Has COVID-19 Changed the Incidence and Profile of Late Presenters for HIV Infection in Lodz, Polish Reference Centre, Poland?

Objectives: The aim of this study was to compare the prevalence and characteristics of HIV late presenters (LPs) and advanced LPs (aLPs) registered in the Lodz HIV centre during the COVID-19 pandemic (2020-2021) with those of the pre-pandemic period (2017-2019). Methods: A retrospective analysis was performed of the predictive factors associated with HIV LPs and aLPs based on multivariable logistic regression. The patient entry into specialist HIV care after diagnosis during the pandemic was analysed. Results: Of 121 newly diagnosed HIV infections during the pandemic, 49.6% had late presentation and 36.4% had advanced HIV disease (AHD). In the pre-pandemic period, out of 154 newly diagnosed patients, 58.4% were LPs and 38.3% were aLPs. Independent risk factors for HIV late presentation were older age (OR: 1.04, 95% CI: 1.01-1.076; p = 0.008), diagnosis in hospital (OR: 5.63, 95% CI: 2.87-11.05; p < 0.001) and negative VDRL as compared to positive VDRL (OR: 2.48, 95% CI: 1.19-5.15; p = 0.015). The same predictive factors were associated with aLPs: older age (OR: 1.07, 95% Cl 1.04-1.11; p < 0.001), HIV diagnosis in hospital (OR: 4.25, 95% CI 2.17-8.29; p < 0.001) and negative VDRL as compared to positive VDRL (OR: 4.95, 95% CI 1.87-13.10; p = 0.001). HIV diagnosis during the pandemic was not a risk factor for late presentation nor for advanced late presentation. However, the time between HIV diagnosis and the first visit to an HIV centre was statistically lower in the pre-pandemic period (p = 0.0048); the median lengths of time between the date of HIV testing, the first visit to the centre and the initiation of ART did not differ between these two periods in LPs and aLPs (p > 0.05). Conclusions: The COVID-19 pandemic did not change the prevalence or characteristics of late presentation and aLPs among newly diagnosed patients, nor did it extend the time to enrolment in HIV care or ART introduction in these groups.

Phylodynamic evolution of HIV-1 A6 sub-subtype epidemics in Poland.

The human immunodeficiency virus type 1 (HIV-1) A6 sub-subtype is highly prevalent in Eastern Europe. Over the past decade, the dissemination of the A6 lineage has been expanding in Poland. The recent Russian invasion of Ukraine may further escalate the spread of this sub-subtype. While evolutionary studies using viral sequences have been instrumental in identifying the HIV epidemic patterns, the origins, and dynamics of the A6 sub-subtype in Poland remain to be explored. We analyzed 1185 HIV-1 A6 pol sequences from Poland, along with 8318 publicly available sequences from other countries. For analyses, phylogenetic tree construction, population dynamics inference, Bayesian analysis, and discrete phylogeographic modeling were employed. Of the introduction events to Poland, 69.94% originated from Ukraine, followed by 29.17% from Russia. Most A6 sequences in Poland (53.16%) formed four large clades, with their introductions spanning 1993-2008. Central and Southern Polish regions significantly influenced migration events. Transmissions among men who have sex with men (MSM) emerged as the dominant risk group for virus circulation, representing 72.92% of migration events. Sequences from migrants were found primarily outside the large clades. Past migration from Ukraine has fueled the spread of the A6 sub-subtype and the current influx of war-displaced people maintains the growing national epidemic.

Circulation of Human Immunodeficiency Virus 1 A6 Variant in the Eastern Border of the European Union-Dynamics of the Virus Transmissions Between Poland and Ukraine.

