CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Results: There was no difference in the proportion of participants with related Grade 2 or higher AEs between groups. The most frequent AEs were mild nasal irritation and congestion; two participants in the Q-GRFT arm withdrew due to nasal congestion. After adjusting for the dilution factor, Q-GRFT was detected at 50-200X the IC 90 in NP and nares swabs at 1 hour and at 1-2X the IC 90 at 24 hours after use (Table); results did not differ by sex. ADA was detectable in low levels in plasma in 46% of participants; ADA's impact on antiviral activity is being assessed. No Q-GRFT was detected in plasma samples (lower limit of quantitation: 3 ng/mL). Acceptability of the nasal spray (somewhat or highly acceptable) was similar between the two groups (87% Q-GRFT vs. 100% placebo, P= 0.28). Conclusion: The Q-GRFT nasal spray administered for a total of 14 doses was well tolerated and demonstrated persistence up to 24 hours in clinically important anatomic sites without systemic absorption. This nasal spray could address the need for an on-demand product for prevention of SARS-CoV-2.

PI-based regimens than from failing 1st-line NNRTI-based regimens. Infrequent emergence of DTG mutations and lower TFV-DP concentrations in unsuppressed vs suppressed suggest that incomplete adherence to TLD was the major mechanism for failure to suppress viremia.

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Viremia and Drug Resistance 2 Years After Routine Switching to Dolutegravir-Based First-Line ART Veronika Whitesell Skrivankova 1 , Jacqueline Huwa 2 , Guy Muula 3 , Geldert D. Chiwaya 2 , Esau Banda 3 , Shameem Buleya 2 , Belinda Chihota 3 , Joseph Chintedza 2 , Carolyn Bolton 3 , Thokozani Kalua 4 , Roger Kouyos 5 , Gilles Wandeler 6 , Matthias Egger 7 , Richard J Lessells 8 1 Institute of Social and Preventive Medicine, Bern, Switzerland, 2 Lighthouse Trust, Lilongwe, Malawi, 3 Centre for Infectious Disease Research in Zambia, Lusaka, Zambia, 4 University of Mayrland, Baltimore in Malawi, Lilongwe, Malawi, 5 University Hospital Zurich, Zurich, Switzerland, 6 University Hospital of Bern, Bern, Switzerland, 7 University of Bern, Bern, Switzerland, 8 KwaZulu-Natal Research Innovation and Sequencing Platform (KRISP), Durban, South Africa Background: People living with HIV (PLHIV) who switch to a dolutegravir (DTG)-based regimen with HIV-1 viremia and possibly NRTI resistance may be at a higher risk of virologic failure and integrase strand transfer inhibitor (INSTI) resistance. We report viral load (VL) and drug resistance from the 2-year follow up of the DTG SWITCH study in Malawi and Zambia. In Malawi, PLHIV were switched irrespective of their VL value whereas in Zambia, only patients with the last routine VL <1000 copies/mL were switched. Methods: We present proportions of patients with viremia (VL >400 copies/ mL) 2 years after switching (+/-90 days) to DTG-based first-line ART between Nov/2019 and Dec/2020, by country and VL at switch. We calculated relative risks (RR) of viremia at 2 years, with exact 95% confidence intervals (CI). We also report major integrase drug resistance mutations (DRM) detected in 2-year samples among participants with VL >1000 copies/mL. Results: Of PLHIV switched during the study period, 1422/1458 (97.5%) in Malawi and 1410/1417 (99.5%) in Zambia had a viral load measurement available at switch and were eligible. Most participants were women; 1409 (91%) in Malawi and 1169 (83%) in Zambia; median time on ART was 6.1 years. Seventy-seven PLHIV were viremic at baseline in Malawi (5.4%), compared to 42 (3.0%) in Zambia. In Malawi, 1149/1422 (81%) participants had a 2-year VL available: among those viremic at switch, 27.8% were viremic at 2 years compared to 3.7% among those suppressed at switch, RR=7.8 (4.2-13.4). In Zambia, 1248/1410 (89%) participants had a 2-year VL; the corresponding percentages were 5.1% and 1.7%, RR=3.1 (0.4-12.0). Viremia at switch was strongly associated with an increased risk of viremia at 2 years in Malawi but not in Zambia (Table). Integrase sequencing was successful for 45 of 62 samples with VL ≥1000 c/mL at 2 years. Two had major INSTI DRM: G118R, E138K, T66A (Malawi); G118R, E138K (Zambia); and both were viremic at switch and/or 1 year. The sample from Malawi also contained NRTI mutations (D67N, K70R, M184V, K219Q). Conclusion: Viremia was uncommon two years after the programmatic switch to DTG-based first-line ART, and only two cases of emergent DTG drug resistance were detected. Still, PLHIV switching to DTG with viremia had a substantially higher risk of viremia at 2 years than PLHIV with viral suppression at switch. The Zambian policy of only switching virologically suppressed patients may have reduced the risk of developing viremia and virologic failure on DTG.

