Suchergebnisse

IntroductionSequencing of the third hypervariable loop allows to identify genotype‐based HIV tropism. R5‐tropic viruses associated with early stages of infection are preferentially transmitted, while non‐R5 HIV‐1 tropism has been associated with severe immunodeficiency and lower lymphocyte CD4 nadir and may reflect delayed HIV diagnosis. In this study, we investigate the changes in tropism frequency from 2007 to 2013.Materials and MethodsStudy included 194 patients with confirmed HIV infection linked to care in 2007–2013. Baseline plasma samples from treatment naive patients were used for HIV‐1 genotypic tropism assessment based on triplicate V3 loop sequencing. Non‐R5 tropism prediction thresholds were assigned using a false positive rate (FPR) of 10% and 5.75% FPR and associated with clinical and laboratory data (age, gender, date of HIV diagnosis, route of transmission, CDC clinical category at diagnosis, pretreatment HIV viral load, baseline and nadir lymphocyte CD4 counts). For statistics, chi‐square and Mann–Whitney U tests were used, time trends were examined using logistic regression (R statistical platform, v. 3.1.0) for binary variables and linear regression for continuous ones.ResultsOverall non‐R5 tropism frequency for the 5.75% FPR was 15.5% and 27.8% for 10% FPR. Frequency of the non‐R5 tropism predicted using 5.75% FPR increased significantly from 2007 (0%) to 2013 (25%) [OR: 1.44 (95% CI 1.14–1.86), p=0.003, rough slope +3.89%/year] (Figure 1a). With 10% FPR, the frequency changed from 7% (2007) to 33% (2013) [OR: 1.17 (95% CI 0.99–1.39), p=0.054, rough slope +3.0%/year] (Figure 1b). Baseline lymphocyte CD4 count and nadir, as well as pretreatment HIV‐1 viral loads were stable over time of observation (r=0.014, p=0.84; r=0.13, p=0.085; r=0.016, p=0.83 for CD4 baseline, nadir and HIV load, respectively). Frequency of AIDS at HIV diagnosis increased from 21.4% in 2007 to 38.0% in 2013, however trend over time was insignificant [OR: 1.1 (95% CI 0.95–1.31), p=0.19]. Temporal trends for HIV transmission route, gender, non‐B variant frequencies also were not significant.ConclusionsR5 tropism predominates among the treatment naive individuals but increase in the frequency of non‐R5 tropic variants may limit clinical efficacy of the coreceptor inhibitors. Increased prevalence of non‐R5 HIV‐1 may be related to late care entry and higher number of AIDS diagnoses in the recent years.

IntroductionRilpivirine (RPV) is a second‐generation non‐nucleoside reverse transcriptase inhibitor (NNRTI) that was recently approved for the treatment of antiretroviral‐naïve individuals with HIV‐1 viral load of <100,000 copies/ml. As transmission of the drug resistance mutations to this NNRTI may affect treatment outcomes, the frequency of primary, RPV‐associated drug resistance mutations was assessed in this study.MethodsFor the study, 244 viral genome sequences from antiretroviral‐naïve individuals were obtained by bulk sequencing. RPV‐associated mutations were divided into RPV resistance mutations (K101E/P, E138A/G/K/Q/R, V179L, Y181C/I/V, Y188L, H221Y, F227C and M230I/L) according to the International AIDS Society‐USA (IAS‐USA) mutation list and variants potentially affecting RPV susceptibility (L100I, K101H/T, E138S, V179F/D/G/T, G190A/E/S, F227L and M230V) based on the in vitro and in vivo data.ResultsIAS‐USA RPV drug resistance mutations were found in 5.3% sequences, with E138A and E138G being the most common (3.7 and 0.8%, respectively), followed by K101E (0.4%) and Y181C (0.4%), with no significant differences in the frequency between subtype B and non‐B clades. Mutations potentially reducing RPV susceptibility were found in 2.5% of sequences, and they included V179D (1.6%) and G190A (0.8%), with equal distribution among non‐B (n=2, 2.5%) and subtype B (n=4, 2.5%) clades. Clustering of RPV mutations was infrequent.ConclusionsPrevalence of RPV‐associated drug resistance mutations was low in the analysed sample and did not vary across the subtypes. The frequency of variants with potential influence on RPV susceptibility was similar among non‐B variants if compared to B clades. Transmitted drug resistance to RPV is uncommon, which makes this a good option for the treatment of ARV‐naïve patients; however, genotype resistance testing should remain compulsory before starting an RPV‐based regimen.

