Meeting the WHO 90% target : antiretroviral treatment efficacy in Poland is associated with baseline clinical patient characteristics

Introduction: Modern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral load, with the 90% virologic success rate, meeting the WHO target in most clinical settings. The aim of this study was to analyse antiretroviral treatment efficacy in Poland and to identify variables associated with virologic suppression. Methods: Cross-sectional data on 5152 (56.92% of the countrywide treated at the time-point of analysis) patients on cART for more than six months with at least one HIV-RNA measurement in 2016 were collected from 14 Polish centres. Patients’ characteristics and treatment type-based outcomes were analysed for the virologic suppression thresholds of <50 and <200 HIV-RNA copies/ml. CART was categorized into two nucleos(t)ide (2NRTI) plus non-nucleoside reverse transcriptase (NNRTI) inhibitors, 2NRTI plus protease (PI) inhibitor, 2NRTI plus integrase (InI) inhibitor, nucleos(t)ide sparing PI/r+InI and three drug class regimens. For statistics Chi-square and U-Mann Whitney tests and adjusted multivariate logistic regression models were used. Results: Virologic suppression rates of <50 copies/mL were observed in 4672 (90.68%) and <200 copies/mL in 4934 (95.77%) individuals. In univariate analyses, for the suppression threshold <50 copies/mL higher efficacy was noted for 2NRTI+NNRTI-based combinations (94.73%) compared to 2NRTI+PI (89.93%), 2NRTI+InI (90.61%), nucleos(t)ide sparing PI/r+InI (82.02%) and three drug class regimens (74.49%) (p < 0.0001), with less pronounced but significant differences for the threshold of 200 copies/mL [2NRTI+NNRTI-97.61%, 2NRTI+PI-95.27%, 2NRTI+InI-96.61%, PI/r+InI- 95.51% and 86.22% for three drug class cART) (p < 0.0001). However, in multivariate model, virologic efficacy for viral load <50 copies/mL was similar across treatment groups with significant influence by history of AIDS [OR:1.48 (95%CI:1.01–2.17) if AIDS diagnosed, p = 0.046], viral load < 5 log copies/mL at care entry [OR:1.47 (95%CI:1.08–2.01), p = 0.016], baseline lymphocyte CD4 count ≥200 cells/µL [OR:1.72 (95%CI:1.04–2.78), p = 0.034] and negative HCV serology [OR:1.97 (95%CI:1.29–2.94), p = 0.002]. For viral load threshold <200 copies/mL higher likelihood of virologic success was only associated with baseline lymphocyte CD4 count ≥200 cells/µL [OR:2.08 (95%CI:1.01–4.35), p = 0.049] and negative HCV status [OR:2.84 (95%CI:1.52–5.26), p = 0.001]. Conclusions: Proportion of virologically suppressed patients is in line with WHO treatment target confirming successful application of antiretroviral treatment strategy in Poland. Virological suppression rates depend on baseline patient characteristics, which should guide individualized antiretroviral tre0atment decisions

Molecular epidemiology and HIV-1 variant evolution in Poland between 2015 and 2019

Abstract The occurrence of HIV-1 subtypes differs worldwide and within Europe, with non-B variants mainly found across different exposure groups. In this study, we investigated the distribution and temporal trends in HIV-1 subtype variability across Poland between 2015 and 2019. Sequences of the pol gene fragment from 2518 individuals were used for the analysis of subtype prevalence. Subtype B was dominant (n = 2163, 85.90%). The proportion of subtype B-infected individuals decreased significantly, from 89.3% in 2015 to 80.3% in 2019. This was related to the increasing number of subtype A infections. In 355 (14.10%) sequences, non-B variants were identified. In 65 (2.58%) samples, recombinant forms (RFs) were noted. Unique recombinant forms (URFs) were found in 30 (1.19%) sequences. Three A/B recombinant clusters were identified of which two were A6/B mosaic viruses not previously described. Non-B clades were significantly more common among females (n = 81, 22.8%, p = 0.001) and heterosexually infected individuals (n = 45, 32.4%, p = 0.0031). The predominance of subtype B is evident, but the variability of HIV-1 in Poland is notable. Almost half of RFs (n = 65, 2.58%) was comprised of URFs (n = 30, 1.19%); thus those forms were common in the analyzed population. Hence, molecular surveillance of identified variants ensures recognition of HIV-1 evolution in Poland

Meeting the WHO 90% target: antiretroviral treatment efficacy in Poland is associated with baseline clinical patient characteristics

