CROI 2024: Pipeline ART – new drugs and formulations
19 March 2024. Related: Conference reports, Antiretrovirals, CROI 2024 Denver.
Simon Collins, HIV i-Base
CROI 2024 included a wealth of studies on longer-acting pipeline compounds that could lead to new HIV drugs, many in novel combinations and using only two drugs.
Some studies are already in phase 2/3 with currently approved drugs and some are being studied for both treatment and prevention.
The context for the continued need for better treatment and the potential of longer-acting formulations was given in an excellent plenary talk by Charles Flexner from Johns Hopkins University, who talked through the development of long-acting formulations over the last ten years, including the different ways these drugs work. This includes news on an injectable formulation of the first-line generic TLD (tenofovir/lamivudine/dolutegravir) and treatments for hepatitis and TB. [1]
Extended dosing especially benefits situations when adherence to oral ART is difficult. Referencing a previous CROI talk 20 years ago, the same opening slides emphasised: “People don’t fail drugs, drugs fail people” – and that this is still just as important today.
A related poster looked at reducing the timeline to developing new drugs by using better ways to predict dosing in human studies from early preclinical animal studies, using early analyses of long-acting cabotegravir and rilpivirine as an example. [2] Eric Freed presented a dynamic talk about HIV assembly and maturation – and also the role of viral changes outside of integrase associated with loss of activity. [3]
Studies of new combinations that include either at least one investigational drug or a significant new indication are summarised below. At least six studies included new clinical data on lenacapavir and numerous others looked at related issues including important early data on capsid inhibitor drug resistance. See also Table 1.
Monthly CAB/RPV-LA injections
Early results when used as first-line ART in people who have difficulty with oral ART. Rough 88% (51/60) achieved undetectable viral load after 24 weeks, although 2/4 with viral failure developed INSTI and NNRTI resistance.
Currently approved as a switch option, this involves achieving and maintaining undetectable viral load using daily oral ART. This study could reduce the barriers for people who could benefit most from CAB/RPV-LA. [4]
Cabotegravir and lenacapavir (with or without rilpivirine)
An INSTI + capsid inhibitor combination using long-acting injections, in 32 people with difficulty adhering to oral drugs. Viral suppression increased from 47% at baseline to 94% (30/32). [5]
Once-weekly oral lenacapavir and islatravir
This combination would only require one pill once a week with the potential to significantly improve quality of life using formulations of two HIV drugs that are already either approved for a limited indication or are about to enter phase 3 studies.
The dual combination maintained high levels of viral suppression at week 24. [6]
Lenacapavir in people with zero or only one other active drug
This poster presented a subgroup analysis from the open-label arm of the phase 2/3 CAPELLA study, in 12 people with no fully sensitive drugs to use in the optimised background regimen, with about half having only one partially sensitive drug. Most participants achieved undetectable viral load over two years, with details presented for those with blips (2/12) or low-level viral load (2/12). [7]
Simplification to lenacapavir + bictegravir
The first clinical data on this dual ART combination in 128 people suppressed on current ART that randomised (2:2:1) to one of two doses of bictegravir vs current ART as control. The study looked to simplify ART in people with otherwise complex combinations. [8]
Lenacapavir with two bNAbs (10-1074 and 3BNC117)
This small switch study in 11 people suppressed on ART enrolled participants who were only sensitive at baseline to one out of the two bNAbs. At 24 weeks 8/10 remained suppressed and two with low level viraemia were <100 c/mL. As background, approximately 50% of people with clade B virus are highly susceptible to both these bNAbs and 90% are highly susceptible to only one. However, baseline sensitivity is still difficult to predict and resistance can easily develop with low levels of only one bNAb. [14]
Doravirine + islatravir
A post-hoc analysis of two phase 3 studies of dual ART using daily doravirine plus islatravir showing high levels of viral suppression even with existing M184V or NNRTI mutations.
bNAbs
bNAbs studies included early results with 10-1074 (zinlirvimab, ZAB), 3BNC117 (teropavimab, TAB), VRC07-523LS, VRC01LS, N6LS (VH3810109) including long-acting formulation, PGT121, PGDM1400, SAR441236 (tri-specific with VRC01, PGDM1400 and 10E8v4), ABBV-382, TMB-365 and TMB-380.
This is an impressive and daunting list but bNAbs as a class currently divide people into those who are either excited by their potential to deliver long-acting formulations and potential to develop immune responses to allow extended periods off-ART, or those who see them as being too complex, requiring sensitivity testing and potentially being too expensive to ever become widely used.