Poster Abstracts

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ACTG 5381: Virologic and Resistance Outcomes After Switch to TLD for Failing 1st- or 2nd-Line ART Carole L. Wallis 1 , Caitlyn McCarthy 2 , Catherine Godfrey 3 , Sarita Shah 4 , Cissy M. Kityo 5 , Urvi M. Parikh 6 , Gary Maartens 7 , Isaac Tsikhutsu 8 , Fatma F. Some 9 , Samuel Pierre 10 , Yvetot Joseph 10 , Charles W. Flexner 11 , Michael D. Hughes 2 , John W. Mellors 6 , for the A5381 Team 1 Bio Analytical Research Corporation South Africa, Johannesburg, South Africa, 2 Harvard TH Chan School of Public Health, Boston, MA, USA, 3 US Department of State, Washington, DC, USA, 4 Emory University, Atlanta, GA, USA, 5 Joint Clinical Research Centre, Kampala, Uganda, 6 University of Pittsburgh, Pittsburgh, PA, USA, 7 University of Cape Town, Cape Town, South Africa, 8 Kenya Medical Research Institute, Kericho, Kenya, 9 Moi University, Eldoret, Kenya, 10 GHESKIO, Port-au-Prince, Haiti, 11 The Johns Hopkins University, Baltimore, MD, USA Background: Most countries recommend tenofovir-lamivudine-dolutegravir (TLD) for individuals starting antiretroviral therapy (ART) or switching from suppressive 1st-line NNRTI- or 2nd-line PI-based ART but country guidelines have been more variable about using TLD for those with unsuppressed (plasma HIV-1 RNA>1000 c/ml) viral load (VL) on ART. We report virologic and resistance outcomes for unsuppressed individuals switching to TLD in the A5381 prospective cohort study. Methods: Participants were adults or adolescents aged >10y with VL>1000 c/ ml switching from 1st-line NNRTI-based (Cohort 1) or 2nd-line PI-based (Cohort 2) ART. Primary endpoints were proportion with VL≤1000 c/ml at 6 months (m) after switch among those still on TLD and proportion with new DTG resistance mutations (baseline and 6m samples were sequenced for those with VL>1000 c/ml at 6m). A case-control study (unsuppressed vs suppressed) evaluated tenofovir diphosphate (TFV-DP) concentrations in dried blood spots. Results: From Dec2019 to Sep2022, 44 participants were enrolled into Cohort 1 (77% female, median age 33y) and 173 were enrolled into Cohort 2 (57% female, median age 41y) at 13 sites in Haiti and Africa. In Cohort 1, median VL was 4.0 log 10 c/ml, CD4 count was 306 cells/mm 3 , time on ART was 5.5y. In Cohort 2, median VL was 4.2 log 10 c/ml, CD4 count was 262 cells/mm 3 , time on ART was 5.4y. Of 42 participants in Cohort 1 on TLD with VL results at 6m, 88% had VL≤1000 c/ml (95% CI: 74%, 96%) and 83% had VL≤200 c/ml (CI: 69%, 93%); 0/42 (0%) had new DTG mutations (CI: 0%, 8%). Of 165 participants in Cohort 2 on TLD with VL results at 6m, 72% had VL≤1000 c/ml (CI: 64%, 78%) and 67% had VL≤200 c/ml (CI: 59%, 74%); 2/163 (1.2%, CI: 0%, 4%) had new DTG mutations (G118R and R263K). Viral suppression declined in both groups over 24m (Table). TFV-DP concentrations were lower among participants with VL >1000 vs ≤1000 at 6m: median 127 vs 663 fmol/punch in Cohort 1 (p=0.19; n=5 pairs) and 169 vs 1029 fmol/punch in Cohort 2 (p<0.001 Conclusion: Participants with unsuppressed VL who switched to TLD had improved but suboptimal virologic suppression (<90%) that did not improve over time. Viral suppression was lower in participants switching from 2nd-line

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