BACKGROUND: The human immunodeficiency virus (HIV) type 1 A6 variant is dominating in high-prevalence Eastern European countries, with increasing prevalence over the remaining regions of Europe. The recent war in Ukraine may contribute to further introductions of this A6 lineage. Our aim was to model the transmission dynamics of the HIV-1 A6 variant between Poland and Ukraine. METHODS: HIV-1 A6 partial pol sequences originating from Poland (n = 1185) and Ukraine (n = 653) were combined with publicly available sequences (n = 7675) from 37 other countries. We used maximum likelihood-based tree estimation followed by a bayesian inference strategy to characterize the putative transmission clades. Asymmetric discrete phylogeographic analysis was used to identify the best-supported virus migration events across administrative regions of Poland and Ukraine. RESULTS: We identified 206 clades (n = 1362 sequences) circulating in Poland or Ukraine (63 binational clades, 79 exclusively Polish, and 64 exclusively Ukrainian). Cross-border migrations were almost exclusively unidirectional (from Ukraine to Poland, 99.4%), mainly from Eastern and Southern Ukraine (Donetsk, 49.7%; Odesa, 17.6% regions) to the Central (Masovian, 67.3%; Lodz, 18.2%) and West Pomeranian (10.1%) districts of Poland. The primary sources of viral dispersal were the Eastern regions of Ukraine, long affected by armed conflict, and large population centers in Poland. CONCLUSIONS: The Polish outbreak of the A6 epidemic was fueled by complex viral migration patterns across the country, together with cross-border transmissions from Ukraine. There is an urgent need to include war-displaced people in the national HIV prevention and treatment programs to reduce the further spread of transmission networks.

Clinical Perspective on Human Immunodeficiency Virus Care of Ukrainian War Refugees in Poland.

BACKGROUND: The Russian invasion of Ukraine forced migration for safety, protection, and assistance. Poland is the primary sheltering country for Ukrainian refugees, providing support including medical care, which resulted in the rapid ∼15% increase in the number of followed-up people with human immunodeficiency virus (HIV) (PWH) in the country. Here, we present the national experience on HIV care provided for refugees from Ukraine. METHODS: Clinical, antiretroviral, immunological, and virologic data from 955 Ukrainian PWH entering care in Poland since February 2022 were analyzed. The dataset included both antiretroviral-treated (n = 851) and newly diagnosed (n = 104) patients. In 76 cases, protease/reverse transcriptase/integrase sequencing was performed to identify drug resistance and subtype. RESULTS: Most (70.05%) of the patients were female, with a predominance of heterosexual (70.3%) transmissions. Anti-hepatitis C antibody and hepatitis B antigen were present in 28.7% and 2.9% of the patients, respectively. A history of tuberculosis was reported in 10.1% of cases. Among previously treated patients, the viral suppression rate was 89.6%; 77.3% of newly HIV diagnosed cases were diagnosed late (with lymphocyte CD4 count <350 cells/µL or AIDS). The A6 variant was observed in 89.0% of sequences. Transmitted mutations in the reverse transcriptase were found in 15.4% treatment-naive cases. Two patients with treatment failure exhibited multiclass drug resistance. CONCLUSIONS: Migration from Ukraine influences the characteristics of HIV epidemics in Europe, with an increase in the proportion of women and hepatitis C coinfected patients. Antiretroviral treatment efficacy among previously treated refugees was high, with new HIV cases frequently diagnosed late. The A6 subtype was the most common variant.

Control of HBV infection in HIV/HBV co-infected patients treated with antiretroviral therapy - experience of Lodz Centre.

Aim of the study: To analyse the impact of combined antiretroviral therapy (cART) on selected markers of hepatitis B virus (HBV) infection, as well as assessment of the degree of fibrosis in antiretroviral patients who had HIV/HBV co-infection. Material and methods: Analysis of HBs antigen (HBsAg), anti-HBs, HBsAg levels, anti-HDV, anti-HCV, as well as assessment of HBV DNA viraemia and liver fibrosis by elastography in people with HIV/HBV co-infection. Results: Among 515 people under the care of the Lodz Centre at the time of treatment initiation 28 people (5.4%) HBsAg was detected. In HIV/HBV coinfected patients 14 people (50%) had anti-HCV and 6 (21.6%) had anti-HDV. In the group of 23 people treated with antiretroviral therapy for more than 12 months, all but one patient achieved HBV viraemia below the detection threshold. Six (26.1%) eliminated HBsAg, 3 (13%) produced anti-HBs. In the group we examined, four patients has fibrosis at level F4 on the Metavir scale - 3 patients were treated for more than 12 months and one patient was treated for less than 12 months. Conclusions: Antiretroviral treatment of patients co-infected with HIV/HBV based on tenofovir (in the form of disoproxil or alafenamide) with emtricitabine or lamivudine leads to virological control of HBV infection.