CROI 2024 provided results to support both views and summaries of key studies are also included in Tables 1 and 2.
Compounds at earlier stages of development, including newly-branded ‘ultra’ long-acting formulations are summarised in Table 3.
- MK-8527: a once-weekly oral NRTTI similar to islatravir, which reduced viral load by at least –1.0 log after 7 days following a single dose.
- GS-1720: a weekly oral integrase inhibitor showing viral load reductions of 2 logs by say 8 and 2.4 logs by day 11 after monotherapy (two daily doses).
- GS-5894: a once-weekly NNRTI with preclinical data suggesting activity against some NNRTI resistance.
- GS-9770: a once-daily oral protease inhibitor that doesn’t need PK boosting.
- Ultra long-acting formulation of cabotegravir allowing 6- or 12-monthly IM injections.
- Ultra long-acting biodegradable and removable 6-monthly dolutegravir implant. Rapid clearance avoids long PK tail.
- Ultra long-acting 6-weekly formulation of bictegravir. Rapid clearance avoids long PK tail.
- A tenofovir implant for women was unfortunately not effective.
Table 1: New combinations, formulations and compounds at CROI 2024
| Name, drug class and dose |
Study design | Results | Comment | Refs |
| CAB/RPV-LA first-line.INSTI + NNRTI. Dual ART. IM monthly injections. |
A retrospective study of 88 people who started LA-CAB/RPV with HIV VL ≥50 copies/mL. Roughly half the participants had were homeless or had housing instability, and 43% with substance use. Results were available for 60/88 people. | At 24 weeks, 51/60 (85%) had undetectable viral load. 4/60 had VL ≥50 copies/mL. Of these, 2/4 had resistance (RT E138K, INSTI R263K; and RT L100I, Y181I) and 2/4 had slow viral decay without resistance. 5/60 had missing VL data. | Currently approved as a switch option, this involves achieving and maintaining undetectable viral load using daily oral ART. This study could reduce the barriers for people who could benefit most from CAB/RPV-LA. | Hickey M et al.
P628. [4] |
| CAB-LA + lenacapavir*
(+/- RPV-LA) |
IM injection(s) every 1 or 2 (70%) mo + SC injection every 6 mo. |
Case series: N=34; 76% male 24 cis/trans female; 41% Black; 38% Latino/a; median age 47 (range 28-75) years. | 32/34 suppressed (VL <75) after starting LEN (94%) at a median of 8 weeks (4-16), with only 16 (47%) being suppressed at baseline. | Gandhi M et al.
P629. [5] |
| Islatravir + lenacapavir*
NRTTI + capsid. Dual ART. Oral weekly. vs daily oral |
Phase 2 RCT (n=104).
Randomised to switch to weekly oral or continue on B/T/TAF. |
At 24 wks 49 (94.2%) vs 48 (92.3%) remained undetectable, in the ISL+LEN vs control groups. No data was available for 2 vs 4 pts respectively.
One VL increase to 251 copies/mL) resuppressed without changing ART. No rebounds were seen with B/F/TAF. |
First once-weekly oral combination. Large phase 3 studies are expected but not yet listed. | Colson A et al.
O208. [6] |
| Lenacapavir* + OBR.
Capsid inhibitor |
Substudy of the phase 2/3 CAPELLA study in people with MDR HIV. Results were presented for 19 participants who at baseline had zero fully active drugs (n=12) to use in the background ART. Of these 6/12 had one partially active drug and 1/12 had two. | 8/12 pts had VL <50 c/mL at wks 26, 52 & 104), including 2/12 with LEN resistance (M66I) who resuppressed with OBR change.
2/12 with VL ≥50 c/mL throughout, had stable low level viral load (at <600 and <3000 c/mL, despite LEN resistance at W4 [M66M/I]). |
Although these are small numbers most people with very limited option maintained undetectable viral load over two years. Longer follow-up is need for those who remained detectable, especially with early evidence of resistance, | Segal-Maurer S et al.
P630. [7] |
| Oral lenacapavir* + bictegravir Capsid inhibitor + INSTI. Dual ART. Once-daily oral 75 mg bictegravir + LEN 25 mg (n=50) or 50 mg (n-51). |
Open label phase 2/3 study randomised (2:2:1) 128 pts on stable ART to bictegravir + lenacapavir vs current ART (n=25). | Primary endpoint of VL >5- c/mL at wk 24 only occurred in one (in 50 mg arm). | First data of this daily dual ART reported high efficacy and tolerability at week 24. | Mounzer K et al.