IntroductionCCR5 (R5) tropic viruses are associated with early stages of infection, whereas CXCR4 (X4) HIV‐1 tropism has been associated with severe immunodeficiency. We investigated the temporal changes in the genotype‐predicted tropism frequency and the phylogenetic relationships between the R5 and non‐R5 clades.MethodsA cohort of 194 patients with a newly diagnosed HIV infection that was linked to their care from 2007 to 2014 was analyzed. Baseline plasma samples were used to assess the HIV‐1 genotypic tropism with triplicate V3‐loop sequencing. The non‐R5 tropism prediction thresholds were assigned using a false positive rate (FPR) of 10 and 5.75% and associated with clinical and laboratory data. The transmission clusters were analyzed using pol sequences with a maximum likelihood and Bayesian inference.ResultsThe overall non‐R5 tropism frequency for 5.75% FPR was 15.5% (n=30) and 27.8% (n=54) for 10% FPR. The frequency of the non‐R5 tropism that was predicted using 5.75% FPR increased significantly from 2007 (0%) to 2014 (n=5/17, 29.4%) (p=0.004, rough slope +3.73%/year) and from 0% (2007) to 35.3% (2014, n=6/17) (p=0.071, rough slope +2.9%/year) using 10% FPR. Increase in the asymptomatic diagnoses over time was noted (p=0.05, rough slope +3.53%/year) along with a tendency to increase the lymphocyte CD4 nadir (p=0.069). Thirty‐two clusters were identified, and non‐R5 tropic viruses were found for 26 (30.95%) sequences contained within 14 (43.8%) clusters. Non‐R5 tropism was associated with subtype D variants (p=0.0001) and the presence of CCR5 Δ32/wt genotype (p=0.052).ConclusionsR5 tropism predominates among the treatment of naive individuals, but the increases in the frequency of non‐R5 tropic variants may limit the clinical efficacy of the co‐receptor inhibitors. The rising prevalence of non‐R5 HIV‐1 may indicate transmission of X4 clades.

IntroductionIn Poland, the HIV epidemic has shifted recently from being predominantly related to injection drug use (IDU) to being driven by transmissions among men‐who‐have‐sex‐with‐men (MSM). The number of new HIV cases has increased in the recent years, while no current data on the transmitted drug resistance associated mutations (tDRM) frequency trend over time are available from 2010. In this study, we analyze the temporal trends in the spread of tDRM from 2008 to 2013.Materials and MethodsPartial pol sequences from 833 antiretroviral treatment‐naive individuals of European descent (Polish origin) linked to care in 9 of 17 Polish HIV treatment centres were analyzed. Drug resistance interpretation was performed according to WHO surveillance recommendations, subtyping with REGA genotyping 2.0 tool. Time trends were examined for the frequency of t‐DRM across subtypes and transmission groups using logistic regression (R statistical platform, v. 3.1.0).ResultsFrequency of tDRM proved stable over time, with mutation frequency change from 11.3% in 2008 to 8.3% in 2013 [OR: 0.91 (95% CI 0.80–1,05), p=0.202] (Figure 1a). Also, no significant differences over time were noted for the subtype B (decrease from 8.4% 2008 to 6.2% in 2013 [OR: 0.94 (95% CI 0.79–1.11), p=0.45] and across non‐B variants [change from 22.6% 2008 to 23.1% in 2013, OR: 0.94 (95% CI 0.75–1.19), p=0.62]. When patient groups were stratified according to transmission route, in MSM there was a trend for a NNRTI t‐DRM decrease (from 6.8% 2008 to 1% in 2013, OR: 0.61 (95% CI 0.34–1.02), p=0.0655, slope −0.74%/year) (Figure 1b), related to the subtype B infected MSM (decrease from 7% 2008 to 1% in 2013, OR: 0.61 (95% CI 0.34–1.03), p=0.0662, slope −0.75%/year). Overall tDRM frequency decrease was also noted for the heterosexually infected patients [from 17.6% 2008 to 10.3% in 2013, OR: 0.83 (95% CI 0.67–1.02, p=0.077, slope −2.041%/year)] but did not associate with drug class (Figure 1c). In IDUs, the trends in t‐DRM frequency were not significant over time (change from 1.9% in 2008 to 0 in 2013 [OR:1.24 (95% CI 0.73–2.26), p=0.4)].ConclusionsThe frequency of t‐DRM in Poland is generally stable over time. Decrease in the overall tDRM frequency in heterosexual infected cases and NNRTI resistance in subtype B infected MSM may be related to the higher treatment efficacy of current cART.

AbstractIntroduction: 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.