Gut Microbiota Diversity in HIV-Infected Patients on Successful Antiretroviral Treatment is Linked to Sexual Preferences but not CD4 Nadir.

The effects of HIV infection and antiretroviral therapy (ART) on the gut microbiome are poorly understood and the literature data are inconsistent. The aim of this study was to assess the alpha and beta diversity of the fecal microbiota in HIV-infected patients on successful antiretroviral therapy with regard to sexual preferences and CD4 nadir. Thirty-six HIV-infected ART-treated patients with HIV viremia below 20 copies/ml and CD4 > 500 cells/µl were divided into two subgroups based on CD4 nadir. The composition of the intestinal microbiota was assessed by 16SrRNA sequencing (MiSeq Illumina). The alpha and beta diversity were analyzed according to CD4 nadir count and sexual preference. Several alpha diversity indexes were significantly higher in the MSM group than in heterosexual patients. The alpha diversity did not differ significantly between patients with CD4 nadir > 500 cells/µl and CD4 nadir < 200 cells/µl. Beta diversity was also associated with sexual preference. A significant difference in Weighted Unifrac was observed between all MSM and all non-MSM participants (p = 0.001). The MSM group was more diverse and demonstrated greater distances in Weighted Unifrac than the non-MSM group. The relative abundance of the Prevotella enterotype was higher in the MSM than the non-MSM group. Sexual preferences demonstrated a stronger influence on alpha and beta diversity in HIV-infected patients following successful antiretroviral treatment than HIV infection itself. The observed lack of association between CD4 nadir and alpha and beta diversity may be caused by the restoration of the faecal microbiota following antiretroviral treatment.

Real-life study of dual therapy based on dolutegravir and ritonavir-boosted darunavir in HIV-1-infected treatment-experienced patients.

BACKGROUND: Dual therapy based on dolutegravir and ritonavir-boosted darunavir (DTG/DRV/r) is a combination of well-known drugs with a high genetic barrier to HIV resistance. METHOD: A retrospective analysis of all HIV-1 infected treatment-experienced patients who switched to DTG/DRV/r from May 2014 till March 2017 in 4 Polish centres-results of a 48-week treatment. RESULTS: The study group consisted of 59 men and 17 women. Median baseline parameters were: age- 42.7 years, CD4 cells count- 560.5 cells/µl, CD4 cells nadir- 150 cells/µl, number of prior antiretroviral regimens- 3. The introduction of dual therapy was primarily due to virologic failure (30 patients), adverse events on previous regimens (17 patients) and therapy simplification (27 patients). At week 48 the treatment was continued in 70/76 of patients and the median CD4 cells count increased from 560.5 to 641.0 cells/µl. The therapy was discontinued in six patients (1 -virologic failure, 1 -decrease of estimated glomerular filtration rate (eGFR), 1 -myalgia, 3 -lost to follow-up). At week 48 six patients had detectable viremia, but only in one patient viremia was higher than 200 copies/ml. At week 48 the level of serum total cholesterol of the investigated subjects was statistically significantly higher than at the moment of dual therapy introduction (185.8 mg/dl vs. 174.8 mg/dl- p<0.05). However, in patients previously not treated with TDF, there were no changes in lipid parameters during therapy. Proteinuria was observed in 13.2% of patients before the switch to dual therapy and in 7.1% of patients at week 48. CONCLUSIONS: The investigated dual therapy was effective and safe. The observed increase in lipid parameters only concerned the patients who had used a TDF-based regimen prior to analysed dual treatment.