P642. [8] |
| Lenacapavir* – other studies
Various. Multiple studies including |
Le Hingrat et al reported on 8 people using LEN with an OBR that include 2 or fewer sensitive drugs. Capsid mutations were observed in 6/8 (five N73D mutations and one double mutation (Q66H+R69K). Two had persistently high viral loads without capsid mutations. Demirdjian S et al reported 14/258 people with CA mutations (M66I, Q67H/K/N, K70H/N/R/S, N74D/H, A105T/S, and T107A/C/ N/S): with fold-changes ranging from 43.5 to >1000.
Nguyen B et al reported that M66I, confers >80,000-fold resistance to lenacapavir. Hansen D et al reported that naturally occurring polymorphisms in capsid have little impact on sensitivity to lenacapavir. |
Le Hingrat Q et al. P 682.Demirdjian S et al. P681.Nguyen B et al. P302.Hansen D et al. P304.[9, 10, 11, 12] |
||
| Doravirine + islatravir.
NNRTI + NRTTI. Dual ART. Once-daily |
Post-hoc analyses from of results from two phase 3 switch studies (one open label and one RCT) to look at other impact of M184V or NNRTI mutations at baseline on clinical failure (CF) or low-level viraemia (LLV).
N=889 on DOR/ISL. |
46 (5.2%) had M184M/I/V at baseline; none had confirmed viraemia on DOR/ISL. 2/46 (4.3%) had ≥1 viral blips (HIV-1 RNA ≥50 copies/mL followed by <50 copies/mL at next measurement).
20 (6.5%) in the baseline ART control group had M184M/I/V at baseline: 2/20 (10%) developed CV, and none had LLV or viral blips. 46 (5.2%) had M184M/I/V at baseline; none had confirmed viraemia on DOR/ISL. 2/46 (4.3%) had ≥1 viral blips (HIV-1 RNA ≥50 copies/mL followed by <50 copies/mL at next measurement). |
High continued suppression irrespective of previous M184V or NNRTI mutation at baseline.
Notably high viral suppression was reported in 273/287 pts with baseline NNRTI mutations. |
Asante-Appiah E et al. P694
[13] |
*Lenacapavir requires an oral loading dose of 600 mg on days 1 and 2 of treatment.
Abbreviations: BL: baseline, bNAb: broadly neutralising monoclonal antibody, SC = subcutaneous, IM = intramuscular, IV = intravenous, OBR = optimised background regimen, pt = participant, VL = viral load, mo = month/monthly, wk = week.
Table 2: bNAb studies at CROI 2024
| Name, drug class and dose |
Study design | Results | Comment | Refs |
| Lenacapavir* + 2 bNAbs: teropavimab (TAB; 3BNC117) or zinlirvimab (ZAB, 10-1074).Capsid inhibitor + 2 x bNAbsLEN SC every 6 mo + TAB (30 mg/kg IV + ZAB (Group 1, 10 mg/kg IV; Group 2, 30 mg/kg IV). |
Switch study to LEN + 2 bNAbs with randomised to either 10 or 30 mg doses of 10-1074.
N=11 virally suppressed. Only needed baseline sensitivity to one of the two bNAbs. |
At wk 26, 8/10 pts remained undetectable.
Group 1: 2/4 had rebound but still <100 c/mL (i) one had sensitivity to TAB with acute COVID-19; and (ii) sensitivity to ZAB & at Week 26. Group 2: all 6/6 pts remained undetectable. |
This tiny study had such a low threshold for viral failure that that makes these few cases difficult to interpret.
Detecting bNAbs sensitivity is still challenging and clinical results do not always match baseline predictions. |
Eron J et al. O120
[14] |
| CAB-LA + VRC07-523LS
INSTI + bNAb. Dual ART. Monthly CAB-LA IM injections + bNAb infusions every 8 wks. |
Phase 2 ACTG A5357, First stage switch to oral CAB + 2 NRTIs followed by monthly CAB-LA IM injections and bNAb infusions every 8 weeks.
Previous suppressed on ART for more than two years and testing sensitive to the bNAb at baseline. |
61/71 (86%) completed with data at wk 44.10/71 (14%) stopped early (5 had viral failure (2 still <200 c/mL, 1 with R263K resistance), 1 death (unrelated to study), and 4 pt/doctor request.
