. Hagins D, Kumar P, Saag M, et al. Switching to Bictegravir/Emtricitabine/Tenofovir Alafenamide in Black Americans With HIV-1: A Randomized Phase 3b, Multicenter, Open-Label Study [Supplemental Material: Appendix]. JAIDS. 2021.

26. Makhoul J, Barnes A, Werner L, et al. Retrospective Study Comparing the Rate of HIV Blips With Combined Antiretroviral Therapy [Poster 1584]. Paper presented at: IDWeek; Oct. 11-15, 2023; Boston, MA.

27. Lima V, Harrigan R, Montaner JS. Increased reporting of detectable plasma HIV-1 RNA levels at the critical threshold of 50 copies per milliliter with the Taqman assay in comparison to the Amplicor assay. J Acquir Immune Defic Syndr. 2009;51(1):3-6.

28. Eron J, Garner W, Wei L, et al. Retesting of suspected low-level HIV-1 viral load blips: A new paradigm to prevent extra clinic visits and unnecessary patient anxiety. [Presentation 948]. Paper presented at: ID Week; 28 October, 2016; New Orleans, LA.

Abbreviations

3TC=lamivudine
ABC=abacavir
AE=adverse event
ARV=antiretroviral
ATV=atazanavir
BIC=bictegravir
c/mL=copies per mL
CAB=cabotegravir
CD4=cluster of differentiation 4
CG=Cockcroft-Gault
CVF=confirmed virologic failure
DRV=darunavir
DTG=dolutegravir
FTC=emtricitabine
IM=intramuscular
IN=integrase
INSTI=integrase strand transfer inhibitor
INSTI-R=integrase strand transfer inhibitor resistance
LOCF=last observation carried forward
mITT-E=modified ITT exposed
NNRTI=non‑
nucleos(t)ide reverse transcriptase inhibitor
NNRTI-R=non‑
nucleos(t)ide reverse transcriptase inhibitor resistance
NRTI=nucleos(t)ide reverse transcriptase inhibitor
NRTI-R=nucleos(t)ide reverse transcriptase inhibitor resistance
OLE=open‑label extension
PI=protease inhibitor

PI-R=protease inhibitor resistance
PR=protease
PWH=people with HIV
Q8W=every 8 weeks
RPV=rilpivirine
RT=reverse transcriptase
SAE=serious adverse event
STR=single-tablet regimen
TAF=tenofovir alafenamide
TAM=thymidine analog mutation
TDF=tenofovir disoproxil fumarate
TRAE=treatment-related adverse event
URTI=upper respiratory tract infection
WHO=World Health Organization

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