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.

Comparison of clinical course of Mpox among HIV-negative and HIV-positive patients: A 2022 cohort of hospitalized patients in Central Europe.

Mpox has become the most significant orthopoxviral infection among humans. Since May 2022, there has been a multicountry outbreak of mpox across six continents. Retrospective observational cohort study of 94 patients with probable or confirmed mpox of whom 86.2% were hospitalized in Hospital for Infectious Diseases in Warsaw, Poland between May 16 and October 30, 2022. Most patients were young (median age: 31, IQR: 25-43 years), predominantly (88.3%) Polish men who have sex with men exposed most commonly in Poland (82.7%), Spain (6.2%), or Germany (4.9%). The median observed mpox incubation period was 7 (IQR: 4-8) days with the median hospitalization time of 7 (range: 2-24, IQR: 5-11) days. History of sexually transmitted infections (STIs) was common in the group (previous syphilis or hepatitis C virus in 33.3% and 17.3%, respectively, 6.2% of early syphilis or gonorrhea). A significant proportion (n = 43, 45.7%) of mpox cases were people with human immunodeficiency virus (HIV), all except one were on stable and virologically effective (88.4% with HIV viral load <50 copies/mL) antiretroviral treatment. Chemsex was reported in 34.6% of hospitalized cases, more commonly among people with HIV (48.5% vs. 25.0%, p = 0.029). None of the mpox infected patients presented with advanced HIV infection. Despite the fact that 6.3% of cases presented with >50 skin lesions the course of the disease was self-limited with no severe cases or deaths. There were no significant clinical or laboratory differences or complication rates between patients with and without HIV coinfection. Epidemiological and clinical characteristics of mpox in Poland are similar to other countries, but there were no targeted, population oriented interventions or vaccination programs. Mpox diagnosis provided an opportunity to screen and diagnose other STIs. As Central European populations, including refugees from Ukraine, are largely unvaccinated against mpox access to preventive vaccinations and antiviral therapy should be maximized.

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.

Study of the first clinical cases on monkeypox in Poland.

Monkeypox is a viral, zoonotic, emerging infectious disease that has become the most significant orthopoxviral infection among humans since the eradication of smallpox. It is endemic in Central and West Africa, and since May 2022 it has caused a multi-country outbreak in six continents. So far, no clinical cases of this disease have been observed in Poland. Monkeypox can be transmitted by any person, regardless of gender identity or sexual preferences, through direct contact with the secretion from skin lesions or through fomites contaminated with infectious material. Therefore, people infected with the monkeypox virus require isolation until the skin lesions heal completely and the scabs fall off, which is equivalent to the end of their infectivity. The paper presents a study of the first nine clinical cases of monkeypox in Poland, along with photographic documentation. All patients were young men, the vast majority of whom had contact with multiple sexual partners, and presented a higher prevalence of human immunodeficiency virus (HIV) infection than in the general population. The course of the disease was self-limited and no specific antiviral treatment was required by any of the patients. Nonetheless, there was a change in the route of transmission of the infection to sexual contact and an atypical clinical course of the disease, which resulted both in skin lesions initially appearing in the anogenital area, skin lesions occurring at various stages of development, and the appearance of skin lesions before the onset of general symptoms. In one of the patients, skin changes were not observed at all.

Inflammatory Bowel Disease in Adult HIV-Infected Patients-Is Sexually Transmitted Infections Misdiagnosis Possible?

BACKGROUND: The aim of our study was to describe 50 cases of inflammatory bowel disease (IBD) and HIV co-existence that are under medical supervision in Warsaw. METHODS: This was a retrospective descriptive study. Fifty HIV-infected patients, diagnosed with IBD during the years 2001-2019, were identified. IBD was diagnosed endoscopically and then confirmed by biopsy. All data was obtained from medical records. RESULTS: All studied patients were male with a median age of 33 years old (range 20-58 years). All, except one, were men who have sex with men (MSM). The median CD4 cell count was 482 cells/µL (range 165-1073 cells/µL). Crohn's disease (CD) was diagnosed in 7 patients (14%), ulcerative colitis (UC) in 41 patients (82%), and 2 patients (4%) had indeterminate colitis. Forty-nine patients (98%) reported a history of unprotected receptive anal intercourse and different sexual transmitted infections (STIs). Only in 10 patients (20%) were one or more IBD relapses observed. CONCLUSIONS: We recommend HIV testing for every MSM with IBD suspicion. Moreover, STIs testing should be performed in every IBD patient with colorectal inflammation, using molecular and serological methods. Persons who reported unprotected receptive anal intercourse seem to have the biggest risk of STI-associated proctitis or proctocolitis mimicking IBD.