12/71 (17%) pts met the safety endpoint: 11/12 with grade ≥3 AEs (mostly chills, myalgia, fatigue) with one discontinuation due to a grade 1 infusion-related reaction. |
Even with bNAb sensitivity at baseline and monthly CAB-LA injections, the probability of VF at or prior to week 44 was 7.3% (95% CI 3.2 to 16.0%).
Even though this overall risk of viral failure qas high, this was a small study with a low threshold to define failure. |
Taiwo B et al. O119
[15] |
| N6LS (VH3810109)
bNAb monotherapy, then ART. Single IV infusion or SC injection. Part 1: 40 mg/kg IV and 280 mg IV. Part 2: 700 mg IV, 70 mg IV or 700 mg SC. |
BANNER study. Open-label, 2-part, randomised dose-ranging monotherapy study in 62 treatment-naive adults. Monotherapy with a single IV infusion or SC injection, followed by 48 weeks of standard-of- care ART for 48 wks. Largely male (94%), median (range) age was 29 (18-61) years. |
At BL, median VL ranged from 4.1 to 4.5 log10 c/mL across dose groups. Median (range) maximum VL decline ranged from −0.43 (−1.29 to −0.12; 70 mg IV group) log10 c/mL to −1.72 (−2.60 to −0.60; 40 mg/kg IV group) log10 c/mL and was reached in a median of 9 days (Figure). Among responders, median (range) time to rebound ranged from 13 (10-22; 70 mg IV group) days to 35 (12-78; 40 mg/kg IV group) days. | Results support the ongoing development of N6LS into phase 2b. | Losos J et al. O117.
[16] |
| High-dose N6LS (VH3810109) ± recombinant human hyaluronidase PH20.
bNAb pouch delivery. Single dose of N6LS delivered in a pouch under the skin with rHuPH20. |
Phase 1 SPAN study. Open-label, 3-part study on safety, tolerability, and PK in 24 HIV negative adults, n=8 in each group.
Part 1: 20 mg/kg SC + rHuPH20 2000 U/mL. Part 2: 60 mg/kg IV. Part 3: 3000 mg SC + rHuPH20 2000 U/mL. |
32 injection site reactions (ISRs) in part 1 and 3 reported by 15/16 pts, 17 were grade 3 (all injection site erythema based on size; mean duration: 2.9 days [part 1] and 5.7 days [part 3].
All resolved within ≤7 days except for 1 in part 3 that took 27 days. |
rHuPH20 delivers a long-acting dose of N6LS in a pouch under the skin to provide 6 months of cover.
Unclear whether more serious skin reactions would be seen in a larger study but these are already grade 3. |
Win B et al. P639.
[17] |
| SAR441236
VRC01, PGDM1400 and 10E8v4. Trispecific bNAb targeting three regions (CD4, v2/v3 and MPER). Single SC or IV injections of SAR441236 (from 0.3 to 10 mg/kg) or 4 doses at 30 mg/kg IV (every 12 weeks with 72 weeks of follow-up). |
ACTG A5377 phase 1 dose escalation study to look at PK and viral load. N=52 in two studies:
(1) single escalation doses in 27 pts on stable ART and (2) 12-weekly infusions in 24 treatment-naive. |
PK results predicted 3-monthly dosing, with 38% higher levels in naive pts with detectable viral load.
Only 7/24 naive pts enrolled in part 2. The mean change to day 7: –0.10 log with 1 mg/ kg (n = 5) and –0.38 log with 30 mg/kg (n = 2). No grade 3 or higher AEs. |
First study in HIV+ people.
Safe and well tolerated supporting combination antibodies but very little impact on viral load. |
Tsibris A et al. O118.[18] |
| PGT121, PGDM1400, and VRC07-523LS.
Triple bNAb targeting three regions. No ART. |
N=12 HIV+ on stable ART. Screened for bNAb sensitivity at baseline. Stopped ART on day 1. | 10/12 stayed undetectable for at least 28 weeks.
5/12 for at least 38-44 weeks. 2/12 viral rebound with baseline resistance to PGT121 and PGDM14. |
Viral load remained undetectable for 24 to 44 weeks without ART in this small study but 2/12 rebounded early due to lack of sensitivity to one or more bNAbs at baseline. | Juelg BD et al. O121.
[19] |
* Lenacapavir requires an oral loading dose of 600 mg on days 1 and 2 of treatment.
