CROI 2019 Abstract eBook
mL and TND Status Overall and by BL HIV-1 RNA Subgroup were estimated using non-parametric Kaplan-Meier method. Results: At Week 48 similar proportion of subjects had snapshot TND in the 2DR and 3DR arms (77% [553/716] vs 73% [525/717], adjusted difference 3.8%, 95% CI -0.6%, 8.2%) and proportions were also similar at earlier visits: Weeks 4 (34% vs 32%), 8 (52% vs 49%), 12 (60% vs 57%), 16 (59% vs 56%), 24 (65% vs 63%), and 36 (65% vs 68%). While similar response rates were seen in subjects with BL VL ≤100,000c/mL, response rates were higher in 2DR vs 3DR subjects with BL VL >100,000 c/mL. (Table). Median time for 2DR vs 3DR to TND was 57 days for both overall, 57 days for both in ≤100,000c/mL at BL strata, and 113 days vs 169 days for BL >100,000c/mL subgroup. Conclusion: DTG/3TC and DTG+TDF/FTC had similar proportions of TND by snapshot at all Weeks. Snapshot response rates based on TND status at Week 48 were similar between arms at ≤100,000c/mL BL subgroup and higher for DTG/3TC in >100,000c/mL BL category. Median time to TND was similar overall and in BL VL≤100,000c/mL subgroup, and less for DTG/3TC vs DTG+TDF/ FTC if >100,000c/mL at BL. These data, utilizing a more stringent snapshot criteria, continue to demonstrate the effectiveness and potency of DTG+3TC in treatment-naïve subjects.
therapy, we observed a positive relationship between plasma residual viremia and HIV cellular reservoir size under the maintenance DTG+3TC dual therapy.
492 IMPACT OF DUAL THERAPY ON THE CD4/CD8 RATIO IS SIMILAR TO TRIPLE THERAPY AT 48 WEEKS María I. Figueroa 1 , Antonio Camiro-Zuñiga 2 , Juan Sierra Madero 2 , Jaime Andrade Villanueva 3 , Jose R. Arribas 4 , Javier R. Lama 5 , Diego M. Cecchini 6 , Gustavo Lopardo 7 , Brenda Crabtree-Ramírez 2 , Pablo F. Belaunzaran-Zamudio 2 , Patricia Patterson 1 , Valeria I. Fink 1 , Omar G. Sued 1 , Pedro Cahn 1 , for the GARDEL- ANDES study group 1 Fundación Huésped, Buenos Aires, Argentina, 2 Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico, 3 Hospital Civil Fray Antonio Alcalde, Guadalajara, Mexico, 4 La Paz University Hospital, Madrid, Spain, 5 Asociacion Civil Impacta Salud y Educacion, Lima, Peru, 6 Hospital Argerich, Buenos Aires, Argentina, 7 Centro de Estudios Infectológicos, Buenos Aires, Argentina Background: The requirement for lifelong ART for HIV infection has highlighted interest in dual therapy (DT) to minimize cumulative drug exposure. One of the enduring concerns regarding DT is its impact on markers of immune dysfunction and its potential clinical implications. A recent retrospective study suggests that when compared with triple therapy (TT), DT regimens might decrease the CD4/CD8 ratio. A low CD4/CD8 ratio has been associated to an increase in non-AIDS associated events, and thus warrants further investigation in patients treated with DT Methods: Sub-analysis of the GARDEL and ANDES randomized controlled trials, both based on ritonavir-boosted protease inhibitors (bPI) plus 3TC. Patients’ CD4/CD8 ratios were compared between DT and TT arms at baseline and at 12, 24, 36 and 48 weeks. Follow-up was censored at any of the following: virological failure, opportunistic infection, severe disease (defined as requiring hospitalization) or pregnancy. Main outcomes were median CD4/CD8 ratio and proportion of patients achieving a CD4/CD8 ratio >1, both measured at 48 weeks of follow-up. Subgroup analysis of patients >50 years of age, baseline CD4 count <200 cells/ml, HIV viral load >100,000 copies/ml and bPI treatment were performed. Comparisons were made utilizing regression to the median and multilevel models. Analyses were performed with STATA v12.0. Results: All 571 patients from both studies were included (292 with DT and 279 with TT). 