Introduction: Modern combined antiretroviral therapies (cART) allow to effectively suppress HIV-1 viral load, with the 90% virologic success rate, meeting the WHO target in most clinical settings. The aim of this study was to analyse antiretroviral treatment efficacy in Poland and to identify variables associated with virologic suppression. Methods: Cross-sectional data on 5152 (56.92% of the countrywide treated at the time-point of analysis) patients on cART for more than six months with at least one HIV-RNA measurement in 2016 were collected from 14 Polish centres. Patients’ characteristics and treatment type-based outcomes were analysed for the virologic suppression thresholds of <50 and <200 HIV-RNA copies/ml. CART was categorized into two nucleos(t)ide (2NRTI) plus non-nucleoside reverse transcriptase (NNRTI) inhibitors, 2NRTI plus protease (PI) inhibitor, 2NRTI plus integrase (InI) inhibitor, nucleos(t)ide sparing PI/r+InI and three drug class regimens. For statistics Chi-square and U-Mann Whitney tests and adjusted multivariate logistic regression models were used. Results: Virologic suppression rates of <50 copies/mL were observed in 4672 (90.68%) and <200 copies/mL in 4934 (95.77%) individuals. In univariate analyses, for the suppression threshold <50 copies/mL higher efficacy was noted for 2NRTI+NNRTI-based combinations (94.73%) compared to 2NRTI+PI (89.93%), 2NRTI+InI (90.61%), nucleos(t)ide sparing PI/r+InI (82.02%) and three drug class regimens (74.49%) (p < 0.0001), with less pronounced but significant differences for the threshold of 200 copies/mL [2NRTI+NNRTI-97.61%, 2NRTI+PI-95.27%, 2NRTI+InI-96.61%, PI/r+InI- 95.51% and 86.22% for three drug class cART) (p < 0.0001). However, in multivariate model, virologic efficacy for viral load <50 copies/mL was similar across treatment groups with significant influence by history of AIDS [OR:1.48 (95%CI:1.01–2.17) if AIDS diagnosed, p = 0.046], viral load < 5 log copies/mL at care entry [OR:1.47 (95%CI:1.08–2.01), p = 0.016], baseline lymphocyte CD4 count ≥200 cells/µL [OR:1.72 (95%CI:1.04–2.78), p = 0.034] and negative HCV serology [OR:1.97 (95%CI:1.29–2.94), p = 0.002]. For viral load threshold <200 copies/mL higher likelihood of virologic success was only associated with baseline lymphocyte CD4 count ≥200 cells/µL [OR:2.08 (95%CI:1.01–4.35), p = 0.049] and negative HCV status [OR:2.84 (95%CI:1.52–5.26), p = 0.001]. Conclusions: Proportion of virologically suppressed patients is in line with WHO treatment target confirming successful application of antiretroviral treatment strategy in Poland. Virological suppression rates depend on baseline patient characteristics, which should guide individualized antiretroviral tre0atment decisions

Week 96 efficacy and safety results of the phase 3, randomized EMERALD trial to evaluate switching from boosted-protease inhibitors plus emtricitabine/tenofovir disoproxil fumarate regimens to the once daily, single-tablet regimen of darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) in treatment-experienced, virologically-suppressed adults living with HIV-1

International audienceDarunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) 800/150/200/10 mg was investigated through 96 weeks in EMERALD (NCT02269917).Virologically-suppressed, HIV-1-positive treatment-experienced adults (previous non-darunavir virologic failure [VF] allowed) were randomized (2:1) to D/C/F/TAF or boosted protease inhibitor (PI) plus emtricitabine/tenofovir-disoproxil-fumarate (F/TDF) over 48 weeks. At week 52 participants in the boosted PI arm were offered switch to D/C/F/TAF (late-switch, 44 weeks D/C/F/TAF exposure). All participants were followed on D/C/F/TAF until week 96. Efficacy endpoints were percentage cumulative protocol-defined virologic rebound (PDVR; confirmed viral load [VL] ≥50 copies/mL) and VL < 50 copies/mL (virologic suppression) and ≥50 copies/mL (VF) (FDA-snapshot analysis).Of 1141 randomized patients, 1080 continued in the extension phase. Few patients had PDVR (D/C/F/TAF: 3.1%, 24/763 cumulative through week 96; late-switch: 2.3%, 8/352 week 52–96). Week 96 virologic suppression was 90.7% (692/763) (D/C/F/TAF) and 93.8% (330/352) (late-switch). VF was 1.2% and 1.7%, respectively. No darunavir, primary PI, tenofovir or emtricitabine resistance-associated mutations were observed post-baseline. No patients discontinued for efficacy-related reasons. Few discontinued due to adverse events (2% D/C/F/TAF arm). Improved renal and bone parameters were maintained in the D/C/F/TAF arm and observed in the late-switch arm, with small increases in total cholesterol/high-density-lipoprotein-cholesterol ratio. A study limitation was the lack of a control arm in the week 96 analysis.Through 96 weeks, D/C/F/TAF resulted in low PDVR rates, high virologic suppression rates, very few VFs, and no resistance development. Late-switch results were consistent with D/C/F/TAF week 48 results. EMERALD week 96 results confirm the efficacy, high genetic barrier to resistance and safety benefits of D/C/F/TAF