Abbreviations: BL: baseline, bNAb: broadly neutralising monoclonal antibody, SC = subcutaneous, IM = intramuscular. IV = intravenous, OBR = optimised background regimen, pt = participant, VL = viral load.
Table 3: Early phase 1 studies on new compounds and formulations at CROI 2024
| Name | Drug class | Dose | Study design | Results | Comment | Ref |
| MK-8527 | NRTTI.
Similar to islatravir. |
Oral weekly. | N= 31 pts given single doses of 0.5, 1.0, 3.0 and 10 mg. | Mean decrease in VL at day 7 was ≥1.0 with IQ >4 with all doses. Tolerability generally good. | Dose to take forward not yet decided. | Carstens RP. et al. O115.
[20] |
| MK-8527 | NRTTI.
Similar to islatravir. |
Oral weekly. | 2 x ph1 dose-finding studies in HIV negative pts.
(1) 0.5–200 mg; fasted and 25 mg with high fat meal. (2) 3 x once-weekly doses up to 40 mg. |
Some food effect: reduced Cmax, no impact on AUC, 22% increase in intracelluar TP. Median half-life 216–291 hrs. | Good tolerability, no serious AEs.
PK supports weekly dosing. |
Gillespie G et al. O129.
[21] See also: Diamond TL. et al. P638. [22] |
| GS-1720 | INSTI. | Weekly oral. | Open-label, 10 day phase 1b study in treatment naive or viraemic (n=7).
450 mg on Day 1 and 2. |
VL reductions:
Day 8: –2.04 (95% CI 1.72, 2.36). Day 11: –2.44 (95% CI: 2.04, 2.83). No SAEs, Grade 3 or higher and no INSTI resistance. |
First results in HIV+ people.
VL reductions of >2 logs. Median half-life of 9.4 days with a single GS-1720 dose of 450 mg. |
Fichtenbaum CJ. et al. O116.
[23] |
| GS-5894 | NNRTI. | Once-weekly oral. | Preclinical studies. | Greater activity against a panel of 32 NNRTI-resistant isolates. | Early stages of once-weekly NNRTI.
Phase 1 |
Lansdon E et al. P636.
[24] |
| GS-9770 | Unboosted protease inhibitor. | Daily oral. | Preclinical studies. | Limited data include high potency and bioavailability, | Early stages on a daily oral protease inhibitor. | Han X et al. P637.
[25] |
| Ultra long-acting integrase inhibitors | ||||||
| Cabotegravir stearate (XVIR-110).
Cabotegravir pro-drug. |
Ultra long-acting INSTI. | 6 or 12 monthly IM injections. | PK study in rats and beagles. | Results support dosed once- or twice-yearly. |
Results support dosed once- or twice-yearly. |
Kearney BP et al. P656.
[26] |
| Dolutegravir implant. | Ultra long-cting implant. | 6-monthly implant. | PK studies in 6 female mice. | Plasma DTG concentrations well above the 4× PA-IC90 for ≥180 days. |
Biodegradable and removable, with drug levels falling within a week or removal. | Benhabbour SR. et al. P137. [27]
See also mouse study Foster EG et al. P557. [28] |
| Bictegravir | Ultra-longer acting INSTI.
Solid injectable formulation. |
Pre-clinical 6-weekly formulation. | 2 x preclinical PK in rats and macaques. | Maintained target levels in rats for 6 weeks and then dropped below Ctrough within a week. | Target levels within 3 hours and maintained for 42 days. No behavioural changes. | Arshad U et al. P653 (rats). [29]
Nayan MU. et al. P654. (macaques). [30] |
| bNAbs – early stage | ||||||
| 4E10 | bNAb
(MPER). |
Animal studies. | Two studies including bispecific in macaques and for prevention. | 0/3 animals became infected after high-dose challenge vs 3/3 controls. | Data showing bNAbs prevents infection in animals. | Arora J et al. P372. [31]
Parsons MS. et al. P412. [32] |
| ABBV-382 | bNAb
(anti-α4β7). |
Early preclinical. | NA | NA | Ng T et al. P411.
[33] |
|
| TMB-365/TMB-380 | Dual bNAbs. | 8-weekly one-hour infusions. | 3 doses in people suppressed on ART. N=30 using 2400, 3200 and 4800 mg.
Followed for 12 to |
30/30 completed the study.
No SAEs, grade 3/4 AEs or acute infusion events. |
First data in people living with HIV.