Atypical Pulmonary Tuberculosis as the First Manifestation of Advanced HIV Disease-Diagnostic Difficulties.

Tuberculosis (TB) is the leading cause of morbidity, hospitalisations, and mortality in people living with HIV (PLWH). The lower CD4+ T-lymphocyte count in the course of HIV infection, the higher risk of active TB, and the higher odds for atypical clinical and radiologic TB presentation. These HIV-related alterations in TB presentation may cause diagnostic problems in patients not knowing they are infected with HIV. We report on a patient without any background medical conditions, who was referred to a hospital with a 4-month history of chest and feet pains, mild dry cough, fatigue, reduced appetite, and decreasing body weight. Chest X-ray revealed mediastinal lymphadenopathy, bilateral reticulonodular parenchymal opacities, and pleural effusion. A preliminary diagnosis of lymphoma, possibly with a superimposed infection was established. Further differential diagnostic process revealed pulmonary TB in the course of advanced HIV-1 disease, with a CD4+ T-lymphocyte count of 107 cells/mm3. The patient completed anti-tuberculous therapy and successfully continues on antiretroviral treatment. This case underlines the importance of screening for HIV in patients with newly diagnosed TB.

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.

Transmission Networks of HCV Genotype 1a Enriched With Pre-existing Polymorphism Q80K Among HIV-Infected Patients With Acute Hepatitis C in Poland.

BACKGROUND: Hepatitis C virus (HCV) resistance-associated variants (RAVs) have been shown to adversely affect treatment response of direct-acting antivirals. Identifying pre-existing RAVs and transmission networks among HIV/HCV genotype 1 (G1)-infected patients from Poland will assist in shaping surveillance strategies for HCV. METHODS: NS3 and NS5A sequences were obtained from samples of 112 direct-acting antiviral-naive G1 patients (45 G1a and 67 G1b), of which 74 were chronically infected and 38 were diagnosed with acute hepatitis C (AHC). RAVs were identified using geno2pheno, and 98 concatenated NS3/NS5A alignments were constructed to identify transmission clusters using a maximum likelihood approach. RESULTS: G1a was notably more prevalent compared with G1b among men-having-sex-with-men (MSM) (60.0% vs. 31.3%, P = 0.004), AHC cases (46.7% vs. 25.4%, P = 0.019), and patients diagnosed with syphilis (52.2% vs. 24.5%, P = 0.009). The overall NS3/NS5A RAVs frequency was 14.3% with variants occurring more often in G1a compared with G1b (27.5% vs. 5.2%, P = 0.005), mostly for NS3 due to the high prevalence of polymorphism Q80K. NS5A RAVs were only found in 2.9% of sequences. Significant clustering was observed for 73.5% of the Polish sequences, however, more common in G1a MSM compared with G1b (50.0% vs. 25.9%, P = 0.02). The identified clusters contained sequences originating from up to 5 Polish cities, located within a mean distance of 370 km. CONCLUSIONS: Close clustering of Polish strains suggests the presence of compartmentalized epidemics of MSM that fuel the spread of G1a variants. Particularly patients with AHC form a national transmission network, including clusters enriched with the NS3 Q80K polymorphism.

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.

The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus.

UNLABELLED: Debio-025 is an oral cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus activity in vitro. Its effect on viral load as well as its influence on intracellular Cyp levels was investigated in a randomized, double-blind, placebo-controlled study. Mean hepatitis C viral load decreased significantly by 3.6 log(10) after a 14-day oral treatment with 1200 mg twice daily (P < 0.0001) with an effect against the 3 genotypes (1, 3, and 4) represented in the study. In addition, the absence of viral rebound during treatment indicates that Debio-025 has a high barrier for the selection of resistance. In Debio-025-treated patients, cyclophilin B (CypB) levels in peripheral blood mononuclear cells decreased from 67 +/- 6 (standard error) ng/mg protein (baseline) to 5 +/- 1 ng/mg protein at day 15 (P < 0.01). CONCLUSION: Debio-025 induced a strong drop in CypB levels, coinciding with the decrease in hepatitis C viral load. These are the first preliminary human data supporting the hypothesis that CypB may play an important role in hepatitis C virus replication and that Cyp inhibition is a valid target for the development of anti-hepatitis C drugs.