The high incidence of late presenters for HIV/AIDS infection in the Lodz province, Poland in the years 2009-2016: we are still far from the UNAIDS 90% target.

The present study retrospectively analyses the prevalence of late diagnosis in patients with newly-diagnosed HIV infection in Lodz, Poland from January 2009 to December 2016, and assesses the predictive factors associated with late presenters. Late presentation is defined as a diagnosis of HIV with a CD4 count<350 cells/µL, or the occurrence of an AIDS- defining event, regardless of the CD4 cell count. Two hundred and fifty-nine (62.86%) patients were late presenters, 178 of whom (68.72%) were advanced late presenters (CD4 cell count below 200 cells/µL). Multivariate factors associated with late HIV presentation included referral from physician for HIV testing (OR: 3.95, 95% CI 2.42-6.46), older age (OR: 1.81, 95% CI: 1.38-2.38) and route of HIV transmission. Heterosexual patients (OR 1.98, 95% CI: 1.01-3.90), active drug users (OR: 3.49, 95% CI: 1.63-7.48) and patients who did not report the route of transmission (OR: 4.29, 95%: CI 1.45-12.62) were more likely to present late than MSM subjects. In conclusion, the majority of HIV-infected patients are still diagnosed late. There is a need for expanded testing not only in MSM group, in which HIV prevalence is the highest, but also in intravenous drug users, or among subjects who are heterosexual or from a higher age group.

The influence of NAFLD on the risk of atherosclerosis and cardiovascular diseases.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed countries and is associated with obesity, dyslipidaemia, diabetes, and metabolic syndrome. Atherosclerosis and cardiovascular diseases are also highly prevalent in this group of patients, due to the presence of shared risk factors. The incidences of coronary artery calcification, hypertension, aortic valve sclerosis, diastolic dysfunction, atherosclerotic plaques, and increased carotid intima-media thickness were more common in patients with NAFLD than in those without. The present paper reviews the medical literature concerning the association between NAFLD and cardiovascular events.

Intestinal Barrier Impairment and Immune Activation in HIV-Infected Advanced Late Presenters are Not Dependent on CD4 Recovery.

Damage of the mucosal barrier in HIV infection, microbial translocation, and immune activation can persist even in patients on successful antiretroviral therapy (ART) especially advanced late presenters. The aim of this study was to find factors that determine immune activation and bacterial translocation in HIV-infected advanced late presenters on suppressive ART. Forty-three late presenters (CD4 < 200 cells/µl prior to ART) on successful ART (more than 2 years of ART) with optimal and suboptimal CD4 recovery were enrolled into this study. The serum concentrations of intestinal fatty acid-binding peptide (I-FABP), zonulin-1, programmed cell death-1 protein (PCDP-1), and soluble (s)CD14 were measured using the ELISA test. We found higher serum levels of I-FABP and sCD14 in successfully antiretroviral-treated advanced late presenters compared to healthy subjects (p < 0.0001 and p = 0.0004). The serum concentration of PCDP-1 and zonulin-1 in HIV-infected patients did not differ from healthy controls. The levels of microbial translocation and immune activation markers were not associated with the degree of CD4 recovery. A serum concentration of I-FABP above 2.03 ng/ml was independently associated with a shorter ART (OR 0.78; p = 0.03). Older age was related to serum levels of sCD14 above 2.35 µg/ml (OR 1.1; p = 0.01). Higher serum levels of I-FABP and sCD14 in successfully antiretroviral-treated advanced late presenters compared to healthy subjects suggest an incomplete reconstruction of the intestinal barrier and sustained immune activation despite good CD4 recovery. It was not the CD4 level, but the length of the suppressive ART that was found to be associated with the restoration of the intestinal barrier.

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. M: ethods 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.