No viral load data yet. |
Markowitz M et al. P640.
[34] |
| TAF implant | Implant. | Implant. | Phase 1 safety and tolerability in African women. | The implant failed both acceptability and didn’t delivery sufficient drug. | Alternative formulations are needed. | Gengiah TN et al. O123.
[35] Also: P1136. [36] |
References
Unless stated otherwise, all references are to the programme and abstracts of the Conference on Retroviruses and Opportunistic Infections, 3 – 6 March 2024, Denver, Colorado, USA.
- Flexner CW. The end of oral? How long-acting formulations are changing the management of infectious diseases. CROI 2024, Denver. Plenary session 03.
https://www.croiconference.org/abstract/the-end-of-oral-how-long-acting-formulations-are-changing-the-management-of-infectious-diseases/ (abstract)
https://watch.croiwebcasts.org/croi2024/ap/52288 (webcast) - Pertinez H et al. Preclinical to human scaling of pharmacokinetics for long-acting injectable antiretrovirals. CROI 2024, Denver. Poster abstract 615.
https://www.croiconference.org/abstract/preclinical-to-human-scaling-of-pharmacokinetics-for-long-acting-injectable-antiretrovirals/ - Freed EO. HIV Assembly, Maturation Inhibitors, and Drug Resistance. Oral abstract 27.
https://www.croiconference.org/abstract/hiv-assembly-maturation-inhibitors-and-drug-resistance/ (abstract)
https://watch.croiwebcasts.org/croi2024/ap/52162 (webcast) - Hickey M et al. 24-week viral suppression in patients starting long-acting CAB/RPV without HIV viral suppression. CROI 2024, Denver. Poster abstract 628.
https://www.croiconference.org/abstract/24-week-viral-suppression-in-patients-starting-long-acting-cab-rpv-without-hiv-viral-suppression/ - Gandhi M et al. Case series examining the long-acting combination of lenacapavir and cabotegravir: call for a trial. CROI 2024, Denver. Poster abstract 629.
https://www.croiconference.org/abstract/case-series-examining-the-long-acting-combination-of-lenacapavir-and-cabotegravir-call-for-a-trial/ - Colson A et al. Efficacy and safety of weekly islatravir plus lenacapavir in PWH at 24 weeks: a phase ii study. CROI 2024, Denver. Oral abstract 208.
https://www.croiconference.org/abstract/efficacy-and-safety-of-weekly-islatravir-plus-lenacapavir-in-pwh-at-24-weeks-a-phase-ii-study (abstract)
https://watch.croiwebcasts.org/croi2024/ap/52354 (webcast) - Segal-Maurer S et al. Lenacapavir efficacy in CAPELLA patients with no fully active agents in optimized background regimen. CROI 2024, Denver. Poster abstract 630.
https://www.croiconference.org/abstract/lenacapavir-efficacy-in-capella-patients-with-no-fully-active-agents-in-optimized-background-regimen/ - Mounzer K et al. Phase II study of switch to daily BIC + LEN in individuals on a multitablet HIV treatment regimen. CROI 2024, Denver. Poster abstract 642.
https://www.croiconference.org/abstract/phase-ii-study-of-switch-to-daily-bic-len-in-individuals-on-a-multitablet-hiv-treatment-regimen/ - Le Hingrat Q et al. Rapid selection of HIV-2 capsid mutations after failure of a lenacapavir-containing regimen. CROI 2024, Denver. Poster abstract 682.
https://www.croiconference.org/abstract/rapid-selection-of-hiv-2-capsid-mutations-after-failure-of-a-lenacapavir-containing-regimen/ (abstract) - Demirdjian S et al. Phenotypic characterization of replication-impaired lenacapavir-resistant HIV clinical isolates. CROI 2024, Denver. Poster abstract 681.
https://www.croiconference.org/abstract/phenotypic-characterization-of-replication-impaired-lenacapavir-resistant-hiv-clinical-isolates/ (abstract) - Nguyen B et al. Crosstalk between resistance to the HIV-1 capsid inhibitor lenacapavir and viral fitness. CROI 2024, Denver. Poster abstract 302.
https://www.croiconference.org/abstract/crosstalk-between-resistance-to-the-hiv-1-capsid-inhibitor-lenacapavir-and-viral-fitness/ - Hansen D et al. Impact of capsid polymorphisms on viral fitness and the susceptibility to lenacapavir. CROI 2024, Denver. Poster abstract 304.