268 with DT and 243 with TT completed 48 weeks of follow-up. DT had no statistically significant difference when compared to TT on the median CD4/CD8 ratio at 48 weeks of follow-up (0.632 vs 0.617, p=0.729) or on the proportion of patients that achieved a CD4/CD8 ratio >1 (17.9% vs 19.3%, p=0.678). Median increase in CD4/CD8 ratio from baseline to week 48 was similar between both groups (0.273 vs 0.261, p=0.125). The rest of the subgroup analysis showed no further differences Conclusion: With the recently reported virologic success of DT regimens, addressing its long-term impact on immune markers remains an important subject. These results show that the impact of DT regimens on the CD4/CD8 ratio is similar to that of TT during the first year of treatment. Longer follow-up of larger populations of patients on DT should address the rates of non-AIDS associated events related to these regimens. Also, these results should be confirmed in InSTI-based DT
491 RESIDUAL HIV-1 RNA, HIV-1 DNA, AND DRUG PLASMA CMIN IN DUAL DTG+3TC, ANRS 167 LAMIDOL Charlotte Charpentier 1 , Gilles Peytavin 1 , Charles Burdet 1 , Roland Landman 1 , Minh Le 1 , Christine Katlama 2 , Gilles Collin 1 , Aida Benalycherif 3 , André Cabié 4 , France Mentré 1 , Yazdan Yazdanpanah 1 , Diane Descamps 1 , Veronique Joly 1 , for the LAMIDOL study group 1 AP–HP, Hôpital Bichat-Claude Bernard, Paris, France, 2 AP–HP, Hôpitaux Universitaires Pitié Salpêtrière, Paris, France, 3 IMEA, Paris, France, 4 CHU Fort de France, Fort de France, Martinique Background: The aim of this study was to assess HIV cellular reservoir size, plasma residual viremia and drug plasma concentrations in virologically- suppressed patients receiving a dual-class therapy: DTG+3TC. Methods: Patients were those included in the ANRS 167 LAMIDOL, a non comparative open-label, single arm, multicenter trial. HIV total DNA was measured at D0 and W48 of DTG+3TC using real-time PCR (Biocentric®; limit of quantification [LOQ]=10 c/PCR). Ultra-sensitive plasma viral load (USpVL) was measured to assess plasma residual viremia at D0, W24 and W48. The maximum volume of available plasma was centrifuged, the pellet was resuspended, and USpVL was determined using COBAS® HIV-1, v2.0. The LOQ depended on the available volume of plasma (3 c/mL in 90% of cases). USpVL was considered to be below the limit of detection (LOD) when no PCR signal was detected. The evolution of the USpVL over time was analyzed using a linear mixed effects model. The relationship between HIV DNA and USpVL was studied using linear regression. Total and unbound plasma DTG concentrations (Cmin) were measured using UPLC-MS/MS. Results: Paired D0 and W48 HIV total DNA results were obtained in 100 patients. Two and four patients showed HIV DNA below the LOQ at D0 and W48, respectively. Median (IQR) HIV DNA was 2.49 log10 c/106 PBMC (2.17-2.95) at D0 and 2.52 (2.09-2.89) at W48 (p=0.28). Plasma residual viremia was measured in 101, 101 and 99 patients at D0, W24 and W48 of DTG+3TC, respectively. The proportion of patients with USpVL Conclusion: No change was observed, during the first year of DTG+3TC maintenance dual therapy, in plasma residual viremia level or in HIV cellular reservoir size with stable plasma DTG Cmin. As described under triple-class
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