https://www.croiconference.org/abstract/impact-of-capsid-polymorphisms-on-viral-fitness-and-the-susceptibility-to-lenacapavir/ - Asante-Appiah E et al. Switching to doravirine/islatravir maintains viral suppression regardless of archived mutations. CROI 2024, Denver. Poster abstract 694.
https://www.croiconference.org/abstract/switching-to-doravirine-islatravir-maintains-viral-suppression-regardless-of-archived-mutations/ - Eron JJ. et al. Lenacapavir plus bNAbs for people with HIV and sensitivity to either teropavimab or zinlirvimab. CROI 2024, Denver. Oral abstract 120.
https://www.croiconference.org/abstract/lenacapavir-plus-bnabs-for-people-with-hiv-and-sensitivity-to-either-teropavimab-or-zinlirvimab/ (abstract)
https://www.croiwebcasts.org/console/player/52085 (webcast) - Taiwo B et al. Safety and Efficacy of VRC07-523LS plus long-acting cabotegravir in the phase II ACTG A5357 trial. CROI 2024, Denver. Oral abstract 119.
https://www.croiconference.org/abstract/safety-and-efficacy-of-vrc07-523ls-plus-long-acting-cabotegravir-in-the-phase-ii-actg-a5357-trial/ (abstract)
https://www.croiwebcasts.org/console/player/52084 (webcast) - Losos J et al. VH3810109 (N6LS) in adults with HIV-1 who are ART-naive: phase IIa BANNER efficacy data. CROI 2024, Denver. Oral abstract 117.
https://www.croiconference.org/abstract/vh3810109-n6ls-in-adults-with-hiv-1-who-are-art-naive-phase-iia-banner-efficacy-data/ (abstract)
https://www.croiwebcasts.org/console/player/52080 (webcast) - Win B et al. High-dose VH3810109 (N6LS) ± recombinant human hyaluronidase PH20: phase I SPAN study safety results. CROI 2024, Denver. Poster abstract 639.
https://www.croiconference.org/abstract/high-dose-vh3810109-n6ls-±-recombinant-human-hyaluronidase-ph20-phase-i-span-study-safety-results/ - Tsibris A et al. A first-in-human study of the trispecific HIV-1 broadly neutralizing antibody, SAR441236. CROI 2024, Denver. Oral abstract 118.
https://www.croiconference.org/abstract/a-first-in-human-study-of-the-trispecific-hiv-1-broadly-neutralizing-antibody-sar441236/ (abstract)
https://www.croiwebcasts.org/console/player/52081 (webcast) - Juelg BD. et al. Therapeutic efficacy of a triple combination of HIV-1 broadly neutralizing antibodies. CROI 2024, Denver. Late-breaker oral abstract 121.
https://www.croiconference.org/abstract/therapeutic-efficacy-of-a-triple-combination-of-hiv-1-broadly-neutralizing-antibodies/ abstract)
https://www.croiwebcasts.org/console/player/52086 (webcast) - Carstens RP. et al. Single dose administration of MK-8527, a novel NRTTI, in adults with HIV-1. CROI 2024, Denver. Oral abstract 115.
https://www.croiconference.org/abstract/single-dose-administration-of-mk-8527-a-novel-nrtti-in-adults-with-hiv-1/ (abstract)
https://www.croiwebcasts.org/console/player/52078 (webcast) - Gillespie G et al. Safety and pharmacokinetics of MK-8527, a novel nRTTI, in adults without HIV. CROI 2024, Denver. Oral abstract 129.
https://www.croiconference.org/abstract/safety-and-pharmacokinetics-of-mk-8527-a-novel-nrtti-in-adults-without-hiv/ (abstract)
https://www.croiwebcasts.org/console/player/52100 (webcast) - Diamond TL. et al. Discovery of MK-8527: a long-acting HIV-1 nucleoside reverse transcriptase translocation inhibitor. CROI 2024, Denver. Poster abstract 638.
https://www.croiconference.org/abstract/discovery-of-mk-8527-a-long-acting-hiv-1-nucleoside-reverse-transcriptase-translocation-inhibitor/ - Fichtenbaum CJ. et al. Antiviral activity, safety, and pharmacokinetics of GS-1720: a novel weekly oral InSTI. CROI 2024, Denver. Oral abstract 116.
https://www.croiconference.org/abstract/antiviral-activity-safety-and-pharmacokinetics-of-gs-1720-a-novel-weekly-oral-insti/ (abstract)
https://www.croiwebcasts.org/console/player/52079 (webcast) - Lansdon E et al. Preclinical characterization of GS-5894, a potent NNRTI with once-weekly oral dosing potential. CROI 2024, Denver. Poster abstract 636.
https://www.croiconference.org/abstract/preclinical-characterization-of-gs-5894-a-potent-nnrti-with-once-weekly-oral-dosing-potential/ - Han X et al. Discovery of GS-9770: A novel unboosted once daily oral HIV protease inhibitor. CROI 2024, Denver. Poster abstract 637.
https://www.croiconference.org/abstract/discovery-of-gs-9770-a-novel-unboosted-once-daily-oral-hiv-protease-inhibitor/ - Kearney BP. et al. Cabotegravir stearate (XVIR-110), an InSTI prodrug, provides ultra-long acting cabotegravir exposure. CROI 2024, Denver. Poster abstract 656.
https://www.croiconference.org/abstract/cabotegravir-stearate-xvir-110-an-insti-prodrug-provides-ultra-long-acting-cabotegravir-exposure/ - Benhabbour SR. et al. Safety and pharmacokinetics of ultra-long-acting dolutegravir in-situ forming implant. CROI 2024, Denver. Poster abstract 1137.
https://www.croiconference.org/abstract/safety-and-pharmacokinetics-of-ultra-long-acting-dolutegravir-in-situ-forming-implant/ - Foster EG et al. Long-acting dolutegravir formulation reduces fetal drug exposure. Poster abstract 557.
https://www.croiconference.org/abstract/long-acting-dolutegravir-formulation-reduces-fetal-drug-exposure/ - Arshad U et al. Preclinical pharmacokinetics of a novel long-acting bictegravir solid injectable in rats. CROI 2024, Denver. Poster abstract 653.
https://www.croiconference.org/abstract/preclinical-pharmacokinetics-of-a-novel-long-acting-bictegravir-solid-injectable-in-rats/ - Nayan MU. et al. Shape-shifting tail decay is the pharmacokinetic profile of an ultra-long acting bictegravir prodrug. CROI 2024, Denver. Poster abstract 654.
https://www.croiconference.org/abstract/shape-shifting-tail-decay-is-the-pharmacokinetic-profile-of-an-ultra-long-acting-bictegravir-prodrug/ - Arora J et al. MHRP.01, an MPER targeting bNAb, enables further definition of the 4E10-class of bNAbs. CROI 2024, Denver. Poster abstract 372.
https://www.croiconference.org/abstract/mhrp-01-an-mper-targeting-bnab-enables-further-definition-of-the-4e10-class-of-bnabs/ - Parsons MS. et al. 10e8.4/iMAb bispecific antibody for immunoprophylaxis against high-dose intravenous shiv exposure. CROI 2024, Denver. Poster abstract 412.
https://www.croiconference.org/abstract/10e8-4-imab-bispecific-antibody-for-immunoprophylaxis-against-high-dose-intravenous-shiv-exposure/ - Ng T et al. ABBV-382, an anti-α4β7 Ab that enhances HIV-1 antigen presentation for immune- mediated viral control. CROI 2024, Denver. Poster abstract 411.
https://www.croiconference.org/abstract/abbv-382-an-anti-α4β7-ab-that-enhances-hiv-1-antigen-presentation-for-immune-mediated-viral-control/ - Markowitz M et al. A dose escalation study of safety & PK of TMB-365 & TMB-380 in people with suppressed HIV. CROI 2024, Denver. Poster abstract 640.
https://www.croiconference.org/abstract/a-dose-escalation-study-of-safety-pk-of-tmb-365-tmb-380-in-people-with-suppressed-hiv/ - Gengiah TN et al. Phase I safety, tolerability and pharmacokinetics of tenofovir alafenamide implants in African women
CROI 2024, Denver. Oral abstract 123.
https://www.croiconference.org/abstract/phase-i-safety-tolerability-and-pharmacokinetics-of-tenofovir-alafenamide-implants-in-african-women/ (abstract)
https://watch.croiwebcasts.org/croi2024/ap/52092 (webcast) - Gengiah TN et al. CAPRISA 018 Trial: Acceptability of Tenofovir Alafenamide Implants for HIV PrEP in African Women. CROI 2024, Denver. Poster abstract.1136,
https://www.croiconference.org/abstract/caprisa-018-trial-acceptability-of-tenofovir-alafenamide-implants-for-hiv-prep-in-african-women/